Smart Shape-Memory Polymeric String for the Contraction of Blood Vessels in Fetal Surgery of Sacrococcygeal Teratoma.
Shape-memory polymers (SMPs) are promising materials in numerous emerging biomedical applications owing to their unique shape-memory characteristics. However, simultaneous realization of high strength, toughness, stretchability while maintaining high shape fixity (Rf ) and shape recovery ratio (Rr ) remains a challenge that hinders their practical applications. Herein, a novel shape-memory polymeric string (SMP string) that is ultra-stretchable (up to 1570%), strong (up to 345 MPa), tough (up to 237.9 MJ m-3 ), and highly recoverable (Rf averagely above 99.5%, Rr averagely above 99.1%) through a facile approach fabricated solely by tetra-branched poly(ε-caprolactone) (PCL) is reported. Notably, the shape-memory contraction force (up to 7.97 N) of this SMP string is customizable with the manipulation of their energy storage capacity by adjusting the string thickness and stretchability. In addition, this SMP string displays a controllable shape-memory response time and demonstrates excellent shape-memory-induced contraction effect against both rigid silicone tubes and porcine carotids. This novel SMP string is envisioned to be applied in the contraction of blood vessels and resolves the difficulties in the restriction of blood flow in minimally invasive surgeries such as fetoscopic surgery of sacrococcygeal teratoma (SCT).


Isolated reversible hypoglossal nerve palsy as the initial manifestation of pre-eclampsia.
Isolated hypoglossal nerve lesions often reflect sinister neoplastic or vascular pathology. Rarely, reversible lesions occur, perhaps via mechanisms similar to Bell's palsy. We report a patient with reversible isolated hypoglossal nerve palsy as the first and predominant early manifestation of pre-eclampsia and speculate on the pathogenesis behind this abnormality.


Interference and priming within and across visual fields in a lexical decision task.
A lower-case target word or non-word was laterally presented by itself or simultaneously with an upper-case distractor word in the same or in the opposite visual field. The distractor words were either semantically associated or unrelated to the target. Subjects performed a lexical decision task on the target. Two kinds of selection within and across visual fields were investigated. Selection of an external target relevant for the response (filtering) and selection of an internal target by automatic priming. No lateral asymmetry was found for automatic priming. Filtering was equally efficient within hemispheres, but strongly asymmetrical across hemispheres. Unrelated distractor words presented to the right hemisphere interfered less with target processing in the left hemisphere than vice versa. Thus, all distractor words received equivalent semantic processing; those presented to the right hemisphere, however, were least costly to exclude from task-relevant processing in the left hemisphere.


High-throughput phenotyping for non-destructive estimation of soybean fresh biomass using a machine learning model and temporal UAV data.
Biomass accumulation as a growth indicator can be significant in achieving high and stable soybean yields. More robust genotypes have a better potential for exploiting available resources such as water or sunlight. Biomass data implemented as a new trait in soybean breeding programs could be beneficial in the selection of varieties that are more competitive against weeds and have better radiation use efficiency. The standard techniques for biomass determination are invasive, inefficient, and restricted to one-time point per plot. Machine learning models (MLMs) based on the multispectral (MS) images were created so as to overcome these issues and provide a non-destructive, fast, and accurate tool for in-season estimation of soybean fresh biomass (FB). The MS photos were taken during two growing seasons of 10 soybean varieties, using six-sensor digital camera mounted on the unmanned aerial vehicle (UAV). For model calibration, canopy cover (CC), plant height (PH), and 31 vegetation index (VI) were extracted from the images and used as predictors in the random forest (RF) and partial least squares regression (PLSR) algorithm. To create a more efficient model, highly correlated VIs were excluded and only the triangular greenness index (TGI) and green chlorophyll index (GCI) remained. More precise results with a lower mean absolute error (MAE) were obtained with RF (MAE = 0.17 kg/m2) compared to the PLSR (MAE = 0.20 kg/m2). High accuracy in the prediction of soybean FB was achieved using only four predictors (CC, PH and two VIs). The selected model was additionally tested in a two-year trial on an independent set of soybean genotypes in drought simulation environments. The results showed that soybean grown under drought conditions accumulated less biomass than the control, which was expected due to the limited resources. The research proved that soybean FB could be successfully predicted using UAV photos and MLM. The filtration of highly correlated variables reduced the final number of predictors, improving the efficiency of remote biomass estimation. The additional testing conducted in the independent environment proved that model is capable to distinguish different values of soybean FB as a consequence of drought. Assessed variability in FB indicates the robustness and effectiveness of the proposed model, as a novel tool for the non-destructive estimation of soybean FB.


Diagnosis of infantile subglottic hemangioma and the effect of oral propranolol.
To investigate the clinical characteristics of infantile subglottic hemangioma (SGH), and to observe the safety and efficacy of propranolol in the treatment of SGH. The data of 21 children diagnosed with SGH and treated with propranolol in our hospital from March 2013 to January 2021 were retrospectively analyzed and followed up. Among the 21 cases, there were 7 males and 14 females. SGH was found 11 left-sided, 9 right-sided and 1 bilateral-sided. The clinical manifestations included stridor (13/21), respiratory distress (6/21), barking cough (5/21), feeding difficulty (4/21), three concave sign (4/21), cyanosis (2/21) and hoarseness (1/21). 8 patients had multiple cutaneous hemangiomas. The age of presentation ranged from 1 to 8 months, with a median of 1.1 months. 18 cases (85.7 %) had a history of misdiagnosis, 14 bronchitis/pneumonia, 5 laryngomalacia, 2 laryngeal obstruction and 1 asthma. The median ages at diagnosis were 3 months, with a range of 1.2-28 months. The treatment duration ranged from 6 to 25.6 months, with an average of (14.3 ± 4.9) months. Age at termination of treatment ranged from 9 to 38 months, with a median of 18.6 months, and only 2 cases were beyond 2 years old at that time. No adverse side effects from propranolol therapy occurred and all 21 cases were cured. We advocate a strong index of suspicion for SGH presenting with respiratory symptoms under 2 years old who has poor effect or repeated condition after routine treatment. Laryngoscopy combined with contrast-enhanced CT can confirm the diagnosis of SGH. Oral propranolol is safe and effective, and that early diagnosis and intervention of propranolol without further delay are crucial to the successful management. We advocate continue propranolol treatment beyond 18 months of age, furthermore, 2 years old may be the best time for therapy termination.


[Neonatal exposure to active pulmonary tuberculosis in a maternity ward: screening and clinical course of a cohort of exposed infants].
Few data are available on the impact of a tuberculosis exposure on newborns in a maternity ward. To describe the screening and clinical course of infants exposed during the neonatal period to a caregiver with bacillary tuberculosis. Infants exposed during the postnatal period in a maternity unit in Paris, from March to August 2005, to a caregiver with bacillary tuberculosis were included in a standardized screening protocol. The screening performed at baseline (M0) and at 3 months (M3) included a clinical evaluation, a tuberculin skin test (TST), and a chest X-ray. A preventive treatment for tuberculosis with isoniazid and rifampicin for 3 months was systematically proposed. At M0, 182 of the 217 infants (84%) with significant exposure were evaluated. Data were available for 172 infants. The median age at M0 was 4.9 months (IQR=3.8-6.2). At M0, 4 of 172 infants (2.3%) had latent TB infection. Between M0 and M3, 19 infants (11%) were lost to follow-up and 1 on 153 developed a latent TB infection. No cases of tuberculosis disease were diagnosed. The treatment was administered properly in 83% of cases and side effects were observed in 11% of infants without any serious adverse event. Four infants received no treatment and 11 stopped their treatment prematurely. In the absence of neonatal massive exposure, although low (2.9%), the risk of latent TB infection requires close monitoring of the infants exposed. However, in the context of a mild exposure in the maternity unit, surveillance without systematic initiation of TB preventive treatment could be discussed.


The Prevalence, Associated Factors for Lung Metastases Development and Prognosis in Ovarian Serous Cancer Based on SEER Database.
Ovarian carcinoma (OC) is one of the 3 most common gynecological malignancies, and the prognosis of patients with lung metastasis was the worst. SEER documented OC patients, diagnosed between 2010 and 2016, were included in the study. Univariable and multivariable logistic regression analyses were performed to identify associated factors for lung metastases (LM) development. Kaplan-Meier analysis was used to estimate the overall survival for OC patients with LM. A total of 10146 eligible serous ovarian cancer (SOC) patients were included, the prevalence of LM was 3.77% (N = 378). Patients with T4 stage (χ2 = 128.515; P = 0.000), N1 stage (χ2 = 49.536; P = 0.000), right laterality (χ2 = 18.756; P = 0.000) (compared with left side), undifferentiated grade (χ2 = 36.174; P = 0.000), bone metastasis (χ2 = 183.529); P = 0.000), brain metastasis (χ2 = 117.539; P = 0.000), liver metastasis (χ2 = 442.472; P = 0.000) had a larger probability of LM than other groups. Results showed that T3/N1 stage, bone metastases, liver metastases, chemotherapy, surgery were positively correlated with LM. Multivariable cox analysis showed that age, bone metastasis, no chemotherapy, no surgery were independent risk factors in SOC-LM patients. This study provided new research insights on the prevalent LM in patients with SOC. The factors associated with LM development and prognosis can be potentially used for LM early screening and professional care.


Treatment of reverse osmosis membrane by sodium hypochlorite and alcohols for enhanced performance using the swelling-fastening effect.
Chemicals soaking is generally acknowledged as a convenient and efficient method to improve the performance of reverse osmosis (RO) membranes. The conventional soaking of RO membranes in alkaline sodium hypochlorite (NaClO) usually promotes extensive hydrolysis and cleavage amide bonds, resulting in improved water flux but declined salt rejection. Here, alcohols were added into the NaClO solution to regulate the chlorination processes using their "swelling-fastening" effect. The alcohols could interact with polyamide chains, and thus swell the polyamide network. Due to this interaction, the NaClO has less probability of attacking the polyamide chains. Hence, the chlorine-promoted hydrolysis was partly eased, which could weaken the decrease of salt rejection. Besides, after removing alcohols as well as the dissolved small oligomers and fragments of polyamide, the network was compacted and the loosened sites were healed, which is also beneficial to increase the difficulty of salt penetration. The treatment of RO membrane by the NaClO and alcohols could produce a hydrophilic surface with increased water flux and high salt rejection. The membrane chloridized at 2000 ppm NaClO exhibited a water flux improvement of 20.28% and a salt rejection declination of 0.95%. When treated with 2000 ppm NaClO associated with 5% methanol, the water flux improved 20.13% with little declination in salt rejection.


The effect of pictured visual cues on elicited sentence imitation.
In one experiment language-normal 6 1/2-year-old and 4 1/2-year-old children (N = 68) were asked to imitate sentences with or without pictured visual cues. In a second experiment groups of language-disordered children (N = 43) also 4 1/2 and 6 1/2 years of age were asked to imitate sentences with and without pictured visual cues. In both experiments there was no significant difference in the syntactical and grammatical quality of elicited imitations between conditions. Older children performed better than young children in both experiments. It was concluded that pictured visual cues do not affect the syntactical and grammatical quality of language-normal and language-disordered children's elicited sentence imitations.


Adenovirus strand nomenclature: a proposal.
Thirty-six scientists have agreed to standardize the nomenclature of DNA strands of all adenovirus serotypes according to certain criteria.


Identification of the replication terminator protein binding sites in the terminus region of the Bacillus subtilis chromosome and stoichiometry of the binding.
DNase I footprinting of the interaction between the replication terminator protein (RTP) of Bacillus subtilis and the inverted repeat region (IRR) at the chromosome terminus, to which it binds to block the clockwise replication fork, showed that two major regions of 41 base pairs (bp) were protected from cleavage. These regions corresponded approximately to the imperfect inverted repeats (IRI and IRII) identified previously. Band retardation analyses of the interaction between RTP and portions of the IRR established that each inverted repeat (IRI or IRII) contained two RTP binding sites. By sedimentation equilibrium in the ultracentrifuge, RTP was found to exist as a dimer of 29 kDa at neutral pH and concentrations above 0.2 g/l. Quantitative studies of the RTP-IRR interaction using [3H]RTP and [32P]IRR showed that the fully saturated complex contained eight RTP monomers per IRR. It is concluded that a dimer of RTP binds to each of the four sites in IRR. The apparent dissociation constant for the interaction was estimated (in the presence of 50% glycerol) to be 1.2 x 10(-11) M (dimer of RTP). Glycerol was found to have a marked effect on the affinity of RTP for the IRR and on the relative amounts of the interaction complexes formed; in the absence of glycerol the dissociation constant was approximately 50-fold higher and there was pronounced co-operative binding of RTP dimers to adjacent sites in each inverted repeat. Examination of the DNA sequence in IRI and IRII identified two 8 bp direct repeats in each. The regions protected from DNase I cleavage in each inverted repeat and the protection afforded by a core sequence spanning just one of the 8 bp direct repeats were consistent with each 8 bp repeat representing a recognition sequence for the RTP dimer. A model describing the binding of RTP to the IRR is presented.


Clinicopathological features of gastric adenocarcinoma patients with metachronous distant metastasis.
Metachronous distant metastasis influences the postoperative survival of gastric adenocarcinoma patients with radical gastrectomy. We retrospectively reviewed 108 gastric adenocarcinoma patients with metachronous distant metastasis admitted to our hospital between January 2006 and December 2011. First, these patients were divided into two groups according to the time of metastasis: the early metastasis group (EMG) and late metastasis group (LMG). Second, according to the survival time after metastasis, these patients were divided into the longer survival group (LSG) and shorter survival group (SSG). Chi-square and Fisher exact tests were used to analyze associations between categorical variables. Survival data were estimated using the Kaplan-Meier method. Multivariate analyses of the prognostic factors related to overall survival were conducted using the Cox stepwise proportional hazards test. Results shows that the EMG was significantly associated with depth of invasion (p = 0.005), Union for International Cancer Control (UICC) stage (p = 0.003), degree of differentiation (p = 0.002), and vascular invasion (p = 0.001). The SSG was significantly associated with depth of invasion (p = 0.026) and normal carcinoembryonic antigen (CEA) level of after metastasis (p = 0.003). Survival analysis showed that depth of invasion (p < 0.001), degree of differentiation (p = 0.001), and vascular invasion (p = 0.011) were independent prognostic factors for gastric adenocarcinoma patients with metachronous distant metastasis. Gastric adenocarcinoma patients with metachronous distant metastasis exhibit characteristics that can be used to effectively estimate the possibility of early distant metastasis and the prognosis of these patients.


Decompressive craniectomy in paediatric traumatic brain injury: a systematic review of current evidence.
Paediatric traumatic brain injury (pTBI) is one of the most frequent neurological presentations encountered in emergency departments worldwide. Every year, more than 200,000 American children suffer pTBIs, many of which lead to long-term damage. We aim to review the existing evidence on the efficacy of the decompressive craniectomy (DC) in controlling intracranial pressure (ICP) and improving long-term outcomes in children with pTBI. A comprehensive search of the MEDLINE and EMBASE databases led to the screening of 212 studies, 12 of which satisfied inclusion criteria. Data extracted included the number and ages of patients, Glasgow Coma Scale scores at presentation, treatment protocols and short- and long-term outcomes. Each of the nine studies including ICP as an outcome reported that it was successfully controlled by DC. The 6-12 month outcome scores of patients undergoing DC were positive, or superior to those of medically treated groups in nine of 11 studies. Mortality was compared in only two studies, and was lower in the DC group in both.Very few studies are currently available investigating short- and long-term outcomes in children with TBI undergoing DC. The currently available evidence may support a beneficial role of DC in controlling ICP and improving long-term outcomes.


Impact of Acetic Acid Supplementation in Polyhydroxyalkanoates Production by Cupriavidus necator Using Mixture-Process Design and Artificial Neural Network.
The trend in bioplastic application has increased over the years where polyhydroxyalkanoates (PHAs) have emerged as a potential candidate with the advantage of being bio-origin, biodegradable, and biocompatible. The present study aims to understand the effect of acetic acid concentration (in combination with sucrose) as a mixture variable and its time of addition (process variable) on PHA production by Cupriavidus necator. The addition of acetic acid at a concentration of 1 g l-1 showed a positive influence on biomass and PHA yield; however, the further increase had a reversal effect. The addition of acetic acid at the time of incubation showed a higher PHA yield, whereas maximum biomass was achieved when acetic acid was added after 48 h. Genetic algorithm (GA) optimized artificial neural network (ANN) was used to model PHA concentration from mixture-process design data. Fitness of the GA-ANN model (R2: 0.935) was superior when compared to the polynomial model (R2: 0.301) from mixture design. Optimization of the ANN model projected 2.691 g l-1 PHA from 7.245 g l-1 acetic acid, 12.756 g l-1 sucrose, and the addition of acetic acid at the time of incubation. Sensitivity analysis indicates the inhibitory effect of all the predictors at higher levels. ANN model can be further used to optimize the variables while extending the bioprocess to fed-batch operation.


Aquaculture production of hatchling Hawaiian Bobtail Squid (Euprymna scolopes) is negatively impacted by decreasing environmental microbiome diversity.
The Hawaiian Bobtail Squid (Euprymna scolopes) is a model organism for investigating host-symbiont relationships. The current scientific focus is on the microbiome within E. scolopes, while very little is known about the microbiome of the tanks housing E. scolopes. We examined the hypothesis that bacterial communities and geochemistry within the squid tank environment correlate with the production of viable paralarval squid. Total DNA was extracted from sediment and filtered water samples from 'productive' squid cohorts with high embryonic survival and paralarval hatching, 'unproductive' cohorts with low embryonic survival and paralarval hatching. As a control total DNA was extracted from environmental marine locations where E. scolopes is indigenous. Comparative analysis of the bacterial communities by the 16S rRNA gene was performed using next generation sequencing. Thirty-eight differentially abundant genera were identified in the adult tank waters. The majority of the sequences represented unclassified, candidate or novel genera. The characterized genera included Aquicella, Woeseia and Ferruginibacter, with Hyphomicrobium and Rhizohapis were found to be more abundant in productive adult tank water. In addition, nitrate and pH covaried with productive cohorts, explaining 67% of the bacterial populations. The lower abundance of nitrate-reducing bacteria in unproductive adult tank water could explain detected elevated nitrate levels. We conclude that microbiome composition and water geochemistry can negatively affect E. scolopes reproductive physiology in closed tank systems, ultimately impacting host-microbe research using these animals. These results identify the tight relationship between the microbiome and geochemistry to E. scolopes. From this study, it may be possible to design probiotic counter-measures to improve aquaculture conditions for E. scolopes.


Caregiving and Confidence to Avoid Hospitalization for Children with Medical Complexity.
To test associations between parent-reported confidence to avoid hospitalization and caregiving strain, activation, and health-related quality of life (HRQOL). In this prospective cohort study, enrolled parents of children with medical complexity (n = 75) from 3 complex care programs received text messages (at random times every 2 weeks for 3 months) asking them to rate their confidence to avoid hospitalization in the next month. Low confidence, as measured on a 10-point Likert scale (1 = not confident; 10 = fully confident), was defined as a mean rating <5. Caregiving measures included the Caregiver Strain Questionnaire, Family Caregiver Activation in Transition (FCAT), and caregiver HRQOL (Medical Outcomes Study Short Form 12 [SF12]). Relationships between caregiving and confidence were assessed with a hierarchical logistic regression and classification and regression trees (CART) model. The parents were mostly mothers (77%) and were linguistically diverse (20% spoke Spanish as their primary language), and 18% had low confidence on average. Demographic and clinical variables had weaker associations with confidence. In regression models, low confidence was associated with higher caregiver strain (aOR, 3.52; 95% CI, 1.45-8.54). Better mental HRQOL was associated with lower likelihood of low confidence (aOR, 0.89; 95% CI, 0.80-0.97). In the CART model, higher strain similarly identified parents with lower confidence. In all models, low confidence was not associated with caregiver activation (FCAT) or physical HRQOL (SF12) scores. Parents of children with medical complexity with high strain and low mental HRQOL had low confidence in the range in which intervention to avoid hospitalization would be warranted. Future work could determine how adaptive interventions to improve confidence and prevent hospitalizations should account for strain and low mental HRQOL.


Arctic versus temperate comparison of risk assessment metrics for 2-methyl-naphthalene.
Reliable risk assessment approaches for Arctic environments are requested to manage potential impacts associated with increased activities in Arctic regions. We performed toxicity tests on Arctic and temperate species exposed to the narcotic acting oil component, 2-methyl naphthalene. The experimental results were used to quantify concentration causing lethality to 50% of exposed individuals and no-effect concentration (individual level). For estimates at community level, the hazardous concentrations affecting 5% and 50% of the species were calculated from sensitivity distribution curves. These survival metrics were then used to elucidate whether temperate toxicity data used in risk assessment are sufficiently representative for the Arctic. Taking data uncertainty into consideration, we found no regional difference in tolerances to 2-methyl naphthalene either at the species level or at the community level. Hence these data support a conclusion that values of survival metrics for temperate regions are transferrable to the Arctic for the chemical 2-methyl naphthalene, as long as extrapolation techniques are properly applied and uncertainties are taken into consideration.


Cytochemical, histological, and phylogenetic distribution of a 38,000-dalton protein associated with transverse tubules.
A major protein in detergent extracts of skeletal muscle appears at 38,000 daltons in electrophoretic separations. Previous investigations have provided indirect evidence that a 38-kD skeletal muscle protein is membrane associated, and this inference has served as the basis for speculations on 38-kD protein function. In the present study, affinity purified, polyclonal antisera against 38-kD protein from skeletal muscle are produced for immunolocalization and biochemical assays. Immunoblots of two-dimensional electrophoretic separations show that this protein is heterogenously charged at pI approximately 6.4. This 38-kD protein is not extracted from muscle in low ionic strength or high ionic strength buffers, in isotonic buffers from pH 4 to pH 8 or in buffers containing 5 mM EGTA. The 38-kD protein is extracted, however, by isotonic, pH 7.0 buffer containing 1.0% Triton-X. Light microscope observations using indirect immunofluorescence of anti-38-kD labeled tissue show the protein distributed in a reticular pattern within cross-sectional muscle but not at the cell surface. Longitudinal sections show the protein concentrated in periodic, transverse bands. Purified fractions of muscle plasma membrane analyzed by immunoblotting contain 38-kD protein. Immunoblots using anti-38 kD show that this protein is present in all vertebrate skeletal muscle examined, however, the protein is present only in cardiac muscle that contains transverse tubules. The antibody does not recognize aldolase, another 38-kD striated muscle protein.


Bone marrow transplantation as treatment for X-linked immunodeficiency with hyper-IgM.
We report a 10-year-old boy with a severe form of immunodeficiency with hyper-IgM who underwent successful bone marrow transplantation with his HLA-matched sister as donor. Busulfan (20 mg/kg) and cyclophosphamide (200 mg/kg) were used as conditioning. The post-transplant course was uneventful. He is alive 25 months later with full hematological and immunological reconstitution.


Pre-eclampsia is associated with reduced resolvin D1 and maresin 1 to leukotriene B4 ratios in the plasma.
Omega-3 and omega-6 fatty acids can be endogenously converted into mediators with pro-inflammatory (eg, leukotriene B4/LTB4) or anti-inflammatory/pro-resolving activities (eg, resolvin D1/RvD1 and maresin 1/MaR1). Recent data indicate an imbalance of LTB4 and MaR1 levels in pre-eclampsia (PE), but the relative production of these mediators, including RvD1, and the role of these mediators in the disease pathogenesis remain unclear. Therefore, this study aimed to investigate the plasma levels of LTB4, RvD1, and MaR1 in pregnant women with or without PE and non-pregnant controls and their association with clinical/laboratory parameters of PE women. LTB4, RvD1, and MaR1 plasma levels were measured by competitive enzyme immunoassay in 19 non-pregnant, 20 normotensive pregnant, and 21 PE women. Plasma concentrations of LTB4 were higher and RvD1 were lower in PE women than in normotensive pregnant women, who presented higher levels of LTB4 and similar levels of RvD1 to non-pregnant women. MaR1 levels did not differ among the groups. Pre-eclampsia women had decreased RvD1/LTB4 and MaR1/LTB4 ratios. Considering only the PE group, positive correlations were observed among all the mediators tested, between LTB4 and white blood cell count and between RvD1 and creatinine levels. However, all lipid mediators correlated negatively with body mass index before pregnancy. LTB4 also correlated negatively with maternal age. Our findings suggest that the PE state results in systemic overproduction of LTB4 in relation to RvD1 and MaR1, and that these lipid mediators may be involved with the disease pathogenesis.


Improving artificial neural networks with a pruning methodology and genetic algorithms for their application in microbial growth prediction in food.
The application of Artificial Neural Networks (ANN) in predictive microbiology is presented in this paper. This technique was used to build up a predictive model of the joint effect of NaCl concentration, pH level and storage temperature on kinetic parameters of the growth curve of Lactobacillus plantarum using ANN and Response Surface Model (RSM). Sigmoid functions were fitted to the data and kinetic parameters were estimated and used to build the models in which the independent variables were the factors mentioned above (NaCl, pH, temperature), and in some models, the values of the optical densities (OD) vs. time of the growth curve were also included in order to improve the error of estimation. The determination of the proper size of an ANN was the first step of the estimation. This study shows the usefulness of an ANN pruning methodology. The pruning of the network is a process consisting of removing unnecessary parameters (weights) and nodes during the training process of the network without losing its generalization capacity. The best architecture has been sought using genetic algorithms (GA) in conjunction with pruning algorithms and regularization methods in which the initial distribution of the parameters (weights) of the network is not uniform. The ANN model has been compared with the response surface model by means of the Standard Error of Prediction (SEP). The best values obtained were 14.04% of SEP for the growth rate and 14.84% for the lag estimation by the best ANN model, which were much better than those obtained by the RSM, 35.63% and 39.30%, respectively. These were very promising results that, in our opinion, open up an extremely important field of research.


Small Cell Neuroendocrine Carcinoma: A Rare Nasopharyngeal Malignancy with Aggressive Clinical Course.
Primary small cell neuroendocrine carcinoma is uncommon in head and neck region, with occasional cases in nasopharynx. Distinction from other round cell tumors is imperative to ensure optimal patient management. We present a case of a 30-year-old woman who presented with a rapidly growing nasopharyngeal mass.


Family history, surgery, and APC mutation are risk factors for desmoid tumors in familial adenomatous polyposis: an international cohort study.
Ability to identify patients with familial adenomatous polyposis who have a high risk of developing desmoid tumors may affect decisions in clinical practice. Our aim was to assess several risk factors for desmoid tumor development in an international cohort of patients with familial adenomatous polyposis and to evaluate the clinical relevance of risk factors. This was a retrospective cohort study. Polyposis registries in The Netherlands, France, Denmark, Finland, and Italy provided information on familial adenomatous polyposis patients with desmoid tumors. We used univariate and multivariable analyses of data from registries in The Netherlands, France, Denmark, and Finland to test whether gender, APC mutation site, previous colorectal surgery, colorectal cancer, and family history for desmoid tumors contribute to risk of developing desmoid tumors at any location, or specifically at an intra-abdominal location. The effect of family history was tested with a generalized linear mixed model. : Of 2260 patients with familial adenomatous polyposis from 912 families in The Netherlands, France, Denmark, and Finland, 220 patients (10%) had desmoid tumors (101 men). In 387 patients with desmoid tumors (including 167 patients from the Italian registry), the median age at diagnosis of the first desmoid tumor was 31 years (range, 4 months-74 years). Desmoid locations were intra-abdominal (53%), abdominal wall (24%), extremities (9%), and unknown sites or combinations of sites (14%). Multivariable analysis of risk factors for desmoids at any location showed surgery (OR, 2.58; P = .0004), an APC mutation 3' of codon 1444 (OR, 3.0; P < .0001), and a positive family history (P < .0001) to be independently associated with desmoid development. When only intra-abdominal location was analyzed, APC mutation site was not associated with desmoid development. Selection bias may have occurred. A positive family history for desmoid tumors, abdominal surgery, and APC mutation site are significant risk factors for development of desmoid tumors. The results may have implications for determining the optimal management of FAP patients and guide future studies.


The enhancement of atrazine sorption and microbial transformation in biochars amended black soils.
Generally, biochar plays an important role in controlling migration and accumulation of pollutants in soil. In this dissertation, biochars derived from wheat straws at various pyrolysis temperatures are used to investigate how biochar amendment affects adsorption and microbial degradation of atrazine (typical diffuse herbicide) in soils. In order to explore the influence of soil components, soil samples with different organic matter content are collected from typical agricultural sites, which are characterized as black soils in the northeast region of China. The basic sorption characteristics of biochars from wheat straws prepared at diverse pyrolysis temperature are analyzed, along with the comparisons of the sorption difference in the raw soil and soil amended with biochars at four levels of ratio (0.1%, 0.5%, 1.0% and 2.0%). By incubation experiments, atrazine degradation in non-sterile and sterile soils and effects of atrazine degradation rate after biochar amendment are also studied. Atrazine degradation is significantly enhanced in biochar amended soils, which may be because that biochar supplement can promote the growth and metabolism of microorganisms in the soil. Our findings reveal that wheatstraw- derived biochars may be effective remediation reagents for activating degradation of the soil functional microorganism and enhancing sorption of organic matter content, which can be applied to environmental-friendly accelerate the remediation of atrazine contaminated black soils.


Effect of testosterone on insulin sensitivity, oxidative metabolism and body composition in aging men with type 2 diabetes on metformin monotherapy.
To evaluate the effect of testosterone replacement therapy (TRT) on body composition, insulin sensitivity, oxidative metabolism and glycaemic control in aging men with lowered bioavailable testosterone (BioT) levels and type 2 diabetes mellitus (T2D) controlled on metformin monotherapy. We conducted a randomized, double-blind, placebo-controlled study in 39 men aged 50-70 years with BioT levels <7.3 nmol/L and T2D treated with metformin monotherapy. Patients were randomized to testosterone gel (TRT, n = 20) or placebo (n = 19) for 24 weeks. Lean body mass (LBM), total and regional fat mass were measured using whole-body dual-energy X-ray absorptiometry scans. Whole-body peripheral insulin sensitivity, endogenous glucose production (EGP) and substrate oxidation were assessed by euglycaemic-hyperinsulinaemic clamp with glucose tracer and combined with indirect calorimetry. Coefficients (β) represent the placebo-controlled mean effect of intervention. LBM (β = 1.9 kg, p = 0.001) increased after TRT, while total fat mass (β = -1.3 kg, p = 0.009), fat mass trunk (β = -0.7 kg, p = 0.043), fat mass legs (β = -0.7 kg, p = 0.025), fat mass arms (β = -0.3 kg, p = 0.001), and HDL cholesterol (β = -0.11 mmol/L, p = 0.009) decreased after TRT compared with placebo. Insulin-stimulated glucose disposal rates did not change in response to TRT compared with placebo (p = 0.18). Moreover, glycated haemoglobin, and basal and insulin-stimulated rates of EGP, lipid- and glucose-oxidation were unaltered after TRT. TRT in aging men with lowered BioT levels and T2D controlled on metformin monotherapy improved body composition; however, glycaemic control, peripheral insulin sensitivity, EGP and substrate metabolism were unchanged.


Designing host materials for sulfur cathodes: from physical confinement to surface chemistry.
Sulfiphilic surfaces: The design of novel host materials for sulfur cathodes in lithium-sulfur batteries has been achieved through modification of the surface chemistry, by employing sulfiphilic surfaces with high electrical conductivity to develop stable, high-energy batteries. Compared to the physical-confinement technique, systems prepared by this method exhibited remarkable enhancements of both capacity and cycling stability.


Bit conversion of technical factors in vascular procedures.
The development of a conversion technique demonstrates the value of understanding and using the practical applications of basic radiographic principles. The formula can be used to upgrade the quality of vascular studies.


Hemoglobinopathies, merozoite surface protein-2 gene polymorphisms, and acquisition of Epstein Barr virus among infants in Western Kenya.
Epstein Barr virus (EBV)-associated endemic Burkitt's Lymphoma pediatric cancer is associated with morbidity and mortality among children resident in holoendemic Plasmodium falciparum regions in western Kenya. P. falciparum exerts strong selection pressure on sickle cell trait (SCT), alpha thalassemia (-α3.7/αα), glucose-6-phosphate dehydrogenase (G6PD), and merozoite surface protein 2 (MSP-2) variants (FC27, 3D7) that confer reduced malarial disease severity. The current study tested the hypothesis that SCT, (-α3.7/αα), G6PD mutation and (MSP-2) variants (FC27, 3D7) are associated with an early age of EBV acquisition. Data on infant EBV infection status (< 6 and ≥ 6-12 months of age) was abstracted from a previous longitudinal study. Archived infant DNA (n = 81) and mothers DNA (n = 70) samples were used for genotyping hemoglobinopathies and MSP-2. The presence of MSP-2 genotypes in maternal DNA samples was used to indicate infant in-utero malarial exposure. Genetic variants were determined by TaqMan assays or standard PCR. Group differences were determined by Chi-square or Fisher's analysis. Bivariate regression modeling was used to determine the relationship between the carriage of genetic variants and EBV acquisition. EBV acquisition for infants < 6 months was not associated with -α3.7/αα (OR = 1.824, P = 0.354), SCT (OR = 0.897, P = 0.881), or G6PD [Viangchan (871G > A)/Chinese (1024 C > T) (OR = 2.614, P = 0.212)] and [Union (1360 C > T)/Kaiping (1388G > A) (OR = 0.321, P = 0.295)]. There was no relationship between EBV acquisition and in-utero exposure to either FC27 (OR = 0.922, P = 0.914) or 3D7 (OR = 0.933, P = 0.921). In addition, EBV acquisition in infants ≥ 6-12 months also showed no association with -α3.7/αα (OR = 0.681, P = 0.442), SCT (OR = 0.513, P = 0.305), G6PD [(Viangchan (871G > A)/Chinese (1024 C > T) (OR = 0.640, P = 0.677)], [Mahidol (487G > A)/Coimbra (592 C > T) (OR = 0.948, P = 0.940)], [(Union (1360 C > T)/Kaiping (1388G > A) (OR = 1.221, P = 0.768)], African A (OR = 0.278, P = 0.257)], or in utero exposure to either FC27 (OR = 0.780, P = 0.662) or 3D7 (OR = 0.549, P = 0.241). Although hemoglobinopathies (-α3.7/αα, SCT, and G6PD mutations) and in-utero exposure to MSP-2 were not associated with EBV acquisition in infants 0-12 months, novel G6PD variants were discovered in the population from western Kenya. To establish that the known and novel hemoglobinopathies, and in utero MSP-2 exposure do not confer susceptibility to EBV, future studies with larger sample sizes from multiple sites adopting genome-wide analysis are required.


Inappropriate rightward saccades after right hemisphere damage: Oculomotor analysis and anatomical correlates.
Patients with right hemisphere damage and visual neglect have severe problems to orient attention towards left-sided objects, often associated with the tendency to produce inappropriate rightward saccades. In its most severe form, this tendency can assume the compulsive character of a rightward deviation of gaze as soon as the visual scene deploys (so-called "magnetic attraction of gaze"). However, little is known about the exact nature of inappropriate rightward saccades, their relation with impaired conscious perception of left-sided stimuli, and their lesional correlates. To explore these issues, we studied three groups of patients with right brain damage: patients with signs of left visual neglect associated to left homonymous hemianopia, neglect patients without hemianopia, and patients without neglect or hemianopia. Participants searched for a gap missing within a target, presented among distractors. Manual responses for target detection were required, while participants were encouraged to move their eyes during search. Endogenous attention could be summoned to the target location by a central cue. All the three groups of patients produced inappropriate rightward saccades, which could not be completely overcome by the endogenous orienting of attention induced by the cues. Anatomical analysis indicated a specific implication of damage to the right frontal eye field and to a long-range white matter tract, the fronto-parietal superior longitudinal fasciculus. Fronto-parietal networks in the right hemisphere appear thus to be essential to integrate covert and overt orienting of attention, and to thoroughly explore space in order to become aware of the multiple competing objects around us.


Maximum a posteriori Bayesian estimation of oral cyclosporin pharmacokinetics in patients with stable renal transplants.
To develop a maximum a posteriori probability (MAP) Bayesian estimator for the pharmacokinetics of oral cyclosporin, based on only three timepoints, and evaluate its performance with respect to a full-profile nonlinear regression approach. 20 adult patients with stable renal transplants given orally administered microemulsified cyclosporin and mycophenolate. Cyclosporin was assayed by liquid chromatography-mass spectrometry. Nonlinear regression and MAP Bayesian estimation were performed using a home-made program and a previously designed pharmacokinetic model including an S-shaped absorption profile described by a gamma distribution. MAP Bayesian estimation using the best limited sampling strategy (before administration, and 1 and 3 hours after administration) was compared with nonlinear regression (taken as the reference method) for the prediction of the different pharmacokinetic parameters and exposure indices. Median relative prediction error was -0.49 and -3.42% for area under the concentration-time curve over the administration interval of 12 hours (AUC12) and estimated peak drug concentration (Cmax), respectively (nonsignificant). Relative precision was 2.00 and 4.32%, and correlation coefficient (r) was 0.985 and 0.955, for AUC12 and Cmax, respectively. This paper reports preliminary results in a stable renal transplant patient population, showing that MAP Bayesian estimation can allow accurate prediction of AUC12 and Cmax with only three samples (0, 1 and 3 hours). Although these results require confirmation by further studies in other clinical settings, using other drug combinations, other analytical methods and commercially available pharmacokinetic software, the method seems promising as a tool for the therapeutic drug monitoring of cyclosporin in clinical practice or for exposure-controlled studies.


Structural, physicochemical and biological properties of spray-dried wine powders.
Different fruit wines, chokeberry, blackcurrant and blueberry, were spray-dried using hydroxypropyl-β-cyclodextrin (HP-β-CD) and inulin (IN). The structural, physicochemical, and biological properties of the spray-dried wine powders were studied over 12months of storage in darkness at 8°C. Identification and quantification of single phenolic compounds before and after storage revealed that HP-β-CD had a positive effect on anthocyanin retention during storage for all microcapsules tested. Similar decreases in anthocyanin were found for blackcurrant and chokeberry powders, ranging from 7.3 to 8.9% with HP-β-CD and 12.3 to 12.5% with IN. Levels of anthocyanin losses in blueberry wine microcapsules were much greater: 19.9% (HP-β-CD) and 22.7% (IN). The high antiradical activities of blackcurrant and chokeberry wine microcapsules were stable and remained unchanged during storage. All wine microcapsules revealed significant activity against medically important bacterial strains. The HP-β-CD samples showed generally higher activity against the test microorganisms compared to IN microcapsules, especially at concentrations of 100mg/mL.


Parietal control of attentional guidance: the significance of sensory, motivational and motor factors.
The lateral intraparietal area (LIP), a portion of monkey posterior parietal cortex, has been implicated in spatial attention. We review recent evidence showing that LIP encodes a priority map of the external environment that specifies the momentary locus of attention and is activated in a variety of behavioral tasks. The priority map in LIP is shaped by task-specific motor, cognitive and motivational variables, the functional significance of which is not entirely understood. We suggest that these modulations represent teaching signals by which the brain learns to identify attentional priority of various stimuli based on the task-specific associations between these stimuli, the required action and expected outcome.


Inhibition of human allergic skin reactions in vivo by pretreatment with cromolyn (disodium cromoglycate).
The effect of cromolyn on allergen-induced allergic skin reactions was studied. Two patients with allergic rhinitis, two patients with bronchial asthma and atopic dermatitis and two patients with allergic rhinitis and atopic dermatitis were included in this study. They were allergic to cedar pollen, house dust mite and house dust, respectively. Scratching with allergen induced wheal and erythema reactions in each patient. Simultaneous application of allergen and cromolyn solution did not modulate allergic reactions; however, pretreatment with cromolyn solution inhibited allergen-induced wheal and erythema reactions significantly.


The effect of peptidase inhibitors on the release of Met5-Enk-Arg6-Phe7 (YGGFMRF) and Met5-enkephalin (YGGFM) from spinal cord induced by substance P in vivo.
Using a preparation for the perfusion of the subarachnoidal spaces of the spinal cord of rats it was found that substance P can stimulate the release of YGGFMRF and YGGFM. We have studied the effect of several peptidase inhibitors (captopril, bestatin, thiorphan) on the recovery of YGGFMRF and YGGFM released from spinal cord by substance P. The recovery of released YGGFMRF was increased by adding captopril to the perfusion medium. A combination of captopril and bestatin in the perfusion medium further increases this YGGFMRF recovery. Intrathecal injection of captopril and bestatin also potentiated the analgesic effect of YGGFMRF and electroacupuncture. These results suggest that substance P may act as a "releaser" of enkephalins in spinal cord and that the dipeptidyl carboxypeptidase and aminopeptidase may be important in the degradation of YGGFMRF in vivo.


Animal models of stroke: do they have value for discovering neuroprotective agents?
There has been a series of high-profile failures of drugs in clinical trials of acute ischaemic stroke that were designed to meet criteria necessary for drug regulatory approval. This has, again, called into question the value of animal models for identifying effective neuroprotective agents. Here, we review evidence that physiological changes (reperfusion, hyperglycaemia, hypothermia and blood pressure) produce comparable changes in outcome in both animal models and human stroke patients, which indicates that the models should identify clinically effective neuroprotective agents. We suggest that most clinical failures have occurred because compounds were administered differently in animal and clinical studies. We review earlier guidelines on the information that is necessary from preclinical studies before a compound enters clinical trials, and propose modifications to these guidelines.


Electrospun silk-based nanofibrous scaffolds: fiber diameter and oxygen transfer.
In this study, silk fibroin was extracted from cocoons of silkworms and fabricated into nonwoven mats by electrospinning method. A new model based on the group method of data handling (GMDH) and artificial neural network (ANN) was developed for estimation of the average diameter of electrospun silk fibroin nanofibers. In this regard, concentration, flow rate, voltage, distance, and speed of collector were used as input parameters and average diameter of the fibers was considered as output parameter. Two models were capable to estimate average diameter of fibers with good accuracy. The average absolute relative deviation for GMDH and ANN models was equal to 3.56 and 2.28 %, respectively. Furthermore, due to importance of oxygen delivery to site of injury to promote wound healing, continuity equation for mass transport was employed for prediction of oxygen profile in the system containing wound dressing and skin. The result showed that our prepared wound dressing is capable to pass the oxygen completely to the skin layer and is not acting as a barrier for oxygen delivery to wound site. Since average nanofibers diameter can influence the mat physical, mechanical and biological properties then this model may serve as a useful guide to obtain tailor made and uniform silk nanofibers at various combinations of process variables.


Self-extracellular RNA promotes pro-inflammatory response of astrocytes to exogenous and endogenous danger signals.
Astrocytes participate in the local innate immune response of the central nervous system. In response to stress such as ischemia, activated cells release endogenous factors known as damage-associated molecular patterns (DAMPs). Self-extracellular RNA (eRNA) is such a ubiquitous alarm signal. However, it is unclear whether eRNA is involved in the early acute phase of cerebral ischemia and is sufficient to sensitize astrocytes towards a DAMP or PAMP (pathogen-associated molecular pattern) reaction. Pro-inflammatory activation upon eRNA stimulation was characterized in primary murine astrocyte cultures. In vivo, an experimental stroke model was used to localize and quantify eRNA in murine brain sections. Using primary cortical neurons and the mouse hippocampal neuronal cell line HT-22, neuronal RNA release upon stress conditions related to cerebral hypoxia/ischemia was analyzed. While low-dose eRNA alone did not promote pro-inflammatory activation of astrocytes in culture, it strongly enhanced the expression of pro-inflammatory cytokines in the presence of either Pam2CSK4, a synthetic PAMP molecule that mimics bacterial infection, or high mobility group box 1 (HMGB1), a prominent DAMP. Synergism of eRNA/Pam2CSK4 and eRNA/HMGB1 was prevented by blockage of the astroglial toll-like receptor (TLR)-2. Inhibition of NF-κB- and mitogen-activated protein kinase-dependent signaling pathways hampered eRNA/Pam2CSK4-mediated pro-inflammatory activation of astrocytes. In vivo, the amount of non-nuclear, presumably extracellular ribosomal RNA in close proximity to neurons significantly accumulated across the infarct core and peri-infarct areas that was accompanied by transcriptional up-regulation of various pro-inflammatory factors. Accordingly, the exposure of neurons to hypoxic/ischemic stress in vitro resulted in the release of eRNA, partly mediated by active cellular processes dependent on the cytosolic calcium level. The DAMP signal eRNA can sensitize astrocytes as active players in cerebral innate immunity towards exogenous and endogenous activators of inflammation (PAMPs and DAMPs) in a synergistic manner via TLR2-NF-κB-dependent signaling mechanisms. These findings provide new insights into the pathogenesis of ischemic stroke and other inflammatory neurological disorders. Further studies will clarify whether administration of RNase in vivo may serve as an effective treatment for inflammatory brain pathologies.


UNBS1450, a steroid cardiac glycoside inducing apoptotic cell death in human leukemia cells.
Cardiac steroids are used to treat various diseases including congestive heart failure and cancer. The aim of this study was to investigate the anti-leukemic activity of UNBS1450, a hemi-synthetic cardenolide belonging to the cardiac steroid glycoside family. Here, we report that, at low nanomolar concentrations, UNBS1450 induces apoptotic cell death. Subsequently, we have investigated the molecular mechanisms leading to apoptosis activation. Our results show that UNBS1450 inhibits NF-κB transactivation and triggers apoptosis by cleavage of pro-caspases 8, 9 and 3/7, by decreasing expression of anti-apoptotic Mcl-1 and by recruitment of pro-apoptotic Bak and Bax protein eventually resulting in cell death.


Leaf consumption by insects in three Eucalyptus forest types in Southeastern Australia and their role in short-term nutrient cycling.
Leaf consumption by insects in three Eucalyptus forest types (E. delegatensis, E. dives and E. pauciflora) in the Brindabella mountains, A.C.T., was studied over a two year period. Foliage consumption was calculated using two methods: (1) sampling of foliage repeatedly through the season and measurement of leaf area loss due to insects and (2) calculation of the mass of leaves consumed, based on frass-fall measurements. Intensive sampling of tree canopies for defoliating insects was also carried out in all three forest types. Defoliation, as estimated by measurement of leaf area loss, did not exceed 10% in any of the forest types except on current year's foliage for two months of one year in the E. dives and E. pauciflora stands. Insect consumption of foliage in all three forest types, as calculated from frass-fall measurements, varied from 2-3% of annual leaf production. The nitrogen, phosphorus, and potassium passing through insect bodies and frass was less than 4% of the total amount falling in other litter. The small amount of leaf consumption occurring in these stands and the small amount of associated nutrient transfer indicate that insect defoliators at low population levels do not affect forest productivity or have significant effects on short term nutrient cycling.


The pharmacology of dienogest.
Dienogest (DNG) is a 19-nortestosterone derivative (a C-19 progestogen) with a cyanomethyl instead of an ethinyl group at the C-17 position, which may make the compound elicit fewer hepatic effects than other C-19 nortestosterone derivatives. Its similarity to norethisterone is reflected in its high endometrial efficacy, which could explain the high stability of the menstrual cycle women achieve when they use DNG in combination with ethinyl estradiol (EE) or with estradiol valerate (E2V). Its strong endometrial efficacy underlies the use of DNG (on its own) to treat endometriosis, and gives it antiproliferative and anti-inflammatory effects in the treatment of endometriotic lesions. Properties derived from its C-19 derivative structure include its short plasma half-life, of about 10h (which means the drug is not accumulated), and its high oral bioavailability, of more than 90%. However, DNG also has some of the properties of typical of progesterone derivatives, including a lack of effect on the metabolic and cardiovascular systems, and considerable antiandrogenic activity, the latter increased by its lack of affinity to the sex-hormone binding globulin (SHBG), in contrast to other C-19 progestogens. DNG has no glucocorticoid and no antimineralocorticoid activity. It also has no antiestrogenic activity, which suggests that it should not antagonize estradiol's beneficial effects. This is important for its use in the treatment of endometriosis, because, due to DNG's low gonadotropic activity, E2 levels are not decreased to zero, in contrast to treatments with gonadotropin-releasing hormone (GnRH) analogues. This maintenance beneficial E2 effects is of particular importance for the general tolerability of the first contraceptive pill to use E2V instead of EE, although clinical endpoint studies are still ongoing. These studies are expected, on the basis of its pharmacology, to demonstrate the cardiovascular safety of the new pill.


Modification of radiation-induced damage to bone marrow stem cells by dose rate, dose fractionation, and prior exposure to cytoxan as judged by the survival of CFUs: application to bone marrow transplantation (BMT).
The relative importance of the effects of dose rate, dose fractionation, and prior exposure to Cytoxan on the recovery of cells in the bone marrow, following conditioning for BMT, remains controversial. Traditionally, bone marrow stem cells and leukemic cells have been considered as having a limited ability to repair radiation-induced damage following total body irradiation (TBI) compared to cells of the lung (the dose-limiting tissue for TBI). We examined the survival response of the bone marrow stem cells of mice (CFUs) at three TBI dose rates (0.47, 0.25 and 0.08 Gy/min). The radiation response of CFUs (compilation Do = 0.75 Gy) was independent of dose rate. One TBI dose fractionation was chosen: two fractions per day, separated by 6 hours, for 3 days. The radiation survival curve of CFUs showed a compilation Do of 1.09 Gy, compared to 0.75 Gy for the one-fraction case. The recovery of CFUs following 2 days of Cytoxan demonstrated an "overshoot," whereas recovery of CFUs was incomplete, even by day 23, following the initiation of the complete conditioning regimen of Cytoxan plus TBI. These data demonstrate no significant effect of dose rate, at least in the range 0.08 to 0.48 Gy/min, on the survival of CFUs following either single or six fractionated TBI doses. However, the statistically significant difference in the Do of CFUs in going from one to six fractions has direct application to bone marrow transplantation techniques. Moreover, Cytoxan, at least at 200 mg/kg for 2 days, prior to TBI, appears to have only a marginal modifying effect on the eventual recovery of CFUs.


The kinetic dissection of transport from metabolic trapping during substrate uptake by intact cells. Uridine uptake by quiescent and serum-activated Nil 8 hamster cells and their murine sarcoma virus-transformed counterparts.
1. We present a theoretical analysis of the tandem processes of transport and metabolic trapping which together constitute uptake of a substrate by intact cells. 2. Transport is assumed to occur by means of a simple carrier here analysed in its general form. Trapping is assumed to occur by a simple enzymic reaction. 3. We show how to obtain the separate parameters of the steps by analysing uptake data over a range of uptake times and substrate concentrations. 4. We present uptake data for uridine and cytosine-beta-D-arabinoside entering Nil 8 hamster fibroblasts, normal and murine sarcoma virus transformed, in the quiescent condition and after stimulation by added serum. We analyse the data in terms of the theory for tandem processes. 5. Transport is characterised by a system having a high Km and a high V for entry. The data for cytosine-beta-D-arabinoside suggest that the cytosine-beta-D-arabinoside system is not far from a symmetric one. The data for uridine transport do not differ when quiescent and serum-activated cells are compared. Transformed cells transport uridine at half the maximum velocity of normal cells, with or without added serum. 6. Trapping of cytosine-beta-D-arabinoside is insignificant. Trapping of uridine occurs by a system with both V and Km at least an order of magnitude smaller than are these parameters for transport. Trapping of uridine by non-transformed cells activated by serum, has twice the V of such cells in the quiescent state. 7. In the virus-transformed cells, the control of uridine trapping by added serum is lost, along with control of growth by this stimulant.


A systematic analysis of FDA-approved anticancer drugs.
The discovery of novel anticancer drugs is critical for the pharmaceutical research and development, and patient treatment. Repurposing existing drugs that may have unanticipated effects as potential candidates is one way to meet this important goal. Systematic investigation of efficient anticancer drugs could provide valuable insights into trends in the discovery of anticancer drugs, which may contribute to the systematic discovery of new anticancer drugs. In this study, we collected and analyzed 150 anticancer drugs approved by the US Food and Drug Administration (FDA). Based on drug mechanism of action, these agents are divided into two groups: 61 cytotoxic-based drugs and 89 target-based drugs. We found that in the recent years, the proportion of targeted agents tended to be increasing, and the targeted drugs tended to be delivered as signal drugs. For 89 target-based drugs, we collected 102 effect-mediating drug targets in the human genome and found that most targets located on the plasma membrane and most of them belonged to the enzyme, especially tyrosine kinase. From above 150 drugs, we built a drug-cancer network, which contained 183 nodes (150 drugs and 33 cancer types) and 248 drug-cancer associations. The network indicated that the cytotoxic drugs tended to be used to treat more cancer types than targeted drugs. From 89 targeted drugs, we built a cancer-drug-target network, which contained 214 nodes (23 cancer types, 89 drugs, and 102 targets) and 313 edges (118 drug-cancer associations and 195 drug-target associations). Starting from the network, we discovered 133 novel drug-cancer associations among 52 drugs and 16 cancer types by applying the common target-based approach. Most novel drug-cancer associations (116, 87%) are supported by at least one clinical trial study. In this study, we provided a comprehensive data source, including anticancer drugs and their targets and performed a detailed analysis in term of historical tendency and networks. Its application to identify novel drug-cancer associations demonstrated that the data collected in this study is promising to serve as a fundamental for anticancer drug repurposing and development.


A Review of the Literature for Individualizing Women's Care Through Breast Cancer Risk Assessment.
Breast cancer is well recognized as a leading type of cancer affecting women in the United States. Although breast cancer screening is well supported in the literature, there is a lack of clear agreement regarding which breast cancer risk calculating tools should be used to develop personalized screening regimens. In this review of 11 primary articles published from 2017 through 2022, we assess current evidence on breast cancer risk assessment in outpatient clinic and mammography settings and the pivotal role of health care providers in influencing patients' choices regarding individualized screenings. Risk assessment is strongly recommended by multiple clinical practice guidelines, yet there is inadequate evidence to endorse one risk assessment tool as best practice. Further research is needed to integrate risk assessment within the clinic workflow and screening encounters. Patient-centered communication and shared decision-making are critical components for managing each woman's perceived risk and objective risk for breast cancer.


Selective destruction of leucocytes by freezing as a potential means of modulating tissue immunogenicity: membrane integrity of lymphocytes and macrophages.
It is now known, when a tissue allograft is transplanted, that antigen recognition alone is not sufficient for lymphocyte activation in the host. "Passenger" leucocytes (antigen-presenting cells) present in the donor tissue are now recognized as a major immunogenic stimulus. Removal of these contaminating leucocytes, using a variety of procedures, has enabled the immunogenicity of allografts to be reduced, thus enhancing the survival of tissue allografts. This initial study explores the possibility of using a cryobiological approach to modulating the immunogenicity of tissues by virtue of the well-recognized differential susceptibility of different cell types to freezing injury. The investigation was prompted by demonstrations that pancreatic islets can secrete insulin in response to a graded glucose challenge after cryopreservation using relatively fast cooling rates which would be expected to be suboptimal for leucocyte survival. Batches of rat peripheral blood lymphocytes, or peritoneal exudate cells (macrophages) were cooled at 0.3, 1, 5, 20, 75, or 200 degrees C/min using three different cryopreservation protocols reported to yield viable pancreatic islets. Cell survival was evaluated in terms of the numbers of cells recovered after freezing as well as a fluorometric viability assay which assessed the membrane integrity of cells. Optimum survival of both lymphocytes and macrophages after freezing and thawing was found at cooling rates in the range of 0.3 to 5 degrees C/min. A significant number (10-40%) of these lymphoid cells survived freezing at 20 degrees C/min and only after cooling at rates greater than 75 degrees C/min was survival reduced to a negligible level.


Health insurance coverage of the working poor.
This study examines the working poor, and their pattern of health insurance coverage. The data indicate that in 1977 almost 22% of the working poor lack health insurance throughout the year. Moreover, children of the working poor were almost twice as likely as children of the poor nonemployed to be without coverage. The implications of the Omnibus Budget Reconciliation Act of 1981 (OBRA) which restricted the working poor's eligibility for Medicaid are discussed. It is argued that being employed, in itself, does not guarantee poor people access to medical care and may, in fact, serve to restrict it.


Increased mutation rates in doubly viral transformed Chinese hamster cells.
An untransformed parental Chinese hamster cell line, one polyoma transformed clone, and two clones containing both SV40 and polyoma DNA were tested for the appearance of variants resistant to 6-thioguanine or oubain. The frequency of such variants was found to be highest in doubly transformed cells. The mutation rate at these loci was correlated with the level of transformation. The mutants observed were stable and had low reversion frequencies with no gross cytogenetic changes. These results establish a quantitative basis for the evaluation of phenotypic variability observed in transformed cell populations.


Partial least squares-based multivariate spectral calibration method for simultaneous determination of beta-carboline derivatives in Peganum harmala seed extracts.
The partial least squares regression method has been applied for simultaneous spectrophotometric determination of harmine, harmane, harmalol and harmaline in Peganum harmala L. (Zygophyllaceae) seeds. The effect of pH was optimized employing multivariate definition of selectivity and sensitivity and best results were obtained in basic media (pH>9). The calibration models were optimized for number of latent variables by the cross-validation procedure. Determinations were made over the concentration range of 0.15-10 microg mL(-1). The proposed method was validated by applying it to the analysis of the beta-carbolines in synthetic quaternary mixtures of media at pH 9 and 11. The relative standard errors of prediction were less than 4% in most cases. Analysis of P. harmala seeds by the proposed models for contents of the beta-carboline derivatives resulted in 1.84%, 0.16%, 0.25% and 3.90% for harmine, harmane, harmaline and harmalol, respectively. The results were validated against an existing HPLC method and it no significant differences were observed between the results of two methods.


[Histological evaluation of brush cytology of rabbit conjunctiva].
The number of the cells and the layers of the conjunctiva which can be obtained by brush cytology was studied on rabbit conjunctiva using cytological and histological methods. About 1,000, 3,500, and 10,000 conjunctival epithelial cells can be obtained by 7, 14, and 20 brush strokes histological observations showed that all varieties of the layers including basal cells were obtained without destroying the basement membrane. This study showed that the brush cytology can offer single cell suspension only from the conjunctival epithelium, and that brush cytology is useful to investigate the conjunctival epithelium by flow cytometry, polymerase chain reaction, and other methods.


Molecular strategy using cis-element 'decoy' of E2F binding site inhibits neointimal formation in porcine balloon-injured coronary artery model.
Transcription factor E2F plays a pivotal role in the transactivation of cell cycle regulatory genes, leading to vascular lesion formation. Double-stranded DNA with high affinity for E2F as 'decoy' cis elements may block the activation of genes mediating the cell cycle, resulting in an effective therapeutic agent for treating intimal hyperplasia. In this study, we tested the feasibility of E2F decoy therapy to treat neointimal formation in a porcine coronary artery balloon injury model. An angioplasty catheter was inserted in the left anterior descending coronary artery of pigs to cause vascular injury. Initially, we tested the feasibility of transfection of FITC-labeled E2F decoy ODN using a hydrogel balloon catheter. Fluorescence due to E2F decoy ODN could be detected throughout the medial layer. Therefore, we transfected E2F decoy ODN into the balloon-injured artery using hydrogel catheter. Of importance, intravascular ultrasound (IVUS) and histological evaluation demonstrated that plaque area in the balloon-injured artery was significantly reduced by E2F decoy ODN compared with mismatched decoy ODN at 1 month after a single transfection (P < 0.01). In contrast, luminal and total vessel areas were significantly increased in vessels treated with E2F decoy ODN as compared with mismatched decoy. Endothelial function after angioplasty was not affected by E2F decoy transfection. Finally, we tested the acute toxicity of E2F decoy ODN in monkeys, and no apparent side-effects were detected. Here, we report the successful in vivo transfer of E2F decoy ODN using a hydrogel catheter to inhibit vascular lesion formation in balloon-injured porcine coronary artery without any apparent side-effects.


Identification and characterization of PtDGAT2B, an acyltransferase of the DGAT2 acyl-coenzyme A: diacylglycerol acyltransferase family in the diatom Phaeodactylum tricornutum.
Diacylglycerol acyltransferase (DGAT) plays a pivotal role in triacylglycerol (TAG) formation in some oleaginous organisms. We describe here the identification of a type 2 DGAT (PtDGAT2B) in the diatom Phaeodactylum tricornutum that contains four putative type 2 acyl-CoA:DGATs, sharing little sequence similarity with each other. TAG synthesis and lipid body formation could be completely restored in a Saccharomyces cerevisiae TAG-deficient quadruple mutant by expressing PtDGAT2B. Up-regulation of PtDGAT2B precedes the accumulation of TAG. Functional analysis of enzyme activity in vivo demonstrated that expression of PtDGAT2B can increase the proportion of unsaturated C(16) and C(18) fatty acids in yeast TAG.


A stable rhombohedral phase in ferroelectric Hf(Zr)1+xO2 capacitor with ultralow coercive field.
Hafnium oxide-based ferroelectric materials are promising candidates for next-generation nanoscale devices because of their ability to integrate into silicon electronics. However, the intrinsic high coercive field of the fluorite-structure oxide ferroelectric devices leads to incompatible operating voltage and limited endurance performance. We discovered a complementary metal-oxide semiconductor (CMOS)-compatible rhombohedral ferroelectric Hf(Zr)1+xO2 material rich in hafnium-zirconium [Hf(Zr)]. X-ray diffraction combined with scanning transmission electron microscopy reveals that the excess Hf(Zr) atoms intercalate within the hollow sites. We found that the intercalated atoms expand the lattice and increase the in-plane and out-of-plane stresses, which stabilize both the rhombohedral phase (r-phase) and its ferroelectric properties. Our ferroelectric devices, which are based on the r-phase Hf(Zr)1+xO2, exhibit an ultralow coercive field (~0.65 megavolts per centimeter). Moreover, we achieved a high endurance of more than 1012 cycles at saturation polarization. This material discovery may help to realize low-cost and long-life memory chips.


A case of reocclusion of the renal artery diagnosed by the color Doppler method with evaluation of blood flow direction in the collateral circulation of the kidney in addition to the non-detectable blood signal in the renal artery.
A 23-year-old woman was referred to our hospital for an interventional procedure for chronic total occlusion of the right renal artery, probably due to fibromuscular dysplasia (FMD), and for control of renal vascular hypertension. Before percutaneous transluminal renal angioplasty (PTRA), aortography revealed collateral circulation to the right kidney from the lower lumbar artery. After PTRA, however, blood flow in the renal side of the collateral circulation flowed outside from the right renal parenchyma. 4 months later, we could not find a blood flow signal in the right renal artery, and there was a contrary flow signal in the right kidney parenchyma continuously from the extrahilar vessel, possibly a collateral artery. These findings indicated reocclusion of the right artery. We confirmed reocclusion of the renal artery and collateral feeding by contrast dynamic computed tomography (CT), and PTRA was performed again without any complications or reocclusion for 5 months. This is the first case report showing that a back-flowing signal in the right renal parenchyma from the extrahilar artery is useful as an indirect finding suggesting reocclusion.


The Mucocele of the Gallbladder.
The gallbladder polyps are a common finding during ultrasonography but only in rare cases they may be a cancer. When a polyp is greater than 1 cm, the cholecystectomy is usually performed. In these images, a polyp of 4 cm corresponding to a collection of mucus (mucocele) is reported. This unusual polyp of the gallbladder was caused by heterotopic intestinal mucosa.


The structural gene for the M1 subunit of ribonucleotide reductase maps to chromosome 11, band p15, in human and to chromosome 7 in mouse.
The genes for the M1 subunit of the enzyme ribonucleotide reductase have been mapped in the human and the murine species by use of two independently derived mouse cDNA clones. Southern blot analysis of rodent x human somatic cell hybrid DNAs confirmed the assignment of RRM1 to the short arm of human chromosome 11. In situ hybridization to human metaphase chromosomes revealed a peak of silver grains over the distal third of band 11p15, a region corresponding to subbands p15.4----p15.5. The mouse Rrml locus was assigned to chromosome 7, where it forms part of a conserved syntenic group of at least seven other genes assigned to human chromosome band 11p15.


Evaluating Rates and Determinants of COVID-19 Vaccine Hesitancy for Adults and Children in the Singapore Population: Strengthening Our Community's Resilience against Threats from Emerging Infections (SOCRATEs) Cohort.
COVID-19 vaccines are crucial for achieving sufficient immunisation coverage to manage the pandemic, but vaccine hesitancy persists. This study aimed to investigate the prevalence and determinants of vaccine hesitancy in adults and in parents for vaccinating their children using an integrated social cognition model. A community-based cohort in Singapore [N = 1623] completed a survey (wave 25) between June and July 2021 which measured their risk perceptions, distress, trust, vaccination beliefs, and vaccine intentions/behaviours. Results indicated low rates of hesitancy (9.9%) for own vaccination, with most concerns citing side effects, safety, and hasty development. Remaining respondents were vaccinated (69%) or intended to vaccinate (21%). The multivariable model (non-vaccinated respondents) indicated that, living with people in poor health, subjective norm, moral norm, benefits, and necessity of vaccination were associated with lower vaccine hesitancy (R2 Cox & Snell: 51.4%; p < 0.001). Hesitancy rates were higher for children's vaccination (15.9%), with male gender, lower perceived vaccine benefits, high COVID-19 risk perceptions, vaccination concerns, and necessity beliefs associated with higher odds of parental vaccine hesitancy (R2 Cox & Snell = 36.4%; p < 0.001). While levels of vaccine acceptance are high, more targeted messages are needed. For adults' vaccination, more emphasis should be on benefits and social gains, while for parental hesitancy, messages related to safety should be prioritised.


The influence of mercury and lead compounds on the circadian rhythm of cytoplasmic RNA in hypothalamic neurons of mice.
Cytophotometric determinations of cytoplasmic RNA were performed at various hours in normal mice and those given a single injection of mercuric citrate or lead citrate. A cosinor analysis of the results has revealed a marked reduction of the amplitude of the rhythm of RNA content a shift of the acrophase to earlier hours in the experimental animals. Moreover, administration of the tested compounds caused a general reduction of the RNA content in the hypothalami.


Astaxanthin protects cognitive function of vascular dementia.
The purpose of this study was to evaluate the effect of astaxanthin (AST) on cognition function, inflammatory response and oxidative stress in vascular dementia (VD) mice. VD mice model was established by left unilateral common carotid arteries occlusion (LUCCAO). Following LUCCAO, AST was intragastrically administered for 30 days. Object recognition test and morris water maze test were used to evaluate cognitive function. Hematoxylin and eosin staining was performed to observe the hippocampal neuron structure. Enzyme-linked immunosorbent assay kit and bicinchoninic acid kit were respectively adopted to measure IL-1β and IL-4 protein expression and superoxide dismutase (SOD) activity and malondialdehyde (MDA) content in hippocampus and prefrontal cortex. AST improved the discrimination ability of VD mice. The escape latency and path length of VD mice treated with AST were dramatically reduced. Besides, AST 200 mg/kg enhanced crossing platform time and the number of times crossing the platform quadrant, and alleviated the morphological impairment in VD mice. Moreover, we found that AST inhibited IL-1β expression and MDA content, whereas promoted IL-4 expression and SOD activity in a dose-dependent manner. AST could improve cognitive impairment and hippocampal neurons in VD mice, which may be related to suppression of inflammatory response and oxidative stress.


Transeptal suturing - a cost-efficient alternative for nasal packing in septal surgery.
Nasal packing is routinely used in septal surgery to prevent postoperative bleeding. To demonstrate the possibility of transeptal suture as a safe and effective way to avoid nasal packing and to improve efficiency. This is a prospective, descriptive, inferential cost study comprising 92 patients. Two randomized groups of patients were analyzed, one with nasal packing and the other with transeptal suture. In the group of transeptal suture no patient experienced postoperative bleeding, and a statistically significant reduction of pain and headache was demonstrated. At the same time, we improved efficiency by saving on material costs. Transeptal suture is an effective and safe alternative to classic nasal packing in septal surgery. Moreover, it improves the efficiency of the intervention by saving costs.


Exploring the role of neutrophil-to-lymphocyte ratio and blood chemistry in head and neck adenoid cystic carcinomas treated with carbon ion radiotherapy.
In recent years, there is an emerging interest in the prognostic role of chemistry blood biomarkers in oncological patients but their role in adenoid cystic carcinomas (ACCs) is still unknown. This study aims to assess the prognostic significance of baseline neutrophil-to-lymphocyte ratio (NLR) and blood chemistry in a series of head and neck ACC patients treated with carbon ion radiotherapy (CIRT). We retrospectively retrieved the data of 49 consecutive head and neck ACC patients treated with CIRT. Univariable and multivariable Cox proportional hazard regression (Cox-ph) analyses were performed to look for a potential association of NLR, and other blood biomarker values, with disease-free survival (DFS), Local Control (LC), Metastasis Free Survival (MFS) and overall survival (OS). No significant association between NLR > 2,5 and DFS, LC, MFS and OS was found with univariable analysis although a trend was reported for DFS (Hazard ratio [HR]: 2,10, 95 % CI: 0,85 - 5,08, p-value = 0,11). Patients with hemoglobin (hb) ≤ 14 g/dL showed significantly better DFS, MFS and OS. Multivariable regression Cox-ph analysis for DFS, adjusted for margin status, clinical target volume and Absolute Number of Monocytes, reported the following statistically significant HRs, for both NLR > 2,5 and hb > 14 g/dL respectively: 4,850 (95 % CI = 1,408 - 16,701, p = 0,012) and 3,032 (95 % CI = 1,095 - 8,393, p = 0,033). Moreover, hb > 14 with HR = 3,69 (95 % CI: 1,23 - 11,07, p-value = 0,02), was a negative independent prognostic predictor for MFS. Pre-treatment NLR and hb values seem to be independent prognostic predictor for clinical outcomes in head and neck ACC patients. If their role will be validated in a larger prospective cohort, they might be worthwhile for a pre-treatment risk stratification in patients treated with CIRT.


Magnetic resonance imaging of paranasal sinus tumors for craniofacial resection.
Computerized tomography (CT) has been shown to be 78% accurate with respect to anatomic extent of tumor when correlated with operative findings and histology in patients undergoing craniofacial resection. To determine whether preoperative evaluation could be improved by the combination of CT and magnetic resonance imaging (MRI), 26 patients with tumor of the paranasal sinuses had undergone MRI before surgery in addition to CT. Ten patients also received Gadolinium-DTPA as a contrast-enhancement agent during MRI. The radical approach offered by craniofacial resection allows accurate evaluation of imaging techniques and when these are compared with histologic findings, a 94% correlation is found. The use of Gadolinium further improves the accuracy of tumor delineation to 98%. Despite the intrinsic disadvantage of absent bone detail, MRI demonstrates the extent of tumor better than CT and can distinguish it from inflammed mucosa, retained secretions, and normal mucosa provided the correct sequences are used.


CO2 -Enabled Cyanohydrin Synthesis and Facile Iterative Homologation Reactions*.
Thermodynamic and kinetic control of a chemical process is the key to access desired products and states. Changes are made when a desired product is not accessible; one may manipulate the reaction with additional reagents, catalysts and/or protecting groups. Here we report the use of carbon dioxide to accelerate cyanohydrin synthesis under neutral conditions with an insoluble cyanide source (KCN) without generating toxic HCN. Under inert atmosphere, the reaction is essentially not operative due to the unfavored equilibrium. The utility of CO2 -mediated selective cyanohydrin synthesis was further showcased by broadening Kiliani-Fischer synthesis under neutral conditions. This protocol offers an easy access to a variety of polyols, cyanohydrins, linear alkylnitriles, by simply starting from alkyl- and arylaldehydes, KCN and an atmospheric pressure of CO2 .


A rational approach to the use of fine-needle aspiration biopsy in the evaluation of primary and recurrent neoplasms in children.
Fine-needle aspiration (FNA) has been recommended as a technique for accurate evaluation and diagnosis of childhood malignancies. Very little data exist regarding the limitations and utility of FNA in children. We reviewed our experience over the past 5 years to assess the clinical use of FNA and its limitations. One hundred seventy-three FNAs were performed in 156 patients who ranged in age from 7 months to 18 years. Sixty-three patients were female and 110 were male. Thirty-seven aspirations were obtained to evaluate new masses in children with previously diagnosed malignancies. FNA allowed diagnosis of the malignancy in 90% of patients with solid tumors, whereas only 9 of 19 patients with lymphomas were diagnosed accurately with FNA. The specificity was 99.7%. Inadequate material was obtained in 13 aspirates. Insufficient material was obtained in 14% of patients who had FNA as their initial diagnostic tool. Four false-negatives were obtained while evaluating children for recurrent disease. There were 16 true-negative biopsies. These data suggest that FNA is an excellent tool for diagnosing both recurrent malignancies as well as previously undiagnosed solid tumors in the pediatric population but is inadequate to diagnose children with suspected undiagnosed lymphomas. Negative studies should be considered nondiagnostic and followed by open biopsies when clinical suspicion of malignancy is high.


The association between trough blood concentration and systemic exposure of tacrolimus: Comparison between once-daily (Advagraf®) and twice-daily (Prograf®) formulation in de novo kidney transplant recipients.
Available data of early conversion from twice-daily tacrolimus (TAC-BID) to once-daily tacrolimus (TAC-OD) in de novo kidney transplant (KT) recipients are limited. We conducted a prospective study of early conversion to TAC-OD in de novo KT recipients. Eligible patients were enrolled to receive TAC-BID (Prograf®) and then converted to TAC-OD (Advagraf®) by 1:1 ratio, approximately 14 days after KT (range 9-22). Blood samples were investigated for pharmacokinetic parameters before and 7-14 days after the conversion. Fifteen patients were included and provided AUC0-24 of 202.9 ± 44.4 ng h/mL for TAC-BID (pre-conversion) and 193.0 ± 63.4 ng h/mL for TAC-OD (post-conversion) (p = 0.41). Mean trough blood concentration (Cmin) of TAC-BID and TAC-OD was 6.4 ± 1.4 ng/mL and 4.9 ± 1.6 ng/mL (p = 0.01). Correlation coefficient (r) between Cmin and AUC0-24 of TAC-BID and TAC-OD were 0.620 and 0.875. Additional analysis found that patients with a drop of Cmin > 30% had a significant lower AUC0-24 after conversion. Renal function remains stable. We conclude that early conversion to TAC-OD is safe and well tolerated with an indifferent systemic exposure. However, patients with a drop of Cmin > 30% after conversion to TAC-OD will require additional dose adjustment.


Clinical efficacy of botulinum toxin type A reconstituted and refrigerated 1 week before its application in external canthus dynamic lines.
BACKGROUND; Allergan Inc. recommends that its botulinum toxin type A (BTX-A; BOTOX) must be refrigerated and applied within 4 hours after its reconstitution to avoid losing its biologic effectiveness. The objective was to compare clinical efficacy in treating external canthus dynamic lines with reconstituted and refrigerated toxin (BTX-A) 1 week before its application versus fresh toxin (BTX-A). This study was a double-blind, randomized, clinical trial. A total of 30 patients aged 30 to 60 years having a minimum of one and maximum of six external canthus dynamic lines were treated in one canthus with 15 U of BTX-A reconstituted and refrigerated at 4 degrees C 1 week before being applied and in the other with 15 U of fresh BTX-A. Patients were followed-up on Day 10 and Weeks 6, 12, and 18; assessment included a neuroconduction study of the facial nerve and the investigators' photographic evaluation of the number of external canthus dynamic lines at maximum smile. Outcome measurement did not show statistically significant differences between both groups. BTX-A, reconstituted and refrigerated 1 week before its application, has similar clinical efficacy in treating external canthus dynamic lines as does fresh BTX-A.


Do young patients with renal cell carcinoma feature a distinct outcome after surgery? A comparative analysis of patient age based on the multinational CORONA database.
We analyzed the distinct clinicopathological features and prognosis of patients with renal cell carcinoma age 40 years or less compared to a reference group of patients 60 to 70 years old. Overall 2,572 patients retrieved from a multicenter international database comprised of 6,234 patients with surgically treated renal cell carcinoma were included in this retrospective study. Clinical and histopathological features of 297 patients 40 years old or younger (4.8%) were compared to those of 2,275 patients (36.5%) 60 to 70 years old, who served as the reference group. Median followup was 59 months. The impact of young age and further parameters on disease specific mortality and all cause mortality was evaluated by multivariate Cox proportional hazards regression analyses. Young patients more frequently underwent nephron sparing surgery (27% vs 20%, p = 0.008) and regional lymph node dissection compared to older patients (38% vs 32%, p = 0.025). Organ confined tumor stage (81% vs 70%, p <0.001), smaller tumor diameter (4.5 vs 4.7 cm, p = 0.014) and chromophobe subtype (10% vs 4%, p <0.001) were significantly more frequent in young patients. On multivariate analysis older patients had a higher disease specific (HR 2.21, p <0.001) and all cause mortality (HR 3.05, p <0.001). The c indices for the Cox models were 0.87 and 0.78, respectively. However, integration of the variable age group did not significantly increase the predictive accuracy of the disease specific and all cause mortality models. Young patients with renal cell carcinoma (40 years old or younger) have significantly different frequencies of clinical and histopathological features, and a significantly lower all cause and disease specific mortality compared to patients 60 to 70 years old.


Questioning behaviour in general practice: a pragmatic study.
To study the extent to which general practitioners' questioning behaviour in routine practice is likely to encourage the adoption of evidence based medicine. Self recording of questions by doctors during consultations immediately followed by semistructured interview. Urban Australian general practice. Random sample of 27 general practitioners followed over a half day of consultations. Rate of recording of clinical questions about patients' care which doctors would like answered; frequency with which doctors found answers to their questions. Doctors asked a total of 85 clinical questions, at a rate of 2.4 for every 10 patients seen. They found satisfactory answers to 67 (79%) of these questions. Doctors who worked in small practices (of one or two doctors) had a significantly lower rate of questioning than did those in larger practices (1.6 questions per 10 patients v 3.0 patients, P = 0.049). No other factors were significantly related to rate of questioning. These results do not support the view that doctors routinely generate a large number of unanswered clinical questions. It may be necessary to promote questioning behaviour in routine practice if evidence based medicine and other forms of self directed learning are to be successfully introduced.


Fetal growth retardation associated with maternal administration of immunosuppressive drugs.
Since maternal-fetal immunogenetic disparity facilitates growth of the fetoplacental unit, nonspecific depression of the maternal immune system by immunosuppressive drugs could result in previously unrecognized adverse effects such as fetal growth retardation. To test this hypothesis, groups of 6 to 8 primigravid Fischer female rats mated with DA or Fischer male rats were treated with saline (controls) or either cyclophosphamide (Cytoxan) or azathioprine (Imuran) in doses similar to those used therapeutically in human subjects. It was found that these drugs caused an increased incidence of fetal death and produced fetal and neonatal growth retardation. Smaller placentas and fetuses reflected a decrease in cell number rather than cell size whereas water, fat, and protein content were only minimally affected. Analyses of mean maternal weight gain, spleen weight assays, and changes in the lymph nodes draining the uterus indicate that effects detrimental to the offspring are primarily the result of immunologic and cytotoxic mechanisms. Moreover, a review of the literature suggests that these immunosuppressive agents are also associated with small-for-gestational age infants in human pregnancies.


Relative biological activities of Asn1-,Val5-angiotensin II, Ile5-angiotensin II and Sar1-angiotensin II in man.
Biological activities of asn1-,val5-angiotensin II (Hypertensin, Ciba, Asn1-,Val5-ANG II), ile5-angiotensin II (human angiotensin II, Ile5-ANG II) and sar1-angiotensin II (Sar1-ANG II) were compared in man. In 7 normal men 5 pmol/kg X min each of Asn1-,Val5-ANG II, Ile5-ANG II and Sar1-ANG II was infused iv from 0900 h to 0930 h at 1-week intervals. Average increments of blood pressure at the end of the infusions were 11/12, 23/20 and 36/30 mmHg, respectively (significant differences among the 3: P less than 0.001), average decrements of plasma renin activity were 0.30, 0.32 and 0.27 ng/ml X H, respectively (no significant difference among the 3), average increments of plasma aldosterone were 1.1, 2.3 and 4.4 ng/100 ml, respectively (significant difference between the former 2: P les than 0.001, between the latter 2: P less than 0.02), and durations of blood pressure rise after the cessation of these infusions (T) were 2-5 (average 5) min, 10-25 (average 20) min and 35-60 (average 40) min, respectively (significant difference between the former 2:less than P 0.01, between the latter 2: P less than 0.001). From these results it is evident that the pressor and steroidogenic actions of Ile5-ANG II are significantly stronger than those of Asn1-,Val5-ANG II and that the duration of pressor action of the former is much longer than that of the latter. Therefore, when the activities of angiotensin II (ANG II) derivatives are compared with those of ANG II in man, Ile5-ANG II--natural human ANG II--should always be used instead of Asn1-,Val5-ANG II. The pressor and steroidogenic actions and T of Sar1-ANG II are significantly stronger or longer than those of Ile5-ANG II. The reason for this is thought to be that Sar1-ANG II is bound tightly to the vascular and adrenal ANG II receptors and is not readily metabolized.


Practical use of hepatitis C virus kinetics monitoring in the treatment of chronic hepatitis C.
Prevention of hepatitis C virus (HCV) infection complications can be achieved by antiviral therapy based on the use of a combination of pegylated interferon (IFN)-alpha and ribavirin. The steady-state kinetics of HCV infection represents the treatment target. The goal is cure, which is achieved when all infected cells have been cleared from the body. Because of their intrinsic properties, real-time polymerase chain reaction (PCR) methods are rapidly replacing other technologies for routine quantification of HCV-RNA during antiviral therapy. The virological response at week 12 of therapy is currently used to tailor treatment duration in HCV genotype 1 infection only. Recent reports suggest that the virological response at week 4 could be used to tailor treatment duration, whatever the HCV genotype.


New approach to the splenic vessels.
The transperitoneal approach is used systematically for an arterial or a venous splenorenal anastomosis. However, this approach is associated with high morbidity and mortality rates. Because of our anatomical and surgical findings we have used the retroperitoneal approach to the splenic hilus by means of the lumbar region. The first splenorenal arterial anastomosis with this approach was done in 1972. The approach has proved to be less aggressive since it avoids the danger of damaging the pancreas, it is a more direct approach to the splenic vessels and it provides better exposure and facilitates the anastomosis. In addition, the loss or infection of ascitic fluid in cirrhotic patients is avoided with this approach, as well as intraoperative hemorrhaging caused by the great surplus circulation. There has been neither mortality nor complications in the 13 cases of arterial and venous splenorenal anastomoses that we have done with this method.