Management of sporadic desmoid-type fibromatosis: a European consensus approach based on patients' and professionals' expertise - a sarcoma patients EuroNet and European Organisation for Research and Treatment of Cancer/Soft Tissue and Bone Sarcoma Group initiative.
Desmoid-type fibromatosis (DF) is a rare monoclonal, fibroblastic proliferation characterised by a variable and often unpredictable clinical course. It may affect nearly all parts of the body including extremities, trunk and abdomen. Considering the variable clinical presentations, anatomic locations and biological behaviours, an individualised treatment approach is required. No established or evidence-based approach for the treatment of this neoplasm is available as of today. Therefore, we propose a consensus treatment algorithm based on a round table meeting bringing together sarcoma experts from the European Organisation for Research and Treatment of Cancer (EORTC) Soft Tissue and Bone Sarcoma Group (STBSG) with patient advocates from Sarcoma Patients EuroNet (SPAEN). The aim of the meeting was to develop - for the first time ever - a consensus approach based on professionals' AND patients' expertise. As a fundamental prerequisite, all patients should be discussed in a multidisciplinary setting in centres or professional networks with a specific expertise in the disease.


Authorial intentions and metaphor comprehension.
Three experiments investigated the role of authorial intentions in metaphor comprehension. In these studies, subjects read metaphoric (e.g., "A family album is like a museum"), literal (e.g., "An art gallery is like a museum"), and anomalous (e.g., "A tortoise shell is like an art gallery") comparisons and rated their degree of meaningfulness (Experiment 1), made speeded decisions as to whether each phrase was meaningful or not (Experiment 2), or wrote out interpretations of each comparison statement (Experiment 3). The subjects were told that the comparisons were written either by famous 20th century poets or by a computer program that randomly generated the statements from a list of words. Our general hypothesis was that knowing that intentional agents (the poets) authored the different comparisons should facilitate subjects' comprehension of the metaphors. Experiment 1 showed that subjects rated both metaphoric and literal comparisons as being more meaningful in the poet condition than when these statements were supposedly written by computer. Experiment 2 demonstrated that subjects were faster in making their meaningfulness judgments for metaphors in the poet condition than in the computer context, but that subjects were also slower in rejecting anomalous comparisons when these were supposedly written by the poets. Experiment 3 indicated that subjects produced more meanings or interpretations for comparisons presumably written by poets than by computer. These results highlight the importance of implied, authorial intentions in understanding metaphorical statements. We discuss the implications of this work for psycholinguistic theories of figurative language comprehension, as well as for theories of literary interpretation.


Poncirus Trifoliata (L.) Raf. Extract Inhibits the Development of Atopic Dermatitis-like Lesions in Human Keratinocytes and NC/Nga mice.
This study investigated the anti-allergic effect of Poncirus trifoliata (L.) Raf. (PT) on human keratinocytic HaCaT cells in vitro and on 2,4-dinitrochlorobenzene (DNCB)-induced atopic dermatitis-like lesions in vivo. The release of TARC, MCP-1, IL-6 and IL-8 is increased by IFN-γ and TNF-α in HaCaT cells, and PT extract suppressed the increased production of TARC, MCP-1, IL-6, and IL-8. PT extract recovered the expression of filaggrin decreased by IFN-γ and TNF-α. in vivo experiment, PT administration decreased the skin severity score, thickening of the epidermis, movement of inflammatory cells into the dermis, and serum IgE level as compared to DNCB treatment. Moreover, the decrease of filaggrin and loricrin induced by DNCB treatment was recovered by PT administration. The levels of IL-4, IL-5, IL-13 and eotaxin in mouse splenocytes increased after treatment with concanavalin A, and the secretions of IL-4, IL-5, IL-13 and eotaxin were lower in the PT-treated group than in the DNCB group. These findings may indicate that PT is useful in drug development for the treatment of AD.


Response to acute changes in salinity of two different muscle type creatine kinase isoforms, from euryhaline teleost (Oreochromis mossambicus) gills.
Two CKM isoforms (CKM1 and CKM2) from the gills of tilapia (Oreochromis mossambicus) were obtained after transfer from freshwater (FW) to seawater (SW, 25 ppt). Based on the 5' and 3' RACE, the identity of CKM1 and CKM2 was determined to be 59% in the 5'-untranslated region (5'-UTR) and 41.9% in the 3'-UTR. Using Northern blot hybridization with the CKM1 and CKM2 3'-UTR probes, CKM1 and CKM2 were found to be expressed in muscle, heart and gill. The levels of these two different CK isoforms (CKM1 and CKM2) were shown to be different in FW than after acute SW transfer, showing that CKM isoforms respond to changes in salinity.


Improved biocompatibility of intraocular lenses by heparin surface modification: a 12-month implantation study in monkeys.
To evaluate the long-term biocompatibility and potential side effects of heparin surface modification of a poly(methyl methacrylate) intraocular lens (IOL), a heparin surface modified IOL was implanted in the left posterior chamber of 24 cynomolgus monkeys and a reference IOL (without surface modification) was implanted in the right eye in 12 of these animals. Twelve eyes were not operated on. Eleven eyes in seven monkeys were lens extracted as a control of the surgical method. Slitlamp examinations and intraocular pressure recordings were made one day, one and two weeks, and 1, 2, 2 1/2, 3 1/2, 6, 8, 10, and 12 months after the operation. Eleven monkeys were sacrificed after 3 1/2 months and the remaining animals after 12 months for morphological examination of the eyes. Slitlamp and morphological examinations showed that cell deposits, pigmentation, and posterior synechias were significantly less in eyes with heparin surface modified IOLs than in eyes with reference IOLs throughout the 12-month observation period. The intraocular pressure was equally reduced in eyes with heparin surface modified IOLs and reference IOLs for about one month, after which it returned to normal. No side effects following the implantation of heparin surface modified IOLs were observed. We concluded that heparin surface modification of IOLs is efficient for long-term reduction of cell deposits and posterior synechias after implantation in monkey eyes and may also be effective in lowering the degree of side effects to IOL implantation in humans.


Variation in the terminology and methodologies applied to the analysis of water holding capacity in meat research.
Studies examining meat quality variation, possibly resulting from animal physiology, processing, or ingredient additions, are likely to include at least one measure of water holding capacity (WHC). Methods for evaluating WHC can be classified as direct or indirect. Direct methods either gauge natural release of fluids from muscle or require the application of force to express water. The indirect methods do not actually measure WHC. They attempt to separate meat into two or three categories based on predictions of direct method results: the extreme of high and low WHC and an optional 'normal' group. Considerable statistical analyses are required to generate these predictive models. Presently, there are inconsistent terms (e.g., water holding, WHC, water binding, water binding potential/capacity) used to describe WHC and no standardized techniques recommended to evaluate it. To ensure that results can be compared across different laboratories, a better consensus must be reached in how these terms are employed and how this critical parameter is determined.


Biodegradable Long-Acting Injectables: Platform Technology and Industrial Challenges.
Long-acting injectables have been used to benefit patients with chronic diseases. So far, several biodegradable long-acting platform technologies including drug-loaded polymeric microparticles, implants (preformed and in situ forming), oil-based solutions, and aqueous suspension have been established. In this chapter, we summarize all the marketed technology platforms and discuss their challenges regarding development including but not limited to controlling drug release, particle size, stability, sterilization, scale-up manufacturing, etc. Finally, we discuss important criteria to consider for the successful development of long-acting injectables.


The effect of EDTA with and without ultrasonics on removal of the smear layer.
This study evaluated in vitro effectiveness of 17% EDTA with and without ultrasonics on smear layer removal. One hundred and five extracted premolars randomly divided into seven groups were instrumented with different final irrigating protocols: group A (Sal3US), saline for 3 minutes with ultrasonics; groups B (Na3) and C (Na3US), 1% sodium hypochlorite for 3 minutes without and with ultrasonics, respectively; groups D (ED3) and E (ED3US), 17% EDTA for 3 minutes without and with ultrasonics, respectively; and groups F (ED1) and G (ED1US), 17% EDTA for 1 minute without and with ultrasonics, respectively. Specimens were examined under scanning electron microscope and scored for smear layer and debris removal. Statistical analysis showed that groups with EDTA and ultrasonic irrigation, groups E (ED3US) and G (ED1US), had significantly more specimens with complete smear layer and debris removal. There was no significant difference between groups E (ED3US) and G (ED1US). A 1-minute application of combined use of EDTA and ultrasonics is efficient for smear layer and debris removal in the apical region of the root canal.


Fabrication of two-dimensional metal-organic framework nanosheets/PDA composites as mixed-mode stationary phase for chromatographic separation.
The synthesis of two-dimensional metal-organic frameworks (2D MOFs)/polymer core-shell composites is reported which were composed of polydopamine modified 2D Zr-1,3,5-(4-carboxylphenyl)-benzene (2D Zr-BTB) nanosheets and silica microspheres via a double-solvent approach. In this way, the composites were obtained under the condition of two solvents with different polarities to avoid agglomeration and uneven modification of most MOFs particles on the surface of the silica, existing inevitably in the one-pot method. Compared with the reported MOFs@silica composites adopting one-pot solvent method, the prepared composites exhibited significantly enhanced separation performance for sulfonamides, antibiotics, nucleosides, and polycyclic aromatic hydrocarbons compounds. Furthermore, the retention mechanisms were demonstrated by studying the relationships of chromatographic retention factors of tested analytes versus a variety of parameters under RPLC and HILIC modes, respectively. The superior chromatographic repeatability and stability were validated through the relative standard deviations of the retention time and/or column efficiency, which were found to be less than 0.8% and 0.9%, respectively. The material showed efficient separation ability for several types of compounds and provided another selectivity for preparing composites based on 2D MOFs nanosheets and other functional molecules.


Humanized tumor mice--a new model to study and manipulate the immune response in advanced cancer therapy.
The immunological impact on antibody-based anticancer therapies remains incompletely understood due to the lack of appropriate animal models for in vivo analysis. Here, we present a novel humanized tumor mouse (HTM) model, generated by concurrent transplantation of human hematopoietic stem cells (HSCs) and human breast cancer cells in neonatal NOD-scid IL2Rγ(null) mice. Five weeks after intrahepatic transplantation, a functional human immune system was developed in all organs, and, in addition, tumor cells were detectable in lung and bone marrow (early dissemination). After 3 months posttransplant, tumor-cell effusions and macroscopic tumors associated with liver or spleen were found. Furthermore, disseminated cells in different lymphoid and nonlymphoid organs were measurable. Tumor growth was accompanied by specific T-cell maturation and tumor cell-specific T-cell activation. In addition, Natural-Killer cell accumulation and activation were observed in HTM, which was further enhanced upon IL-15 treatment facilitating the possibility of immune cell modulation in, e.g., antibody-dependent cellular cytotoxicity-based immunotherapeutic approaches. This novel mouse model makes it possible to combine transfer of MHC mismatched tumor cells together with human HSCs resulting in a solid coexistence and interaction without evidence for rejection. Overall, humanized tumor mice represent a powerful in vivo model that for the first time permits the investigation of human immune system-related target cancer therapy and resistance.


Prevention and Management of Common Adverse Effects of Ketamine and Esketamine in Patients with Mood Disorders.
The emerging roles of ketamine and esketamine as effective rapid-acting antidepressants hold promise for patients suffering from treatment-resistant depression and/or major depressive disorder with suicidality. Practitioner familiarity with common tolerability/safety concerns along with pragmatic prevention and management strategies are needed to reduce patient burden and improve the acceptability and accessibility of these treatments. The most common treatment-emergent adverse events associated with ketamine/esketamine are dissociation, anxiety, nausea, increased blood pressure, and headache. The majority of side effects are mild, transient, dose dependent, and attenuate with subsequent treatments. Patient selection, baseline physical and psychiatric assessments, and an appropriate setting are critical first steps in the prevention and mitigation of adverse events. Patient education and supportive interventions play central roles in the prevention and management of select adverse events. Severe and/or clinically significant adverse effects may necessitate the judicious use of adjunctive medications. Moreover, practitioners must remain vigilant to the potential for abuse liability and long-term adverse events, for which there are insufficient data. This article succinctly reviews common treatment-emergent adverse events of ketamine and esketamine within the context of mood disorders, and provides practical suggestions for prevention and management at point-of-care.


Sonographic examination does not predict twin growth discordance accurately.
To assess the accuracy of estimating birth weight among twins with discordancy (intra-pair difference in actual birth weight of more than 25%) and to determine the relative accuracy of an intra-pair difference in abdominal circumference (delta AC) of 20 mm or more or in estimated fetal weight (delta EFW) of 25% or more for the identification of discordant growth in twins. Over a 6-year period, we identified all non-anomalous twin pairs with gestational ages greater than 23 weeks and sonographic examinations within 3 weeks of birth. Ultrasonographic biometry of both twins included AC, head circumference, and femur length; these indices were used to estimate fetal weight by Hadlock's formula. Likelihood ratios, receiver-operating characteristic curves, and prediction limits were applied to assess the accuracy of the two diagnostic methods to predict an abnormal outcome. A total of 242 twin pairs were studied. The mean gestational age among the 21 twins with abnormal growth (30.6 +/- 4.6 weeks) was significantly less than among the 221 twins with normal growth (33.2 +/- 4.0 weeks) (P < .005). The biometric measurements of fetal parts, sonographic estimate of fetal weight, and actual birth weight for both fetuses were significantly less for discordant twin pairs (P < .05). The accuracy of predicting birth weight, as determined by mean error and percentage of the estimate within 10% of the actual weight, was similar between the groups. Receiver-operating characteristic curves showed that both diagnostic tests yielded areas under the two curves not significantly different from the area under the nondiagnostic line (P > .05). Most important, prediction limit calculations indicated that a 90% certainty that the actual birth weight discordance was at least 25% was achievable only if delta AC was 172 mm or greater or delta EFW was 112% or more. The most popular current methods (difference in AC or EFW) for predicting discordant growth in twin gestations have limited accuracy when held to a standard for discordance that requires a birth weight difference of at least 25%.


A nomogram prognostic index for risk-stratification in diffuse large B-cell lymphoma in the rituximab era: a multi-institutional cohort study.
We aimed to establish a predictive prognostic risk-stratification model for diffuse large B-cell lymphoma (DLBCL) in the rituximab era. The data of 1406 primary DLBCL patients from the Sun Yat-Sen University Cancer Center were analysed to establish a nomogram prognostic index (NPI) model for predicting overall survival (OS) based on pre-treatment indicators. An independent cohort of 954 DLBCL patients from three other hospitals was used for external validation. Age, performance status, stage, lactate dehydrogenase, number of extranodal sites, BCL2, CD5 expression, B symptoms and absolute lymphocyte and monocyte count were the main factors of the NPI model and could stratify the patients into four distinct categories based on their predicted OS. The calibration curve demonstrated satisfactory agreement between the predicted and actual 5-year OS of the patients. The concordance index of the NPI model (0.794) was higher than the IPI (0.759) and NCCN-IPI (0.750), and similar results were obtained upon external validation. For CD5 + DLBCL patients, systemic treatment with high-dose methotrexate was associated with superior OS compared to R-CHOP-based immunochemotherapy alone. We established and validated an accurate prediction model, which performed better than IPI and NCCN-IPI for prognostic stratification of DLBCL patients.


Significance of subchorionic haemorrhage and pregnancy outcome in threatened miscarriage to predict miscarriage, pre-term labour and intrauterine growth restriction.
Subchorionic haemorrhage in the 1st trimester of pregnancy can be seen in some patients and the significance of it is controversial. In this study, subchorionic haemorrhage was found to be significantly associated with increased risk of miscarriage and IUGR. On the other hand, we did not see a significant relation between pre-term labour and subchorionic haemorrhage. We hope these findings will help clinicians in their practice about pregnancy follow-up.


Impacts of reducing air pollutants and CO2 emissions in urban road transport through 2035 in Chongqing, China.
The road transport sector in megacities is confronted with pressing local air pollution and carbon dioxide (CO2) control issues. To determine effective policy instruments for saving energy and the co-control of air pollutants and CO2, several mainstream measures were examined and compared in Chongqing's road transport sector from 2017 to 2035. An integration assessment framework was developed by combining the Long-range Energy Alternatives Planning (LEAP) system and a set of quantitative methods for evaluating the co-benefits of emission reductions (including the air pollutant equivalent (APeq), co-control coordinate system, and pollutant reduction cross-elasticity (Elsa/b)). Results showed that the shifting transportation modes scenario presented the most significant potential for energy-saving and emission reductions, reducing energy use by 30.9% and air pollutants and CO2 emissions by approximately 27-32% compared with the business as usual (BAU) scenario in 2035. The improving energy efficiency scenario also provided significant co-benefits for reducing air pollutants and CO2 emissions. Nevertheless, the promoting alternative fuel scenario may increase fine particulate matter (PM2.5) emissions by 2.2% compared to BAU in 2035 under the cleanness of regional electricity in 2017. Our findings suggest that the shifting transportation modes were effective measures to reduce air pollutants and CO2 in the short term synergistically, and highlighted the importance of cleaner electricity generation to develop electric vehicles in the medium and long term.


Anhydride-linked β-cyclodextrin-bonded silica stationary phases with enhanced chiral separation ability in liquid chromatography.
β-Cyclodextrin can be functionalized by derivation of reactive hydroxyl on the ring due to its special chiral environment and structural characteristics, which can be used to identify or separate a variety of chiral substance. In this manuscript, a series of excellent chiral stationary phases for high-performance liquid chromatography were developed for enantioseparation by using anhydride modified β-cyclodextrin bearing chiral (R/S)-α-phenethylamine or (S)-(+)-2-amino-1-propanol. They were characterized by elemental analysis, Fourier transform infrared spectra (FT-IR), thermogravimetric analysis (TGA), scanning electron microscopy (SEM), and BET. These chiral stationary phases presented good resolution and repeatability, about 17 kinds of enantiomers were effectively separated. And most of enantiomers were separated better than those reported in the literature in the same both normal and reversed phase modes. The RSD values of Rs for repeatability and column-to-column were below 0.44% and 2.83%, respectively. All results revealed that these new CSPs show great prospect for chiral separation in actual applications.


Volar plating: functional recovery of the pronator quadratus.
The pronator quadratus (PQ) is reflected in the surgical approach to the distal radius. This study explores the functional strength of PQ, 12 months after volar plating without repair of PQ. A total of 135 patients were identified from our prospectively collected database. All volunteers had grip strength and pronation power tested in the treated and contralateral forearms at 45, 90 and 135 degrees of elbow flexion using a custom-built torque measuring device and hydraulic hand dynamometer to evaluate forearm pronation. Twenty-seven participants were included in the study. No significant difference was identified in mean peak pronation torque between the volar plated and non-treated forearms. Pronation strength was identified as being independent of angle of elbow flexion. Grip strength was correlated with forearm pronation showing no significant difference between groups. Our results suggest adequate long-term (15-32 months) functional recovery of the pronator quadratus after volar plating. III.


A private practice experience with adenocarcinoma of the prostate in men less than 50 years old.
We have found a sharp increase in the number of men less than 50 years old with adenocarcinoma of the prostate. In the last 4 years we have found 9 new patients less than 50 years old, which far exceeds the expected number. Prompted by this increase we reviewed our experience with prostatic carcinoma in young men. Our findings of 11 of 256 patients (4 per cent) and good survival from 6 months to 15 years (90 per cent) are at variance with previously published reports. We attribute the increased number of patients with adenocarcinoma of the prostate to our willingness to biopsy small "unimportant" nodules in the prostate. Whether these findings reflect an actual increase in the incidence of prostatic carcinoma in young men or simply an increase in the frequency of diagnosis of previously unrecognized lesions is not clear.


Dehydrated human amnion/chorion membrane allografts for myelomeningocele and wound reconstruction.
A growing body of literature demonstrates the clinical promise of dehydrated human amnion/chorion membrane (dHACM), a cryopreserved tissue product derived from placental amniotic membrane, to enhance post-operative wound healing. The purpose of this study is to review the potential of dHACM to facilitate post-surgical and myelomeningocele wound repair. A comprehensive literature search of PubMed was conducted to identify studies investigating dHACM use in pediatric and surgical wound care published from inception to October 2020. For each study, patient characteristics, wound characteristics, and outcomes following dHACM application were documented and assessed. Of the 190 articles reviewed, 15 publications were included in the final analysis. Results demonstrated that the average wound healing time varied across clinical indications (e.g., 14 days for trauma reconstruction to 116 days for Moh's surgery repair). Across indications, pediatric patients had shorter healing periods compared to adults (P < 0.01). Chronic wounds (> four weeks old) were documented in both adult (n = 3) and pediatric (n = 2) wound repair publications; all chronic surgical wounds demonstrated complete wound closure with dHACM. No complications from dHACM use were reported. Advantages of dHACM included increased patient satisfaction, cost-savings, and faster wound healing. We then present two cases of myelomeningocele wound repair facilitated successfully by dHACM. Overall, dHACM proves to successfully expedite wound repair in pediatric patients with chronic or complicated wounds such as those from myelomeningocele repair. It is important for surgeons to consider wound duration, size, and patient age to better predict graft success in enhancing wound repair.


Clinical evaluation of a restorative resin with organic filler. Preliminary report and discussion.
Assessment of 192 Class III and V Isopast restorations was made up to 18 months after insertion. Within this time, there was no evidence to suggest early, marked marginal failure. Continued evaluation is required to assess marginal adaptation and discolouration over a longer period.


Inverted papilloma of the renal pelvis.
The authors describe a case of inverted papilloma. It is relatively rare and generally appears as a benign tumour.


Ultrastructural localization of immunoglobulin and fibrin in lichen planus.
To demonstrate the exact localization of immunoglobulin and fibrin deposits in skin lesions of lichen planus, we employed the peroxidase-antiperoxidase technique, both light and electron microscopically. IgM is shown to be deposited preferentially in and on the cytoid bodies all over their cut surface in a typical stippled pattern, partly obscuring the characteristic fibrillar substructure. All other structures such as the basal lamina are devoid of IgM deposits. Fibrin (F) is also present in cytoid bodies but in a lesser amount; it is characteristically deposited on and along the basal lamina and its reduplications in the uppermost strata of the dermis. Our results indicate that IgM deposition in cytoid bodies occurs at a very early stage during the formation of these structures and that fibrinogen exhibits a specific affinity not only to cytoid bodies but also to basal lamina material.


The effect of oxidants on neutrophil-mediated degradation of glomerular basement membrane collagen.
The contribution of activated oxygen species to neutrophil-mediated degradation of basement membrane collagen was investigated. In preliminary experiments, pre-exposure of either albumin or glomerular basement membrane to neutrophil myeloperoxidase with H2O2 and chloride increased their susceptibility to proteolysis 2-3-fold. In the basement membrane model, neutrophils are stimulated by trapped immune complexes to adhere, produce oxidants and degranulate. Degradation, measured as the amount of hydroxyproline solubilised, was due to neutral proteinases, particularly elastase, and depended on cell number and the amount of proteinase released. Experiments with oxidant scavengers and inhibitors and with neutrophils from donors with chronic granulomatous disease or myeloperoxidase deficiency showed that oxidants did not affect degradation of the basement membrane when this was measured on a per cell basis. However, oxidative inactivation of the released granule enzymes occurred. Activities of elastase, beta-glucuronidase and lysozyme were 1.5-2-times higher in the presence of catalase, but were unaffected by superoxide dismutase or hydroxyl radical scavengers. Inactivation did not occur with chronic granulomatous disease or myeloperoxidase deficient neutrophils. When related to the activity of released elastase, or to other degranulation markers, collagen degradation was decreased in the presence of catalase, or with chronic granulomatous disease or myeloperoxidase deficient cells. This implies that the basement membrane was made more digestible by myeloperoxidase-derived oxidants, as occurred in the cell-free experiments. Taken together, the results indicate that neutrophil oxidants have two opposing effects. They increase the susceptibility of the collagen to proteolysis and inactivate the proteinases responsible.


Lactotripeptides effect on office and 24-h ambulatory blood pressure, blood pressure stress response, pulse wave velocity and cardiac output in patients with high-normal blood pressure or first-degree hypertension: a randomized double-blind clinical trial.
Contrasting data partially support a certain antihypertensive efficacy of lactotripeptides (LTPs) derived from enzymatic treatment of casein hydrolysate. Our aim was to evaluate this effect on a large number of hemodynamic parameters. We conducted a prospective double-blind randomized clinical trial, which included 52 patients affected by high-normal blood pressure (BP) or first-degree hypertension. We investigated the effect of a 6-week treatment with the LTPs isoleucine-proline-proline and valine-proline-proline at 3 mg per day, assumed to be functional food, on office BP, 24-h ambulatory BP monitoring (ABPM) values, stress-induced BP increase and cardiac output-related parameters. In the LTP-treated subjects, we observed a significant reduction in office systolic BP (SBP; -5±8 mm Hg, P=0.013) and a significant improvement in pulse wave velocity (PWV; -0.66±0.81 m s(-1), P=0.001; an instrumental biomarker of vascular rigidity). No effect on 24-h ABPM parameters and BP reaction to stress was observed from treatment with the combined LTPs. LTPs, but not placebo, were associated with a mild but significant change in the stroke volume (SV), SV index (markers of cardiac flow), the acceleration index (ACI) and velocity index (VI) (markers of cardiac contractility). No effect was observed on parameters related to fluid dynamics or vascular resistance. LTPs positively influenced the office SBP, PWV, SV, SV index, ACI and VI in patients with high-normal BP or first-degree hypertension.


The value of quantitative gallium-67 single-photon emission tomography in the clinical management of malignant external otitis.
Malignant external otitis (MEO) is a severe infectious disorder usually caused by Pseudomonas aeruginosa, which most frequently affects diabetic patients. Due to its rarity, the diagnosis of MEO is often not made promptly. Extension into deeper structures or chronic osteomyelitis may occur without signs of infection on local clinical examination. Of the imaging techniques, magnetic resonance imaging provides a fairly adequate picture of the spread of the disease, but, as with computed tomography (CT) scanning and bone scintigraphy, the images remain unchanged for a long time after disease regression. The objective of this study was to establish whether quantitative gallium-67 single-photon emission tomography (SPET) represents an accurate method for the assessment of infection and, moreover, for the monitoring of therapeutic effect. Eight patients (five males, three females) with the clinical diagnosis of MEO were studied. In three patients antibiotic treatment was prolonged for several weeks because visual analysis of gallium scintigraphy still showed slightly increased uptake in the affected area on the first follow-up scan. In one patient, it was decided to stop antibiotic treatment despite a slight increase in uptake on the second follow-up scan. Lesion to non-lesion (L/NL) ratios obtained from 67Ga SPET images at initial diagnosis and during follow-up were assessed in correlation with clinical and biochemical data and with the results of CT scans. In addition to a raised erythrocyte sedimentation rate (ESR), all patients showed increased uptake on the affected side, with L/NL ratios ranging from 1.4 to 3.6 at the time of diagnosis. CT scans failed to demonstrate abnormalities in four patients. Including four scans demonstrating slightly increased uptake in the affected area, L/NL ratios after 6-8 weeks of antibiotic treatment were 1.0+/-0.1. Despite a persistently elevated ESR in the majority of patients, none of them demonstrated local recurrence or complications during follow-up. In all patients, leucocyte count was within the normal range throughout the course. No relation was found between the slightly increased uptake on the follow-up scans and surgical treatment. It is concluded that in addition to the visual analysis of 67Ga SPET imaging, L/NL ratios should be calculated for a more accurate assessment of disease activity in MEO. Despite visually slightly increased uptake, L/NL ratios of 1.0+/-0.1 during follow-up are highly indicative of complete recovery, regardless of ESR values or leucocytosis. CT scans are of little value for diagnosis or for monitoring of therapeutic effect.


Development of ST-elevation Myocardial Infarction Programs in Developing Countries: Global Challenges and Solutions.
Cardiovascular disease (CVD) is the leading cause of death worldwide; approximately 80% of CVD deaths occur in low-income and middle-income countries (LMICs). The epidemiologic transition to a high burden of ischemic heart disease (IHD) has happened with greater rapidity in LMICs than in high-income countries. The absolute number of individuals with premature IHD has increased substantially. Higher event rates are observed compared with high-income countries. The technological capability to do extraordinary things for patients has increased, as has patient demand, in a setting of constrained resources and expensive health care of variable quality.


[Preserving of continence in the treatment of familial polyposis of the colon. Technic of peeling off of the rectal mucosa].
The paper deals with the problem of preserving the rectum in the therapy of familial polyposis of the colon. According to our own experience and recent publications we cannot support the preservations of the rectum. Nevertheless, in order to preserve continence, we peel off the cylinder of the mucosa of the rest of the rectum (Devine und Ravitch). We have modified this procedure according to the Hochenegg pull-through and have operated successfully on two patients.


Rapid and high-capacity ultrasonic assisted adsorption of ternary toxic anionic dyes onto MOF-5-activated carbon: Artificial neural networks, partial least squares, desirability function and isotherm and kinetic study.
The present paper focused on the ultrasonic assisted simultaneous removal of fast green (FG), eosin Y (EY) and quinine yellow (QY) from aqueous media following using MOF-5 as a metal organic framework and activated carbon hybrid (AC-MOF-5). The structure and morphology of AC-MOF-5 was identified by SEM, FTIR and XRD analysis. The interactive and main effects of variables such as pH, initial dyes concentration (mgL-1), adsorbent dosage (mg) and sonication time (min) on removal percentage were studied by central composite design (CCD), subsequent desirability function (DF) permit to achieved real variable experimental condition. Optimized values were found 7.06, 5.68, 7.59 and 5.04mgL-1, 0.02g and 2.55min for pH, FG, EY and QY concentration, adsorbent dosage and sonication time, respectively. Under this conditions removal percentage were obtained 98.1%, 98.1% and 91.91% for FG, EY and QY, respectively. Two models, namely partial least squares (PLS) and multi-layer artificial neural network (ANN) model were used for building up to construct an empirical model to predict the dyes under study removal behavior. The obtained results show that ANN and PLS model is a powerful tool for prediction of under-study dyes adsorption by AC-MOF-5. The evaluation and estimation of equilibrium data from traditional isotherm models display that the Langmuir model indicated the best fit to the equilibrium data with maximum adsorption capacity of 21.230, 20.242 and 18.621mgg-1, for FG, EY and QY, respectively, while the adsorption rate efficiently follows the pseudo-second-order model.


Effect of blinking on tear elimination as evaluated by dacryoscintigraphy.
To document the change in drainage of tears that occurs with blinking, the authors evaluated 17 lacrimal systems of 12 individuals with dacryoscintigraphy. A significant difference in tear drainage was found by keeping the eyelids closed during the first 2 minutes after drop placement (P less than 0.03), but not from 2 to 5 minutes (P greater than 0.4). Retardation of tear drainage after droplet placement can be achieved by simple eyelid closure for 2 minutes.


Patient understanding and satisfaction in informed consent for total knee arthroplasty: a randomized study.
Informed consent is a critical component of all surgical procedures, but patients' understanding and recall of the potential risks/benefits is poor. We hypothesized that utilization of multiple standardized education modalities in the informed consent process would allow for better retention and a more informed patient. A total of 151 patients undergoing primary total knee arthroplasty (TKA) were randomized to 3 groups: group 1 received standardized informed consent and a paper handout detailing the risks/benefits of TKA; group 2 received standardized informed consent, a paper handout, and a video discussing the risks/benefits of TKA; and group 3 followed the same process as group 2 plus formal nurse education. All patients completed a 15-item questionnaire (risks, indications, and expectations) immediately following this consent process on the morning of surgery and 6 weeks postoperatively. We used t-test and analysis of variance for data analyses. There was no difference (P = 0.79) in satisfaction with the consent process between the 3 groups; 92-97% of the patients rated the consent process as good to excellent at all time points. The number of correct answers did not differ significantly between the groups at any time period (P = 0.31-0.81). Scores dropped significantly (P = 0.004) from preoperatively to the 6-week postoperative visit in all groups combined. A higher level of satisfaction with the process was reflected in higher scores preoperatively in all groups (P = 0.028). Preoperatively, patients satisfied with the consent process may have better recall of risks/benefits and expectations of surgery. Neither retention nor satisfaction was influenced by reinforcement methods, such as video or nurse education; they may therefore be unnecessary.


Single flap approach with or without enamel matrix derivative in the treatment of severe supraosseous defects: a retrospective study.
To comparatively evaluate the clinical effectiveness of the single flap approach (SFA) with and without enamel matrix derivative (EMD) in the treatment of supraosseous defects (SDs) associated with deep pockets. Twenty patients, each contributing one SD associated with a deep (≥ 6 mm) pocket and treated with buccal SFA either alone (SFA group; n = 10) or in combination with EMD (SFA+EMD group; n =10), were retrospectively selected. Clinical parameters (probing depth, PD; clinical attachment level, CAL; gingival recession, REC) had been assessed at pre-surgery and 12 months post-surgery. Complete wound closure was observed in 70% and 80% of defects treated with SFA and SFA+EMD, respectively. Treatments resulted in a significant PD reduction of 3.1±1.0 mm (p=0.005). In SFA+EMD group, 100% of closed pockets was obtained, while 90% of closed pockets was observed in SFA group. Both treatments resulted in a significant CAL gain of 2.1±0.9 mm and 1.9±1.7 mm in SFA and SFA+EMD group, respectively (p= 0.465). In both groups, REC significantly increased 1.0±1.1 mm in SFA group and 1.1±1.1 mm in SFA+EMD group (p= 0.722). Within their limits, the findings of present study suggest that SFA may represent a valuable option for the surgical treatment of SDs associated with deep pockets. EMD did not result in a significant clinical benefit to the procedure. SFA may represent a valuable option in obtaining pocket closure when treating SDs associated with deep residual pockets.


Challenges and way forward.
Schistosomiasis, helminthic zoonoses and NTDs constitute a considerable majority of the diseases of poverty in the world. The RNAS+ targeted zoonoses are not only problems to human and animal health, but also cause poverty in 1 billion poor livestock keepers as well as result in 2.3 billion cases of human illness and 1.7 million human deaths a year. The gaps in research of those targeted zoonoses are urgently addressed by identifying the research priority, fulfilled by improving the multisectoral cooperation and strengthening the interventions in the control programme.


The mothering perceptions of women abused by their partner.
This study examined how abused women perceived their mothering. Findings reveal the women's continuous struggle to function as good mothers in the face of the violence. Their main struggle--to create a buffer between "the children's world" and the "violent world"--was directed at preventing the abuse from affecting their functioning as mothers, restraining and "fixing" their partner's violence, and shielding their children from it. Although the women felt that they have succeeded in this task, they also referred to their children's exposure to violence. The discussion centers on the split evident in the women's narratives between their mothering and their experience of violence.


Whole Murine Brain Imaging Based on Optical Elastic Scattering.
Imaging whole brains is one of the central efforts of biophotonics. While the established imaging modalities used in radiology, such as MRI and CT, have enabled in vivo investigations of various cognitive and affective processes, the prevailing resolution of one-cubic-millimeter has limited their use in studying the "ground-truth" of neuronal activities. On the other hand, electron microscopy (EM) visualizes the finest anatomic structures at a resolution of around 30 nm. However, the extensive tissue preparation process and the required large-scale morphological reconstruction restrict this method to small sample volumes. Light microscopy (LM) has the potential to bridge the above two spatial scales, with a resolution ranging from a few hundred nanometers to a few micrometers. Recent advances in tissue clearing have paved the way for optical investigation of large intact tissue volumes. However, most of these LM studies rely on fluorescence-a nonlinear optical process to provide contrast. This chapter introduces an alternative type of LM that is solely based on a linear optical process-elastic scattering, which has some unique advantages over conventional LM methods for the investigation of large-scale biological systems, such as intact murine brains. Here, we will first lay out the background and the motivation of developing this scattering-based method. Then, the basic principle of this approach will be introduced, including controlling tissue scattering and coherent imaging. Next, we explore current implementation and practical considerations. Up-to-date results and the utility of this method will also be demonstrated. Finally, we discuss current limitations and future directions in this promising field.


Elephants as an animal model for self-domestication.
Humans are unique in their sophisticated culture and societal structures, their complex languages, and their extensive tool use. According to the human self-domestication hypothesis, this unique set of traits may be the result of an evolutionary process of self-induced domestication, in which humans evolved to be less aggressive and more cooperative. However, the only other species that has been argued to be self-domesticated besides humans so far is bonobos, resulting in a narrow scope for investigating this theory limited to the primate order. Here, we propose an animal model for studying self-domestication: the elephant. First, we support our hypothesis with an extensive cross-species comparison, which suggests that elephants indeed exhibit many of the features associated with self-domestication (e.g., reduced aggression, increased prosociality, extended juvenile period, increased playfulness, socially regulated cortisol levels, and complex vocal behavior). Next, we present genetic evidence to reinforce our proposal, showing that genes positively selected in elephants are enriched in pathways associated with domestication traits and include several candidate genes previously associated with domestication. We also discuss several explanations for what may have triggered a self-domestication process in the elephant lineage. Our findings support the idea that elephants, like humans and bonobos, may be self-domesticated. Since the most recent common ancestor of humans and elephants is likely the most recent common ancestor of all placental mammals, our findings have important implications for convergent evolution beyond the primate taxa, and constitute an important advance toward understanding how and why self-domestication shaped humans' unique cultural niche.


High-throughput 16S rRNA gene sequencing of the microbial community associated with palm oil mill effluents of two oil processing systems.
Palm Oil Mill Effluents (POME) are complex fermentative substrates which habour diverse native microbial contaminants. However, knowledge on the microbiota community shift caused by the anthropogenic effects of POME in the environment is up to date still to be extensively documented. In this study, the bacterial and archaeal communities of POME from two palm oil processing systems (artisanal and industrial) were investigated by Illumina MiSeq Platform. Despite the common characteristics of these wastewaters, we found that their microbial communities were significantly different with regard to their diversity and relative abundance of their different Amplicon Sequence Variants (ASV). Indeed, POME from industrial plants harboured as dominant phyla Firmicutes (46.24%), Bacteroidetes (34.19%), Proteobacteria (15.11%), with the particular presence of Spirochaetes, verrucomicrobia and Synergistetes, while those from artisanal production were colonized by Firmicutes (92.06%), Proteobacteria (4.21%) and Actinobacteria (2.09%). Furthermore, 43 AVSs of archaea were detected only in POME from industrial plants and assigned to Crenarchaeota, Diapherotrites, Euryarchaeota and Nanoarchaeaeota phyla, populated mainly by many methane-forming archaea. Definitively, the microbial community composition of POME from both type of processing was markedly different, showing that the history of these ecosystems and various processing conditions have a great impact on each microbial community structure and diversity. By improving knowledge about this microbiome, the results also provide insight into the potential microbial contaminants of soils and rivers receiving these wastewaters.


Impact of Endodontic Kinematics on Stress Distribution During Root Canal Treatment: Analysis of Photoelastic Stress.
Structural defects created by endodontic treatment are the most common cause of major dental failures. This study analyzed levels of stress produced by endodontic instruments during the root canal treatment by photoelastic analysis of stress. Twenty-four human premolars were randomly divided into 4 groups (n = 6) according to instrumentation protocol: ProTaper Next (GPT), One Shape (GOS), Wave One Gold (GWO), and TF Adaptive (GTF). The evaluation of the photoelastic model was performed at 4 dental zones: dental-crown region, cervical third of root, middle third of root, and apical third of root. Silicone molds were prepared (2 × 15 mm), and pinjets were used inside the root canals to fixate teeth. Photoelastic resin (2:1 ratio) was poured into the silicone molds to form photoelastic models. A transmission polariscope was used to analyze the positions of interest and recorded with a digital camera. Tardy's method was used to quantify the fringe order (n) and calculate the maximum stress value (τ) at each selected point. Data were analyzed with two-way analysis of variance, Tukey test (P < .05), fringe descriptive analysis. All groups showed a significant increase in the level of stress created during biomechanical preparation of the root canals. In the quantitative analysis, there was no statistically significant difference among the groups (P > .05). In the qualitative analysis, GPT and GTF instruments achieved greater levels of stresses compared with GWO and GOS instruments. At the beginning of instrumentation, stresses were concentrated at the coronary level and the end of instrumentation at the middle and apical root level. All endodontic systems resulted in accumulation of stress along the dental structure. Stress was found in different concentrations along the tooth and at different levels.


Treatment for right colon polyps not removable using standard colonoscopy: combined laparoscopic-colonoscopic approach.
For complex right colon polyps, not removable using colonoscopy, right colon resection is considered the optimal treatment. Combined endoscopic-laparoscopic surgery, using both laparoscopy and CO2 colonoscopy, has been introduced as a new approach for these complex colon polyps with intent to avoid bowel resection. This study aimed to evaluate the safety and outcomes of combined endoscopic-laparoscopic surgery used for treatment of complex right colon polyps. This is a retrospective study of patients undergoing combined endoscopic-laparoscopic surgery for treatment of benign right colon polyps from 2003 to 2008. This is a single-institution study. Twenty-three patients with complex right colon polyps were included. The main outcome measures included the length of hospital stay, postoperative complications, and polyp recurrence. Of 23 patients, 20 (87%) patients had their polyp removed successfully by combined endoscopic-laparoscopic surgery and 3 (13%) needed laparoscopic resection, after laparoendoscopic evaluation. The median length of hospital stay was 2 days (range, 1-5), and there were no postoperative complications. Median follow-up time was 12 months. Three patients had recurrent polyps, and the recurrence-free interval at 36 months was 55.7% (95% CI = 8.6%, 87.0%). All recurrences were benign polyps and were removed by colonoscopic snaring. Combined endoscopic-laparoscopic surgery can be safely offered to selected patients with benign right colon polyps that can not be removed by colonoscopy. This combined approach may provide a viable alternative to right colon resection for complex benign colon lesions and warrants future investigation.


Involvement of TRPV1-ANO1 Interactions in Pain-Enhancing Mechanisms.
Primary sensory neurons detect potentially dangerous environmental situations via many "sensor" proteins located on the plasma membrane. Although receptor-type cation channels are thought to be the major sensors in sensory neurons, anion channels are also important players in the peripheral nervous system. Recently, we showed that transient receptor potential vanilloid 1 (TRPV1) interacts with anoctamin 1 (ANO1, also called TMEM16A) in primary sensory neurons and that this interaction enhanced TRPV1-mediated pain sensation. In that study, we induced ANO1 currents by application of capsaicin to small DRG neurons and showed that ANO1-dependent depolarization following TRPV1 activation could evoke more action potentials. Furthermore, capsaicin-evoked pain-related behaviors in mice were strongly inhibited by a selective ANO1 blocker. Together these findings indicate that selective ANO1 inhibition can reduce pain sensation. We also investigated non-specific inhibitory effects on ion channel activities to control ion dynamics via the TRPV1-ANO1 complex. We found that 4-isopropylcyclohexanol (4-iPr-CyH-OH) had an analgesic effect on burning pain sensations through its inhibition of TRPV1 and ANO1 together. Additionally, 4-iPr-CyH-OH did not have clear agonistic effects on TRPV1, TRPA1, and ANO1 activity individually. These results indicate that 4-iPr-CyH-OH could function globally to mediate TRP-ANO1 complex functions to reduce skin hypersensitivity and could form the basis for novel analgesic agents.


Body composition and respiratory function in healthy non-obese children.
The purpose of the present paper was to evaluate the role that body composition plays in lung function, among healthy children and adolescents. Cross-sectional study was undertaken using sex- and age-stratified sampling among healthy children and adolescents aged 6-18 years. Spirometry was performed on every child who fulfilled inclusion criteria. Fat mass (FM) and fat-free mass (FFM) were calculated from triceps skinfold thickness and arm circumference. Multiple logistic regression was used to obtain adjusted prevalence odds ratios (OR) and 95% confidence intervals (95%CI) between low pulmonary function (PF) of schoolchildren and body composition expressed in FM and FFM. Calculations of OR imply that the outcome is dichotomous (low PF/normal PF), therefore those children who had parameters of pulmonary function below the 25th percentile were classed as cases and the rest of the subjects were considered as controls. A total of 2408 children were included; 1270 (53%) of them were male and 1138 (47%), female. Among boys the increase of FFM was associated with an increase of forced expiratory volume in 1 s (FEV1). Among girls the increase of FFM was associated with an increase of FEV1, forced vital capacity, and peak expiratory flow. The increase in FM was associated with a decrease of spirometric parameters in both genders, with a stronger effect among boys. The present study confirms the negative effect of body fat on the PF of children and adolescents, even though obese subjects were excluded. The effect is different between boys and girls.


Thiourea-Capped Nanoapatites Amplify Osmotic Stress Tolerance in Zea mays L. by Conserving Photosynthetic Pigments, Osmolytes Biosynthesis and Antioxidant Biosystems.
Salinity is one of the most prevalent abiotic stresses which not only limits plant growth and yield, but also limits the quality of food products. This study was conducted on the surface functionalization of phosphorus-rich mineral apatite nanoparticles (ANPs), with thiourea as a source of nitrogen (TU-ANPs) and through a co-precipitation technique for inducing osmotic stress tolerance in Zea mays. The resulting thiourea-capped apatite nanostructure (TU-ANP) was characterized using complementary analytical techniques, such as EDX, SEM, XRD and IR spectroscopy. The pre-sowing of soaked seeds of Zea mays in 1.00 µg/mL, 5.00 µg/mL and 10 µg/mL of TU-ANPs yielded growth under 0 mM, 60 mM and 100 mM osmotic stress of NaCl. The results show that Ca and P salt acted as precursors for the synthesis of ANPs at an alkaline pH of 10-11. Thiourea as a source of nitrogen stabilized the ANPs' suspension medium, leading to the synthesis of TU-ANPs. XRD diffraction analysis validated the crystalline nature of TU-ANPs with lattice dimensions of 29 nm, calculated from FWHM using the Sherrer equation. SEM revealed spherical morphology with polydispersion in size distribution. EDS confirmed the presence of Ca and P at a characteristic KeV, whereas IR spectroscopy showed certain stretches of binding functional groups associated with TU-ANPs. Seed priming with TU-ANPs standardized germination indices (T50, MGT, GI and GP) which were significantly declined by NaCl-based osmotic stress. Maximum values for biochemical parameters, such as sugar (39.8 mg/g at 10 µg/mL), protein (139.8 mg/g at 10 µg/mL) and proline (74.1 mg/g at 10 µg/mL) were recorded at different applied doses of TU-ANP. Antioxidant biosystems in the form of EC 22.214.171.124 catalase (11.34 IU/g FW at 10 µg/mL), EC 126.96.36.199 APX (0.95 IU/G FW at 10 µg/mL), EC 126.96.36.199 SOD (1.42 IU/g FW at 5 µg/mL), EC 188.8.131.52 POD (0.43 IU/g FW at 5 µg/mL) were significantly restored under osmotic stress. Moreover, photosynthetic pigments, such as chlorophyll A (2.33 mg/g at 5 µg/mL), chlorophyll B (1.99 mg/g at 5 µg/mL) and carotenoids (2.52 mg/g at 10 µg/mL), were significantly amplified under osmotic stress via the application of TU-ANPs. Hence, the application of TU-ANPs restores the growth performance of plants subjected to induced osmotic stress.


Endodontic management of C-shaped root canal system of mandibular first molar by using a modified technique of self-adjusting file system.
C-shaped canal system is a seldom-found root canal anatomy which displays a challenge in all stages of endodontic treatment. According to the literature, this type of canal morphology is not a common finding in the mandibular first molar teeth. This case report presents endodontic management of a mandibular first molar with a C-shaped canal system. Root canal system was cleaned and shaped by nickel-titanium (NiTi) rotary instruments combined with self-adjusting file (SAF). Obturation was performed using warm, vertical condensation combined with the injection of warm gutta-percha. Follow-up examination 12 months later showed that the tooth was asymptomatic. The radiological findings presented no signs of periapical pathology. The clinician must be aware of the occurence and complexity of C-shaped canals in mandibular first molar teeth to perform a successful root canal treatment. The supplementary use of SAF after application of rotary instruments in C-shaped root canals might be a promising approach in endodontic treatment of this type of canal morphology.


Size of the nanovectors determines the transplacental passage in pregnancy: study in rats.
The objective of the study was to examine whether the size of silicon nanovectors (SNVs) inhibits their entrance into the fetal circulation. Pregnant rats were intravenously administered with SNVs or saline. The SNVs were spherical particles with 3 escalating diameters: 519 nm, 834 nm, and 1000 nm. The maternal and fetal distribution of SNVs was assessed. In animals that received 1000 or 834 nm SNV, silicon (Si) levels were significantly higher in the maternal organs vs the saline group, whereas the silicon levels in fetal tissues were similar to controls. However, in animals receiving 519 nm SNVs, fetal silicon levels were significantly higher in the SNV group compared with the saline group (5.93 ± 0.67 μg Si per organ vs 4.80 ± 0.33, P = .01). Larger SNVs do not cross the placenta to the fetus and, remaining within the maternal circulation, can serve as carriers for harmful medications in order to prevent fetal exposure.


Low intensity pulsed ultrasound accelerates delayed healing process by reducing the time required for the completion of endochondral ossification in the aged mouse femur fracture model.
The aim of this study is to clarify the effect of low intensity pulsed ultrasound (LIPUS) on shortening of the fracture healing period and endochondral ossification during the fracture healing process. We first established a model of aging-related delayed union fractures consisting of aged mouse (C57BL/6J; 40 weeks old) with closed femur fractures. We compared the healing process of 40-week-old mice to the healing process of 8-week-old (young) mice using radiological and histological analysis. In aged mice, some cartilage formation was observed 10 days after the fracture; however, endochondral ossification and hard callus bridging were observed 21 and 28 days after the fracture, respectively, whereas cartilage remained in the callus on day 28, suggesting delayed endochondral ossification following bone remodeling. Meanwhile, in aged mice with LIPUS treatment, cartilage formation was similar to that in aged mice without LIPUS; however, hard callus bridging and bone remodeling were observed 21 and 28 days after fracture, respectively, suggesting that LIPUS shortened the healing period due to promotion of endochondral ossification. Immunohistochemical analysis showed marked expression of vascular endothelial growth factor and neovascularization in the fibrous tissue comprising the periosteum that surrounded the whole callus. A cell migration test involving primary cultured human endothelial cells also showed promotion of cell migration by LIPUS. These results suggested that endothelial cell migration and neovascularization, which were observed around fracture sites, played a part in the mechanism of promotion of endochondral ossification by LIPUS.


ATP-dependent chromatin-remodeling complexes in DNA double-strand break repair: remodeling, pairing and (re)pairing.
The genomic integrity of a eukaryotic cell is challenged by over 10,000 chromosomal lesions per day. Therefore the cell has evolved efficient mechanisms to recognize, signal, and repair DNA breaks. Defects in any of these steps can lead to chromosomal aberrations and cancers. As these lesions must be repaired in the context of chromatin, both chromatin-modifying and nucleosome-remodeling enzymes have been implicated in DNA damage repair. We reported recently that the RSC and Swi/Snf ATP-dependent chromatin-remodeling complexes are involved in DSB repair specifically by homologous recombination. Here we discuss how such enzymes might be recruited to DNA breaks, why so many remodelers are recruited to sites of DSBs, and a possible functional connection between RSC's roles in sister chromatid cohesion and DSB repair.


Identification and molecular cloning Moplaa gene, a homologue of Homo sapiens PLAA, in Magnaporthe oryzae.
Magnaporthe oryzae has been used as a model fungal pathogen to study the molecular basis of plant-fungus interactions due to its economic and genetic importance. In this study, we identified a novel gene, Moplaa, which is the homologue of Homo sapiens PLAA encoding a phospholipase A(2)-activating protein. Moplaa is conserved in some eukaryotic organisms by multiple alignment analysis. The function of the Moplaa gene was studied using the gene target replacement method. The Moplaa deletion mutant exhibited retarded growth and conidial germination, reduced conidiation, appressorial turgor pressure and pathogenicity to rice CO-39. Reintroduction of the gene restored defects of the Moplaa deletion mutant.


Suspected Sarcocystis infections of the bovine placenta and foetus.
Protozoan parasites resembling Sarcocystis schizonts were found in the brains of 2 bovine foetuses and the placentas of another 4. As typical of Sarcocystis, the organisms were located mainly within vascular endothelial cells, and frequently the zoites within the schizonts were arranged in a rosette or palisade fashion. Pathological changes noted were placentitis, myocarditis, pulmonary vasculitis and encephalitis. Attempts to demonstrate Toxoplasma by animal inoculation and serology were unsuccessful.


Ribosome footprint profiling enables elucidating the systemic regulation of fatty acid accumulation in Acer truncatum.
The accumulation of fatty acids in plants covers a wide range of functions in plant physiology and thereby affects adaptations and characteristics of species. As the famous woody oilseed crop, Acer truncatum accumulates unsaturated fatty acids and could serve as the model to understand the regulation and trait formation in oil-accumulation crops. Here, we performed Ribosome footprint profiling combing with a multi-omics strategy towards vital time points during seed development, and finally constructed systematic profiling from transcription to proteomes. Additionally, we characterized the small open reading frames (ORFs) and revealed that the translational efficiencies of focused genes were highly influenced by their sequence features. The comprehensive multi-omics analysis of lipid metabolism was conducted in A. truncatum. We applied the Ribo-seq and RNA-seq techniques, and the analyses of transcriptional and translational profiles of seeds collected at 85 and 115 DAF were compared. Key members of biosynthesis-related structural genes (LACS, FAD2, FAD3, and KCS) were characterized fully. More meaningfully, the regulators (MYB, ABI, bZIP, and Dof) were identified and revealed to affect lipid biosynthesis via post-translational regulations. The translational features results showed that translation efficiency tended to be lower for the genes with a translated uORF than for the genes with a non-translated uORF. They provide new insights into the global mechanisms underlying the developmental regulation of lipid metabolism. We performed Ribosome footprint profiling combing with a multi-omics strategy in A. truncatum seed development, which provides an example of the use of Ribosome footprint profiling in deciphering the complex regulation network and will be useful for elucidating the metabolism of A. truncatum seed oil and the regulatory mechanisms.


Ouabain stimulates atrial natriuretic peptide secretion via the endothelin-1/ET(B) receptor-mediated pathway in beating rabbit atria.
Ouabain has been reported to increase the secretion of atrial natriuretic peptide (ANP) in vitro. However, the mechanism by which ouabain increases ANP secretion is not well known. Therefore, the purpose of the present study was to investigate the underlying mechanism of ouabain-stimulated ANP secretion. A perfused beating rabbit atrial model was used. The ANP and ET-1 levels in the atrial perfusates were measured by radioimmunoassays. Ouabain (1.0, 3.0 and 6.0 μmol/L) significantly increased atrial ANP secretion in a dose-dependent manner, while the endothelin (ET)-1 levels were increased by the higher doses (3.0 and 6.0 μmol/L) of ouabain. Ouabain-increased atrial ET-1 release was blocked by PD98059 (30.0 μmol/L), an inhibitor of mitogen-activated protein kinase (MAPK). Nifedipine (1.0 μmol/L), an inhibitor of L-type Ca(2+) channels, completely abolished ouabain-increased ANP secretion without changing the ouabain-induced atrial dynamics. KB-R7943 (3.0 μmol/L), an inhibitor of Na(+)-Ca(2+) exchangers, completely blocked the effects of ouabain-increased atrial dynamics, but did not modulate ouabain-increased ANP secretion. ET-1 significantly stimulated atrial ANP release in a dose-dependent manner. The effects of ET-1 and ouabain on ANP secretion were completely blocked by BQ788 (0.3 μmol/L), an inhibitor of ET-1 type B (ET(B)) receptors, but not by BQ123 (0.3 μM), an inhibitor of ET-1 type A receptors. Ouabain-increased atrial ANP secretion was blocked by PD98059 and indomethacin (30.0 μmol/L), an inhibitor of cyclooxygenase. Ouabain significantly stimulated atrial ANP secretion via an ET-1-ET(B) receptor-mediated pathway involving MAPK signaling pathway activation and prostaglandin formation.


Normal lymphocytes from leukemic samples as an internal quality control for fluorescence intensity in immunophenotyping of acute leukemias.
Multiparametric flow cytometry has become an indispensable but complex tool for the diagnosis of acute leukemias. Interpretation of immunophenotypic data within a six-parameter analytical space relies on the standardization and validation of the instrument, the reagents, and the procedure. To address whether or not residual normal lymphocytes, usually present within leukemic samples, can serve as internal quality control for fluorescence intensity, 116 leukemic and 35 normal samples were analyzed. Eight laboratories participated in the study and recruited a total of 151 individuals including 29 patients with B-cell precursor acute lymphoblastic leukemia (BCP-ALL), 77 with acute myeloid leukemia (AML), 10 with T-cell precursor acute lymphoblastic leukemia (T-ALL), and 35 normal bone marrow donors. Lymphocytes were gated according to the CD45hi/SSClo gating strategy, after which median fluorescence intensities (MFI) as well as percentages of positive cells (%positive) for CD19, CD22, CD7, and CD3 were recorded. Nonparametric statistics were used to compare variation within and between laboratories. Normal lymphocytes within leukemic samples do not show substantial differences compared to lymphocytes from normal controls with respect to expression of CD19, CD22, CD7, and CD3. In particular, longitudinal control charts of MFI values for CD3 antigen provide useful information on analytical and instrument performance. Residual normal lymphocytes can serve as internal quality control for studies addressing fluorescence intensity in the setting of immunophenotyping of acute leukemias.


Calcium hydroxide content and hydration degree of cement in cementitious composites containing calcium silicate slag.
Calcium silicate slag (CSS) is a secondary solid waste produced by the technology of extracting Al2O3 from fly ash. CSS was used in the present study to replace part of the cement to prepare cementitious composites. The calcium hydroxide (CH) content of the cementitious composites containing CSS (including the CH content produced by cementitious composites hydration, consumed by pozzolanic reaction of CSS, and residual in cementitious composites) and the hydration degree of cement are analyzed by observing the phase, content, and microscopic of CH. Results show that different replacement rates of CSS can reduce the CH content by approximately 7.59%-53.93%, which is determined by the mineral composition of CSS and its pozzolanic properties. In addition, the incorporation of CSS increases the hydration degree of the cement in the cementitious composites. This research can provide a new way for the utilization of CSS.


Resurfacing exposed bone of the lower leg using muscle flap transposition.
Although there are a variety of covering methods for skin defects accompanying exposed bone in the lower leg, in patients in whom closure with a local skin flap is not possible, I recommend the use of a muscle flap as the first choice. Muscle flap transfer has many advantages over other methods, and the result with this procedure is usually excellent. The grafting of mesh skin onto the transposed muscle is recommended. Good cosmetic results will be obtained by grafting the mesh skin without expanding it too much. The use of a myocutaneous flap for the lower leg is not recommended from a cosmetic point of view, and there are no particular advantages in the use of this method. The use of a muscle flap is adequate to achieve the intended curative result.


Low pre-operative heart rate variability and complexity are associated with hypotension after anesthesia induction in major abdominal surgery.
Significant hypotension after induction of general anesthesia is common and has the potential for serious complications. This study aimed to determine if pre-operative heart rate variability (HRV) was associated with post-induction hypotension in patients undergoing major abdominal surgery. Patients undergoing semi-elective major abdominal surgery were consecutively recruited during pre-admission clinic assessment. Exclusion criteria included cardiac conduction disease, arrhythmias or severe liver or renal disease. Ten minutes of electrocardiogram at 1024 Hz were recorded a median of 3 days pre-operatively. Pre-operative HRV parameters were compared in patients who experienced significant hypotension (fall in systolic and mean arterial pressure (MAP) >30% baseline and MAP ≤60 mmHg) versus those who remained haemodynamically stable after induction of general anesthesia with propofol and fentanyl. Patients who experienced hypotension after general anesthesia induction had significantly lower pre-operative HRV (SDNN 16 vs. 37 ms, p < 0.001), reduced spectral power (total power 262 vs. 1236 ms2, p = 0.002) and reduced correlation dimension, a measure of signal complexity (0.11 vs. 2.13, p < 0.001). Hypotension occurred relatively frequently in our cohort and was associated with a higher ASA grade (36 vs. 6% ASA 3, p = 0.036), hence post-induction hypotension and lower HRV may be associated with severity of illness or poor physiological reserve. Pre-operative HRV was a useful screening tool in identifying patients undergoing major abdominal surgery who were at risk of haemodynamic instability after anesthesia induction.


Assessment of extraction options for a next-generation biofuel: Recovery of bio-isobutanol from aqueous solutions.
Isobutanol is a widely used platform compound and a raw material for synthesizing many high value-added compounds. It also has excellent fuel properties and is an ideal gasoline additive or substitute with a very broad development space. Isobutanol production by biological fermentation has the advantages of a comprehensive source of raw materials, low cost, environmental protection, and sustainability. However, it also has disadvantages such as many impurities, low isobutanol concentration, and difficulty separating the water + isobutanol azeotrope. Thus, it is necessary to explore an appropriate downstream separation process for the water + isobutanol azeotrope. K2CO3 with a strong salting-out effect was used as the salting-out agent, and the salting-out of isobutanol from aqueous solutions was investigated at 298.15 K. The effect of the initial salt concentration in the aqueous solution, the recovery of isobutanol, and the effect of dehydration were investigated in detail. The e-NRTL-RK model was employed to generate the binary parameters for isobutanol and water, and electrolyte pair parameters for water/isobutanol and ions to reproduce the phase diagram with high accuracy. The processes of solvent extractive distillation, and salting-out + distillation were simulated by Aspen Plus. The energy consumptions for the solvent-based and salting-out-based processes were compared. The salting-out + distillation process turned out to be more energy-saving than the solvent extraction process.


NKX6.3 Regulates Reactive Oxygen Species Production by Suppressing NF-kB and DNMT1 Activities in Gastric Epithelial Cells.
NKX6.3 plays an important role in gastric epithelial differentiation and also acts as a gastric tumor suppressor. The specific aim of this study was to determine whether NKX6.3 contributes to gastric mucosal barrier function by regulating reactive oxygen species (ROS) production. NKX6.3 reduced ROS production and regulated expression of anti-oxidant genes, including Hace1. In addition, NKX6.3 reduced DNMT1 expression and activity by down-regulating NF-kB family gene transcription. Silencing of Hace1 recovered ROS production, whereas knock-down of DNMT1 and NF-kB reduced ROS production and induced Hace1 expression by hypomethylating its promoter region. In addition, NKX6.3 inhibited CagA effects on cell growth, ROS production, and NF-kB and DNMT1 activity. In gastric mucosae and cancers, NKX6.3 and Hace1 expression was significantly reduced. The NKX6.3 expression was positively correlated with Hace1 and Nrf2 genes, but negatively correlated with DNMT1. Hypermethylation of Hace1 gene was observed only in gastric mucosae with H. pylori, atrophy and intestinal metaplasia. Thus, these results suggest that NKX6.3 inhibits ROS production by inducing the expression of Hace1 via down-regulating NF-kB and DNMT1 activity in gastric epithelial cells.


Effects on penile reflexes and plasma hormones of hyperprolactinemia induced by MtTW15 tumors.
The effects of severe hyperprolactinemia induced by MtTW15 tumors (prolactin- and growth-hormone-secreting pituitary adenoma) on penile reflex activity and blood hormones were examined. There was no significant adverse effect of hyperprolactinemia on penile reflexes at 7, 14, or 21 days after tumor inoculation. However, a virtual elimination of penile reflex activity was observed 34 days after inoculation. Additionally, significant decrements in serum testosterone and dihydrotestosterone and an elevation in progesterone were seen at this time concomittant with greatly increased prolactin levels. The results suggest that erectile dysfunction may contribute to hyperprolactinemia-induced copulatory failure.


Immunoreactive pancreatic secretory trypsin inhibitor in normal, inflammatory and neoplastic gallbladders.
Operative specimens from normal, inflammatory and neoplastic gallbladders were analyzed for immunoreactive pancreatic secretory trypsin inhibitor (irPSTI) using a peroxidase-antiperoxidase method. In normal and inflammatory gallbladders no irPSTI was demonstrated, while irPSTI was found in neoplastic gallbladders.


[Familial type of hypophyseal nanism. Apropos of 7 families in western Algeria].
Eighteen pituitary dwarfs belonging to 7 different West Algerian families were studied. Eleven patients from 4 families presented isolated growth hormone deficiency, 7 patients from 3 families had multiple pituitary hormone deficiencies. Serum GH levels before and after standard pharmacological stimulations were below 2 ng/ml in all cases. Three of 10 hGH treated patients increased significantly their growth rate (8.5 +/- 0.5 cm/year) during the first year of treatment; growth was moderate (5.3 +/- 0.8 cm/year) in 3 patients and poor (4.5 cm/year) in 2 patients. In 2 cases the follow-up is insufficient.


An evaluation of wrist and forearm movement during purposeful activities and range of movement exercises after surgical repair of a distal radius fracture: A randomized crossover study.
Following surgical repair of distal radius fractures, range of movement (ROM) exercises are the primary approach for restoring movement during early rehabilitation. Specified purposeful activities can also be used, but the movement produced by activities is not well-understood. The study aimed to evaluate and compare movement during purposeful activity and ROM exercises METHODS: Thirty-five adults with a surgically repaired distal radius facture undertook two 10-minutes interventions: purposeful activity (PA) and active ROM exercises (AE), separated by a 60 minute washout, in random order. Data collection occurred during a single session on the same day. Electrogoniometry was used to measure time-accumulated position (TAP), a global metric of movement range and amount, maximum active end range, movement repetitions, excursions >75% of available ROM, and active time. Data were analyzed using linear mixed and generalized linear mixed regression models. Purposeful activities selected were predominantly household or food preparation. TAP was significantly higher during AE than PA: -1878 [-2388, -1367], p ≤.001, for wrist extension/flexion. PA produced significantly greater movement repetitions for wrist extension/flexion and deviation, excursions beyond 75% of available ROM, and active time, than AE. During PA the wrist was extending/flexing a mean of 97% [92, 101], of the time, compared with 43% [40, 47], during AE. There were no significant differences in maximum end range for wrist extension between PA, 33.7° [29.8, 37.5] and AE, 34.5° [30.7, 38.4], or for ulnar deviation. ROM exercises produced higher volumes of sustained joint position than purposeful activity but activities, selected for importance and challenge, produced significantly higher volumes of continuous, repetitious motion in equivalent ranges of movement as exercise repetitions. The study challenges therapists to consider the rehabilitative potential of movement produced by activity for restoring movement and function in the early postoperative weeks.


Management of Granulomatous Lobular Mastitis and Risk Factors Associated with Recurrence.
Granulomatous lobular mastitis (GM), an inflammatory breast lesion with unknown etiology, is prone to recur. There is no global consensus on the optimal treatment at present. This study was conducted to show our step-by-step systemic procedure and discuss the recurrence risk factors of GM. The medical record database was retrospectively searched for patients with GM treated in our hospital between January 2015 and September 2021. Patients were divided into non-recurrence group (group A) and recurrence group (group B). Demographic and clinical characteristics, treatment and follow-up were collected and analyzed. A total of 885 GM patients were included in our study, all of whom received step-by-step systemic management. The mean age was 33.2 ± 5.2 years. There were 760 (85.9%) patients in group A and 125 (14.1%) in group B. Univariate analysis showed that there was no statistically significant difference between the two groups in size of mass, pregnancy, hyperprolactinemia, bacterial cultures, erythema nodosum. Multivariate analysis showed that patients with purulent nipple discharge, skin lesion, bilateral disease and patients who need the combination of surgery and medication to achieve complete remission had higher risk of recurrence. We built a step-by-step systemic procedure for GM, and the recurrence rate was 14.1%. Prolactin level and microbiological results are important for the management of GM. Purulent nipple discharge, skin lesion, bilateral disease and patients who need the combination of surgery and medication to achieve complete remission are associated with GM recurrence. Prolonged maintenance therapy may secure a better prognosis.


Genetic polymorphisms and the risk of accelerated renal function decline in women.
Reduced glomerular filtration rate is an important predictor of cardiovascular disease and death. Genetic polymorphisms, particularly in genes involved in the renin-angiotensin system (RAS), may influence the rate of renal function decline. We examined the relation between specific single nucleotide polymorphisms (SNPs), including those in the RAS, apolipoprotein E and alpha-adducin, and renal function decline assessed by estimated glomerular filtration rate (eGFR) over an 11-year period in 2578 Caucasian participants of the Nurses' Health Study. Logistic regression was used to examine the associations between genotype and risk of eGFR decline of >or=25%. After 11 years between creatinine measurements, the eGFR declined by >or=25% in 423 of 2578 (16%) women. The angiotensinogen (AGT) A-20C polymorphism was associated with a higher risk of renal function decline when two risk alleles were present than if one or no alleles were present (CC vs AA and AC) OR 1.83 (95% CI 1.02-3.26; p = 0.04). The angiotensin II type 1 receptor (AT(1)R) A1166C polymorphism was marginally associated with a higher risk of renal function decline when two risk alleles were present (CC vs AA, OR = 1.41; 95% CI 0.98-2.01; p = 0.06). The alpha-adducin G460W polymorphism was associated with a lower risk of renal function decline when any number of risk alleles were present (WG vs GG, OR = 0.78, 95% CI 0.61-0.99, p = 0.04; WW vs GG, OR = 0.46; 95% CI 0.20-1.07, p = 0.07). Linear regression analysis with change in eGFR as the outcome showed a larger decline of 3.5 (95% CI 0.5 to 6.4, p = 0.02) ml/min/1.73 m(2) in AGT A-20C CC homozygotes. No other polymorphisms were significantly associated with renal function decline or absolute change in eGFR over the study period. Genetic variants in the angiotensinogen, angiotensin II type 1 receptor and alpha-adducin genes may contribute to loss of renal function in the general female Caucasian population.


Atopic eczema in a multiracial country (Malaysia).
A total of 14,342 patients with skin diseases who had attended either the National University of Malaysia skin clinic or a private dermatological office were analysed. Five hundred and thirty-four cases (3.7%) had atopic eczema, the prevalence being highest among the Malays (4.3%). The prevalence of atopic eczema among clinic attenders is lower in all three major Malaysian races when compared with studies from England.


Ion-exchange macroporous hydrophilic gel monolith with grafted polymer brushes.
The grafting of functional polymers to the pore surface of macroporous monolithic polyacrylamide cryogels was found to be an efficient and convenient method for the preparation of macroporous polyacrylamide gels, so-called cryogels (pAAm cryogels), with both controlled extent of functional group incorporated and with tailored surface chemistries. Anion-exchange polymer chains of poly(2-(dimethylamino)ethyl methacrylate) (pDMAEMA) and poly([2-(methacryloyloxy)ethyl]-trimethylammonium chloride) (pMETA), and cation-exchange polymer chains of polyacrylate have been grafted onto pAAm cryogels using potassium diperiodatocuprate as initiator. It was possible to achieve the ion-exchange capacity up to 0.2-0.5 mmol/ml. The graft polymerization did not alter the macroporous structure of the pAAm cryogel, however the flow rate of solutes through the cryogel matrix decreased with increase in the density of polymer grafted. The sorption of low-molecular-weight (metal ion, dye) and high-molecular-weight (protein) substances on the grafted monolithic pAAm column has been studied. The results indicate that a 'tentacle'-type binding of protein to grafted polymer depended on the architecture of the grafted polymer layer and took place after a certain degree of grafting has been reached. The binding of proteins by tentacle-like polymer chains allowed for increasing the binding capacity for proteins on the grafted pAAm cryogels up to 6-12 mg/ml.


Management of Hypothalamic Obesity.
Energy homeostasis, appetite, and satiety are modulated by a complex neuroendocrine system regulated by the hypothalamus. Dysregulation of this system resulting in hypothalamic obesity (HO) is caused by brain tumors, neurosurgery, and/or cranial irradiation. Craniopharyngioma (CP) is a paradigmatic disease with regard to the development of HO. Initial hypothalamic involvement of CP and/or treatment-related damage to hypothalamic-pituitary axes result in HO. Attempts to control HO with lifestyle interventions have not been satisfactory. No generally accepted pharmacologic or bariatric therapy for HO in CP has been effective in randomized controlled trials. Accordingly, prevention of HO is recommended.


A hierarchical classifier using new support vector machines for automatic target recognition.
A binary hierarchical classifier is proposed for automatic target recognition. We also require rejection of non-object (non-target) inputs, which are not seen during training or validation, thus producing a very difficult problem. The SVRDM (support vector representation and discrimination machine) classifier is used at each node in the hierarchy, since it offers good generalization and rejection ability. Using this hierarchical SVRDM classifier with magnitude Fourier transform (|FT|) features, which provide shift-invariance, initial test results on infra-red (IR) data are excellent.


Maternal Tobacco Smoking During Pregnancy and Children's Emotional and Behavioral Trajectories: The EDEN Mother-Child Birth Cohort Study.
The nature of the relationship between maternal tobacco smoking during pregnancy and the occurrence of children's behavioral problems is still a matter of controversy. We tested this association using data collected among a sample of pregnant women and their offspring followed up from birth to early adolescence (age 12 years), accounting for multiple parent, child, and family characteristics. Data come from 1424 mother-child pairs participating in the Étude des Déterminants pré et post-natals précoces du développement psychomoteur et de la santé de l'ENfant mother-child cohort in France. Using repeated measures (3, 5.5, 8, and 11.5 years) of the mother-reported Strengths and Difficulties Questionnaire, we estimated trajectories of children's emotional and behavioral difficulties. Two aspects of maternal smoking were studied: The timing (nonsmoker, smoking during the periconceptional period, or throughout pregnancy) and the level of use (cigarettes/day) during the first trimester of pregnancy. Robust Poisson regression models controlled for confounding factors including maternal mental health and socioeconomic characteristics using propensity scores with the overlap weighting technique. Contrary to bivariate analyses, in propensity score-controlled regression models, maternal smoking throughout pregnancy was no longer significantly associated with offspring emotional or behavioral difficulties. Maternal heavy smoking (≥10 cigarettes/day) remained significantly associated with intermediate levels of conduct problems (RR 1.25, 95% CI 1.19 to 1.31). The association between maternal smoking in pregnancy and offspring's emotional and behavioral difficulties appears to be largely explained by women's other characteristics. However, maternal heavy smoking appears to be related to offspring behavioral difficulties beyond the role of confounding characteristics. The relationship between maternal smoking during pregnancy (in two modalities: Timing and level of smoking) and behavioral difficulties in children is still a matter of debate. While the relationship between any maternal tobacco use and offspring behavioral difficulties appears to be largely explained by confounding factors, heavy maternal smoking in the first trimester of pregnancy seems to be associated with offspring behavioral difficulties beyond the socioeconomic and mental health characteristics transmitted across generations.


Genetic evidence for the nature, and excision repair, of DNA lesions resulting from incorporation of 5-bromouracil.
Escherichia coli mutants defective in DNA uracil N-glycosidase (ung-) or endonuclease VI active against apurinic/apyrimidinic sites in DNA (xthA-) exhibit enhanced sensitivity towards 5-bromodeoxyuridine relative to the wild type strain, pointing to involvement of these enzymes in repair of bromouracil-induced lesions in DNA. Mutants defective in DNA polymerase I, either in polymerizing activity (polAl-) or (5' leads to 3')-exonuclease activity (polA107-) exhibit unusually high sensitivity (including marked lethality) in the presence of 5-bromodeoxyuridine. The results indicate that DNA polymerase I, and its associated (5'--3')-exonuclease activity, are involved in repair of bromouracil-induced lesions and are not readily replaced, if at all, by DNA polymerases II and III. Thermosensitive mutant in DNA ligase gene (lig ts7) shows high sensitivity towards 5-bromodeoxyuridine at 42 degrees C indicating the role of the enzyme in repair of bromouracil-induced lesions in DNA. Involvement of DNA uracil N-glycosidase, and endonuclease active against apurinic/apyrimidinic sites in recognition and repair of 5-bromouracil-induced damage permits of some inferences regarding the nature of this damage (lesions), in particular dehalogenation of incorporated bromouracil to uracil residues.


Neurologic presentations of panic disorder in childhood and adolescence.
Four children with panic disorder, two boys and two girls between the ages of nine and 16 years, are discussed. They presented with complaints suggesting neurological disorder: 'dizziness', headache, episodic anxiety and 'blackout spells'. Neurological examinations and investigations were normal. Depression and/or anxiety were prominent in all cases. Drug treatment and psychotherapy were of some benefit. Four other children with attention deficit disorders are presented, whose mothers have panic disorder. This association points towards common biochemical influences and suggests that tricyclic drugs may be preferable to CNS stimulants as a form of treatment.


Beyond the Clinical Trials: Off-Protocol Therapeutic Hypothermia.
Mild therapeutic hypothermia has been extensively studied and validated as an effective and safe treatment for term and near-term infants with moderate and severe hypoxic encephalopathy meeting narrow inclusion criteria. Unanswered questions remain about whether cooling treatment can be optimized to improve outcomes even further, and whether it is reasonable to offer treatment to infants excluded from the foundational studies. Consideration of "off-protocol" cooling practices requires methodical review of available evidence and analysis using both a clinical and a research ethical framework.


A model for the generation of movements requiring endpoint precision.
A model is proposed in which movement accuracy is regulated by means of corrective actions taken at discrete intervals throughout the course of a movement. A movement, as represented by its tangential velocity profile, cna be decomposed into a series of one or more submovements. Each submovement consists of a prototype velocity profile which can be scaled in magnitude and duration. For planar two-joint movements, we demonstrate that these submovements can be mathematically represented either in terms of velocity profiles or in terms of the underlying joint torque profiles. In either case, the submovements superimpose linearly to produce the composite movement. The model provides a very good fit to tangential velocity profiles recorded from human subjects during three-dimensional arm movements with constraints on accuracy and speed. The model assumes that when a submovement is present, its onset is associated with a change in the direction of the hand path and/or a zero crossing or inflection in at least one of the components of the velocity vector. The model is consistent with a strategy in which precision is achieved by periodic discrete actions which redirect the moving arm in order to bring the hand closer to the target. Since submovements were also observed in slow movements where accuracy constraints had been relaxed, we hypothesize that the strategy of superimposing a series of submovements to make one composite movement may be a general one. We suggest that it would be particularly appropriate for the process of learning a new motor skill.


CD8+ T cells specific for the islet autoantigen IGRP are restricted in their T cell receptor chain usage.
CD8+ T cells directed against beta cell autoantigens are considered relevant for the pathogenesis of type 1 diabetes. Using single cell T cell receptor sequencing of CD8+ T cells specific for the IGRP265-273 epitope, we examined whether there was expansion of clonotypes and sharing of T cell receptor chains in autoreactive CD8+ T cell repertoires. HLA-A*0201 positive type 1 diabetes patients (n = 19) and controls (n = 18) were analysed. TCR α- and β-chain sequences of 418 patient-derived IGRP265-273-multimer+ CD8+ T cells representing 48 clonotypes were obtained. Expanded populations of IGRP265-273-specific CD8+ T cells with dominant clonotypes that had TCR α-chains shared across patients were observed. The SGGSNYKLTF motif corresponding to TRAJ53 was contained in 384 (91.9%) cells, and in 20 (41.7%) patient-derived clonotypes. TRAJ53 together with TRAV29/DV5 was found in 15 (31.3%) clonotypes. Using next generation TCR α-chain sequencing, we found enrichment of one of these TCR α-chains in the memory CD8+ T cells of patients as compared to healthy controls. CD8+ T cell clones bearing the enriched motifs mediated antigen-specific target cell lysis. We provide the first evidence for restriction of T cell receptor motifs in the alpha chain of human CD8+ T cells with specificity to a beta cell antigen.


Changes in the quantity and activity of cytochrome P-450 isozymes in primary cultured rat hepatocytes.
Hepatocytes from male Sprague-Dawley rats pretreated with a cytochrome P-450 inducer, 3-methoxy-4-aminoazobenzene (3-MeO-AAB), 3-methylcholanthrene (MC) or phenobarbital (PB), were cultured in vitro, and changes in the quantity and activity of microsomal cytochrome P-450 isozymes in the cells were determined by means of immunochemical methods and a bacterial mutation test, respectively. The results of enzyme-linked immunosorbent assay using monoclonal antibodies against rat P-450 isozymes revealed that the amount of cytochrome P-450d induced by 3-MeO-AAB or MC declined rapidly during culture and fell to 10 to 15% of the initial value after 24 h. A similar tendency was observed with PB-induced cytochrome P-450b/e. By contrast, cytochrome P-450c in MC-induced hepatocytes declined more slowly than cytochrome P-450d and remained at 45 to 60% of the initial value after 24 h. Similar quantitative changes of the individual cytochrome P-450 isozymes in culture were also observed by immunoblotting using the anti-cytochrome P-450 monoclonal antibodies. Changes in the activities of individual cytochrome P-450 isozymes in hepatocytes by culture were in accordance with the quantitative changes of the cytochromes, as determined by a mutation test using Salmonella typhimurium TA 98 and carcinogenic aromatic amines. These results indicate that microsomal cytochrome P-450c in primary cultured rat hepatocytes is more stable in culture, in terms of both quantity and activity, than cytochrome P-450d and P-450b/e.


Electrochemical detection of celiac disease-related anti-tissue transglutaminase antibodies using thiol based surface chemistry.
Celiac disease is an autoimmune disorder that affects the gastrointestinal tract upon ingestion of gluten, which triggers the production of antibodies against gliadin and tissue transglutaminase, activating an inflammatory response and inducing tissue damage in the small intestine resulting in malabsorption. The measurement of these antibodies in an individual's blood can be used to screen for celiac disease and the criteria for definitive diagnosis is currently being revised to be based on serological analysis rather than biopsy. In the work reported here, an electrochemical immunosensor for the detection of human anti-tissue transglutaminase antibodies was developed, consisting of gold-based self-assembled monolayers of a carboxylic group terminated bipodal alkanethiol that is covalently linked to tissue transglutaminase, the antigen for the immunorecognition of circulating autoantibodies. The presence of the autoantibodies was recorded using horseradish peroxidase labeled anti-human antibodies, which provided an enzyme based electrochemical signal. Optimization and characterization of the surface of the sensor was carried out by electrochemical impedance spectroscopy and surface plasmon resonance. The immunosensor gave a stable quantitative response to different antibody concentrations after 30 min with a limit of detection of 390 ng/mL and an RSD of 9%, n=3. The developed immunosensor was tested with calibrator solutions as well as with real patients' samples, and the results compared to those obtained from Eurospital's Eu-tTG IgA and IgG ELISA kits, showing an excellent degree of correlation.