Distinct mechanisms for talker adaptation operate in parallel on different timescales.
The mapping between speech acoustics and phonemic representations is highly variable across talkers, and listeners are slower to recognize words when listening to multiple talkers compared with a single talker. Listeners' speech processing efficiency in mixed-talker settings improves when given time to reorient their attention to each new talker. However, it remains unknown how much time is needed to fully reorient attention to a new talker in mixed-talker settings so that speech processing becomes as efficient as when listening to a single talker. In this study, we examined how speech processing efficiency improves in mixed-talker settings as a function of the duration of continuous speech from a talker. In single-talker and mixed-talker conditions, listeners identified target words either in isolation or preceded by a carrier vowel of parametrically varying durations from 300 to 1,500 ms. Listeners' word identification was significantly slower in every mixed-talker condition compared with the corresponding single-talker condition. The costs associated with processing mixed-talker speech declined significantly as the duration of the speech carrier increased from 0 to 600 ms. However, increasing the carrier duration beyond 600 ms did not achieve further reduction in talker variability-related processing costs. These results suggest that two parallel mechanisms support processing talker variability: A stimulus-driven mechanism that operates on short timescales to reorient attention to new auditory sources, and a top-down mechanism that operates over longer timescales to allocate the cognitive resources needed to accommodate uncertainty in acoustic-phonemic correspondences during contexts where speech may come from multiple talkers.


Identification of an octamer-binding site in the human kappa light-chain enhancer.
Octamer motifs contribute to the function and tissue specificity of immunoglobulin heavy- and light-chain gene promoters and the heavy-chain enhancer. A variant octamer-binding site within a conserved region of the human kappa light-chain gene enhancer which contributes to the function of this enhancer has been identified.


Thyroid microsomal membrane proteins. Effects of solubilization on molecular size.
The molecular size of microsomal membrane proteins from frozen porcine thyroids before and after solubilization by proteolytic and non-proteolytic techniques has been investigated by means of polyacrylamide-gel electrophoresis in the presence of 1% sodium dodecylsulfate. When thyroid microsomal membrane proteins are solubilized by non-proteolytic methods such as high pH, n-butanol, or deoxycholate, no major change in the electrophoretic pattern compared to untreated microsomes has been observed, thereby suggesting that these non-proteolytic methods are capable of extracting membrane proteins from thyroid microsomes without altering their molecular size. However, treatment of microsomes with protein-solubilizing levels of trypsin (1-5 mug trypsin per mg thyroid protein) results in degradation of all major proteins with a molecular weight greater than 30 000. The high-molecular-weight proteins are particularly susceptible to attack by trypsin. Thus, these experiments indicate that the use of trypsin to solubilize thyroid microsomal membrane proteins, particularly thyroid peroxidase, will result in fragmented proteins and should be avoided if intact membrane proteins are desired.


Influence of bromide on the performance of the amphipod Hyalella azteca in reconstituted waters.
Poor performance of the amphipod Hyalella azteca has been observed in exposures using reconstituted waters. Previous studies have reported success in H. azteca water-only exposures with the addition of relatively high concentrations of bromide. The present study evaluated the influence of lower environmentally representative concentrations of bromide on the response of H. azteca in 42-d water-only exposures. Improved performance of H. azteca was observed in reconstituted waters with >0.02 mg Br/L. Environ Toxicol Chem 2016;35:2425-2429. Published 2016 Wiley Periodicals Inc. on behalf of SETAC. This article is a US Government work and, as such, is in the public domain in the United States of America.


Clinical and genetic high-risk strategies in understanding vulnerability to psychosis.
Neurodevelopmental processes active during the adolescent period have been hypothesized to participate in the deterioration in functioning associated with the onset of schizophrenia. A number of studies are now underway evaluating individuals in an ultra high-risk clinical state with neuroimaging assessments repeatedly over time, to determine whether particular neural changes predict an imminent onset of psychosis. However, the results of such studies will be difficult to interpret without reference to studies examining the distribution of these neural indicators in the non-clinically-affected first-degree relatives of patients with schizophrenia. Recent work deriving primarily from twin and family studies (i.e., genetic high-risk designs) indicates that some of the alterations in brain function and structure in schizophrenia are primarily genetically mediated and also appear in some of their unaffected first-degree relatives, while other alterations are present in individuals who manifest the illness phenotype but not in relatives at genetic risk. Whereas the primarily genetically mediated deficits shared by at-risk but non-symptomatic relatives are not likely to show differential change in the premorbid period, and may be necessary but clearly not sufficient for the development of psychotic symptoms, the deficits specific to patients who manifest the illness phenotype are good candidates for marking the neurobiological processes associated with the emergence of psychotic symptoms at the time of schizophrenia onset. Preliminary results from longitudinal studies of individuals ascertained initially in a prodromal (i.e., "clinical high-risk") state appear to be interpretable within this framework.


Ultrastructural localization of fibronectin mRNA in chick embryo by in situ hybridization using 35S or biotin labeled cDNA probes.
We have studied the expression of the fibronectin gene in 7 day-old chick embryo (stage 32) by in situ hybridization at the light and electron microscope levels, using a 397 base-pairs chicken cDNA, labeled by radioisotope or biotin-11dUTP. Cryostat sections of whole chick embryos displayed a selective label on the upper layer of the dermis, fibrous sclera and mesenchymal cells but not on cartilagenous sclera cells. These results show that the expression of the fibronectin gene varies in relation to the morphogenetic events. Hybridization at the ultrastructural level on thin sections of sclera embedded in Lowicryl K4M showed a selective labelling on various cell compartments. Biotin-11dUTP and radiolabeled probes were compared. The labeling was found precisely on the membrane of the rough endoplasmic reticulum and on the nuclear envelope. A few silver grains were located on the nucleus and in the perinucleolar region. This study shows that the postembedding in situ hybridization is a powerful procedure to study the expression of the extracellular protein genes and gives further information on the localization of mRNA.


Management of seminoma with bulky abdominal disease.
Thirty-three cases of seminoma with palpable abdominal disease were treated at the Cancer Control Agency of B.C. between 1948 and 1983. Twenty-three had disease confined to the abdomen (Stage IIB), eight had simultaneous involvement of mediastinal and supraclavicular nodes (Stage IIIB) and two had bone or pulmonary metastases (Stage IV). Five and 10-year disease-specific actuarial survivals for the whole group were 87% and 81%, respectively. Corresponding relapse-free survival was 64%. Of the twenty-three IIB cases, 15 had primary treatment with abdominal radiation only, and eight had prophylactic mediastinal/supraclavicular radiation. Although relapse in IIB was more common in the group receiving abdominal radiation only, survival was unchanged. For the entire IIB group, 5- and 10-year disease-specific actuarial survivals were 91% and 84%, respectively, and corresponding relapse-free survival was 74%. The eight IIIB patients were treated primarily with radiation. Four patients relapsed, all in extranodal sites. Two of these died of disease. Both Stage IV patients required radiation and chemotherapy for long-term disease control. Stage IIB disease can be treated primarily with abdominal radiation, but radiation alone is inadequate when bulky abdominal disease is associated with supradiaphragmatic lymphatic spread or hematogenous metastases.


Network meta-analysis on the effects of finerenone versus SGLT2 inhibitors and GLP-1 receptor agonists on cardiovascular and renal outcomes in patients with type 2 diabetes mellitus and chronic kidney disease.
To evaluate the cardiovascular and renal benefits of finerenone, sodium-glucose cotransporter-2 inhibitors (SGLT2i) and glucagonlike peptide-1 receptor agonists (GLP-1 RA) in patients with Type 2 Diabetes Mellitus (T2DM) and chronic kidney disease (CKD) with network meta-analysis. Systematic literature searches were conducted of PubMed, Cochrane Library, Web of Science, Medline and Embase covering January 1, 2000 to December 30, 2021. Randomized control trials (RCTs) comparing finerenone, SGLT-2i and GLP-1 RA in diabetics with CKD were selected. We performed a network meta-analysis to compare the two drugs and finerenone indirectly. Results were reported as risk ratio (RR) with corresponding 95% confidence interval (CI). 18 RCTs involving 51,496 patients were included. Finerenone reduced the risk of major adverse cardiovascular events (MACE), renal outcome and hospitalization for heart failure (HHF) (RR [95% CI]; 0.88 [0.80-0.97], 0.86 [0.79-0.93], 0.79 [0.67,0.92], respectively). SGLT-2i were associated with reduced risks of MACE (RR [95% CI]; 0.84 [0.78-0.90]), renal outcome (RR [95% CI]; 0.67 [0.60-0.74], HHF (RR [95% CI]; 0.60 [0.53-0.68]), all-cause death (ACD) (RR [95% CI]; 0.89 [0.81-0.91]) and cardiovascular death (CVD) (RR [95% CI]; 0.86 [0.77-0.96]) compared to placebo. GLP-1 RA were associated with a lower risk of MACE (RR [95% CI]; 0.86 [0.78-0.94]). SGLT2i had significant effect in comparison to finerenone (finerenone vs SGLT2i: RR [95% CI]; 1.29 [1.13-1.47], 1.31 [1.07-1.61], respectively) and GLP-1 RA (GLP-1 RA vs SGLT2i: RR [95% CI]; 1.36 [1.16-1.59], 1.49 [1.18-1.89], respectively) in renal outcome and HHF. In patients with T2DM and CKD, SGLT2i, GLP-1 RA and finerenone were comparable in MACE, ACD and CVD. SGLT2i significantly decreased the risk of renal events and HHF compared with finerenone and GLP-1 RA. Among GLP-1 RA, GLP-1 analogues showed significant effect in reducing cardiovascular events compared with exendin-4 analogues.


Variability in the secretion of corticotropin-releasing hormone, adrenocorticotropic hormone and cortisol and understandability of the hypothalamic-pituitary-adrenal axis dynamics--a mathematical study based on clinical evidence.
In this article, we have developed a simple mathematical model that captures the vital mechanisms of the hypothalamic-pituitary-adrenal (HPA) axis self-regulatory activities. For this, a system of three-component non-linear delay differential equations has been proposed and analysed to observe the ultradian and circadian variabilities of the hormone secretion of the HPA axis in normal subjects. Our analysis reveals that a feedback mechanism is sufficient to show the ultradian variability of the hormone secretion pattern but fails to show the circadian variability. A central nervous system-driven pulse generator coupled with the primary feedback mechanism can exhibit the ultradian as well as circadian variability in the hormone secretion of the HPA axis. The model can also predict different dynamics of the normal HPA axis following physiological changes (viz. adrenalectomy and hypophysectomy) and pathological changes (viz. infusion of different hormones).


[Novel full-length cDNA cloning from normal adrenal gland and pheochromocytoma and functional prediction].
To investigate methodology of cloning full-length cDNA from tissues of normal adrenal gland and pheochromocytoma and predict their function. 104 samples from normal adrenal gland and 22 samples from pheochromocytoma were examined by expressed sequence tags (EST) sequencing, bioinformatics analysis, in silico cloning, rapid amplification of cDNA ends and RT-PCR. Among the 126 samples of novel full-length cDNA cloning 104 were from normal adrenal gland, and 22 from pheochromocytoma (PC). Among the novel genes 50 were cloned by direct sequencing of clones, 74 by in silico cloning, and 2 by rapid amplification of cDNA ends, and the localization of chromosomes was made with UniGene searching and radiation hybrid (RH) procedure. Comparison of homology and analysis of motif or domain showed that some genes may be important functional genes, such as those coding signaling proteins, proteins associated with ion channel, enzymes involved in hormone production, important transcription factors, translation initiation factors, etc. 7 of the novel full-length cDNAs are new isoforms produced by alternative splicing. 126 novel full-length cDNAs have been cloned from adrenal tissues by large-scale EST sequencing and bioinformatic tools in a rather short time, some of which may play an important role in regulating adrenal functions and tumorigenesis of adrenal gland.


Leveraging transcriptome and epigenome landscapes to infer regulatory networks during the onset of sexual maturation.
Despite sexual development being ubiquitous to vertebrates, the molecular mechanisms underpinning this fundamental transition remain largely undocumented in many organisms. We designed a time course experiment that successfully sampled the period when Atlantic salmon commence their trajectory towards sexual maturation. Through deep RNA sequencing, we discovered key genes and pathways associated with maturation in the pituitary-ovarian axis. Analyzing DNA methylomes revealed a bias towards hypermethylation in ovary that implicated maturation-related genes. Co-analysis of DNA methylome and gene expression changes revealed chromatin remodeling genes and key transcription factors were both significantly hypermethylated and upregulated in the ovary during the onset of maturation. We also observed changes in chromatin state landscapes that were strongly correlated with fundamental remodeling of gene expression in liver. Finally, a multiomic integrated analysis revealed regulatory networks and identified hub genes including TRIM25 gene (encoding the estrogen-responsive finger protein) as a putative key regulator in the pituitary that underwent a 60-fold change in connectivity during the transition to maturation. The study successfully documented transcriptome and epigenome changes that involved key genes and pathways acting in the pituitary - ovarian axis. Using a Systems Biology approach, we identified hub genes and their associated networks deemed crucial for onset of maturation. The results provide a comprehensive view of the spatiotemporal changes involved in a complex trait and opens the door to future efforts aiming to manipulate puberty in an economically important aquaculture species.


A paper-based point-of-care testing device for the colourimetric estimation of bilirubin in blood sample.
A paper-based colourimetric assay for the Point-of-Care Testing (PoCT) of bilirubin has been developed based on the formation of a green-coloured copper-bilirubin complex from a blue-coloured tetraamminecopper(II) sulphate complex. The reaction was studied and optimized by UV-Visible absorption spectroscopy and translated onto a paper strip. Hydrophobic circular well patterns on Whatman chromatography paper were created by wax printing. The tetraamminecopper(II) sulphate complex was drop cast and dried on the reagent zones in the wax-patterned paper. The images of reagent zones captured using a scanner were analyzed using ImageJ software. Bilirubin spiked blood serum was tested in the concentration range of 1.2 to 950 µM. The PAD exhibited sensitivities of 0.4197 a.u/μM and 0.1040 a.u/μM for concentration ranges of bilirubin 1.2 to 96 μM and 105 to 950 μM respectively and a low detection limit of 0.799 µM. The method is highly selective to bilirubin, even in the presence of other biomarkers in serum. A plasma separation membrane incorporated PAD was fabricated for the final testing and quantification of bilirubin from whole blood.


Use of anorectic amphetamine-like drugs by Brazilian women.
The history of anorectic drug use was investigated in 2370 subjects in São Paulo and Brasília cities. Socio-demographic data and the number of previous treatments to lose weight were obtained. When the last treatment was drug-based, the substance(s) used, its duration, the occurrence of adverse reactions, and whether it was adequate were studied. There was a prevalence of female patients, 92.7%, in both cities and as many as 72.4% of them had already undergone from 1 to >10 previous treatments. Out of those patients, 75.37% had undergone pharmacological treatment, 79.2% of those with amphetamine-like anorectic drugs. Treatment was longer than 3 months in half of the cases, and 60% of the subjects had a Body Mass Index below 29.9. Over 50% of the subjects was given amphetamine-like drugs through compounded formulas containing four or more substances, which had been specifically tailored by the doctor for each patient. On the other hand, 86.3% of all the subjects reported adverse reactions to the amphetamine-like drugs, 37.4% of them sought medical advice, and 3.9% required hospitalization. In conclusion, the use of amphetamine-like drugs in Brazil is particularly prevalent among women and this use is strongly related to the culture of slimness as a symbol of beauty.


Striatal morphological and functional alterations induced by prenatal alcohol exposure.
Prenatal alcohol exposure (PAE) is an insidious yet preventable cause of developmental disability. The prenatal stage is a critical period for brain development with the concurrence of high vulnerability to the acute and prolonged effects of PAE. There is substantial evidence from both human observations and laboratory experiments that PAE is a common risk factor that predisposes to an array of postnatal mental disorders, including emotional, cognitive, and motor deficits. Although it is well accepted that PAE causes substantial morbidity, available treatments are limited. One reason is the lack of sufficient understanding about the neuroalterations induced by PAE, and how these changes contribute to PAE-induced mental disorders. Among a number of brain structures that have been explored extensively in PAE, the striatum has attracted great attention in the last 20 years in the field of PAE neurobiology. Interestingly, in animal models, the striatum has been considered as a pivotal switch of brain dysfunction induced by PAE, such as addiction, anxiety, depression, and neurodegeneration. In this review, we focus on recent advances in the understanding of morphological and functional changes in brain regions related to alterations after PAE, in particular the striatum. Because this region is central for behavior, emotion and cognition, there is an urgent need for more studies to uncover the PAE-induced alterations at the circuit, neuronal, synaptic and molecular levels, which will not only improve our understanding of the neuroplasticity induced by PAE, but also provide novel biological targets to treat PAE-related mental disorders with translational significance.


Early and late physical and psychosocial effects of primary surgery in patients with oral and oropharyngeal cancers: a systematic review.
The purpose of this systematic review is to explore early and late physical and psychosocial effects of primary surgery for oral and oropharyngeal cancers and to investigate the factors that influence these effects. PubMed, Cinahl, and PsycInfo were searched for studies concerning patients diagnosed with oral and oropharyngeal cancers and treated with primary surgery and which followed the treatment trajectory from time of diagnosis to 10 years after surgery; these studies reported the quantitative assessments and qualitative experiences of the patient's physical and psychosocial well-being. Of the 438 articles accessed, 20 qualified for inclusion, of which 16 and 4 were quantitative and qualitative articles, respectively, and mainly quality-of-life assessments. Time of measurement ranged from time of diagnosis to 9 years after the surgical procedure. The total number of patients included in this review was 3386; of these, 1996 were treated by surgery alone and 1390 with combined surgery and adjuvant radiation therapy and/or chemotherapy. The studies showed that because of the nature of their disease, patients are negatively affected by the different types of surgical treatment for oral and oropharyngeal cancers, with both early and late interrelated effects, and by the side effects of adjuvant therapy.


Overexpression of ROMO1 and OMA1 are Potentially Biomarkers and Predict Unfavorable Prognosis in Gastric Cancer.
One of the worst types of cancers is gastric cancer and no specific tumor marker is found in relation to it. Reactive oxygen species modulator 1 (ROMO1) and the overlapping with the M-AAA protease 1 homolog (OMA1) proteins are the most important mitochondrial membrane proteins, which are involved in modulating reactive oxygen species (ROS) production and the regulation of mitochondrial structure dynamics. If these proteins do not function properly, oxidative stress increases in the cell, and this can initiate the cancer or worsen the condition. In this study, ROMO1 and OMA1 gene expressions in 40 fresh frozen gastric cancer tissue and healthy adjacent tissues were evaluated by real-time PCR, and some of the important parameters related to oxidative stress such as TAC, TOS, MDA, and TTG in the serum of cancer patients compared to healthy people were measured by spectrophotometric and fluorometric techniques. We observed that ROMO1 and OMA1 gene expressions in gastric cancer tissues increased compared to that in healthy adjacent tissues. In addition, oxidative stress parameters including TOS, OSI, and MDA in the serum of cancer patients have increased significantly and the parameters including TAC and TTG have decreased. The results in our study represented that ROMO1 and OMA1 gene expressions in gastric cancer tissue have increased compared to that in healthy adjacent tissues, and oxidative stress levels have also increased significantly in relation to these proteins; therefore, these two proteins may be considered as an important cause of gastric cancer, and even introduced as tumor markers.


"Aqua-space", a new headspace method for isolation of natural floral aromas using humidified air as a carrier gas.
A new method called "Aqua-space" was developed for the isolation of the natural fragrances of plants. Living flowers were enclosed in a space under simulated natural conditions, and humidified air was pumped into the space as a fragrance carrier. In a comparison among three isolation methods, i.e., Aqua-space, headspace, and solvent extraction, the Aqua-space method proved to be the most effective in retaining natural fragrances with abundant oxygenated components key to floral fragrances.


The stigma of schizophrenia from patients' and relatives' view: A pilot study in an Italian rehabilitation residential care unit.
To identify the constituent elements of the stigma from the perspective of those having first-hand experiences of it. Subjective experiences of stigma were explored in six focus groups: three with people suffering from schizophrenia and three with patients' relatives. Focus group sessions were tape-recorded, transcribed and analyzed by means of an inductive method, forming categories from the texts, as a basis for coding. Analysis aimed at establishing a typology of stigmatization experiences from the spoken words of the focus group participants. Four dimensions of stigma were identified: access to social roles; internalization of stigma; quality of mental health services, public image of mental illness. The most frequently found topics concerned experiences of marginalization and discrimination that people with schizophrenia experience in their daily life. These results mirror the findings of similar studies obtained in other cultural contexts.


[The application and development of computer vision technology in radiotherapy].
In this paper, the principle of computer vision was introduced and several typical radiotherapy devices based on computer vision were described, including their principle and applications.


Antioxidant activity and antibacterial activity of peach gum derived oligosaccharides.
In this study, peach gum derived oligosaccharides (PGDO) were prepared from peach gum polysaccharides by hydrolysis using hydrogen peroxide (H2O2) under following conditions: time, 8h; temperature, 55 °C; H2O2 concentration, 4% (v/v); and NaOH concentration, 2.0 M. The antioxidant activity and antibacterial activity of PGDO were estimated. There were no significant chemical changes in the backbones of the peach gum polysaccharides treated with H2O2. The PGDO showed high hydroxyl radical scavenging activity (86.12%) and 2, 2-diphenyl-β-picrylhydrazyl radical scavenging activity (91.70%) at the concentration of 100 μg/mL as well as high reducing capacity at the concentration of 50 μg/mL. In addition the PGDO had high antibacterial activity against Bacillus subtilis, Staphylococcus aureus, and Escherichia coli at the concentration of 100 μg/mL.


Tolazoline as an antagonist in free-living lions immobilised with a ketamine-xylazine combination.
A combination of ketamine at 8.0 mg/kg and xylazine at 3.2 mg/kg was found effective in immobilising lions (Panthera leo) for 4 hours. Ataxia and immobilisation were rapidly induced, with stable respiratory rate, heart rate and body temperature recorded. Tolazoline effectively antagonised xylazine via intravenous or intramuscular injection, resulting in a return to mobility within approximately 20 and 60 minutes, respectively. Tolazoline also elevated the respiratory rate. No mortalities occurred during 97 immobilisations of 76 lions.


Fluticasone propionate plasma concentration and systemic effect: effect of delivery device and duration of administration.
Inhaled corticosteroids are the preferred therapy in persistent asthma. Dry powder inhalers (DPIs) generate a larger particle size compared with metered-dose inhalers (MDIs), which affects pulmonary deposition, bioavailability, and subsequent systemic effects of fluticasone propionate (fluticasone). To examine the relationship of fluticasone pharmacokinetics and cortisol suppression for 2 fluticasone formulations (DPI and MDI) administered in adults over 1-week and 6-week treatment periods. Two previous studies conducted in adults by the Asthma Clinical Research Network examined relative efficacy and systemic effect of fluticasone from MDI and DPI. Sample sets (n=33) were analyzed for fluticasone after administration of 352 microg from the MDI, and 400 microg from the DPI formulation, twice daily, after a 1-week treatment period. The second study's sample sets (n=9) were analyzed for fluticasone after 6 weeks therapy at 352 microg twice daily from the MDI formulation, allowing achievement of steady state. ANOVA revealed a significant trend of increasing fluticasone area under the curve from 0 to time t (AUC(0-->t)) when comparing DPI with MDI for 1 week with MDI for 6 weeks (P<.0001). Similarly, ANOVA revealed increasing cortisol suppression between these groups (P=.007). Linear regression demonstrated that increasing fluticasone AUC(0-->t) was significantly correlated with cortisol suppression (P<.0001; r(2)=0.41). MDI for 6 weeks showed increasing fluticasone AUC (P=.0008, t test) compared with MDI for 1 week, suggesting accumulation. Fluticasone plasma concentrations are significantly greater after MDI compared with DPI, and cortisol suppression is associated with fluticasone plasma concentrations. Accumulation of fluticasone concentrations suggests that time to steady state exceeds 1 week of treatment with MDI.


Histological and immunohistochemical findings in experimental rhabdomyosarcomas. Comparisons between original tumors, tumor recurrences and allotransplants in nude mice.
Cellular heterogeneity, a regular property of malignant neoplasms, can constitute the basis for phenotypic shifting in malignant tumors. A disturbance of the balanced interactions as happens as result of all therapy measurements between tumor cell subpopulations and between tumor and host offers the possibility to profound changes on the basis of cellular heterogeneity. As tumor model we used methylcholanthrene-induced murine rhabdomyosarcomas, which were allotransplanted into nude mice. The original as well as the allotransplanted sarcomas were submitted repeated operative tumor mass reductions, comparable to an insufficient tumor surgery in man. The histology and the cellular differentiation were evaluated by light microscopy and immunohistochemical marker expression (vimentin, desmin and myoglobin). Our findings document that primary tumors, their recurrences after incomplete tumor removal, and allotransplants inclusive of their surgically induced recurrences were histologically and immunohistochemically not identical in every case when compared with each other, but despite the experimental procedures they retained basic criteria necessary for the rhabdomyosarcoma diagnosis. Changes in sarcoma histology and cellular marker expression are not only reflected by dedifferentiation but can also comprise differentiation (maturation) processes. After artificial breakdown of intratumoral cellular interactions and tumor/host relations, unknown sarcoma inherent factors directed to retaining basic properties obviously preponderate, at least for the moment, over accidental new cell clones with differing phenotypic characteristics, which could be expected by cellular heterogeneity and would result in a markedly changed tumor.


High-resolution real-time three-dimensional acoustic imaging system with a reflector.
We propose an acoustic real-time three-dimensional (3-D) diagnostic imaging system based on a hybrid array-reflector configuration that realizes high time and spatial resolutions with a modest computational load. All the elements on a small dense array were excited with proper time delays to transmit a broad beam similar to that of a single transmitter element. The echo was gathered by a concave reflector and received by the dense array. The image of the target was reconstructed by numerical back projection from the defocused image distributed on the array. With this scheme, images of the whole measurement area can be reconstructed from a single transmit and receive event. The number of elements can be reduced to about 1/8.2 that of a dense 2-D array of a digital beamforming system having the same spatial resolution. By weighting individual elements, the sidelobe level could be suppressed to less than -21 dB. The maximum theoretical frame rate is 5000 3-D images/s. This method has a higher signal-to-noise ratio than that of defocused multi-element digital beamforming methods, overcoming conventional phased array performance. The proposed scheme is suited for purposes that require high time and spatial resolutions, such as cardiology.


ADHD animal model characterization: transcriptomics and proteomics analyses.
Mechanisms underlying behavioral abnormalities of patients with attention-deficit hyperactivity disorder (ADHD) disorder are still unknown. It is worth clarifying alterations in the brain of animal models for ADHD. The animals with neonatal treatment with 6-hydroxydopamine (6-OHDA) and congenic wiggling (Wig) rats show motor hyperactivities during a period of darkness at 4 weeks of age. In rats with 6-OHDA lesions, subcutaneous injection of methamphetamine attenuates hyperactivity, the reverse of its effect in Wig rats. To understand mechanisms underlying such behavioral abnormalities, transcriptomics and proteomics analyses may provide novel information in brain research. The expression of genes and proteins in brain regions can be measured by DNA microarray and two-dimensional gel electrophoresis, respectively. We have shown different expressions of genes and proteins in brains of rats with neonatal 6-OHDA lesions and Wig rats.


Expression of antioxidant enzymes in rat lungs after inhalation of asbestos or silica.
Several studies indicate that active oxygen species play an important role in the development of pulmonary disease (asbestosis and silicosis) after exposure to mineral dust. The present study was conducted to determine if inhaled fibrogenic minerals induced changes in gene expression and activities of antioxidant enzymes (AOE) in rat lung. Two different fibrogenic minerals were compared, crocidolite, an amphibole asbestos fiber, and cristobalite, a crystalline silicon dioxide particle. Steady-state mRNA levels, immunoreactive protein, and activities of selected AOE were measured in lungs 1-10 days after initiation of exposure and at 14 days after cessation of a 10-day exposure period. Exposure to asbestos resulted in significant increases in steady-state mRNA levels of manganese-containing superoxide dismutase (MnSOD) at 3 and 9 days and of glutathione peroxidase at 6 and 9 days. An increase in steady-state mRNA levels of copper, zinc-containing superoxide dismutase (CuZnSOD), was observed at 6 days. Exposure to asbestos also resulted in overall increased enzyme activities of catalase, glutathione peroxidase and total superoxide dismutase in lung. In contrast, silica caused a dramatic increase in steady-state levels of MnSOD mRNA at all time periods and an increase in glutathione peroxidase mRNA levels at 9 days. Activities of AOE remained unchanged in silica-exposed lungs. In both models, increases in gene expression of MnSOD correlated with increased amounts of MnSOD immunoreactive protein in lung and the pattern and extent of inflammation. These data indicate that the profiles of AOE are dissimilar during the development of experimental asbestosis or silicosis and suggest different mechanisms of lung defense in response to these minerals.


The effects of vitamin E on immune regulation after thermal injury.
Studies were conducted on four groups of rats, each group consisting of 10 rats with burn + vitamin E, burn + saline solution, control + vitamin E and control + saline solution. Before and after burning 250 mg (2 cm3) of vitamin E was given intramuscularly. On the same days 2 cm3 of saline solution was given to the controls. The rats were burned over 30 per cent of their body surface area and then inoculated intraperitoneally with 40 units of tetanus toxoid. Complement fixation and acid phosphatase tests were carried out on the days 15 and 21 postburn. On day 21, the rats were killed and the spleens removed and weighted. In the groups that received vitamin E, the spleen weight and complement fixation test increased significantly while the acid phosphatase in serum decreased. In the clinical study, 17 burned patients with over 20 per cent deep partial or full skin thickness burns and eight healthy persons were studied. Nine of the 17 burned patients received vitamin E on 3 consecutive days, on day 4 blood was taken for analysis. The results showed that the number of T-cells decreased significantly in burn patients (P less than 0.05) whereas they increased significantly (P less than 0.05) in burn patients who received vitamin E. It is concluded from these experimental and clinical studies that vitamin E stimulates both cellular and humoral immunity. Therefore, the use of vitamin E in combination with conventional therapy in burn patients can be recommended.


Effects of Kinesio Taping on Muscle Contractile Properties: Assessment Using Tensiomyography.
Although functional effects of kinesio taping (KT) have been widely studied, its effects on contractile properties of the target muscle remain unclear. Tensiomyography is suitable for quantifying muscle stiffness and rate of force development upon imposed twitch contraction. To test the hypothesis that KT has effects on contractile properties of targeted muscle using tensiomyography. Prospective cohort study. Performance laboratory of a sports rehabilitation center. A total of 11 healthy volunteers. Tensiomyography measurements before KT facilitation technique applied (pre-KT), 45 minutes, and 24 hours after KT (post-KT1 and post-KT2, respectively) without removing the tape. Maximal radial displacement, contraction time, delay time, sustain time, relaxation time, and velocity of contraction. Significant effects were shown for maximal radial displacement (P = .004), contraction time (P = .013), relaxation time (P = .035), and velocity of contraction (P = .0033), but not for delay time (P = .060) and sustain time (P = .078). Post hoc testing indicated a significant decrease in maximal radial displacement for post-KT1 only (from 6.33 [1.46] to 4.87 [2.14] mm), and a significant increase in contraction time for both post-KT1 and post-KT2 (from 30.87 [11.39] to 39.71 [13.49] ms, and 37.41 [14.73] ms, respectively). Post hoc testing also showed a significant decrease in relaxation time for post-KT2 (from 65.97 [53.43] to 47.45 [38.12] ms), and a significant decrease in velocity of contraction for both post-KT1 and post-KT2 (from 0.22 [0.08] to 0.15 [0.09] mm/s, and 0.16 [0.07] mm/s), respectively. The findings indicate that KT leads to an increased muscle stiffness and a reduced muscle rate of force production despite the facilitation technique applied.


Elemental Concentrations in the Shells of the Mussel Perna perna: Discrimination of Origin.
The potential use of elemental concentrations and element:calcium (Ca) ratios as indicators of provenance for bivalve mollusks on the Brazilian coast is evaluated herein for the first time. The approach was applied to shells of the mussel Perna perna (target of extractive fisheries) from geographically close areas but under distinct environmental and anthropogenic influences. Both concentrations of the elements normalized by Ca and the total concentrations can be applied to discriminate the mussels' origin. However, the canonical approach using the total concentrations indicated variations regarding the discriminatory power, and the concentrations of the elements normalized by Ca were more robust in differentiating the provenance of the shells. The origin of mussels was better discriminated by six elementary ratios: Al:Ca, Fe:Ca, K:Ca, Mg:Ca, Mn:Ca and Na:Ca. Thus, monitoring studies aiming to discriminate the origin of P. perna individuals along their distribution based on these elementary ratios of the shell are recommended.


[Thermic investigations of the nystagmus induced in the Brunning's positions V-I in patients with unilateral, peripheral vestibular lesion].
There were examined 50 persons with unilateral peripheral lesion of vestibular system. Each patient was tested by method, in which inversion of nystagmus direction in respect of ampullopetal and ampullofugal stimulation followed cause of change of head's position--position Brünnings V-I--during irrigation 30 degrees C. Results obtained during these method were compared with effects of caloric Hallpike test. The method described in these paper could supply to classic caloric test.


Intensity modulated radiotherapy (IMRT) for pediatric cancer patients: the advantage and fear of second malignant neoplasm.
Intensity-modulated radiotherapy is used for delivering more efficient homogenous dose to the target and lowering of dose to the surrounding normal tissues. However, a second malignant neoplasm may develop after prolonged latent period. The use of modern precise radiotherapy techniques in the pediatric age group has many controversial issues in spite of its proven dosimetric distribution advantages and the considerable decrease of normal tissue complication probability (NTCP). This concern is due to many factors; mainly the exposure of a larger volume of normal tissues to low dose radiotherapy. Children have more proliferating tissues compared to the adults. However, the epidemiological data did not detect an increase in the incidence of radiation-induced second malignancy. This issue is still controversial as IMRT and other precise radiotherapy techniques were not widely used except recently. This may entail a thorough careful follow up for children treated with these techniques to detect any incidence increase.


PFOS-induced apoptosis through mitochondrion-dependent pathway in human-hamster hybrid cells.
Perfluorooctane sulfonate (PFOS) was listed as one of the persistent organic pollutants (POPs) in Stockholm Convention in 2009. Recent evidence showed that PFOS could induce apoptosis both in vivo and in vitro. However, the apoptotic mechanisms induced by PFOS as well as the possible relationship between apoptosis and other PFOS-induced endpoints, remain unclear. In the present study, normal human-hamster hybrid (AL) cells and mtDNA-depleted (ρ(0) AL) cells were exposed to PFOS, and assayed for cytotoxicity, mutagenicity, and apoptosis (caspase-3/7, caspase-9 activities). Our results showed that PFOS decreased cell viability in a time- and concentration-dependent manner in AL cells, but not in ρ(0) AL cells. However, long-term exposure to PFOS failed to induce the mutagenic effects at the CD59 locus in AL cells. Exposure to 200 μM PFOS significantly increased the activities of caspase-3/7 and caspase-9 in AL cells, but the activities of these caspases were not affected in ρ(0) AL cells. In addition, PFOS increased the levels of reactive oxygen species (ROS), superoxide anion (O2(-)), as well as nitric oxide (NO), and decreased mitochondrial membrane potential (MMP) at the concentrations of 100 and 200μM in AL cells. On the other hand, exposure to PFOS had no effect on intracellular ROS, O2(-), and NO production in ρ(0) AL cells. Caspase-3/7 activity, which was increased by 200 μM PFOS, could be suppressed by ROS/O2(-) scavengers and nitric oxide synthases (NOSs) inhibitors in AL cells. These results implicate that PFOS-induced apoptosis and oxidative stress is mediated by a mitochondrion-dependent pathway and that the induction of apoptosis might be a protective function against mutagenesis in AL cells exposed to PFOS.


Clinical effectiveness of a staff training intervention in mental health inpatient rehabilitation units designed to increase patients' engagement in activities (the Rehabilitation Effectiveness for Activities for Life [REAL] study): single-blind, cluster-randomised controlled trial.
Mental health inpatient rehabilitation services focus on people with complex psychosis who have, for example, treatment-refractory symptoms, cognitive impairment, and severe negative symptoms, which impair functioning and require lengthy admission. Engagement in activities could lead to improvement in negative symptoms and function, but few trials have been done. We aimed to investigate the effectiveness of a staff training intervention to increase patients' engagement in activities. We did a single-blind, two-arm, cluster-randomised controlled trial in 40 mental health inpatient rehabilitation units across England. Units were randomly allocated to either a manual-based staff training programme delivered by a small intervention team (intervention group, n=20) or standard care (control group, n=20). The primary outcome was patients' engagement in activities 12 months after randomisation, measured with the time use diary. With this measure, both the degree of engagement in an activity and its complexity are recorded four times a day for a week, rated on a scale of 0-4 for every period (maximum score of 112). Analysis was by intention-to-treat. Random-effects models were used to compare outcomes between study groups. Cost-effectiveness was assessed by combining service costs with the primary outcome. This study is registered with Current Controlled Trials (ISRCTN25898179). Patients' engagement in activities did not differ between study groups (coefficient 1·44, 95% CI -1·35 to 4·24). An extra £101 was needed to achieve a 1% increase in patients' engagement in activities with the study intervention. Our training intervention did not increase patients' engagement in activities after 12 months of follow-up. This failure could be attributable to inadequate implementation of the intervention, a high turnover of patients in the intervention units, competing priorities on staff time, high levels of patients' morbidity, and ceiling effects because of the high quality of standard care delivered. Further studies are needed to identify interventions that can improve outcomes for people with severe and complex psychosis. National Institute for Health Research.


Cricopharyngeal Achalasia: Management and Associated Outcomes-A Scoping Review.
There is little consensus regarding the efficacy and safety of treatment options for cricopharyngeal (CP) achalasia. The purpose of this scoping review is to assess the literature regarding the various treatments for this disease. PubMed was searched for all articles addressing treatment of adult CP achalasia between January 1990 and June 2019. In total, 351 peer-reviewed results were reviewed by 3 otolaryngologists for inclusion. After review of titles, abstracts, and full texts, 60 articles were selected. Among included studies, 55% were retrospective and 45% were prospective. Forty-five percent of studies were case series. CP achalasia etiologies included idiopathic (28%), cerebrovascular accident (CVA) (28%), neurologic disease (17%), head and neck radiation treatment (11%), Zenker's diverticulum (10%), and myositis (5%). Most commonly employed treatments were botulinum toxin injection (40%), endoscopic CP myotomy (30%), dilation with either balloon or bougie (25%), and open CP myotomy (15%). A proportion of patients were treated with more than 1 approach. Most studies included both subjective and objective outcome measures. Complications were reported most often in patients with a history of head and neck radiation. Small sample sizes and heterogeneity of causes and treatments of CP achalasia, as well as short duration of follow-up, make it challenging to assess the superiority of one treatment over another. There is a need for a prospective study that more directly compares outcomes of administration of botulinum toxin, dilation, and CP myotomy in patients with CP achalasia of similar etiologies.


Exploring synergies in the water-food-energy nexus by using an integrated hydro-economic optimization model for the Lancang-Mekong River basin.
The Water-Food-Energy nexus study identifies developmental challenges and trade-offs present along the transboundary river basins. Intensive reservoir development for hydropower production impacts existing actors in the Lancang-Mekong River Basin. Concerns from these stakeholders highlight three major trade-offs that occur between hydropower and irrigation (HP-AG), hydropower and fisheries (HP-F), and irrigation and fisheries (AG-F). Dam construction has an impact not only on power production but also on ecosystems and ultimately the livelihood of people. In this study, we quantify the effects of reservoir operation on hydropower generation, irrigated crop production and fisheries yield in the Tonle Sap lake through a novel hydro-economic model at the whole basin scale. Our main finding is that trade-offs can be turned into synergetic opportunities. First, the dam operation can increase water availability for irrigation without severely harming hydropower production, raising irrigated crop revenue by 49% and reducing crop losses during droughts by 30%. Second, eco-friendly management increases fisheries yield by up to 75%, but decreases both irrigated crop production (-48%) and power production (-17%). Reservoirs can, therefore, benefit the whole basin by releasing more water in months with high irrigation demand (April and December) and by minimizing the adverse effects of flow fluctuations on the livelihood of farmers and fishers living downstream. Our results also reveal the overlooked trade-off between irrigated agriculture and fisheries. Cross-sectoral and transboundary partnerships should strengthen stakeholder participation in decision-making. Local solutions such as enhanced reservoir operation can respond to the broader global issue of natural resource trade-offs and sharing. Our alternative narrative enhances the dialogue about fair and efficient water use among Mekong riparian countries.


Effect of dimethyl sulfoxide on phosphoryl transfer catalyzed by yeast hexokinase.
Hexokinase is a phosphotransferase that catalyzes phosphoryl transfer from ATP to glucose much more rapidly than the transfer from ATP to water (i.e., hydrolysis). Dimethyl sulfoxide has opposite effects on these two phosphotransferase activities: it enhances ATP hydrolysis and inhibits glucose phosphorylation. Xylose, a sugar that is non-phosphorylatable by hexokinase, enhances ATPase activity which is additive to activation by dimethyl sulfoxide, indicating that the mechanism of activation by dimethyl sulfoxide is different from that of xylose. These results suggest that it is possible to change the specificity of the enzyme in the presence of dimethyl sulfoxide.


Loss of Shp2 in alveoli epithelia induces deregulated surfactant homeostasis, resulting in spontaneous pulmonary fibrosis.
Type II alveolar epithelial (AT-II) cells produce pulmonary surfactant proteins that are essential for alveolar function. AT-II is a major target in lung injury, and ineffective repair of damaged alveolar epithelia has been postulated to cause pulmonary fibrosis. Previous studies have shown that tyrosine phosphatase Shp2 is expressed highly in the embryonic lung epithelial buds, and Shp2 activity is required for FGF-induced lung branching morphogenesis. To investigate in vivo function of pulmonary Shp2, we generated alveoli epithelia-specific Shp2-knockout (Shp2(Δ/Δ)) mice. Shp2(Δ/Δ) mice exhibit marked reduction in surfactant proteins, disorganized lamellar bodies, increased alveolar epithelial apoptosis, and interstitial pulmonary fibrosis without preceding inflammation. Mechanistically, Shp2 acts to mediate expression of thyroid transcription factor 1 (TTF1) and ATP-binding cassette subfamily A member 3 (ABCA3). Shp2 also plays a central role in mediating FGF/GAB/ERK activity, required for epithelial repair program. Together, our results identify a novel role of tyrosine phosphatase Shp2 in surfactant homeostasis, and deregulation of Shp2 triggers spontaneous pulmonary fibrosis with minimal inflammation.


Trends of pH decrease in the Mediterranean Sea through high frequency observational data: indication of ocean acidification in the basin.
A significant fraction of anthropogenic carbon dioxide (CO2) released to the atmosphere is absorbed by the oceans, leading to a range of chemical changes and causing ocean acidification (OA). Assessing the impact of OA on marine ecosystems requires the accurate detection of the rate of seawater pH change. This work reports the results of nearly 3 years of continuous pH measurements in the Mediterranean Sea at the Strait of Gibraltar GIFT time series station. We document a remarkable decreasing annual trend of -0.0044 ± 0.00006 in the Mediterranean pH, which can be interpreted as an indicator of acidification in the basin based on high frequency records. Modeling pH data of the Mediterranean outflow allowed to discriminate between the pH values of its two main constituent water masses, the Levantine Intermediate Water (LIW) and the Western Mediterranean Deep Water (WMDW). Both water masses also exhibited a decline in pH with time, particularly the WMDW, which can be related to their different biogeochemical nature and processes occurring during transit time from formation sites to the Strait of Gibraltar.


Polyetheretherketone (PEEK) for medical applications.
Polyetheretherketone (PEEK) is a polyaromatic semi-crystalline thermoplastic polymer with mechanical properties favorable for bio-medical applications. Polyetheretherketone forms: PEEK-LT1, PEEK-LT2, and PEEK-LT3 have already been applied in different surgical fields: spine surgery, orthopedic surgery, maxillo-facial surgery etc. Synthesis of PEEK composites broadens the physicochemical and mechanical properties of PEEK materials. To improve their osteoinductive and antimicrobial capabilities, different types of functionalization of PEEK surfaces and changes in PEEK structure were proposed. PEEK based materials are becoming an important group of biomaterials used for bone and cartilage replacement as well as in a large number of diverse medical fields. The current paper describes the structural changes and the surface functionalization of PEEK materials and their most common biomedical applications. The possibility to use these materials in 3D printing process could increase the scientific interest and their future development as well.


Angiogenesis in rat uterine cicatrix after injection of autologous bone marrow mesenchymal stem cells.
Results of injection of autologous bone marrow mesenchymal stem cells with transfected GFP gene into the rat uterine horn cicatrix were studied by light microscopy. Large groups of blood vessels with blood cells inside were seen after injection of autologous bone marrow cells into the cicatrix on the right horn, formed 2 months after its ligation; no groups of vessels of this kind were found in the cicatrix in the contralateral horn. Examination of unstained sections in reflected UV light showed sufficiently bright fluorescence in the endothelium and outer vascular membrane in the uterine horn cicatrix only on the side of injection. Hence, autologous mesenchymal stem cells injected into the cicatrix formed the blood vessels due to differentiation into endotheliocytes and pericytes. The expression of GFP gene not only in the vascular endothelium, but also in vascular outer membranes indicated that autologous mesenchymal stem cells differentiated in the endothelial and pericytic directions.


A case-control study to evaluate the impact of the breast screening programme on mortality in England.
Over the past 30 years since the implementation of the National Health Service Breast Screening Programme, improvements in diagnostic techniques and treatments have led to the need for an up-to-date evaluation of its benefit on risk of death from breast cancer. An initial pilot case-control study in London indicated that attending mammography screening led to a mortality reduction of 39%. Based on the same study protocol, an England-wide study was set up. Women aged 47-89 years who died of primary breast cancer in 2010 or 2011 were selected as cases (8288 cases). When possible, two controls were selected per case (15,202 controls) and were matched by date of birth and screening area. Conditional logistic regressions showed a 38% reduction in breast cancer mortality after correcting for self-selection bias (OR 0.62, 95% CI 0.56-0.69) for women being screened at least once. Secondary analyses by age group, and time between last screen and breast cancer diagnosis were also performed. According to this England-wide case-control study, mammography screening still plays an important role in lowering the risk of dying from breast cancer. Women aged 65 or over see a stronger and longer lasting benefit of screening compared to younger women.


Uncommon terpenoids with anti-inflammatory activity from the Hainan soft coral Sinularia tumulosa.
One novel sesquiterpenoid containing an unprecedented eight-membered cyclic peroxide motif, sinulatumolin A (1), along with four new related terpenoids, namely sinulatumolins B-E (2-4 and 6), were isolated from South China Sea soft coral Sinularia tumulosa. The structures of all the isolates were elucidated by detailed spectroscopic analysis, chemical transformations, and single X-ray diffraction analysis. Compound 1 represents the first example of sesquiterpene bearing an eight-membered cyclic peroxide ring from soft coral. All the new compounds isolated were evaluated for their anti-inflammatory activity. Compounds 1, 3, 4 and 6 displayed significant TNF-α inhibitory activity being comparable with that of the positive control dexamethasone (IC50 = 8.7 μM), with IC50 values of 7.5, 2.6, 5.5, and 3.6 μM, respectively.


Epidermal nucleases: purification and characterization of ribonuclease from mammalian epidermis.
The major ribonuclease of adult guinea pig epidermis has been isolated and purfied over 1000-fold by a combination of ammonium sulfate fractionation, affinity and ion-exchange chromatography, and electrophoresis. The purified enzyme is free from phosphodiesterase and phosphatase activities. The ribonuclease is optimally active near neutrality in phosphate buffer, with a Km of 3mu g/ml toward [14-C]RNA from Erhlich ascites tumor cells. (here are no metal requirements for activity. The enzyme catalyzes the endonucleolytic hydrolysis of high molecular weight yeast RNA and it also hydrolyzes polycytidylic and polyuridylic acids, but not polyadenylic, polyguanylic, and polyinosinic acids. The apparent molecular weight of the active enzyme is 28 500.


Neoadjuvant systemic therapy in patients undergoing nephroureterectomy for urothelial cancer: a multidisciplinary systematic review and critical analysis.
The benefit of neoadjuvant systemic therapy (NAST) is not yet supported by randomized controlled trials in upper tract urothelial carcinoma (UTUC), but the evidence is increasing. This narrative systematic review was conducted to evaluate the available evidence on the role of NAST in patients undergoing radical nephroureterectomy (RNU) for UTUC. We searched for all relevant articles or conference abstracts published and indexed in PubMed, Embase, and Scopus on July 19, 2021. The study was reported according to the PRISMA criteria and designed within the PICOS framework. We included studies comparing patients with non-metastatic UTUC who received neoadjuvant chemotherapy (NAC) or immunotherapy (NAI) with patients who underwent definitive surgery alone or surgery plus adjuvant systemic therapy. Prospective uncontrolled studies were also included. We identified 27 reports (NAC, N.=24 and NAI, N.=3) published between 2010 and 2021. Twenty of the 24 studies on NAC were retrospective comparative analyses, whereas the remaining four were prospective single-arm studies. One of the three NAI studies exclusively enrolled patients with UTUC. NAC was associated with improved survival and better pathological response relative to surgery alone, but there was no clear advantage when compared to surgery plus adjuvant chemotherapy. Overall, the drug-induced toxicity and risk of disease progression were acceptable but the inherent bias across study designs, inadequate reporting and heterogeneous definition of primary outcomes render it difficult to synthesize results, compare centers, and inform practice. The current level of evidence supporting NAST for UTUC is relatively low and the inability to predict responsiveness and thereby pinpoint the optimal candidates remains a major challenge. There is a need to compare NAST to adjuvant therapies using clearly defined primary endpoints as minimum reporting standards developed by a multidisciplinary team.


Hydrocarbon pollution in the sediment from the Jarzouna-Bizerte coastal area of Tunisia (Mediterranean Sea).
This study investigated the presence and origin of hydrocarbon pollution in industrial waste water sediments found near the Jarzouna (Bizerte, Tunisia) oil refinery. Analyses of surface sediments (layer 1) and deep sediments (layer 2) showed that Total Hydrocarbon (TH) concentrations ranged from 602 +/- 7.638 microg/g in layer-1 to 1270 +/- 2.176 microg/g in layer-2. The results suggest that the deeper the sediment, the higher the level of total hydrocarbon found. The sedimentary Non Aromatic Hydrocarbon (NAH) and Aromatic Hydrocarbon (AH) concentrations ranged from 66.22 +/- 1.516 to 211.82 +/- 10.670 microg/g for NAH, and from 13.84 +/- 0.180 to 115.60 +/- 2.479 microg/g for AH. The high variability of these concentrations was associated with the location of the sediment collection sites. Aliphatic biomarker analysis revealed petroleum contamination close to the refinery rejection site, and biogenic sources further away. Petroleum contamination may be associated with increased industrial activity in the area of Jarzouna-Bizerte in the Mediterranean Sea.


Management of Newly Diagnosed Acute Myeloid Leukemia in the Elderly: Current Strategies and Future Directions.
The incidence of acute myeloid leukemia (AML) increases with age, and the majority of cases occur in adults aged >55 years. The prognosis of AML in older adults is generally poor; however, AML is a heterogeneous disease regardless of age, and prognosis depends on cytogenetic changes, genetic mutations, and patient characteristics. Several lines of evidence support offering treatment to the vast majority of older patients, and the survival benefit associated with this approach generally outweighs the risk of toxicity. Response and long-term survival using intensive induction regimens are significantly lower in older patients, although a small proportion of patients can achieve durable remissions. Selection of patients for intensive induction therapy requires comprehensive assessment of disease characteristics, performance status, and comorbidities. In unfit patients, options for treatment include hypomethylating agents, low-dose ara-C, or consideration of a clinical trial if available. The incorporation of novel therapies into treatment, such as FLT3 inhibitors and antibody-drug conjugates, offers significant promise in older patients, although, thus far, increased responses using novel agents have often not translated to improved survival outcomes. The development of reduced-intensity conditioning regimens and improvements in supportive care has increased the use of allogeneic stem cell transplant (ASCT) in older patients. Selection of patients for ASCT requires an estimation of the trade-off between toxicity and risk of relapse.


Three hundred years of botany in Edinburgh.
This week the tercentenary of the Royal Botanic Garden, Edinburgh, is being celebrated with, among other things, the opening of an exhibition hall given by an anonymous donor. This article traces the fortunes of the Garden during the past three hundred years.


Endoscopic repair of bile leaks after laparoscopic cholecystectomy.
Laparoscopic cholecystectomy has quickly eclipsed open cholecystectomy as the standard approach to symptomatic gallstones and acalculous biliary disease. Procedure-related morbidity and mortality continue to be defined, but a higher incidence of bile duct injuries has been reported to date using present technology and procedure. Key principles in the management of these problems include definition of the anatomy, relief of any impedance to biliary-enteric flow, and drainage of significant extrahepatic fluid collections. A cooperative, multispecialty approach involving surgeons, radiologists, and gastroenterologists is critical to successful outcomes. Future studies will help streamline the management of bile duct injuries and aid physicians in their selection of the best approach for each individual patient.


HIF prolyl-hydroxylase 2 is the key oxygen sensor setting low steady-state levels of HIF-1alpha in normoxia.
Hypoxia-inducible factor (HIF), a transcriptional complex conserved from Caenorhabditis elegans to vertebrates, plays a pivotal role in cellular adaptation to low oxygen availability. In normoxia, the HIF-alpha subunits are targeted for destruction by prolyl hydroxylation, a specific modification that provides recognition for the E3 ubiquitin ligase complex containing the von Hippel-Lindau tumour suppressor protein (pVHL). Three HIF prolyl-hydroxylases (PHD1, 2 and 3) were identified recently in mammals and shown to hydroxylate HIF-alpha subunits. Here we show that specific 'silencing' of PHD2 with short interfering RNAs is sufficient to stabilize and activate HIF-1alpha in normoxia in all the human cells investigated. 'Silencing' of PHD1 and PHD3 has no effect on the stability of HIF-1alpha either in normoxia or upon re-oxygenation of cells briefly exposed to hypoxia. We therefore conclude that, in vivo, PHDs have distinct assigned functions, PHD2 being the critical oxygen sensor setting the low steady-state levels of HIF-1alpha in normoxia. Interestingly, PHD2 is upregulated by hypoxia, providing an HIF-1-dependent auto-regulatory mechanism driven by the oxygen tension.


Biosynthesis of cellulose from Ulva lactuca, manufacture of nanocellulose and its application as antimicrobial polymer.
Green nanotechnology has recently been recognized as a more proper and safer tool for medical applications thanks to its natural reductions with low toxicity and avoidance of injurious chemicals. The macroalgal biomass was used for nanocellulose biosynthesis. Algae are abundant in the environment and have a high content of cellulose. In our study, we extracted parent cellulose from Ulva lactuca where consecutive treatments extracted cellulose to obtain an insoluble fraction rich in cellulose. The extracted cellulose has the same results obtained by matching it with reference cellulose, especially the same Fourier transform infrared (FTIR) and X-Ray diffraction (XRD) analysis peaks. Nanocellulose was synthesized from extracted cellulose with hydrolysis by sulfuric acid. Nanocellulose was examined by Scanning electron microscope (SEM) shown by a slab-like region as Fig. 4a and Energy dispersive X-ray (EDX) to examine the chemical composition. The size of nanocellulose in the range of 50 nm is calculated by XRD analysis. Antibacterial examination of nanocellulose was tested against Gram+ bacteria like Staphylococcus aureus (ATCC6538), Klebsiella pneumonia (ST627), and Gram-negative bacteria such as Escherichia coli (ATCC25922), and coagulase-negative Staphylococci (CoNS) to give 4.06, 4.66, 4.93 and 4.43 cm as respectively. Comparing the antibacterial effect of nanocellulose with some antibiotics and estimating minimal Inhibitory Concentration (MIC) of nanocellulose. We tested the influence of cellulose and nanocellulose on some fungi such as Aspergillus flavus, Candida albicans, and Candida tropicalis. These results demonstrate that nanocellulose could be developed as an excellent solution to these challenges, making nanocellulose extracted from natural algae a very important medical material that is compatible with sustainable development.


Aryl hydrocarbon hydroxylase in persons with lung or laryngeal cancer.
To test whether the distribution of AHH inducibility is shifted toward the high end of the range in patients who had lung and laryngeal cancer, we measured this trait in 59 patients (32 lung and 27 laryngeal) who had resectable tumors and had been disease-free for a period of time. The advantage of selecting patients who were free of clinical disease was that measurement of their AHH inducibility should not have been affected by the disease state. Patient and control populations showed no difference in basal and induced AHH activity of AHH inducibility. The mean AHH inducibility in patients who had lung cancer was 3.20 +/- 0.20; in patients who had laryngeal cancer 2.96 +/- 0.18, and for all controls 3.29 +/- 0.04 (no significant difference at p = 0 05). Further analysis of the distribution of AHH inducibility in the patient group compared to controls showed no suggestion of a shift toward the higher end of the range in patients who had lung and laryngeal cancer.


The accelerated atherogenesis of venous grafts might be attributed to aggravated concentration polarization of low density lipoproteins: a numerical study.
We hypothesize that after implantation the much elevated water filtration rate of venous grafts may cause aggravated concentration polarization of low density lipoproteins (LDLs), in turn lead to the accelerated atherogenesis of the grafts. To verify the hypothesis, we numerically simulated the transport of LDLs in various models of arterial bypasses with different grafts (veins or arteries) and geometrical configurations. The results showed that the venous grafts might endure abnormally high lipid infiltration/accumulation within the vessel wall due to severely elevated luminal surface LDL concentration. When compared to the conventional bypass models, the S-type bypass had the lowest luminal surface LDL concentration along its host artery floor, but the highest degree of risk to develop atherosclerotic lesions in its venous graft. Among the three conventional bypass models, the one with 30° anastomosis had the lowest risk to develop atherosclerosis in the venous graft. In conclusion, when compared with the bypass models with arterial grafts, the venous bypass models had rather high levels of LDL concentration polarization (cw) in the vein grafts, especially at the early stages of implantation. This might result in high infiltration/accumulation of LDLs within the walls of the venous grafts, leading to a fast genesis/development of atherosclerosis there.


Complete pathological response and negative postoperative ctDNA were not predictive of discontinuation of adjuvant crizotinib therapy in a patient with locally advanced MET ex14 skipping mutation-positive non-small cell lung cancer: a case report.
Neoadjuvant targeted therapy is an alternative treatment for locally advanced non-small cell lung cancer (NSCLC) patients with driver gene mutation. MET ex14 mutation is considered a driver gene, and crizotinib is the first oral tyrosine kinase inhibitor (TKI) for metastatic MET ex14 mutation-positive NSCLC patients. Here, we reported a case of a locally advanced NSCLC patient harboring MET ex14 mutation who achieved pathological complete response following neoadjuvant crizotinib therapy but developed rapid metastasis due to discontinuation of short-term postoperative adjuvant crizotinib therapy. Although no driver gene mutation was found via next-generation sequencing (NGS) with blood samples before discontinuation of adjuvant crizotinib, the patient was given crizotinib rechallenge. Fortunately, the patient achieved durable complete response. This suggested that neither pathological complete response nor negative circulating tumor DNA (ctDNA) could be an effective predictor for discontinuation of adjuvant targeted therapy. This case report demonstrated the potential of crizotinib as neoadjuvant therapy in MET ex14 mutation-positive NSCLC patients as well as the importance of long-term postoperative therapy even with negative ctDNA in blood.


Design, synthesis, and biological activity of novel purine and bicyclic pyrimidine factor Xa inhibitors.
The synthesis of amidinoaryloxy 9-benzyl-8-methyl-9H-purine, 7,8-dihydropteridine-6(5H)-one and 5,7-dihydropyrimido[4,5-b][1,4]oxazine-6-one inhibitors of Factor Xa is described. These compounds show nanomolar potency against FXa and maintain high selectivity over thrombin and trypsin.


Efficacy and safety of nab-paclitaxel 125 mg/m2 and nab-paclitaxel 150 mg/m2 compared to paclitaxel in early high-risk breast cancer. Results from the neoadjuvant randomized GeparSepto study (GBG 69).
The GeparSepto study demonstrated that the use of nab-paclitaxel instead of paclitaxel prior to anthracycline-based chemotherapy could lead to a significantly increased pCR rate, especially in the triple negative subpopulation. We report efficacy and safety for patients treated with two different doses of nab-paclitaxel in comparison to weekly solvent-formulated paclitaxel. Patients were treated for 12 weeks with either intravenous nab-paclitaxel 150 mg/m2 (nP150) weekly, after study amendment 125 mg/m2 (nP125) weekly or solvent-based paclitaxel 80 mg/m2 (P80) weekly followed by epirubicin 90 mg/m2 and cyclophosphamide 600 mg/m2 on day 1 for four 3-week cycles. 229 patients received nP150, 377 nP125. Baseline characteristics were fairly balanced between these two sequential cohorts as well as compared to 601 patients receiving P80 except for hormone receptor status, HER2 status, and Ki67. Taxane treatment was discontinued in 26.8% (nP150), 16.6% (nP125), and 13.3% of (P80) patients, respectively. Median relative total dose intensity (mRTDI) based on 125 mg/m2 for nP was 103% with nP150, 95% with nP125, 99% with P80 before and 98% with P80 after the amendment. PSN grade 3-4 was observed in 14.5% of patients with nP150, 8.1% of patients with nP125 (p = 0.018), and 2.7% of patients with P80. Overall pCR before the amendment was 33.6% after nP150 and 23.5% after P80 (OR 1.65 [95% CI 1.10-2.50]; p = 0.022); pCR after the amendment was 41.4% after nP125, and 32.4% after P80 (1.48 [95% CI 1.10-1.99]; p = 0.013). Nab-paclitaxel 125 mg/m2 was associated with a better safety profile and compliance without compromising the efficacy compared to nab-paclitaxel 150 mg/m2.


The application of the Palliative Prognostic Index, charlson comorbidity index, and Glasgow Prognostic Score in predicting the life expectancy of patients with hematologic malignancies under palliative care.
The clinical course for hematologic malignancy varies widely and no prognostic tool is available for patients with a hematologic malignancy under palliative care. To assess the application of the Palliative Prognostic Index (PPI), Charlson Comorbidity Index (CCI), and Glasgow Prognostic Score (GPS) as prognostic tools in patients with hematologic malignancies under palliative care. We included 217 patients with pathologically proven hematologic malignancies under palliative care consultation service (PCCS) between January 2006 and December 2012 at a single medical center in Taiwan. Patients were categorized into subgroups by PPI, CCI, and GPS for survival analysis. The median survival was 16 days (interquartile range, 4-47.5 days) for all patients and 204 patients (94%) died within 180 days after PCCS. There was a significant difference in survival among patients categorized using the PPI (median survival 49, 15, and 7 days in patients categorized into a good, intermittent, and poor prognostic group, respectively) and the GPS (median survival 66 and 13 days for GPS 0 and 1, respectively). There was no difference in survival between patients with a GPS score of 0 versus 2, or a CCI score of 0 versus ≥1. The survival time was significantly discriminated after stratifying patients with a good PPI score based on the CCI (median survival 102 and 41 days in patients with a CCI score of 0 and ≥1, respectively) from those with a poor PPI score by using the GPS (median survival 47 and 7 days in patients with GPS scores of 0 and 1-2, respectively). PPI is a useful prognosticator of life expectancy in terminally ill patients under palliative care for a hematologic malignancy. Concurrent use of the GPS and CCI improved the accuracy of prognostication using the PPI.


Mexctenapseudes boeschi, a new tanaidacean genus and species (Crustacea: Peracarida: Apseudomorpha: Parapseudidae) from the Mexican coast of Campeche with the designation of a new related Australian genus to receive Longiflagrum caeruleus (Boesch, 1973).
Two new genera of parapseudid Tanaidacea belonging to the Discapseudes-Halmyrapseudes Complex sensu Heard et al. (=Complex) are designated from Mexican and Australian waters. Mexctenapseudes boeschi n. gen., n. sp. is described from Campeche Mexico and Pseudolongiflagrum n. gen. is designated from Australia. The new Mexican genus displays similarities to the West Pacific and Indian Ocean genera Ctenapseudes Bamber, Ariyananda Silva, 1997 and Longiflagrum Guu, 1995. The new related genus, Pseudolongiflagrum, having affinities with Ctenapseudes and Mexctenapseudes n. gen., is designated to receive Longiflagrum caeruleus (Boesch) known from Australia. A key to the genera within the parapseudid subfamily Parapseudinae Guu is presented and possible factors concerning the ecology, origins, and distribution of the members of the Complex considered.


High efficiency production of germ-line transgenic Japanese medaka (Oryzias latipes) by electroporation with direct current-shifted radio frequency pulses.
Although there have been several studies showing the production of transgenic fish through electroporation techniques, success rates have been low and few studies show germ-line integration and expression. When electroporation has been successful, the device used is no longer commercially available. The goal of this experiment was to find an alternative efficient method of generating transgenic Japanese medaka (Oryzias latipes) using a commercially available electroporation device. The Gene Pulser II and RF module (Bio-Rad Laboratories, USA), along with two reporter gene constructs, were used. In contrast to other electroporation devices, which are based on a single pulse with exponential decay or square wave technology, the Gene Pulser II incorporates a direct current (DC)-shifted radio frequency (RF) signal. With this technique, over 1000 embryos can be electroporated in less than 30 min. The plasmid pCMV-SPORT-beta-gal (Invitrogen, USA) was used in the supercoiled form to optimize parameters for gene transfer into single-celled embryos, and resulted in up to 100% somatic gene transfer. Similar conditions were used to generate fish transgenic for both the pCMV-EGFP plasmid (Clontech, USA) and a cytomegalovirus (CMV) driven phytase-EGFP construct. The conditions used were a voltage of 25 V, a percent modulation of 100%, a radio frequency of 35 kHz, a burst duration of 10 ms, 3 bursts, and a burst interval of 1.0 s. Seventy percent of the embryos electroporated with the pCMV-EGFP construct survived to sexual maturity, and of those, 85% were capable of passing the transgene on to their offspring. Transgenic second generation back-crossed (BC2) fry were subjected to Southern blot analysis, which confirmed germ-line integration, and observation for green fluorescence protein, which confirmed protein expression. DC-shifted RF pulses are effective and efficient in the production of transgenic medaka, and germ-line integration and expression can be achieved without linearization of the transgene vector.


Detrimental effects of high-dose gonadotropin on outcome of IVF: making a case for gentle ovarian stimulation strategies.
Limited data identify detrimental influences of aggressive use of gonadotropins (G) for controlled ovarian hyperstimulation (COH); the underlying mechanisms however remain unclear. We report on the relationship between G dose and in vitro fertilization (IVF) cycle parameters (ovarian response, endometrial thickness [EMT]) and cycle outcome (implantation rate [IR] and clinical pregnancy [CP] rate) in a cohort of women undergoing IVF. Retrospective analysis of fresh embryo transfer (ET) cycles. Univariate and multivariable regression analyses assessed relationship between G dose and outcomes of interest. Higher G dose related positively with advancing age (P < .001) and inversely with EMT (P < .001). The overall CP rate was 30%. Significantly lower IR (.003) and CP rate (.002) were observed across increasing tertiles of G dose. Increasing G dose was identified as an independent negative predictor of EMT after adjusting for age, COH protocol and duration, infertility diagnosis, and ovarian response (P = .016). Adjusting for age, suppression protocol (gonadotropin-releasing hormone agonist vs antagonist), infertility diagnoses, EMT, quality, and cleavage of ET, lower G dose was an independent positive predictor of CP rate (odds ratio for CP rate was 1.57 for G dose in middle compared to the highest G dose quartile (95% confidence interval 1.09-2.24). Stratified analyses identified detrimental associations of higher G dose with CP rate to be relevant in women aged 35 years and younger. Our analyses suggest detrimental influences of higher G dose on the endometrium and confirm the previously reported adverse association between higher G dose and IVF outcome. Gentler COH regimens may be of particular benefit in women aged ≤35 years.


Comparative analysis of whole-blood interferon-γ and flow cytometry assays for detecting post-treatment immune responses in patients with active tuberculosis.
Intracellular cytokine flow cytometry (ICCFC) has been explored to detect tuberculosis (TB) infections; however, there are little data regarding its use to examine the dynamic responses of Mycobacterium tuberculosis (MTB)-specific T-cells after anti-tuberculous therapy. The aim of this study was to analyze both dynamic changes in functional MTB antigen-specific T-cell subsets and interferon-gamma (IFN-γ) levels using ICCFC and the QuantiFERON-TB Gold In-Tube (QFT-IT) test, respectively, following anti-tuberculous treatment in patients with active TB. Twenty-six patients with active TB were enrolled in the study, and QFT-IT and ICCFC were performed simultaneously both before and after treatment. IFN-γ levels (QFT-IT test) and the numbers of IFN-γ- or tumor necrosis factor-alpha (TNF-α)-expressing T-cells (ICCFC assay) were examined after stimulation with MTB antigen. There was no significant reduction in the mean IFN-γ concentrations measured by the QFT-IT test after anti-tuberculous treatment (P = 0.314). ICCFC analysis showed that the numbers of IFN-γ(+) /CD4(-) T-cells, and CD4(+) T-cells producing TNF-α, either alone or in combination with IFN-γ, were significantly reduced after anti-tuberculous treatment. The IFN-γ(+) /TNF-α(+) /CD4(+) T-cell subset showed the greatest difference between untreated and treated patients with active TB (area under the curve = 0.734, P = 0.004). Unlike the QFT-IT test, ICCFC provides diverse immunological information about dynamic changes in the number of MTB antigen-specific T-cells following anti-tuberculous therapy. Thus, analysis of MTB antigen-stimulated T-cell responses using ICCFC might have a role to play in monitoring treatment responses in patients with active TB.


Acculturation level and change in cigarette consumption behaviors among diverse Hispanics/Latinos: the Hispanic Community Health Study/Study of Latinos.
To study associations between language acculturation level and changes in cigarette consumption among the diverse and growing U.S.-based Hispanic/Latino population and inform culturally tailored smoking prevention and cessation strategies. In the Hispanic Community Health Survey/Study of Latinos cohort, we used cigarette consumption behaviors at baseline (2008-2011) and follow-up (2014-2017) and a modified Short Acculturation Scale for Hispanics (SASH) language subscale to measure associations of language acculturation (unidimensional) with changes in cigarette consumption and quitting rates. Weighted multivariable linear and logistic regressions were stratified by daily (n = 1397) and nondaily (n = 633) smoking, and either sex, educational attainment, or migration status. Smokers at baseline (n = 2030) on average were aged 42 years old (SE = 0.5) with a mean SASH-language score of 2.3 (SE = 0.1; range = 1-5), indicating more Spanish language use. Among male daily smokers, we observed increases in smoked cigarettes-per-day (CPD) with unit increases in SASH-language score (1.08, 95% CI: 0.24-1.92). Associations with acculturation trended toward greater increases in CPD and lower odds of quitting as educational attainment increased. Language acculturation level is an important determinant for increased smoking behaviors, particularly among men. Our findings are significant in informing smoking reduction programs for the Hispanic/Latino population.


How does artificial intelligence development affect green technology innovation in China? Evidence from dynamic panel data analysis.
As the global climate problem becomes increasingly serious, the green technology innovation to achieve "carbon peak and carbon neutral" has gradually become the global consensus of major countries, and how the rapid development of artificial intelligence (AI) technology affects green technology innovation (GTI) has received a great deal of attention in the field of economics. Therefore, based on China's inter-provincial panel data from 2006 to 2019, the system GMM, dynamic panel threshold model, and quantile regression model were constructed to examine various influences of AI development on GTI under different environmental regulation intensity, research and development (R&D) investment, and institutional environmental threshold conditions. The findings presented that AI development significantly contributes to GTI and GTFP, with an impact coefficient of 0.0122 and 0.0084, and this influence is mainly reflected in the western region of China and is more obvious in the 2006-2012 period. AI development mainly enhances green technological efficiency, and it has dampening effects on green technological progress during the period 2013-2019. Additionally, there are non-linear threshold effects in the relationship between the level of AI development and GTI when environmental regulatory intensity, R&D investment, and institutional environment are in different level intervals. AI development will boost GTI only when the intensity of environmental regulation and institutional environment is above a certain threshold value. However, the AI development represented by industrial robot applications still has no obvious effect on GTI even when the R&D investment exceeds a certain threshold. Furthermore, the growth effect of AI development on GTI indicates a decreasing nonlinear pattern as the GTI's quantile rises under the condition that R&D investment and institutional environment intensity cross the threshold, while this growth effect increases gradually with the rise of GTI's quantile when the environmental regulation is above the threshold.


Nerve-sparing radical hysterectomy for cervical carcinoma.
With the concept of the improvement of quality of life in the field of surgical oncology, recent studies have questioned the place of radical hysterectomy (RH) in the treatment of cervical carcinoma due to a high rate of long-term postoperative complications involving the pelvic autonomic nerve system. It has been demonstrated that RH frequently causes bladder dysfunction, anorectal mobility disorders, and sexual dissatisfaction in cervical cancer survivors due to surgical trauma involving the sympathetic and parasympathetic branches of the autonomous innervation of the pelvic organs. Nerve-sparing RH was first pioneered by Takashi Kobayashi in Japan and then other Japanese gynecologic surgeons introduced and improved this concept to Western countries. However, nerve-sparing RH has only become popular among gynecologic surgeons during the last two decades. Recently, European gynecologic surgeons modified this concept. Herein, a review of the evolution of nerve-sparing RH, a quick overview of long-term pelvic organ dysfunctions associated with RH, and the technical details of different authors and their oncological outcomes are presented. Today, the lack of randomized studies comparing the effectiveness and complications of RH with nerve-sparing RH is an important barrier to the widespread use of this concept. Nonetheless, while nerve-sparing RH still awaits prospective randomized trials in order to prove that its effectiveness is equal to or greater than that of conventional treatment modalities, and that is has fewer long-term complications, this surgical approach remains attractive for the patients and gynecologic oncologists based on the published results.


Evidence for and against the Naples high- and low-excitability rats as genetic model to study hippocampal functions.
The Naples high- (NHE) and low-excitability (NLE) are two rat lines, selectively bred for high and low activity levels in a Làt-maze, respectively. Because the activity level in a novel environment depends mainly on the integrity of the hippocampal formation, and NLE and NHE rats differ with a similar background of emotionality, arterial blood pressure, and learning ability, they have been proposed as animal model to study hippocampal functions. Our aim is to prove evidence in favor and against this hypothesis. The evidence in favor indicates that NLE/NHE rats have a defective spatial processing, and pertains to (a) Differential activity in a spatial novelty situation (selection trait), proportional to the stimulus complexity rats are exposed to (NHE are hyper- and NLE-rats hypoactive); and (b) Impaired working memory in a six-arm non-reinforced tunnel maze in both lines compared to random-bred rats, that was reversed by the introduction of a reinforcer. In addition, multiple evidence of (i) lower intra- + infrapyramidal mossy fiber terminals in both NLE/NHE vs. controls; (ii) increased sensitivity of hippocampal elements to microinjections of vasopressin (but not oxytocin) and of "delta" (but not "mu") opioids; (iii) lower number of high-affinity glucocorticoid receptors; (iv) lower number of alpha- but not beta-adrenergic receptors in the hippocampus and hypothalamus of NHE rats only; and (v) the genotype-dependent behavior of a DNA fraction with fast turnover, suggest that both NHE/NLE are "disintegrated" at the hippocampal interface. Further, neurobehavioral covariations among individual differences reveal nonlinear, complex relationships, an evidence apparently against the hypothesis.(ABSTRACT TRUNCATED AT 250 WORDS)


Electroformation of giant unilamellar vesicles from erythrocyte membranes under low-salt conditions.
Giant unilamellar vesicles (GUVs) are an attractive experimental model for studying various membrane-related phenomena. The procedure for GUV electroformation from erythrocyte ghosts under physiological conditions was introduced recently; however, it allows preparation of a limited number of GUVs. Here we describe an efficient, reliable, and simple method for electroformation of GUVs from native erythrocyte membranes at low salt concentration, which enables the formation of higher amounts of large, spherical GUVs. GUVs prepared according to the new procedure may not retain original lipid asymmetry; however, they preserved native proteins, lipids, and oligosaccharide heterogeneity and could be a suitable system for functional studies for which larger amounts of GUVs of complex composition are needed.


Corneal endothelial cell changes after Ahmed valve and Molteno glaucoma implants.
Changes in corneal endothelial cell (CEC) indices 24 months after Ahmed valve (New World Medical, Inc., Rancho Cucamonga, CA) and single-plate Molteno implants (Molteno Ophthalmic Limited, Dunedin, New Zealand) were evaluated. This cohort included Ahmed valve (29 eyes) or single-plate Molteno (28 eyes) implants. Preoperative and postoperative central CEC indices were compared. Main outcome measure was endothelial cell count. Twenty-four months postoperatively, no difference in visual acuity improvement or decrease in antiglaucoma medications was observed between groups. The Molteno group showed better postoperative intraocular pressure control (P < .001). An 11.52% (Ahmed) and 12.37% (Molteno) reduction in CEC density (cells/mm(2)) and 3.78 (Ahmed) and 2.48 (Molteno) increase in CEC area (mm(2)) was observed, but no significant between-group difference in CEC density and area or corneal thickness. Twenty-four months after Ahmed valve or Molteno implant, statistically significant quantitative (cell density) and minor qualitative (cell area) changes in central CEC were observed. Both groups appeared to have similar CEC damage.


The temperature dependence of molecular order and the influence of cholesterol in Acholeplasma laidlawii membranes.
2H nuclear magnetic resonance (NMR) of Acholesplasma laidlawii membranes grown on a medium supplemented with perdeuterated palmitic acid shows that at 42 degrees C or above, the membrane lipids are entirely in a fluid state, exhibiting the characteristic 'plateau' in the variation of deuterium quadrupolar splitting with chain position. Between 42 and 34 degrees C there is a well-defined gel-to-fluid phase transition encompassing the growth temperature of 37 degrees C, and at lower temperatures the membranes are in a highly ordered gel state. The 2H-NMR spectra of the gel phase membranes are similar to those of multilamellar dispersions of chain perdeuterated dipalmitoyl phosphatidylcholine (Davis, J.H. (1979) Biophys. J. 27, 339) as are the temperature dependences of the spectra and their moments. The incorporation of large amounts of cholesterol into the membrane removes the gel to fluid phase transition. Between 20 and 42 degrees C, the position dependence of the orientational order of the hydrocarbon chains of the membranes is similar to that of the fluid phase of the membranes without cholesterol, i.e., they exhibit the plateau in the deuterium quadrupolar splittings. However, the cholesterol-containing membranes have a higher average order, with the increases in order being greater for positions near the carbonyl group of the acyl chains. Below 20 degrees C the 2H spectra of the membranes containing cholesterol change dramatically in a fashion suggestive of complex motional and/or phase behaviour.


Voltage-Gated Sodium Channel NaV1.7 Inhibitors with Potent Anticancer Activities in Medullary Thyroid Cancer Cells.
Our results from quantitative RT-PCR, Western blotting, immunohistochemistry, and the tissue microarray of medullary thyroid cancer (MTC) cell lines and patient specimens confirm that VGSC subtype NaV1.7 is uniquely expressed in aggressive MTC and not expressed in normal thyroid cells and tissues. We establish the druggability of NaV1.7 in MTC by identifying a novel inhibitor (SV188) and investigate its mode of binding and ability to inhibit INa current in NaV1.7. The whole-cell patch-clamp studies of the SV188 in the NaV1.7 channels expressed in HEK-293 cells show that SV188 inhibited the INa current in NaV1.7 with an IC50 value of 3.6 µM by a voltage- and use-dependent blockade mechanism, and the maximum inhibitory effect is observed when the channel is open. SV188 inhibited the viability of MTC cell lines, MZ-CRC-1 and TT, with IC50 values of 8.47 μM and 9.32 μM, respectively, and significantly inhibited the invasion of MZ-CRC-1 cells by 35% and 52% at 3 μM and 6 μM, respectively. In contrast, SV188 had no effect on the invasion of TT cells derived from primary tumor, which have lower basal expression of NaV1.7. In addition, SV188 at 3 μM significantly inhibited the migration of MZ-CRC-1 and TT cells by 27% and 57%, respectively.


[Difficulties in interpreting a conspicuous retroperitoneal hematoma due to rupture of the inferior pancreatico-duodenal vessels at the onset of edematous-type acute pancreatitis].
The authors report on a case of conspicuous retroperitoneal haematoma with haemoperitoneum due to rupture of the lower pancreatico-duodenal vessels appearing at onset of an acute oedematous pancreatitis. After stressing the rarity of this event, the authors go on to discuss a number of aetiopathogenetic, diagnostic and therapeutic aspects.


Healthy myeloid-derived suppressor cells express the surface ectoenzyme Vanin-2 (VNN2).
Study of human monocytic Myeloid-Derived Suppressor cells Mo-MDSC (CD14+ HLA-DRneg/low) has been hampered by the lack of positive cell-surface markers. In order to identify positive markers for Mo-MDSC, we performed microarray analysis comparing Mo-MDSC cells from healthy subjects versus CD14+ HLA-DRhigh monocytes. We have identified the surface ectoenzyme Vanin-2(VNN2) protein as a novel biomarker highly-enriched in healthy subjects Mo-MDSC. Indeed, healthy subjects Mo-MDSC cells expressed 68 % VNN2, whereas only 9% VNN2 expression was observed on CD14+ HLA-DRhigh cells (n = 4 p < 0.01). The top 10 percent positive VNN2 monocytes expressed CD33 and CD11b while being negative for HLA-DR, CD3, CD15, CD19 and CD56, consistent with a Mo-MDSC phenotype. CD14+VNN2high monocytes were able to inhibit CD8 T cell proliferation comparably to traditional Mo-MDSC at 51 % and 48 % respectively. However, VNN2 expression on CD14+ monocytes from glioma patients was inversely correlated to their grade. CD14+VNN2high monocytes thus appear to mark a monocytic population similar to Mo-MDSC only in healthy subjects, which may be useful for tumor diagnoses.


Comparative investigations of various modification methods on the gelling, rheological properties and mechanism of fish gelatin.
In this study, κ-carrageenan(κC) and Transglutaminase (TG) were used to modify fish gelatin (FG). Three types of modified gelatin groups FG-κC, FG-TG and FG-κC-TG were prepared. The results showed that the gel strength and textural properties of FG gels were greatly enhanced by κC modification and κC-TG complex modification, whilst pure TG modification weakened the gelling properties. And the pure 0.1 % κC modified FG had the highest gel strength and hardness, respectively. Rheological behavior showed that the complex modified FG samples had the highest viscosity, gelling points, melting points and G'∞. Fourier infrared spectra and LF-NMR analysis showed that κC and κC-TG modification respectively improved the contents of hydrogen and isopeptide that decreased the water mobility but stabilized the helical structure of gelatin gels. Fluorescence intensity showed that three types of modification decreased fluorescence intensity. While, the formation of aggregates and denser gel networks decreased in vitro digestibility of FG.