Dynamics of glucose-induced insulin release during the spontaneous remission of streptozocin diabetes induced in the newborn rat.
Neonatal rats injected with streptozocin (STZ, 100 mg/kg) at birth exhibited an acute diabetes followed by a spontaneous remission. We have previously shown that this recovery from neonatal diabetes is due to B-cell regeneration and reaccumulation of pancreatic insulin stores starting from 3 to 5 days after birth. The B-cell population during this period is heterogeneous with both surviving B-cells that have escaped the toxic effect of STZ and newly formed B-cells. To evaluate to what extent this B-cell population is functionally normal, we have measured in vitro the dynamics of glucose-induced insulin secretion from pancreatic fragments of rats treated with STZ at birth. The insulin responses were tested at intervals after STZ treatment, from day 1 to day 21 using perifusion of pancreatic fragments, and on day 21 and at 5 mo using perfusion of isolated pancreas. While the glucose-induced insulin release was completely obtunded (2% of the normal response) on day 1 after STZ, it could be demonstrated after day 3. Moreover, it increased as a function of age (6% and 36% of the normal responses on day 5 and day 14, respectively). This restoration of the insulin response to glucose closely paralleled the recovery of pancreatic insulin stores (6% and 51% of normal values, respectively, on day 5 and day 14). In sharp contrast with the lack of glucose response in vitro in the adult, glucose-induced insulin release was still detected on day 21 regardless of the in vitro system used (perifusion or perfusion). Furthermore, on day 21 the B-cells of the STZ rats exhibited a tendency toward enhanced insulin response to arginine, which is a prominent feature in adult rats previously treated with STZ at birth.(ABSTRACT TRUNCATED AT 250 WORDS)


Association of baseline frailty and age with postoperative outcomes in metastatic brain tumor patients.
The impact of baseline frailty status versus that of chronological age on surgical outcomes of metastatic brain tumor patients remains largely unknown. The present study aimed to evaluate this relationship for preoperative risk stratification using a large national database. The National Surgical Quality Improvement Program database was queried to extract data of metastatic brain tumor patients who underwent surgery between 2015 and 2019 (n=5,943). Univariate and multivariate analyses were performed to assess the effect of age and modified frailty index-5 (mFI-5) on mortality, major complications, unplanned readmission and reoperation, extended length of stay (eLOS), and non-home discharge. Both univariate and multivariate analyses demonstrated that frailty status was significantly predictive of 30-day mortality, major complications, eLOS, and non-home discharge. Although increasing age was also a significant predictor of eLOS and discharge to non-home destination, effect sizes were smaller compared with frailty. The present study, based on analysis of data from a large national registry, shows that frailty, when compared with age, is a superior predictor of postoperative outcomes in metastatic brain tumor patients. A future prospective study, namely a randomized controlled trial, would be beneficial in helping to corroborate the findings of this retrospective study.


The prevalence of thyroid autoantibodies in autoimmune connective tissue diseases: a systematic review and meta-analysis.
Patients with autoimmune connective tissue disease (ACTD) may have anti-thyroid peroxidase antibody (TPOAb) and anti-thyroglobulin antibody (TgAb). This study aimed to compare the prevalence of thyroid autoantibodies in ACTD patients and controls. All case-control studies published between 1980 and 2019 in English were searched from Medline, Embase, Web of Science, PubMed databases for meta-analysis and subgroup analyses. Total 10,321 ACTD cases and 12,949 healthy controls were included, and the prevalence of thyroid autoantibody positivity was higher in ACTD patients than in controls. Subgroup analysis revealed positive association between TgAb and ACTD in populations from all continents including European, Asian, African, and American. In addition, we found positive association between TgAb positivity and most ACTD cases including RA, SLE, pSS, and UCTD, positive association between TPOAb positivity and all ACTD cases including RA, SLE, pSS, SSc, and UCTD, and positive association between TPOAb positivity and ACTD in European, Asian, and African but not in American populations. Thyroid autoantibodies are more prevalent in ACTD patients than in healthy controls. It is important to screen patients with ACTD for the presence of thyroid autoimmunity, and perform thyroid function tests in clinical evaluation of ACTD patients.


Increased susceptibility to liver damage from pneumoperitoneum in a murine model of biliary atresia.
We hypothesized that livers with biliary atresia (BA) are more susceptible to the harmful effects of a high-pressure CO(2) pneumoperitoneum (PP) than healthy livers. A murine model of BA was used in this experiment. Mice were divided into 6 groups: (1) control Balb/c; (2) control Balb/c, CO(2)-PP; (3) control BA; (4) BA-sham; (5) BA, CO(2)-PP; and (6) BA, air-PP. Mice from groups 2, 5, and 6 underwent an 8-mm Hg-PP for 60 minutes. Liver samples were collected for histology, colorimetry, and flow cytometry analysis 18 to 24 hours after the procedure. Markers of apoptosis were investigated as indicators of acute cell damage. We observed a statistically significant higher rate of apoptosis in livers with BA exposed to a prolonged CO(2)-PP or air-PP compared with control groups. There were no significant differences between groups 1 and 2, or between groups 5 and 6. In this animal model, we have shown that livers with BA are more susceptible than healthy livers to injury by a prolonged PP. This injury was caused by both CO(2) and air-PP, implying that it is the direct result of pressure. These results may have implications for the success of minimally invasive Kasai procedures.


Transport and metabolism of D-glucose in human adipocytes. Studies of the dependence on medium glucose and insulin concentrations.
Uptake and metabolism of the physiologically labelled D-glucose (D-[U-14C]glucose) has been characterized in human adipocytes at several unlabelled D-glucose concentrations in the absence and presence of insulin. Following a 90 min incubation, about 80% of the intracellular radioactivity was incorporated into total lipids at tracer glucose concentration, as well as at higher glucose concentrations in basal and insulin-stimulated cells, whereas 20% was recovered as hydrophilic metabolites. The only 14C-labelled metabolite escaping the cells in detectable amounts was CO2, which accounted about 4%. At trace glucose concentrations (5 mumol/l), the rate of glucose uptake was linear with time. Comparative studies of initial glucose uptake after 10 s and tracer D-glucose conversion to total lipids after 90 min showed high coefficients of correlation between basal rates (r = 0.87), maximal response above basal level to insulin (r = 0.92) and insulin sensitivity (r = 0.78). Thus, under these conditions glucose transport is rate-limiting for net glucose uptake, and measurements over long time intervals of rates for total cell-associated radioactivity or lipogenesis may serve as reliable estimates of initial glucose influx rates. However, the conversion rate of tracer glucose to metabolites decreased progressively with the glucose concentration and with an apparent Km of about 0.2 mmol/l. The three metabolic pathways exhibited similar percentage decreases in their activities, suggesting that a common enzymatic step is rate-limiting. In comparison, the Km for initial D-glucose uptake rate was about 7 mmol/l. Hence, the capacity for total glucose metabolism comprised only a small fraction of the glucose transport capacity at medium glucose concentrations above tracer concentrations. Both basal, half-maximal and maximal insulin-stimulated rates of adipocyte glucose utilization were dependent on the glucose concentration. Thus, comparing lipogenesis at tracer and at 0.5 mmol/l medium glucose concentration, it was shown that the higher medium glucose concentration was associated with a 60% lowering of the basal rate, a 35% reduction in the percentage response above baseline to maximal insulin stimulation and a 4-fold increase in the insulin sensitivity. Obviously, these findings reflect some intracellular step(s) being rate-limiting at medium glucose levels above tracer values.


Construction and analysis of mRNA, lncRNA, and transcription factor regulatory networks after retinal ganglion cell injury.
Retinal ganglion cell (RGC) injury is a critical pathological feature of several optic neurodegenerative diseases. The regulatory mechanisms underlying RGC injury remain poorly understood. Recent evidence has highlighted the important roles of long noncoding RNAs (lncRNAs) in degenerative neuropathy but few studies have focused on lncRNAs associated with RGC injury. In this study, we analyzed dysregulated lncRNAs associated with RGC injury, their potential regulatory functions, and the molecular mechanisms underlying the regulation of lncRNAs and transcription factors (TFs). We analyzed lncRNA and mRNA profiles in the GSE142881 dataset associated with RGC injury and identified 1049 differentially expressed genes (DEGs), with 18 differentially expressed (DE) TFs among 883 DE mRNAs and 312 DE lncRNAs. The predicted DE lncRNAs and DE mRNAs were used to construct a lncRNA-mRNA co-expression network. Functional enrichment analysis was performed to explore the functions of the lncRNAs and mRNAs. The co-expression network between DE lncRNAs and DE mRNAs was highly enriched in inflammatory and immune-related pathways, indicating that they play role in the process of RGC injury. Among the DE mRNAs, we screened 18 DE TFs, including activating transcription factor 3 (ATF3), associated with RGC injury. Co-expression analysis predicted that 13 lncRNAs were potential binding targets of ATF3. The screening of the potential targets of these 13 lncRNAs showed that they were also significantly enriched in functional pathways associated with inflammation and apoptosis. After analysis, we constructed the mRNA-ATF3-lncRNA regulatory network after RGCs injury. In summary, we identified the gene module associated with immune and inflammatory responses after optic nerve injury and constructed a regulatory network of lncRNA-TF-mRNA. The results indicate that lncRNAs, by binding to TFs, can regulate downstream genes and function during RGC injury. The results provide a foundation for further studies of the mechanism of RGC injury and provide insight into the clinical diagnosis and investigation direction of neurodegenerative diseases such as traumatic optic neuropathy and glaucoma.


Optimizing frontal impact occupant protection systems for passengers seated in wheelchairs.
The advent of automated vehicles (AVs) provides an opportunity to design integrated wheelchair seating stations that provide an equivalent level of safety for occupants using wheelchairs as those using vehicle seating. This study designed a frontal occupant protection system for an integrated second-row wheelchair seating station that includes optimized airbags and seatbelt systems. MADYMO models were used to optimize belt geometry for a midsized male ATD seated in a surrogate wheelchair fixture, with and without inclusion of a Self Conforming Rearseat Air Bag (SCaRAB). Sled tests were performed to confirm the benefits of airbag use and optimized belt geometry. Additional modeling was performed with commercial manual and power wheelchairs, to identify the effects of wheelchair design and forward clear space on occupant kinematics and injury measures. Additional sled tests were performed with manual and power wheelchairs to demonstrate effectiveness of the restraint system with commercial products. Simulations and tests both showed improved kinematics using an optimized seatbelt system geometry compared to a commonly used suboptimal D-ring location that places the shoulder belt at a more outboard location. Use of the SCaRAB helped compensate for suboptimal geometry. Results include specific recommendations for belt geometry relative to the wheelchair seating station and airbag parameters suitable for protecting occupants seated in wheelchairs. Restraint systems initially optimized using the surrogate wheelchair also performed well with the two commercial wheelchairs. The clear space required for maneuvering a wheelchair will likely prevent injurious head contact in frontal crashes. This study is the first to design a frontal optimal occupant protection system for an integrated second-row wheelchair seating station, demonstrating that it should be feasible once integrated wheelchair seating stations are included in AVs.


Intestinal permeability in subjects from two different race groups with diverse stone-risk profiles.
It is well established that calcium oxalate stones may be caused by colonic or ileum oxalate (Ox) hyperabsorption (secondary to intestinal dysfunction). Studies have reported that increased intestinal permeability (IP) can cause hyperabsorption of nutrients culminating in passive diffusion of Ox. In South Africa, renal stones occur in the white population (W) but are extremely rare in the black population (B). Previous studies have shown that despite B having a hyperoxalurogenic diet relative to W, urinary Ox in the former is not higher. It has been suggested that different Ox handling mechanisms in the groups are the cause of this disparity. The present study was undertaken to examine whether the IP index, a reliable and accurate measure of intestinal integrity, plays a role in this anomaly. Ten healthy males from each group ingested a dual-sugar isotonic solution containing 5 g lactulose (LA) and 2 g mannitol (MA). IP was assessed by comparing the LA:MA ratio in 5 h urine samples using high performance anion exchange chromatography coupled with pulse amperometric detection to measure the concentration of each sugar. 24 h dietary intake and urine composition were also determined. LA excretion was identical in both groups (0.03 %) while MA excretion was 8.3 % in B and 11.3 % in W. IP index was 0.004 for B and 0.003 for W. It is concluded that IP is not a contributory factor in the apparent different handling of dietary Ox in B and W South Africans. It is speculated that differences in renal transporters may play a role.


Extraction of radioactive rubidium and D-glucose from the artificially perfused intervillous space of the human placenta.
Extraction (Et) of 86Rb and [14C]D-glucose from the artificially perfused intervillous space of the human placenta was measured using [3H]L-glucose as a reference tracer. E. of 86Rb increased slowly from initial values near zero to a late maximum, which indicates that Et was greatly influenced by heterogeneity of indicator transit times through the intervillous space. The ascending part of the plot of -1n(I-Et) against time (t) of 86Rb was approximately linear. In each experiment the time corresponding to zero extraction was estimated by linear extrapolation of the plot. The mean of the times obtained in the individual experiments corresponded to the most frequent transit time of the indicators through the system outside the placenta. These observations suggest that 86Rb is taken up by the trophoblast from the entire space perfused. Under such conditions the rate of the trophoblast uptake can be estimated from the slope of the above plot. Unlike that of 86Rb, Et of [14C]D-glucose increased rapidly to a relatively steady level. This time course of Et may result from combined effects of transit time heterogeneity and rapid back-flux of the tracer.


Directed biosynthesis of analogues of ergot peptide alkaloids with Claviceps purpurea.
Analogues of peptide ergot alkaloids can be obtained by feeding a producing culture of Claviceps purpurea with an analogue of one of the amino acids of the peptide chain of the alkaloid.


Letter to the editor: The clinically relevant MTARC1 p.Ala165Thr variant impacts neither the fold nor active site architecture of the human mARC1 protein.
A study recently published in Hepatology Communications provided insights into a variant of MTARC1 protein, which conveys protection against liver disease. Here, we report a crystal structure of the variant protein at near-atomic resolution and compare it to the structure of the wildtype protein.


Morphology, ultrastructure, genomics, and phylogeny of Euplotes vanleeuwenhoeki sp. nov. and its ultra-reduced endosymbiont "Candidatus Pinguicoccus supinus" sp. nov.
Taxonomy is the science of defining and naming groups of biological organisms based on shared characteristics and, more recently, on evolutionary relationships. With the birth of novel genomics/bioinformatics techniques and the increasing interest in microbiome studies, a further advance of taxonomic discipline appears not only possible but highly desirable. The present work proposes a new approach to modern taxonomy, consisting in the inclusion of novel descriptors in the organism characterization: (1) the presence of associated microorganisms (e.g.: symbionts, microbiome), (2) the mitochondrial genome of the host, (3) the symbiont genome. This approach aims to provide a deeper comprehension of the evolutionary/ecological dimensions of organisms since their very first description. Particularly interesting, are those complexes formed by the host plus associated microorganisms, that in the present study we refer to as "holobionts". We illustrate this approach through the description of the ciliate Euplotes vanleeuwenhoeki sp. nov. and its bacterial endosymbiont "Candidatus Pinguicoccus supinus" gen. nov., sp. nov. The endosymbiont possesses an extremely reduced genome (~ 163 kbp); intriguingly, this suggests a high integration between host and symbiont.


Acute renal failure and hypoglycaemia due to sulphadiazine poisoning.
A 3-year-old girl is described who became oliguric and hypoglycaemic whilst receiving an excessive dose of sulphadiazine. The mechanism of the hypoglycaemia is discussed.


Epidemiological analysis of varicella in Dalian from 2009 to 2019 and application of three kinds of model in prediction prevalence of varicella.
This study described the epidemic characteristics of varicella in Dalian from 2009 to 2019, explored the fitting effect of Grey model first-order one variable( GM(1,1)), Markov model, and GM(1,1)-Markov model on varicella data, and found the best fitting method for this type of data, to better predict the incidence trend. For this Cross-sectional study, this article was completed in 2020, and the data collection is up to 2019. Due to the global epidemic, the infectious disease data of Dalian in 2020 itself does not conform to the normal changes of varicella and is not included. The epidemiological characteristics of varicella from 2009 to 2019 were analyzed by epidemiological descriptive methods. Using the varicella prevalence data from 2009 to 2018, predicted 2019 and compared with actual value. First made GM (1,1) prediction and Markov prediction. Then according to the relative error of the GM (1,1), made GM (1,1)-Markov prediction. This study collected 37,223 cases from China Information System for Disease Control and Prevention's "Disease Prevention and Control Information System" and the cumulative population was 73,618,235 from 2009 to 2019. The average annual prevalence was 50.56/100000. Varicella occurred all year round, it had a bimodal distribution. The number of cases had two peaks from April to June and November to January of the following year. The ratio of males to females was 1.17:1. The 4 to 25 accounted for 60.36% of the total population. The age of varicella appeared to shift backward. Students, kindergarten children, scattered children accounted for about 64% of all cases. The GM(1,1) model prediction result of 2019 would be 53.64, the relative error would be 14.42%, the Markov prediction result would be 56.21, the relative error would be 10.33%, and the Gray(1,1)-Markov prediction result would be 59.51. The relative error would be 5.06%. Varicella data had its unique development characteristics. The accuracy of GM (1,1)-Markov model is higher than GM(1.1) model and Markov model. The model can be used for prediction and decision guidance.


Solitary plasmacytoma of the spine in an adolescent: a case report.
Solitary plasmacytoma of bone is a rare disease in patients younger than 30 years, and only a few cases have been reported in children and adolescents. We report the findings of a destructive lesion of the spine due to solitary plasmacytoma in an adolescent patient.


Brain-Derived Microparticles in Patients with Severe Isolated TBI.
to investigate the presence of circulating microparticles (MPs) of brain tissue origin in the systemic and cerebrovenous blood of patients with severe traumatic brain injury (TBI). Prospective observational study in 15 consecutive patients with severe isolated TBI. We repeatedly measured concentrations of MPs expressing glial fibrillary acidic protein (GFAP), neuron-specific enolase (NSE) and aquaporin-4 (AQP4), in arterial and cerebrovenous blood at admittance to hospital and up to 72 hours after the injury. Concentrations of MPs expressing GFAP and AQP4 were significantly higher in the TBI group compared with healthy controls: GFAP 2.0 [1.1-7.9] vs. 1.3 [1-2.1] × 106/mL, p < 0.001; AQP4 0.1 [0.07-0.22] vs. 0.08 [0.06-0.11] × 106/mL, p < 0.001 (median, range). No transcranial gradients were found. Levels of NSE-expressing MPs were also higher in the TBI group compared with healthy controls: 0.4 [0.25-2.1] vs. 0.26 [0.13-0.98] × 106/mL, p < 0.05; however, regarding NSE-positive non-platelet MPs, there were no differences between patients and controls. Patients with TBI have higher numbers of brain-derived MPs. Further studies are needed, however, to identify specific and sensitive MP markers of brain injury.


Early Postoperative Nociceptive Threshold and Production of Brain-Derived Neurotrophic Factor Induced by Plantar Incision Are Not Influenced with Minocycline in a Rat: Role of Spinal Microglia.
Brain-derived neurotrophic factor (BDNF) from spinal microglia is crucial for aberrant nociceptive signaling in several pathological pain conditions, including postoperative pain. We assess the contribution of spinal microglial activation and associated BDNF overexpression to the early post-incisional nociceptive threshold. Male Sprague-Dawley rats were implanted with an intrathecal catheter. A postoperative pain model was established by plantar incision. Thermal and mechanical nociceptive responses were assessed by infrared radiant heat and von Frey filaments before and after plantar incision. Rats were injected intrathecally the microglial activation inhibitor minocycline before incision, 24 h after incision, or both. Other groups were subjected to the same treatments and the L4-L5 spinal cord segment removed for immunohistochemical analysis of microglia activation and BNDF expression. Plantar incision reduced both thermal latency and mechanical threshold, indicating thermal hypersensitivity and mechanical allodynia. Minocycline temporally reduced thermal withdrawal latency but had no effect on mechanical withdrawal threshold, spinal microglial activity, or dorsal horn BDNF overexpression during the early post-incision period. These results suggest that spinal microglia does not contribute substantially to post-incisional nociceptive threshold. The BDNF overexpression response that may contribute to postoperative hyperalgesia and allodynia is likely derived from other sources.


Corneal tattoo with tea infusion.
Except in animal models of cataractogenesis, the literature on the effects of tea infusion on ocular tissue is scant. In our patient, prolonged exposure to tea infusion may have led to a hypesthetic cornea with secondary limbal stem cell loss. In turn, the eye developed keratinization and corneal neovascularization.


To eat or not to eat. A comparison of current and former animal product limiters.
In this exploratory study, we compared current and former pescatarians, vegetarians and vegans on a number of variables including the motivations for their food choices. Participants were recruited via online message boards as well as through snowball sampling. Of the 247 participants, 196 were currently limiting animal products and 51 were former animal product limiters. Current limiters were more likely to have made a gradual rather than abrupt transition to animal product limitation and were more likely to have joined a vegetarian or vegan group than former limiters. Furthermore, current limiters indicated that their eating pattern was a part of their self identity. These findings shed light on the differences among current and former vegans and vegetarians and can inform individuals interested in promoting animal product limitation for health or ethical reasons.


Dynamics in a discrete two-species competition model: coexistence and over-compensation.
The dynamic features of an over-compensating discrete two-species competition system with stable coexistence are recaptured, and it is shown how the probabilities of the different possible ecological scenarios, e.g. coexistence, may be calculated when the assumption of no over-compensation is loosened. A Bayesian methodology for calculating the probability that stable oscillations or chaos may occur in plant populations or communities is outlined. The methodology is exemplified using an experimental population of Arabidopsis thaliana. It is concluded that, when making ecological predictions it is preferable and possibly important to test for the possibility of chaotic population dynamics due to over-compensation rather than assuming a priori that over-compensation does not occur.


Interdomain B in ZAP-70 regulates but is not required for ZAP-70 signaling function in lymphocytes.
The protein tyrosine kinase ZAP-70 plays an important role in T-cell activation and development. After T-cell receptor stimulation, ZAP-70 associates with the receptor and is phosphorylated on many tyrosines, including Y292, Y315, and Y319 within interdomain B. Previously, we demonstrated that Y292 negatively regulates ZAP-70 function and that Y315 positively regulates ZAP-70 function by interacting with Vav. Recent studies have suggested that Y319 also positively regulate ZAP-70 function. Paradoxically, removal of interdomain B (to create the construct designated Delta), containing the Y292, Y315, and Y319 sites, did not eliminate the ability of ZAP-70 to induce multiple gene reporters in Syk-deficient DT-40 B cells and ZAP-70/Syk-deficient Jurkat cells. Here we show that Delta still utilizes the same pathways as wild-type ZAP-70 to mediate NF-AT induction. This is manifested by the ability of Delta to restore induction of calcium fluxes and mitogen-activated protein kinase activation and by the ability of dominant negative Ras and FK506 to block the induction of NF-AT activity mediated by Delta. Biochemically we show that the stimulated tyrosine phosphorylation of Vav, Shc, and ZAP-70 itself is diminished, whereas that of Slp-76 is increased in cells reconstituted with Delta. Deletion of interdomain B did not affect the ability of ZAP-70 to bind to the receptor. The in vitro kinase activity of ZAP-70 lacking interdomain B was markedly reduced, but the kinase activity was still required for the protein's in vivo activity. Based on these data, we concluded that interdomain B regulates but is not required for ZAP-70 signaling function leading to cellular responses.


Identification of polypropylene glycols and polyethylene glycol carboxylates in flowback and produced water from hydraulic fracturing.
The purpose of the study was to separate and identify the unknown surfactants present in flowback and produced water from oil and gas wells in the Denver-Julesburg Basin (Niobrara Formation) in Weld County, Colorado, USA. Weld County has been drilled extensively during the last five years for oil and gas between 7000-8000 feet below land-surface. Polypropylene glycols (PPGs) and polyethylene glycols carboxylates (PEG-Cs) were found for the first time in these flowback and produced water samples. These ethoxylated surfactants may be used as friction reducers, clay stabilizers, and surfactants. Ultrahigh-performance liquid chromatography/quadrupole-time-of-flight mass spectrometry (UHPLC/QTOF-MS) was used to separate and identify the different classes of PPGs, PEG-Cs, and their isomers. The Kendrick mass scale was applied along with mass spectrometry/mass spectrometry (MS-MS) with accurate mass for rapid and unequivocal identification. The PPGs and their isomers occur at the ppm concentration range and may be useful as "fingerprints" of hydraulic-fracturing. Comparing these detections to the compounds used in the fracturing process from FracFocus 3.0 (https://fracfocus.org), it appears that both PPGs and polyethylene glycols (PEGs) are commonly named as additives, but the PEG-Cs have not been reported. The PEG-Cs may be trace impurities or degradation products of PEGs.


Development of new immunoradiometric assay for CA 125 antigen using two monoclonal antibodies produced by immunizing lung cancer cells.
CA 125 is an antigen associated with non-mucinous epithelial ovarian cancer, which is defined by OC 125 antibody developed by immunizing ovarian cancer cells. We have produced two monoclonal antibodies, 130-22 and 145-9, by using the human lung adenocarcinoma cell line PC-9. Both 130-22 and 145-9 antibodies recognized CA 125 antigen. However, the binding sites seemed to be separate from those of OC 125. Testing by 9 immunoradiometric assays (IRMA), using different combinations of the 3 monoclonal antibodies 130-22, 145-9 and OC 125 demonstrated that the best standard curve for detecting CA 125 could be obtained by a "simultaneous sandwich" assay based on a mixture of 125I-labeled OC 125 and 130-22 or 145-9 coated beads. One-step IRMA, using 130-22 as a tracer and 145-9 as an immunoadsorbent, also showed good reproducibility and sensitivity for measuring CA 125. Antigens were detectable in the culture supernatants of PC-9 cells and 5 of 6 ovarian cancer and endometrial adenocarcinoma cells. These results indicate that one-step IRMA using 130-22 and 145-9 is useful for detecting CA 125 antigen.


Predicting protein tertiary structure and its uncertainty analysis via particle swarm sampling.
We discuss the relationship between the problem of protein tertiary structure prediction from the amino acid sequence and the uncertainty analysis. The algorithm presented in this paper belongs to the category of decoy-based modeling, where different known protein models are used to establish a low dimensional space via principal component analysis. The low dimensional space is utilized to perform an energy optimization via a family of very explorative particle swarm optimizers to find the global minimum. The aim of this procedure is to get a representative sample of the nonlinear equivalent region, that is, protein models that have their energy lower than a certain energy bound. The posterior analysis of this family provides very valuable information about the backbone structure of the native conformation and its possible alternate states. This methodology has the advantage of being simple and fast and can help refine the tertiary protein structure. We comprehensively illustrate the performance of our algorithm on one protein from the CASP-9 protein structure prediction experiment. We also provide a theoretical analysis of the energy landscape found in the tertiary structure protein inverse problem, explaining why model reduction techniques (principal component analysis in this case) serve to alleviate the ill-posed character of this high dimensional optimization problem. In addition, we expand the computational benchmark with a summary of other CASP-9 proteins in the Appendix.


Gene transfer and expression studies in cultured avian neural crest cells differentiating into melanocytes.
Neural crest cells obtained from explanted neural tubes take up, express, and retain exogenous DNA applied by the CaPO4 co-precipitation method during their differentiation into melanocytes. High efficiencies of gene transfer were obtained with both supercoiled DNA and intact phage particles; linear DNA or DNA from the phage yielded very low efficiencies. There is some evidence that transferred gene expression is differentiation dependent. The system should be useful for studies concerned with the analysis of cell developmental genes and their regulatory elements.


Prevalence and management of urinary tract endometriosis: a clinical case series.
To report on the prevalence, surgical management, and outcome of urinary tract endometriosis (UTE) in a cohort of 221 patients undergoing laparoscopic surgery for severe endometriosis. UTE can cause significant morbidity, such as silent kidney or progressive renal function loss. Its frequency is underestimated and data on laparoscopic management are scarce. Between 2007 and 2010, 43 patients were eligible for this single-center, retrospective study. The inclusion criterion was the presence of UTE (ie, bladder and/or ureteral endometriosis). All patients were operated laparoscopically. The prevalence of UTE was 19.5% (43/221). There was no correlation between bladder and ureteral endometriosis (P >.05). Ureteral endometriosis was associated with patient's age (P <.01). Patients with bladder, but not ureteral, involvement complained more frequently about dysuria, hematuria, and urinary tract infections. Intraoperative and magnetic resonance imaging (MRI) findings revealed a moderate to good correlation. UTE was not associated with rectovaginal or bowel endometriosis, but rather with involvement of the uterosacral ligaments (P <.01). Twenty-two patients with bladder endometriosis were treated by mucosal skinning and 11 patients underwent partial cystectomy. Superficial ureteral excision was performed in 4 patients, whereas resection with ureteroureterostomy was done in 9 patients. There was no difference regarding the intra- and postoperative complications in patients with or without UTE. In severe pelvic endometriosis, involvement of the urinary tract is quite common. Laparoscopic management is feasible and safe. Because of the lack of specific symptoms, the preoperative diagnosis of ureteral endometriosis still remains a challenge. Pelvic MRI represents a useful preoperative diagnostic tool.


Simulating nitrogen balance in Canadian agricultural soils from 1981 to 2016.
Agriculture produces food, fiber and biofuels for the world's growing population, however, agriculture can be a major contributor of nitrogen (N) losses including emissions of ammonia (NH3), nitrous oxide (N2O) and nitrate (NO3-) leaching and runoff. A Canadian Agricultural Nitrogen Budget for Reactive N (CANBNr) model was developed to estimate the soil N balance in 3487 soil landscape of Canada polygons from 1981 to 2016. The CANBNr model integrates NH3 emission from fertilizers, manure from housing, storage and field, as well as direct/indirect N2O emissions from fertilizers, manures, crop residues and soil organic matter. The NO3- leaching is estimated based on the residual soil N (RSN) at harvest and drainage derived with the DeNitrification-DeComposition (DNDC) model. From 1981 to 2016, the N input from fertilizer and N fixation increased at a greater rate than N removal in harvested crops in all provinces of Canada, resulting in an increase in the RSN and N losses. In 2016, the Prairie provinces had lower N losses (11.7 kg N ha-1) from N2O, NH3 and NO3- compared with 43.2 kg N ha-1 in central Canada, and 76.5 kg N ha-1 in Atlantic Canada. However, the Prairie provinces had 84.3% of the total Canadian farmland (74.3% of the total Canadian N input), while central Canada had 12.9% of Canadian farmland (21.7% of the total Canadian N input). In the Prairie provinces, the total N2O loss from fertilizer N ranged 4.4-8.6 Gg N whereas NH3 loss ranged from 17.1 to 44.6 Gg N and these values were influenced by both emission intensity and total land area. Total N2O losses from manure were highest in Alberta, Ontario and Quebec resulting in 4.8, 4.4, and 3.4 Gg N and NH3 losses from manure were also highest in these 3 provinces at 61.1, 45.2 and 40.4 Gg N, respectively. Nitrate leaching was impacted by drainage volumes, soil type and N inputs. In the non-growing season, NO3- leaching losses (36-yr average) were 63.3 Gg in Ontario and 57.5 Gg N in Quebec compared with 20.8 Gg N for Ontario and 35.5 Gg N for Quebec in the growing season. In contrast, the Prairie provinces showed higher NO3- leaching in the growing season (23.1-37.4 Gg N) than in the non-growing season (10.4-13.7 Gg N). In summary, total fertilizer N increased the most over the 36 years in the Prairies which resulted in increased RSN and N leaching losses that will require further intervention.


The prophylactic use--or misuse--of antibiotics in transurethral prostatectomy.
One hundred non-infected patients undergoing transurethral prostatectomy were randomized prospectively into a controlled study to determine the influence of a prophylactic aminoglycoside (kanamycin) on the clinical course. In the non-risk patient prophylactic kanamycin had no beneficial influence on the incidence of bacteriuria, fever or length of hospitalization. Its use was associated with the development of a resistant Pseudomonas super infection in 1 patient. Prophylactic kanamycin did not protect the patient with carcinoma of the prostate from bacteriuria. There was no identifiable advantage in the use of routine prophylactic kanamycin in the uninfected, non-risk patient who was undergoing elective transurethral prostatectomy.


De-differentiation in cultures of organoids from luminal-type breast cancer is restored by inhibition of NOTCH signaling.
Estrogen receptor (ER) expression in breast cancer can change during progression and the treatment, but the mechanism has not been well studied. In this study, we successfully prepared organoids from samples obtained from 33 luminal-type breast cancer patients and studied their ER expression. The expression status was well maintained in primary organoids, whereas it decreased after passaging in most of the cases. In fact, the studied organoid lines were classified into those that retained a high level of ER expression (9%), those that completely lost it (9%), and those that repressed it to varying degrees (82%). In some cases, the ER expression was suddenly and drastically decreased after passaging. Marker protein immunohistochemistry revealed that after passaging, the differentiation status shifted from a luminal- to a basal-like status. Differentially expressed genes suggested the activation of NOTCH signaling in the passaged organoids, wherein a NOTCH inhibitor was able to substantially rescue the decreased ER expression and alter the differentiation status. Our findings suggest that the differentiation status of luminal-type cancer cells is quite flexible, and that by inhibiting the NOTCH signaling we can preserve the differentiation status of luminal-type breast cancer organoids.


Energy expenditure of patients with cystic fibrosis.
Resting energy expenditure was measured by open-circuit indirect calorimetry in 71 patients, aged 8.9 to 35.5 years, with cystic fibrosis who had no recent history of acute lung infection. Pulmonary function and nutritional status were studied simultaneously. In most patients, resting energy expenditure was above normal (range 95% to 153% of predicted values for age, sex, and weight as derived from the Harris Benedict equations), and was negatively correlated with pulmonary function (P less than 0.01) and nutritional status (P less than 0.01) when expressed as a percentage of body fat. Pulmonary status was positively correlated with nutritional status (P less than 0.01). We conclude that resting energy expenditure in patients with cystic fibrosis exceeds normal values and that the increase correlates with a deterioration in lung function and nutritional status.


Complications of contact lens wear after radial keratotomy in an animal model.
In 12 rabbits radial keratotomy was performed on one eye with no treatment to the contralateral eye. Cellulose acetate butyrate contact lenses were fitted bilaterally for extended wear. The eyes were monitored weakly for three weeks with a standardized slit-lamp grading method. Corneal neovascularization occurred earlier and progressed further in eyes that had radial keratotomy than in the control eyes (P less than .0025). These results suggested that patients who require contact lenses after radial keratotomy may be at higher risk for complications such as corneal neovascularization.


Arachidonate 15-lipoxygenase from human eosinophil-enriched leukocytes: partial purification and properties.
Arachidonate 15-lipoxygenase was purified from human eosinophil-enriched leukocytes after showing that 15-lipoxygenase activity was 100-fold greater in eosinophils than in neutrophils. Partial purification was achieved using ammonium sulfate precipitation, cation-exchange and hydrophobic-interaction chromatography. New evidence is presented suggesting that 15-lipoxygenase has electrostatic and hydrophobic properties distinct from 5-lipoxygenase. In addition, ATP is shown to inhibit, and phosphatidylcholine is shown to stimulate, 15-lipoxygenase, suggesting a regulatory role for these compounds in the lipoxygenation of arachidonic acid.


As long as it circulates, we've got to keep fighting: COVID-19 and the motivation to get vaccinated.
The first purpose of this research was to explore the relationship between goal-directed motivation and vaccination behavior. The second purpose was to find ways to motivate people to get vaccinated against COVID-19 and infectious diseases in general. According to regulatory focus theory, goal-directed behavior is regulated by two motivational systems - prevention and promotion. Prevention-focused behavior is motivated by needs for security and safety, and it is associated with a strategic preference for vigilant means of goal-pursuit. Promotion-focused behavior is motivated by needs for self-development and growth, and it is associated with a strategic preference for eagerness means. Based on regulatory focus theory, this research examined the proposal that motivation in goal-pursuit and self-regulatory processes would play a central role in shaping vaccination intention and behavior. Two studies tested the relationship between participants' self-reported intention to get vaccinated and regulatory focus. In Study 1, regulatory focus was measured as a chronic variable. In Study 2, regulatory focus was experimentally induced. Study 1 showed that chronic prevention focus moderated the relationship between vaccine safety concerns and vaccination intention. The higher the concerns about vaccine safety, the lower was the probability of expressing an intention to get vaccinated, and the stronger the prevention focus the stronger was the effect. Moreover, vaccine safety concerns mediated the relationship between chronic promotion focus and vaccination intention. The stronger the promotion focus, the lower was the concern over vaccine safety, and thus the higher was the probability of expressing an intention to get vaccinated. In Study 2, a situationally induced regulatory focus moderated the relationship between vaccination intention and vaccine safety concerns. As concerns about vaccine safety decreased, the intention to get vaccinated increased, and the effect was stronger for prevention compared with promotion focus. Implications for public health and health communication are discussed.


Middle ear carcinoid: an indolent tumor with metastatic potential.
Neuroendocrine tumors of the head and neck region may present problems in diagnosis. Middle ear carcinoid is a rare, recently recognized tumor, which to date has not been reported to metastasize. We report the case of a 64-year-old man with a 9-year history of recurrent middle ear neoplasm and ipsilateral cervical lymphadenopathy. A microscopic parathyroid tumor was also identified. The approach to the diagnosis of this unusual combination is presented. The patient had a neuroendocrine tumor metastatic to multiple unilateral cervical lymph nodes, which was morphologically identical to his recurrent middle ear neoplasm. The neoplasm had the morphologic, immunohistochemical, and ultrastructural features of a carcinoid tumor. This case illustrates that middle ear carcinoids may metastasize. We suggest that immunohistochemical studies be performed on all biopsy specimens from neoplasms of the middle ear, as distinction from the more common paraganglioma may be difficult on morphologic grounds alone.


Clinical evaluation of a range of autorefractors.
A practice-based study of nine autorefractors was undertaken to assess reliability and validity. Various statistical methods were used to test aspects of validity of the machines compared with one another. In routine optometric practice the autorefractor is shown to be a useful complement to existing techniques, but there is a measurable difference in the performance of machines from different manufacturers, and even between two models from the same manufacturer.


Increasing cardiac output by fluid loading: effects on indocyanine green plasma disappearance rate and splanchnic microcirculation.
Sufficient cardiac pre-load for maintaining adequate cardiac output is a major goal in the treatment of critically ill patients. We studied the effects of increasing cardiac output by fluid loading on the indocyanine green plasma disappearance rate (ICG-PDR) and gastric mucosal regional CO2 tension (PRco2) as an indicator of splanchnic microcirculation. With approval by our ethics committee and written consent, we studied post-operatively 12 patients (1 female, 11 males; 66 +/- 13 years) with elective coronary artery bypass grafting (n = 10) or aortic valve replacement (n = 2). All patients had received pulmonary artery and left atrial catheterization previously for clinical indications. Cardiac output and filling pressures were measured immediately after intensive care unit (ICU) admission and 1 h after the beginning of fluid loading. Overall, 630 +/- 130 ml of 6% hydroxyethylstarch (130 kDa) was infused with the splanchnic perfusion pressure remaining constant. Norepinephrine and epinephrine dosages were unchanged. The cardiac index increased significantly from 2.8 +/- 0.7 to 3.5 +/- 0.6 l/min/m2 and the stroke volume index from 30 +/- 7 to 38 +/- 8 ml/m2. ICG-PDR showed no significant change, i.e. from 21.2 +/- 6.5 to 21.6 +/- 6.5%/min. Gastric mucosal PRco2 and the Pco2 gap (difference between regional and end-tidal CO2 tension) were constant, i.e. changed from 5.1 +/- 0.8 to 5.5 +/- 1.1 kPa and from 0.9 +/- 0.5 to 1.0 +/- 0.7 kPa, respectively. Increasing cardiac output to supranormal values by fluid loading is not associated with a significant change in ICG-PDR or gastric mucosal PRco2.


Single and multiple dose pharmacokinetics of pindolol.
The pharmacokinetics of pindolol were studied in six healthy individuals following a single 10 mg dose (SD) and multiple (5 mg tid over 6 days) dose (MD). The plasma elimination half-life was identical after SD (4.7 +/- 0,8h) and MD (4.1 +/- 1.1h). Steady state plasma concentrations were reached after 36 h and remained stable thereafter. The variation in steady state concentrations was small in each individual and also between individuals. The steady state concentration of pindolol can be predicted from the pharmacokinetic data obtained after a single dose. The results of the present study suggest that the disposition of pindolol is linear over the concentration range studied.


The effects of feeding and secretin administration on the pancreaticoduodenal papilla of conscious dogs.
The aim of this study was to define the functional role of the pancreaticoduodenal papilla (PDP) in the regulation of pancreatic outflow into the duodenum in response to feeding and secretin administration in conscious dogs. The canine model we developed allowed for measurement of the pancreatic ductal pressure and pancreatic outflow simultaneously in a physiological state without interfering with the flow of pancreatic juice via the intact sphincter of the duodenal papilla. Feeding increased the pancreatic outflow from 2.8 +/- 0.2 to 13.4 +/- 1.3 ml/15 min with a slight increase in the pancreatic ductal pressure from 8.5 +/- 0.6 to 13.7 +/- 1.4 cmH2O. The administration of secretin increased the pancreatic outflow from 2.8 +/- 0.2 to 12.7 +/- 1.0 ml/15 min without increasing the pancreatic ductal pressure. The viscosity of the pancreatic juice increased during exposure to food, but decreased following food intake and secretin administration, after which the PDP seemed to dilate by about 40% of the fasting value. The results suggest that PDP changes its opening to maintain the pancreatic ductal pressure below a certain level, even if pancreatic secretion into the pancreatic duct increases due to food intake and secretin administration.


[Microneurosurgery].
Micronervereconstruction of motor and sensitive nerves in the head and neck area today has an established range of indications. Surgical procedures of external and internal neurolyses, nerve coaptation and nerve transplantation techniques are well standardized. With microneurosurgery of motor nerves, satisfying or good results can be generally obtained. Success rates exceeding 50% following sensitive nerve reconstructions justify the performance of the procedures, more so because of the subjective improvements for the individual patient. Perspectives can be seen in further simplification of surgical methods of harvesting nerve grafts, e.g., by development of minimally invasive, eventually endoscopically guided procedures. Allogenic nerve grafts may also be applied. Initial experiments with nerve distractions are encouraging. A better understanding of nerve lesions on cellular and molecular biological levels may improve our knowledge of posttraumatic regulatory procedures and may lead to future possibilities of nonsurgical treatment options for peripheral and central nerve lesions by guided regeneration.


Enhanced photochemical formation of secondary organic aerosols during the COVID-19 lockdown in Northern China.
To eliminate the spread of a novel coronavirus breaking out in the end of 2019 (COVID-19), the Chinese government has implemented a nationwide lockdown policy after the Chinese lunar New Year of 2020, resulting in a sharp reduction in air pollutant emissions. To investigate the impact of the lockdown on aerosol chemistry, the number fraction, size distribution and formation process of oxalic acid (C2) containing particles and its precursors were studied using a single particle aerosol mass spectrometer (SPAMS) at the urban site of Liaocheng in the North China Plain (NCP). Our results showed that five air pollutants (i.e., PM2.5, PM10, SO2, NO2, and CO) decreased by 30.0-59.8% during the lockdown compared to those before the lockdown, while O3 increased by 63.9% during the lockdown mainly due to the inefficient titration effect of O3 via NO reduction. The increased O3 concentration can boost the atmospheric oxidizing capacity and further enhance the formation of secondary organic aerosols, thereby significantly enhancing the C2 particles and its precursors as observed during the lockdown. Before the lockdown, C2 particles were significantly originated from biomass burning emissions and their subsequent aqueous-phase oxidation. The hourly variation patterns and correlation analysis before the lockdown suggested that relative humidity (RH) and aerosol liquid water content (ALWC) played a key role in the formation of C2 particles and the increased aerosol acidity can promote the conversion of precursors such as glyoxal (Gly) and methyglyoxal (mGly) into C2 particles in the aqueous phase. RH and ALWC decreased sharply but O3 concentration and solar radiation increased remarkably during the lockdown, the O3-dominated photochemical pathways played an important role in the formation of C2 particles in which aerosol acidity was ineffective. Our study indicated that air pollution treatment sponges on a joint-control and balanced strategy for controlling numerous pollutants.


The adhesion mechanism of dental adhesive resin to the alloy. Adhesive ability of dental adhesive resin to the cleaned metal surface obtained by hydrogen gas reduction method.
With the cleaned metal surface without passive film or an oxide layer, chromium, cobalt, and iron show excellent bonding strength, indicating values similar to 18-8 stainless steel. Therefore the existence of a passive film and oxide layer at the interface metal/resin is not essential for metal-resin bonding. The adhesive ability decreases in the order: Cr congruent to Co congruent to Fe greater than Cu greater than Ag greater than Au congruent to Ni greater than Pt greater than Pd.


Sodium-dependent sugar and amino acid transport in isolated goldfish intestinal epithelium: electrophysiological evidence against direct interactions at the carrier level.
The effects of mucosal application of monosaccharides and amino acids on transepithelial and membrane potentials in isolated goldfish intestinal epithelium were investigated. Isosmotic replacement of mucosal mannitol by sugars or L-amino acids resulted in a rapid depolarization of the mucosal membrane potential psi mc followed by a slow repolarization. Phlorizin inhibited the responses to sugar but not those to amino acids. D-Amino acids did not induce any electrical response in the epithelium. Dose-response curves for L-amino acids showed simple saturation. Simultaneous application of L-amino acid and glucose induced transepithelial responses of about 80% of the sum of the separate responses to the application of amino acid or glucose alone. Simultaneous application of different amino acids in saturating concentrations did not increase the magnitude of the electrical responses. From the measured changes in potentials we calculated the change in electromotive force across the mucosal (delta Em) and serosal (delta Es) membrane. The change in Em induced by combined application of alanine and glucose was 90% of the sum of the calculated values induced by glucose and alanine alone. The response of Es to both substrates was accelerated with respect to that of separate substrates alone. We conclude that by application of glucose in addition to alanine the influx of sodium is increased, thereby stimulating the basolaterally located electrogenic Na+/K+-pump. There are no indications for direct interaction of sugars and amino acids at the mucosal membrane of the intestinal epithelial cell.


Somatostatin inhibits the pentagastrin-induced release of serum calcitonin in medullary carcinoma of the thyroid.
The effect of somatostatin on the secretion of calcitonin was studied in four patients with medullary carcinoma of the thyroid (MCT). The basal serum calcitonin level was markedly elevated in all cases. A bolus injection (100 microgram) of somatostatin followed by an intravenous infusion (5 microgram/min) for 60 min suppressed the basal calcitonin level in three of the four patients by 24-42%, while it had no inhibitory effect in one case. In another experiment, the pentagastrin-stimulated (6 microgram/kg s.c.) calcitonin release was partially blocked by a simultaneous i.v. injection of somatostatin (200 microgram) in all four patients studied. These experiments add human calcitonin to the list of hormones whose release in inhibited by somatostatin.


Prediction of the histologic upgrade of ductal carcinoma in situ using a combined radiomics and machine learning approach based on breast dynamic contrast-enhanced magnetic resonance imaging.
To investigate whether support vector machine (SVM) trained with radiomics features based on breast magnetic resonance imaging (MRI) could predict the upgrade of ductal carcinoma in situ (DCIS) diagnosed by core needle biopsy (CNB) after surgical excision. This retrospective study included a total of 349 lesions from 346 female patients (mean age, 54 years) diagnosed with DCIS by CNB between January 2011 and December 2017. Based on histological confirmation after surgery, the patients were divided into pure (n = 198, 56.7%) and upgraded DCIS (n = 151, 43.3%). The entire dataset was randomly split to training (80%) and test sets (20%). Radiomics features were extracted from the intratumor region-of-interest, which was semi-automatically drawn by two radiologists, based on the first subtraction images from dynamic contrast-enhanced T1-weighted MRI. A least absolute shrinkage and selection operator (LASSO) was used for feature selection. A 4-fold cross validation was applied to the training set to determine the combination of features used to train SVM for classification between pure and upgraded DCIS. Sensitivity, specificity, accuracy, and area under the receiver-operating characteristic curve (AUC) were calculated to evaluate the model performance using the hold-out test set. The model trained with 9 features (Energy, Skewness, Surface Area to Volume ratio, Gray Level Non Uniformity, Kurtosis, Dependence Variance, Maximum 2D diameter Column, Sphericity, and Large Area Emphasis) demonstrated the highest 4-fold mean validation accuracy and AUC of 0.724 (95% CI, 0.619-0.829) and 0.742 (0.623-0.860), respectively. Sensitivity, specificity, accuracy, and AUC using the test set were 0.733 (0.575-0.892) and 0.7 (0.558-0.842), 0.714 (0.608-0.820) and 0.767 (0.651-0.882), respectively. Our study suggested that the combined radiomics and machine learning approach based on preoperative breast MRI may provide an assisting tool to predict the histologic upgrade of DCIS.


Clinical evaluation and management of caustic injury in the upper gastrointestinal tract in 95 adult patients in an urban medical center.
Caustic ingestion causes a wide spectrum of injuries; appropriate treatment varies according to the severity and extent of the injury. This retrospective study of adult patients with caustic injury presents the endoscopic findings, treatment regimen, and clinical outcome. Over a 28-year period, 95 consecutive adult patients admitted to an urban emergency hospital for ingestion of caustic materials were studied. Each patient underwent early endoscopy and the injury was graded for severity. There were 61 men and 34 women with an average age of 37.2 years (range 17 to 81). Ingestion was due to a suicide attempt in 49 patients and accidental in 46 patients. Ten patients showed no mucosal damage. The remaining 85 patients had grade I superficial injury in 47 patients, grade II moderate injury in 25 patients, and deep grade III injury in 13 patients. The ingestion of strong acid or strong alkali often produced deep grade III changes while bleach, detergent, ammonia or other substances usually caused grade I injury. Operative interventions were required for 11 patients with grade III injury and 6 patients with grade II injury. Endoscopic grading was predictive for the onset of complications including late esophageal stricture. There were no complications due to endoscopy; one patient with grade III and multiple comorbidities died from multiple organ failure. Upper gastrointestinal endoscopy after caustic ingestion should be performed early to define the extent of injury and guide appropriate therapy. Grade I injuries heal spontaneously. Grade II injuries may be treated conservatively but repeat endoscopy helps define when intervention is needed. Grade III injuries ultimately require surgical intervention.


Measurement invariance and psychometric properties of three positive body image measures among cisgender sexual minority and heterosexual women.
Positive body image is a multidimensional construct consisting of various facets including body appreciation, body image flexibility, and functionality appreciation measured via the Body Appreciation Scale-2 (BAS-2), Body Image-Acceptance and Action Questionnaire-5 (BI-AAQ-5), and Functionality Appreciation Scale (FAS), respectively. Research has supported the unidimensional factor structure of these measures; however, invariance testing based on sexual identity has yet to be conducted. The study's primary aim was to assess the measurement invariance of the BAS-2, BI-AAQ-5, and FAS between sexual minority and heterosexual women. The secondary aim was to assess the psychometric properties of each positive body image measure among each sample. Participants were predominantly White, cisgender women who identified as a sexual minority (n = 310) or heterosexual (n = 360) and completed online questionnaires of positive body image, eating behaviors, and mental and physical health. Results supported invariance with no differences in BAS-2 or BI-AAQ-5 scores. A significant difference with a small effect size was found in FAS scores, with sexual minority women reporting lower FAS scores. Findings supported the BI-AAQ-5 and FAS's incremental validity on perceived mental health. Overall, results suggest that the BAS-2, BI-AAQ-5, and FAS scores can be compared among women of varying sexual identities.


Nanorecycling: Monolithic Integration of Copper and Copper Oxide Nanowire Network Electrode through Selective Reversible Photothermochemical Reduction.
Laser induced selective photothermochemical reduction is demonstrated to locally and reversibly control the oxidation state of Cu and Cu oxide nanowires in ambient conditions without any inert gas environment. This new concept of "nanorecycling" can monolithically integrate Cu and Cu oxide nanowires by restoring oxidized Cu, considered unusable for the electrode, back to a metallic state for repetitive reuse.


Concordance between alizarin red stained skeleton and micro-CT skeleton evaluation methods: A case study in New Zealand White rabbits.
The objective of this study was to examine the fetal skeletons using both alizarin red stain and micro-computed tomography (CT) images; investigate differences, and to determine if the conclusions of the study were the same regardless of the examination method. A candidate drug was given orally by gavage to pregnant New Zealand White rabbits on gestation day (GD) 7 to GD 19 (mating = GD 0) at doses of 0 (control), 0.02, 0.5, 5, and 15 mg/kg/day. Maternal toxicity was evident at ≥0.02 mg/kg/day. The 199 fetal skeletons (totaling 50,546 skeletal elements) obtained at cesarean delivery on GD29 were first stained with Alizarin Red S, then imaged by a Siemens Inveon micro-CT scanner. All fetal skeletons were examined by both methods, without knowledge of dose group, and the results were compared. In total, 33 types of skeletal abnormalities were identified. There was 99.8% concordance of results comparing stain to micro-CT. Ossification of the middle phalanx of the forepaw digit 5 showed the greatest difference between the two methods. Overall, micro-CT imaging is a realistic, and robust alternative to skeletal staining to examine fetal rabbit skeletons in developmental toxicity studies.


A prospective study of college student depressive symptoms, sense of purpose, and response to a COVID-19 campus shutdown.
Individual differences can shape the way major life events are experienced. In this study, we explored the unique and interactive effects of depressive symptoms and sense of purpose on downstream appraisals of a COVID-19 college campus shutdown. Data were from a sample of U.S. college students (n = 152) surveyed prior to widespread COVID-19 transmission (Time 1; early fall 2019), and again just after their university closed as a protective measure (Time 2; mid-spring 2020). Depressive symptoms were positively associated, whereas sense of purpose was negatively associated, with cross-sectional reports of social status change due to shutdown. Depressive symptoms at Time 1 positively predicted perceived external control of the situation at Time 2, and sense of purpose at Time 1 positively predicted changes to worldview at Time 2. Purpose and depressive symptoms evidenced high rank-order stability from Time 1 to Time 2. This study represents a rare documentation of college students' feelings and experiences before, and during, a historical moment. The implications of these findings for future research are discussed.


The information needs of relatives of childhood cancer patients and survivors: A systematic review of qualitative evidence.
To synthesize qualitative research on the information needs of relatives of childhood cancer patients and survivors. Systematic searches of PubMed, PsycINFO, CINAHL, and Scopus identified relevant literature. Extracted data were combined using thematic synthesis. Methodological quality was assessed using the JBI critical appraisal tool for qualitative research. The review included 27 publications, with most research focusing on parents or primary caregivers. Five areas of information needs were identified: treatment, medication, and care; general information about cancer; coping and support; follow-up, late effects, and rehabilitation; and parenting and everyday life. Appropriateness of information depended on health care professionals' aptitude, message characteristics, communication setting, and relatives' personal factors. Preferences for form, sources, and timing for information provision varied. The review identified information needs, communication barriers, and preferences among caregivers and siblings of childhood cancer patients and survivors, highlighting areas requiring further research and clinical consideration in addressing the identified challenges. Caregivers and siblings have unique but similar information needs regarding childhood cancer. To ensure that these needs are met, health care professionals could use eHealth and mHealth technologies, assess each family member's knowledge, and create a safe and supportive environment for questions and feedback.


Complete Genome Sequence of Strain SDCV/USA/Illinois121/2014, a Porcine Deltacoronavirus from the United States.
To investigate the causative agent of swine diarrhea, next-generation sequencing (NGS) was performed on a porcine fecal sample. The NGS reads were assembled, which generated a complete swine Deltacoronavirus genome sequence, that of strain SDCV/USA/Illinois121/2014.


A cognitive-behavioural approach to the management of idiopathic cervical dystonia.
A case is described in which a patient with idiopathic cervical dystonia is treated successfully with cognitive-behavioural therapy. It was hypothesised that although the dystonia was organic in origin, it was exacerbated and perpetuated by catastrophic thoughts and abnormal illness beliefs, and that modification of maintaining cognitive and behavioural responses would lead to improvement. Self-report outcome measures were consistent with this hypothesis and improvements were maintained at 6-month follow-up.


Association analysis of high-mobility group box-1 protein 1 (HMGB1)/toll-like receptor (TLR) 4 with nasal interleukins in allergic rhinitis patients.
High mobility group box 1 (HMGB1) acts as an inflammatory mediator initiator, and has shown to increase in nasal secretions of allergic rhinitis (AR) patients. The purpose of the present study was to investigate the association of HMGB1 and its receptor, toll-like receptor (TLR) 4 with proinflammatory interleukins in AR patients. The interleukin (IL) -4, -5, -13, -17A, -10 in nasal lavage fluid and the serum IgE were examined with enzyme-linked immunosorbent assay (ELISA) in 125 AR patients or 87 healthy subjects (as control). The mRNA levels of HMGB1, receptor for advanced glycation end products (RAGE) and TLR 2, 3 and 4 were examined in these participants with real-time quantitative PCR (RT-qPCR) method. Spearman rank correlation was adopted to analyze the relationship between any two factors of clinical characteristics and laboratory-examined biomarkers. IL-4, -5, -13 and -17A were significantly higher, whereas IL-10 was markedly lower in the nasal lavage fluid samples from AR patients, compared with the control subjects. High expression of HMGB1, TLR2 and TLR4 were observed in the nasal brushing samples from these AR patients, whereas there was no significant difference for the mRNA levels of TLR3 and RAGE. Besides, HMGB1/TLR4 mRNA levels correlated positively with IL-4, -5, -13 and -17A, whereas negatively with IL-10. A linear regression of HMGB1/TLR4 was also found positively with IL-4, -5 (only for TLR4), -13 or -17A, whereas negatively with IL-10. High mRNA levels of HMGB1 and TLR4 were found in the nasal brushing samples in AR patients, correlating positively with IL-4, -5, -13 or -17A, wheareas negatively with IL-10. HMGB1/TLR4 signaling pathway might be well responsive targets as immunotherapy for allergic rhinitis.


The clinicopathological differences of sporadic non-ampullary duodenal epithelial neoplasm depending on tumor location.
Although sporadic non-ampullary duodenal adenoma is speculated to be precancerous lesion, the relationship between adenoma and carcinoma remains unclear due to their rarity. Previous studies on sporadic non-ampullary duodenal epithelial neoplasm (SNADEN) have mainly targeted superficial tumors, like adenoma and early carcinoma. The clinicopathological features, including those of advanced carcinoma, remain poorly investigated. We assessed the clinicopathological features of SNADEN, including advanced carcinoma, focusing on tumor location. We retrospectively collected the data of 410 patients who had been clinically and pathologically diagnosed with SNADEN at 11 institutions in Japan between June 2002 and March 2014. The SNADEN was mucosal neoplasia and invasive carcinoma in 321 (78.3%) and 89 (21.7%) patients, respectively. The proportion of invasive carcinomas in SNADEN was significantly higher on the oral side of the papilla of Vater (oral-Vater) than on the anal side (anal-Vater) (27.9% vs 14.4%, P < 0.001). Undifferentiated-type carcinoma was significantly more frequent with oral-Vater than anal-Vater (38.7% vs 14.8%, P = 0.026). The recurrence rate of surgically R0 resected locally advanced carcinomas was significantly higher with oral-Vater than anal-Vater (46.4% vs 8.3%, P = 0.021). Furthermore, the relapse-free survival with oral-Vater was significantly shorter than with anal-Vater (hazard ratio: 2.35; 95% confidence interval: 1.09-5.50; P = 0.028). The clinicopathological features of SNADEN on oral-Vater were different from those on anal-Vater. SNADEN on oral-Vater was more likely to be invasive carcinomas and might behave more aggressively due to biologically higher malignancy than that on anal-Vater.


Double Vision and Light Sensitivity Symptoms are Associated With Return-to-School Timing After Pediatric Concussion.
To determine the association between academic time loss postconcussion and vision symptoms/impairments among pediatric patients. Cross-sectional. Sports medicine clinic. Pediatric patients seen for care in a sports medicine clinic between the ages 6 and 18 years (n = 212; mean age = 14.3, SD = 2.4 years; 48% female) were evaluated within 21 days of concussion (mean = 9.8, SD = 5.7 days). Patients were grouped based on academic time loss (missed >5 days vs ≤5 days of school) at their initial postconcussion evaluation. Patients rated concussion symptoms using the Health and Behavior Inventory (HBI) and underwent near point of convergence (NPC) testing. We compared groups on specific HBI symptom ratings of dizziness, blurry vision, seeing double, and light sensitivity, as well as NPC break and recovery point distances. Two hundred twelve patients were included; n = 36 (17%) who reported missing >5 days of school. After adjusting for time since injury, parental education level, mechanism of injury, and preinjury anxiety, patients who reported missing >5 days of school had higher ratings of double vision (β = 0.27; 95% confidence interval [CI], 0.01-0.53; P = 0.04) and light sensitivity (β = 0.506; 95% CI, 0.061-0.951; P = 0.02), but not dizziness (β = 0.390; 95% CI, -0.047 to 0.827; P = 0.08) or blurry vision (β = 0.026; 95% CI, -0.352 to 0.404; P = 0.89). Missing >5 days of school was associated with worse double vision and light sensitivity symptoms. Given the importance of vision in learning, assessing postconcussion vision symptoms may facilitate a successful return to school. Clinicians should assess a wide spectrum of vision-specific symptoms to ensure appropriate support during the return-to-school process.


Time and dose-dependent effect of preconditioning with sodium nitroprusside (SNP) and 3-morpholinosydnonimine (SIN-1) on post-thaw semen quality of Karan-Fries (KF) bulls.
A novel strategy, focused on the induction of sub-lethal oxidative stress to optimize sperm cryosurvival, has been used before cryopreservation. The present study compared the effect of preconditioning with various concentrations of nitric oxide-donor (sodium nitroprusside, SNP) and peroxynitrite-generator (3-morpholinosydnonimine, SIN-1) on in vitro sperm functions and lipid peroxidation status (LPO) of cryopreserved Karan-Fries (KF) crossbred bull semen. To optimize the concentration of additives, spermatozoa obtained from 36 ejaculates were supplemented with different concentrations of SNP (0.01, 0.05, 0.1 μM) and SIN-1 (80, 160, 200 μM) versus control in the extender. The post-freezing sperm motility and viability were greater (p < 0.05) in 0.1 μM SNP and 80 μM SIN-1 in comparison to other concentrations used. Furthermore, the spermatozoa obtained from 48 ejaculates were supplemented with 0.1 μM SNP and 80 μM SIN-1 in the extender. A significant increase (p < 0.05) was observed in progressive motility, viability and membrane integrity in SNP and SIN-1 treated extender at 24 h, 15 days, and 2-month post-cryopreservation (PC) periods. There was no significant difference in sperm abnormality in the extended groups and the control group. The seminal plasma of SNP-treated extender had less (p < 0.05) lipid peroxidation as compared to SIN-1 treated and control groups. In post-thaw semen, both SNP and SIN-1 showed a higher (p < 0.05) proportion of acrosome intact (FITC-PNA) sperm with a greater decrease (p < 0.05) in membrane scrambling and lipid peroxidation. SNP and SIN-1 improved (p < 0.05) the proportion of sperm with higher mitochondrial membrane potential (Δψm) as compared to the control. In conclusion, it seems that the preconditioning of SNP and SIN-1 at lower doses may have beneficial effects on post-thawed crossbred bull sperm quality.


Complex fibroblast response to glucocorticoids may underlie variability of clinical efficacy in the vocal folds.
Similar to the hypertrophic scar and keloids, the efficacy of glucorticoids (GC) for vocal fold injury is highly variable. We previously reported dexamethasone enhanced the pro-fibrotic effects of transforming growth factor (TGF)-β as a potential mechanism for inconsistent clinical outcomes. In the current study, we sought to determine the mechanism(s) whereby GCs influence the fibrotic response and mechanisms underlying these effects with an emphasis on TGF-β and nuclear receptor subfamily 4 group A member 1 (NR4A1) signaling. Human VF fibroblasts (HVOX) were treated with three commonly-employed GCs+ /-TGF-β1. Phosphorylation of the glucocorticoid receptor (GR:NR3C1) and activation of NR4A1 was analyzed by western blotting. Genes involved in the fibrotic response, including ACTA2, TGFBR1, and TGFBR2 were analyzed by qPCR. RNA-seq was performed to identify global changes in gene expression induced by dexamethasone. GCs enhanced phosphorylation of GR at Ser211 and TGF-β-induced ACTA2 expression. Dexamethasone upregulated TGFBR1, and TGFBR2 in the presence of TGF-β1 and increased active NR4A1. RNA-seq results confirmed numerous pathways, including TGF-β signaling, affected by dexamethasone. Synergistic pro-fibrotic effects of TGF-β were observed across GCs and appeared to be mediated, at least partially, via upregulation of TGF-β receptors. Dexamethasone exhibited diverse regulation of gene expression including NR4A1 upregulation consistent with the anti-fibrotic potential of GCs.


Annual increase in the frequency of papillary thyroid carcinoma as diagnosed by fine-needle aspiration at a cytology unit in Sicily.
An increased frequency of papillary thyroid carcinoma (PTC) has been reported in the literature, including studies based on fine-needle aspiration cytology (FNAC). To substantiate our own ascertainment of such an increase, we retrieved all the diagnoses of ultrasound-guided FNAC which was performed on 11,389 patients referred for cytological evaluation of a single or dominant thyroid nodule from 1988 to 2010. FNAC yielded 11,258 adequate specimens. The number of patients with PTC was 200 (age 10-83 yrs) and increased significantly from 1988 to 2010 (r= 0.916, P<0.001). Expressing data as percent of FNAC in any given year, PTC and colloid goiter increased, while adenomatous goiter, follicular lesions and anaplastic or medullary thyroid cancer decreased. PTC accounted for 0% of all FNAC diagnoses in 1988 but for 2% in 2010, with a peak of 2.6% in 2006. Of interest, chronic lymphocytic thyroiditis (CLT) also increased, preceding the increase of PTC by 5-6 years. We conclude that in the regions on either side of the Strait of Messina (Italy), PTC has become progressively more frequent during the 23-year period between 1988 and 2010 and that this increase lagged behind the increase of CLT.


[Non-steroidal anti-inflammatory agents. VI. Optically active 3-(4-biphenylyl)-3-oxybutyric, valerianic, caproic and isocaproic acids].
The synthesis of the (+/-) 3-(4-biphenylyl)-3-hydroxybutanoic, pentanoic, hexanoic and isohexanoic acids, and their resolution in to enantiomers are described. The latter were submitted to preliminary assay for antiinflammatory activity: interesting results were obtained above all for the isohexanoic acid derivative.


A toe that pointed the wrong way: An unusual presentation of tetanus.
We report the case of a 15-year-old girl who was initially diagnosed to have a striatal toe. Her condition progressed and she later developed clinical features consistent with tetanus. History of blunt trauma to nose was elicited retrospectively. Antimicrobial therapy with metronidazole and both active and passive immunization was started immediately. The patient went on to make a complete recovery.


Evolution of rRNA gene clusters and telomeric repeats during explosive genome repatterning in TATERILLUS X (Rodentia, Gerbillinae).
A survey of 28S and 5S rRNA gene clusters, and telomeric repeats was performed using single and double FISH in the Taterillus genus (Rodentia, Muridae, Gerbillinae). Taterillus was previously demonstrated to have undergone a very recent and extensive chromosomal evolution. Our FISH results demonstrate that rRNA genes can vary in location and number irrespective of the phylogenetic relationships. Telomeric repeats were detected in pericentromeric and interstitial regions of several chromosomes, thus providing nonambiguous evolutionary footprints of Robertsonian and tandem translocation events. These footprints are discussed in reference to the molecular process of these karyotypical changes. Also, examples of colocation of rDNA clusters and telomeric repeats lend support to their possible involvement in nucleolus formation. Finally, the presence of rRNA genes, and the extensive amplification of telomeric repeats at specific loci within a double X-autosome translocated element which were not observed on the homologous Y1 and Y2, served as basis for an epigenomic hypothesis on X-autosome translocation viability in mammals.


Establishment and partial characterisation of a human fibrosarcoma cell line MR-83.
We describe a mycoplasma-free human fibrosarcoma cell line, MR-83, which grows readily in liquid culture and as clones in semi-solid agar with a plating efficiency of about 0.5%. It has a stable karyotype consisting of a modal number of 49-51 chromosomes, with two translocations and a deletion. The cell line shows resistance to adriamycin in semi-solid agar assay, and responds to Epidermal Growth Factor (EGF) by increased DNA synthesis, as measured by thymidine uptake.


Lacerations of the ulnar artery: hemodynamic, ultrastructural, and compliance changes in the dog.
The hemodynamic and structural changes following single artery laceration were studied in the forelimbs of 25 adult dogs. Consistent back pressure in the distal ulnar artery stump was noted immediately and at 2 and 4 weeks. There were no significant changes in vessel compliance or vessel wall morphology of the proximal or distal stumps. The retrograde pressures of the distal arterial stump may contribute to the relatively high thrombosis rate following arterial repair in the forearm.


Liver transplantation for hepatocellular carcinoma in patients who do not meet the Milan criteria.
To expand the Milan criteria, prognostic factors other than size and number of tumor may be necessary. We analyzed outcome and prognostic factors in patients with hepatocellular carcinoma (HCC) exceeding Milan criteria to select favorable group of patients. Between November 1997 and December 2005, 104 cases of liver transplantation for patients with HCC were performed at our center. Twenty-four patients did not meet the Milan criteria preoperatively. Among these 24 patients, 19 had no major vascular invasion at the time of surgery. We analyzed the survival and prognostic factors of these 19 patients. The mean follow-up period was 33 months (range 6-89). Three-year survival rate in 19 patients was 67.4%. Three-year survival rates were significantly higher when preoperative alpha-fetoprotein was less than 400 ng/ml (86.2 vs. 0%, p<0.001) when Edmonson-Steiner's histological grade 1 or 2 (100 vs. 40%, p = 0.036) and when microvascular invasion was absent (78.6 vs. 30%, p = 0.039). If vascular invasion is absent in preoperative radiological studies, and the preoperative alpha-fetoprotein is less than 400 ng/ml, our findings suggest a good prognosis after liver transplantation for HCC patients who do not meet the Milan criteria.


Susceptibility of Torulopsis glabrata in the presence of six antifungal agents determined by comparison of growth at several pHs.
We describe a method using an automated system whereby fungistatic activities can be determined in several conditions. The process was adapted to Torulopsis glabrata, and it showed that benzalkonium chloride, chlorhexidine gluconate, and thimerosal preserve fungistatic activities in acidic medium, whereas acidification reduces the activity of povidone iodine and poloxamer.


Collateral branching in axonal projections to spinal cord from paramedian reticular nucleus neurons.
Experiments were done in cats to identify neurons in the paramedian reticular nucleus (PRN) sending collateral axons to the region of the intermediolateral nucleus (IML) at different levels of the thoracic cord by using lectin-conjugated horseradish peroxidase (HRP) and double-labeling fluorochrome histochemistry to retrogradely label PRN neurons. Injections of Fast blue (FB) into the spinal cord at the T2 level centered in the region of the IML were coupled with injections of Nuclear yellow (NY) into the ipsilateral cord at either the T4 or T7 levels centered in the region of the IML. Neurons in the PRN retrogradely labeled after diffusion of HRP into the region of the IML at the T2 level were observed throughout the rostrocaudal extent of the ventral PRN. In addition, a few labeled neurons were noted in the ventral portion of the dorsal PRN. About 40% of the neurons in the PRN which were labeled with FB after an injection at the T2 level were also labeled with NY injected into the cord in further caudal segments. These data suggest that the PRN may exert its influence on the cardiovascular system partly through collateral axonal branches to widely separated populations of sympathetic preganglionic neurons in different spinal segmental levels.


Endoscopic Fenestration of a Symptomatic Porencephalic Cyst in an Adult.
A porencephalic cyst is an aberrant accumulation of cerebrospinal fluid within the brain parenchyma. Its occurrence is rare, with an incidence of 3.5 per 100,000 live births. Etiology is considered the result of perinatal cerebral ischemia or hemorrhage, leading to parenchymal loss. Porencephalic cysts are diagnosed radiologically, and management depends on the clinical manifestation. Our case depicts a porencephalic cyst presenting with nondominant parietal lobe symptoms in adulthood. We hypothesize that a membrane between the cyst and ventricle allowed formation of a 1-way valve that led to slowly progressive cyst enlargement, eventually causing mass effect and nondominant parietal lobe symptoms. Endoscopic fenestration of the cyst membrane into the lateral ventricle was successful in reducing cyst volume and improving mass effect.


Spatial distributions of foliar nitrogen and phosphorus in crowns of Eucalyptus grandis.
Eucalyptus grandis trees were grown in plantations with and without added fertiliser to examine the effects of plant nutrition on photosynthesis and growth. Leaves were sampled from known locations within canopies of selected trees and leaf N and P concentrations were measured. Contour maps of N and P distributions were then produced for crowns of trees aged between 6 and 16 months. Gas exchange measurements on sample leaves were used to estimate parameters of a model of C3 photosynthesis as a function of leaf N and P contentrations. Linear relationships were obtained between model parameters and leaf N concentration, but P appeared to be present in excess, since no correlation was found with P contentration. Photosynthetic light response curves were calculated for model leaves with differing N concentrations. The curves show that optimal concentrations of N in leaves depend on mean levels of irradiance during growth.


Preliminary results of a prospective randomized trial comparing concurrent chemoradiotherapy plus adjuvant chemotherapy with radiotherapy alone in patients with locoregionally advanced nasopharyngeal carcinoma in endemic regions of china.
A prospective randomized trial was performed to evaluate the efficacy of concurrent chemotherapy and adjuvant chemotherapy in patients with locoregionally advanced nasopharyngeal carcinoma (NPC) in endemic regions of China. Between July 2002 and September 2005, 316 eligible patients were randomly assigned to receive either radiotherapy alone (RT) or chemoradiotherapy concurrent with adjuvant chemotherapy (CRT). All patients received 70 Gy in 7 weeks using standard RT portals and techniques. The CRT patients were given concurrent cisplatin (40 mg/m(2) on Day 1) weekly during RT, followed by cisplatin (80 mg/m(2) on Day 1) and fluorouracil (800 mg/m(2) on Days 1-5) every 4 weeks (Weeks 5, 9, and 13) for three cycles after completion of RT. All patients were analyzed by intent-to-treat analysis. The two groups were well-balanced in all prognostic factors and RT parameters. The CRT group experienced significantly more acute toxicity (62.6% vs. 32%, p = 0.000). A total of 107 patients (68%) and 97 patients (61%) completed all cycles of concurrent chemotherapy and adjuvant chemotherapy, with a median follow-up time of 29 months. The 2-year overall survival rate, failure-free survival rate, distant failure-free survival rate, and locoregional failure-free survival rate for the CRT and RT groups were 89.8% vs. 79.7% (p = 0.003), 84.6% vs. 72.5% (p = 0.001), 86.5% vs. 78.7% (p = 0.024), and 98.0% vs. 91.9% (p = 0.007), respectively. This trial demonstrated the significant survival benefits of concurrent chemotherapy plus adjuvant chemotherapy in patients with locoregionally advanced NPC in endemic regions of China.


Recommended Ethical Safeguards on Fertilization of Human Germ Cells Derived from Pluripotent Stem Cells Solely for Research Purposes.
Production of human fertilized embryos by using germ cells derived from pluripotent stem cells (PSCs) entails ethical issues that differ fundamentally depending on the aim. If the aim is solely to conduct research, then embryo generation, utilization and destruction must respect for the human embryo as having the innate potential to develop into a human being. If the aim is human reproduction, this technology must never be used to manipulate human life, confuse social order, or negatively affect future generations. Researchers should distinguish the aims and then accordingly establish a consensus on the safeguards needed to proceed with scientifically significant and socially accepted research, or otherwise set a moratorium. Currently, in Japan, germ cell production from human PSCs is permitted, whereas fertilization of these germ cells is not. The Japanese Expert Panel on Bioethics in the Cabinet Office has proposed that all of the following conditions must be met to approve fertilization for research purposes: (1) the research is significant for the life sciences and medicine; (2) the benefits or anticipated benefits are socially accepted; (3) human safety is assured; and (4) safeguards are put in place. If fertilization is ethically approved, I recommend the following safeguards: limitation of the purpose to improving conventional ART as an initial step; permitted culture of human embryos until the appearance of the primitive streak; restriction of the number of embryos produced to the minimum necessary; prohibition of transplantation into a human or animal uterus; and provision of human-derived ova that are not required for ART treatment.


Synthesis and biological characterization of pyridohomotropanes. Structure-activity relationships of conformationally restricted nicotinoids.
The recently discovered nicotinic agonist pyrido[3,4-b]norhomotropane [corrected] (PHT) as well as its N-methyl and 2'-methyl derivatives (syntheses reported herein) were compared with nicotine, nornicotine, and anatoxin a in a series of in vitro and in vivo assays. The results reveal that PHT possesses activity comparable to that of the highly potent agonist, anatoxin a. The inactivity observed relative to PHT of N-methyl- and 2'-methyl-PHT has helped to further define the structure-activity requirements of conformationally restricted nicotinoids.


Scientific molecular basis for treatment of reproductive failure in the human: an insight into the future.
The purpose of this review is to summarize science-based new treatments for human reproductive failure and future developments. First will be discussed popular but erroneous myths of current non-science based treatments. Then will be discussed new treatments and their scientific base, including ovary and egg freezing, and transplantation to preserve fertility in young women undergoing gonadotoxic chemotherapy and radiation for cancer; new perspectives on human epididymal sperm maturation based on a comparison between ICSI (intracytoplasmic sperm injection) with testis sperm versus epididymal sperm; simplifying IVF and reducing cost by more intelligent and milder ovarian stimulation; improving pregnancy rate in older women; searching the genome to find genes which control spermatogenesis and whose deletion or mutation causes spermatogenic failure; and human spermatogenic stem cell culture to treat azoospermia, and to preserve fertility in pre-pubertal boys undergoing cancer treatment. With stem cell biology and molecular understanding of reproductive failure, new therapies for previously untreatable infertility are currently on the near horizon. Conversely our clinical results with new therapeutic approaches are adding to our understanding of the basic science of reproduction. This article is part of a Special Issue entitled: Molecular Genetics of Human Reproductive Failure.


Isolation and characterization of a maize gene encoding chalcone flavonone isomerase.
We report here the first cloning of a chalcone flavonone isomerase gene (CHI) from maize. Northern blot experiments indicate that the maize CHI gene (ZmCHI1) is regulated in the pericarp by the P gene, a myb homologue. The ZmCHI1 gene encodes a 24.3 kDa product 55% and 58% identical to CHI-A and CHI-B from Petunia, respectively. This maize CHI1 gene has four exons and an intron-exon structure identical to the CHI-B gene of Petunia hybrida. RFLP mapping data indicate that some inbred lines contain two additional CHI-homologous sequences, suggesting an organization more complex than that found in Petunia or bean. The possibility that the additional CHI-homologous sequences are responsible for the lack of CHI mutants in maize will be discussed.


The resurrection of a species: Sarcocystis bovifelis Heydorn et al., 1975 is distinct from the current Sarcocystis hirsuta in cattle and morphologically indistinguishable from Sarcocystis sinensis in water buffaloes.
In the mid-1970s, it was established through transmission experiments and ultrastructural studies of sarcocysts by transmission electron microscopy (TEM) that cattle was the intermediate host of three Sarcocystis spp. using dogs, cats and humans, respectively, as definitive hosts. The cat-transmitted species with microscopic sarcocysts was initially named Sarcocystis bovifelis, but it was soon renamed Sarcocystis hirsuta, since it was considered to be identical with a previously named species. In recent years, an apparently new species has been detected in cattle in several countries by molecular methods and TEM and found by both methods to be indistinguishable from Sarcocystis sinensis in water buffaloes. This species was recently named Sarcocystis rommeli. Beginning in August 2014, a thorough review of papers comprising TEM micrographs of thick-walled sarcocysts in cattle was made in order to determine whether S. sinensis-like sarcocysts had been reported previously under other designations. Surprisingly, the review showed that the species S. bovifelis Heydorn et al., 1975 as described from cattle in Germany was S. sinensis-like and that indistinguishable sarcocysts had also been found in cattle in New Zealand and Canada in the 1980s. However, in the New Zealand study, these small sarcocysts were erroneously thought to represent developmental stages of a species with ultrastructurally similar but macroscopic sarcocysts, since the macroscopic cysts were found to be infective for cats. Thus, in the late 1980s, the cat-transmitted S. bovifelis, after having been renamed S. hirsuta, was erroneously synonymised with a second cat-transmitted species in cattle and then slid into obscurity until recently being rediscovered as a S. sinensis-like species in cattle and then named S. rommeli. Following the erroneous synonymisation, the name S. hirsuta has consistently been used for a taxon with macroscopic sarcocysts, and this usage should be continued. The name S. bovifelis should again be used not only for the species originally described from cattle in Germany but also for morphologically indistinguishable taxa recently reported from cattle under the names S. sinensis and S. rommeli. Because of the morphological similarity between S. bovifelis and S. sinensis, it is likely that cats also act as definitive hosts for S. sinensis. The present paper also gives a thorough review of all research in the 1970s pertaining to S. bovifelis, including its development in cats and cattle; a review of reports of S. bovifelis-like sarcocysts in cattle, water buffaloes and other hosts; and a review of reports of the taxon currently named S. hirsuta in cattle. The usage of the name S. sinensis versus Sarcocystis dubeyi for the S. bovifelis-like taxon in water buffaloes is discussed, and the latter name is found to represent a nomen dubium since the original description concerned a mixture of a S. sinensis- and a Sarcocystis hominis-like species. Based on available transmission (TEM) and scanning electron microscopy (SEM) images, the three-dimensional configuration of the cyst wall protrusions of S. bovifelis/S. sinensis and the current S. hirsuta has been inferred and is described. The protrusions of S. bovifelis/S. sinensis are shaped like soft plastic tubes, having a cylindrical basal portion and a flattened distal portion, making them prone to fold over. The protrusions of the current S. hirsuta are thin, flattened and flexible rectangular structures (like a soft cover note book), which are attached to the cyst surface with a narrow stalk. The appearance of both types of protrusions in ultrathin sections viewed by TEM is highly dependent on how the sarcocysts and the protrusions themselves have been sectioned.


Imipramine counteracts corticosterone-induced enhancement of glutamatergic transmission and impairment of long-term potentiation in the rat frontal cortex.
The effects of corticosterone administration lasting for 7 and 21 days were studied ex vivo in rat frontal cortex slices prepared 48 h after the last dose of the hormone. In slices originating from corticosterone-treated animals, the amplitude of extracellular field potentials recorded in cortical layer II/III was increased. Corticosterone administration also resulted in an increase of the mean frequency, but not the mean amplitude, of spontaneous excitatory postsynaptic currents (sEPSCs) in layer II/III pyramidal neurons. These effects were accompanied by a reduced magnitude of long-term potentiation (LTP) of field potentials. In a separate set of experiments, rats were treated with corticosterone for 21 days and additionally with a tricyclic antidepressant, imipramine, beginning on the eighth day of corticosterone administration. In this experimental group, the amplitude of field potentials, the mean frequency of sEPSCs and the magnitude of LTP were not different from the control, indicating that corticosterone-induced modifications of basal glutamatergic transmission and synaptic plasticity were reversed by the antidepressant.


Modifications in the chemical structure of Trojan carriers: impact on cargo delivery.
Carriers with linear or dendrimeric structures displaying different functional groups were synthesized and their delivery properties were studied.