A physical map of the genome of Atlantic salmon, Salmo salar.
A physical map of the Atlantic salmon (Salmo salar) genome was generated based on HindIII fingerprints of a publicly available BAC (bacterial artificial chromosome) library constructed from DNA isolated from a Norwegian male. Approximately 11.5 haploid genome equivalents (185,938 clones) were successfully fingerprinted. Contigs were first assembled via FPC using high-stringency (1e-16), and then end-to-end joins yielded 4354 contigs and 37,285 singletons. The accuracy of the contig assembly was verified by hybridization and PCR analysis using genetic markers. A subset of the BACs in the library contained few or no HindIII recognition sites in their insert DNA. BglI digestion fragment patterns of these BACs allowed us to identify three classes: (1) BACs containing histone genes, (2) BACs containing rDNA-repeating units, and (3) those that do not have BglI recognition sites. End-sequence analysis of selected BACs representing these three classes confirmed the identification of the first two classes and suggested that the third class contained highly repetitive DNA corresponding to tRNAs and related sequences.


Impact of a multi-strain probiotic administration on peri-rectal colonization with drug-resistant Gram-negative bacteria in preterm neonates.
Infections caused by drug resistant Gram-negative bacteria (DR-GNB) are a major health concern for hospitalized preterm neonates, globally. The aim of this study was to investigate the effect of a multi-strain probiotic on the incidence of rectal colonization with DR-GNB in preterm neonates. A double-blind, placebo-controlled, randomized clinical trial was conducted including 200 neonates, randomly allocated to a multi-strain probiotic (n = 100) or placebo (n = 100). Fifteen percent of the neonates showed peri-rectal colonization with DR-GNB on the day of enrolment indicating probable maternal-to-neonate (vertical) bacterial transmission or environmental acquisition at time of delivery, with no difference between groups. Acquisition of further DR-GNB colonization was rapid, with an increase from 15% on the day enrolment to 77% by day 7 and 83% by day 14 of life. By day 7 (corresponding to early gut colonization), neonates in the probiotic group were 57% less likely to have peri-rectal DR-GNB colonization [OR: 0.43 (0.20-0.95); p = 0.04] and by day 14 (corresponding to late gut colonization), neonates in the probiotic group were 93% less likely to have peri-rectal DR-GNB colonization [OR: 0.07 (0.02-0.23); p < 0.001]. Hospitalized neonates showed substantial peri-rectal colonization with DR-GNB at enrolment and further rapid acquisition of DR-GNB in the first 2 weeks of life. The use of a multi-strain probiotic was effective in reducing early and late neonatal gut colonization with DR-GNB. The trial was registered at the Pan African Clinical Trial Registry (PACTR202011513390736).


Sustainable production of biopesticides for common bean root rot control within the biorefinery approach: a Technology Readiness Level 3 experimental proof of concept.
Biopesticides are recognized as an efficient alternative to synthetic pesticides for pest and disease crop management. However, their commercial production processes use grains, generating large amounts of organic waste, even when agriculture waste or byproducts are the feedstock of choice. Frequently, these organic wastes are rich in nutrients that, after adequate treatment, can be used as nitrogen and carbohydrate sources for secondary metabolite production produced by microorganisms during submerged fermentation. In this sense, this study aimed to prove the concept that biopesticides could be produced under a full biorefinery process, using the entire biomass of an underexplored agroindustrial waste-damaged bean-as the main feedstock. A combination of sequential processes, including solid state fermentation, hydrolysis, and submerged fermentation, were designed for the production of two biopesticides (conventional-fungal conidia and second-generation secondary metabolite-cerulenin) from a high potential biological control agent strain Sarocladium oryzae BRM 59907. The combined processes, using damaged common bean grain as the main feedstock, provided biopesticides and organic fertilizer production that successfully controlled common bean root rot disease. This work proved to be possible the biopesticide production using a full biorefinery concept, inside the same productive chain, contributing to a sustainable environment and economy, together with animal and human health safety.


In-vitro and in-vivo assessment of the anti-diabetic, analgesic, and anti-inflammatory potenstials of metal-based carboxylates derivative.
In the current research work, an amide based metal carboxylate chemical ([((5-((5-(2-hydroxyethyl)-4-methylthiazol-3-ium-3-yl)methyl)-2-methylpyrimidin-4-yl)amino)bis((4-((4-methoxy-2-nitrophenyl)amino)-4-oxobutanoyl)oxy)zinc]) was identified as anti-diabetic analgesic and anti-inflammatory. The identified chemical(MT-1) was tested for acute toxicity (the MT-1 was fund safe), antidiabetic analgesic, and anti-inflammatory potentials. The in-vitro study was conducted for antidiabetic enzyme inhibition (α-amylase and α-glucosidase) and the in-vivo studies included analgesic (acetic acid-induced writing and hot plate model) and anti-inflammatory (carrageenan etc induced edema) effects. The tested compound showed 88.63% (IC50 = 3.23 μg/ml) and 89.10%(IC50 = 5.10 μg/ml) againstα-amylase and α-glucosidase respectively. A significant (p < 0.001) analgesic effect was noted by MT-1 in acetic acid-induced animal models with a percent effect of 86.00, 60.,06, and 55.29 at the tested doses of 20, 1,0, and 5 mg/kg respectively. In the case of the hot plate model, the MT-1 showed a significant (p < 0.001) effect with maximum percent prolongation in latency observed after 60 min.08, 22.2,9, and 11.61) against 20, 1,0, and 5 mg/kg. The analgesic effect in the hot plate model was significantly (p < 0.01) reversed by the injection of naloxone (0.125 mg/kg). The paw edema induced by carrageenan, histamine, bradykinin, arachidonic acid, and PGE2 was significantly antagonized with percent attenuation of 34.09, 33.57, 34.60, 34.14, and 48.04 respectively. Furthermore, to predict the interactions between the MT-1 compound and COX-2 molecular docking was carried out and the result was compared with the standard compound. The docking score of MT-1 was predicted as -6.30 while that of Diclofenac was predicted as -6.82. Both compounds made several hydrogen bond interactions with the active site of the COX-2 enzyme. The docking study revealed the potent inhibitory potential of the compound MT-1 against the COX-2 receptor.


αVβ3 Integrin regulates astrocyte reactivity.
Neuroinflammation involves cytokine release, astrocyte reactivity and migration. Neuronal Thy-1 promotes DITNC1 astrocyte migration by engaging αVβ3 Integrin and Syndecan-4. Primary astrocytes express low levels of these receptors and are unresponsive to Thy-1; thus, inflammation and astrocyte reactivity might be necessary for Thy-1-induced responses. Wild-type rat astrocytes (TNF-activated) or from human SOD1G93A transgenic mice (a neurodegenerative disease model) were used to evaluate cell migration, Thy-1 receptor levels, signaling molecules, and reactivity markers. Thy-1 induced astrocyte migration only after TNF priming. Increased expression of αVβ3 Integrin, Syndecan-4, P2X7R, Pannexin-1, Connexin-43, GFAP, and iNOS were observed in TNF-treated astrocytes. Silencing of β3 Integrin prior to TNF treatment prevented Thy-1-induced migration, while β3 Integrin over-expression was sufficient to induce astrocyte reactivity and allow Thy-1-induced migration. Finally, hSOD1G93A astrocytes behave as TNF-treated astrocytes since they were reactive and responsive to Thy-1. Therefore, inflammation induces expression of αVβ3 Integrin and other proteins, astrocyte reactivity, and Thy-1 responsiveness. Importantly, ectopic control of β3 Integrin levels modulates these responses regardless of inflammation.


Generating barcoded libraries for multiplex high-throughput sequencing.
Molecular barcoding is an essential tool to use the high throughput of next generation sequencing platforms optimally in studies involving more than one sample. Various barcoding strategies allow for the incorporation of short recognition sequences (barcodes) into sequencing libraries, either by ligation or polymerase chain reaction (PCR). Here, we present two approaches optimized for generating barcoded sequencing libraries from low copy number extracts and amplification products typical of ancient DNA studies.


[Effects of EDTA on (Na+-K+) ATPase bound to human erythrocyte membranes].
Membranes preincubation with high EDTA concentration induced an alteration on (Na"-K+) ATPase kinetic behaviour. This effect can be related to a change in calcium content tightly bound to the membranes.


Induction of tolerance to non-H-2 alloantigens is not restricted by the MHC molecules expressed on the donor cells in cyclophosphamide-induced tolerance.
A long-lasting skin tolerance to non-H-2 alloantigens has been reported to be readily induced, when the recipient mice were primed intravenously (i.v.) with 5 x 10(7) spleen cells (SC) plus 1.5 x 10(7) bone marrow cells (BMC) from the H-2 identical strains of mice, and treated intraperitoneally (i.p.) with 200 mg/kg CP 2 days later. The present study was conducted in order to clarify whether or not tolerance induction to non-H-2 alloantigens in cyclophosphamide (CP)-induced tolerance is restricted by H-2 alloantigens on donor cells. When BALB/c (BALB; H-2d) female mice were primed i.v. with fully allogeneic [H-2 plus minor histocompatibility (H) antigen-disparate C57BL/10 (B10; H-2b) female SC plus BMC and treated i.p. with CP 2 days later, the survival of H-2 identical B10.D2 nSnSlc (B10.D2; H-2d) female skin was moderately prolonged, but the survival of fully allogeneic B10 female skin was not. When semiallogeneic (B10 x B10.D2) (H-2bxd) female cells or H-2 identical B10.D2 female cells were used as the tolerogen, the survival of B10.D2 female skin was prolonged moderately or permanently, respectively. There was no significant difference between the prolongations of B10.D2 female skin graft survival in the BALB mice treated with the B10 cells followed by CP, and the (B10 x B10.D2) cells followed by CP. Similar results were observed in H-Y antigen-disparate combinations. These results strongly suggest that tolerance induction to non-H-2 alloantigens is not restricted by the products of donor MHC in CP-induced tolerance.


Polyacrylamide gel as a medium for DNA dissociation and reassociation.
Several properties of thermal denaturation and renaturation of DNA in polyacrylamide gels were investigated: (1) Following electrophoresis the DNA band was scanned and shown to increase in absorbance with increasing temperature. The increase was proportioned to DNA concentration across the peak. (2) The dependence of the Tm on salt concentration over a hundred fold range was similar to that found for DNA in free solution. (3) Denaturation of several DNA samples ranging in G + C content from 26 to 71% was compared in gels and free solution. The relationship between Tm and % G + C was virtually identical for both sets of DNAs. (4) The kinetics of DNA renaturation in the gel was followed. Reassociation of bacteriophage T4 DNA was 2nd order and proceeded more rapidly in polyacrylamide gels than in free solution.


Pneumococcal Vaccination in Children: A Systematic Review and Meta-Analysis of Cost-Effectiveness Studies.
Pneumococcal conjugate vaccines (PCVs) have significantly reduced disease burden caused by Streptococcus pneumoniae, a leading cause of childhood morbidity and mortality globally. This systematic review and meta-analysis aimed to assess the incremental net benefit (INB) of the 13-valent PCV (PCV13) and 10-valent PCV (PCV10) in children. We performed a comprehensive search in several databases published before May 2022. Studies were included if they were cost-effectiveness or cost-utility analyses of PCV13 or PCV10 compared with no vaccination or with each other in children. Various monetary units were converted to purchasing power parity, adjusted to 2021 US dollars. The INBs were calculated and then pooled across studies stratified by country income level, perspective, and consideration of herd effects, using a random-effect model. Seventy studies were included. When herd effects were considered, PCV13 was cost-effective compared with PCV10 from the payer perspective in both high-income countries (HICs) (INB, $103.94; 95% confidence interval, $75.28-$132.60) and low- and middle-income countries (LMICs) (INB, $53.49; 95% confidence interval, $30.42-$76.55) with statistical significance. These findings were robust across a series of sensitivity analyses. PCV13 was cost-effective compared with no vaccination across perspectives and consideration of herd effects in both HICs and LMICs, whereas findings were less consistent for PCV10. PCVs were generally cost-effective compared with no vaccination in HICs and LMICs. Our study found that PCV13 was cost-effective compared with PCV10 when herd effects were considered from the payer perspective in both HICs and LMICs. The results are sensitive to the consideration of herd effects.


The Changes in 1H-MRS Metabolites in Cuprizone-Induced Model of Multiple Sclerosis: Effects of Prior Psychological Stress.
Stress is considered as an important risk factor in the progression and the onset of many disorders such as multiple sclerosis. However, metabolite changes as a result of demyelination under the detrimental effects of stress are not well understood. Thus, 36 female Wistar rats (i.e., groups (1) no-cuprizone (Cont), (2) no-stress + cuprizone-treated (Cup), (3) physical stress + cuprizone-treated (P-Cup), (4) psychological stress + cuprizone-treated (Psy-Cup), (5) physical stress + no-cuprizone-treated (P), (6) psychological stress + no-cuprizone-treated (Psy)) were used in this study. Following induction of repetitive stress, cuprizone treatment was carried out for 6 weeks to instigate demyelination in all groups except the control animal. Relative metabolite concentrations of the brain were investigated by single-voxel proton magnetic resonance spectroscopy (reporting N-acetyl-aspartate (NAA), glycerophosphocholine with phosphocholine (tCho) relative to total creatine (tCr)). According to 1H-MRS, rats in the Cup group indicated a reduction in NAA/ tCr (p < 0.001) as well as tCho/ tCr (p < 0.05) compared with that in the Cont group. In contrast, in both stress + cuprizone-treated groups, NAA/tCr and tCho/tCr ratios remarkably increased versus the Cup group (p < 0.001) and the Cont group (p < 0.001 for the Psy-Cup group and p < 0.05 for the P-Cup group). Both P and Psy groups revealed normal metabolite concentrations similar to the Cont group 6 weeks post stress. Seemingly, in the case of cuprizone alone, decreased level of metabolites is mainly relevant to neuronal cell impairments. Meanwhile, as a result of oxidative stress enhancement due to stress exposure, oligodendrocyte becomes the main victim indicating the increased level of metabolite ratios.


Undifferentiated shock in a cirrhotic patient: Ascites matters.
In cirrhotic patients with undifferentiated shock, early CT with emphasis in ascitic fluid density should be performed to exclude rare causes of shock such as secondary peritonitis or hemoperitoneum.


EMX homeobox genes regulate microphthalmia and alter melanocyte biology.
Melanocytes are specialized cells that produce melanin, the pigment responsible for skin, hair and retina color. They derive during embryogenesis from the precursor cells melanoblasts, which are neural crest cells committed to the pigment cell lineage. The differentiation of melanoblasts into melanocytes involves the expression of melanocyte-specific genes, particularly those responsible for melanin production, such as Tyr, Tyrp-1 and Dct, the expression of which depends on the melanocyte-specific transcription factor microphthalmia (Mitf). We have developed and executed a functional screen on melanocytes, with the aim of identifying genes involved in pigment cell biology. We have found Emx1 and Emx2, two highly related homeobox genes that when overexpressed in melanocytes can downregulate Mitf, Tyrp1, Dct and Tyr. Constitutive expression of Emx alters pigment cell morphology and growth properties: it confers TPA independence but not the ability to grow in soft agar. Spatial and temporal expression of Emx and Mitf during embryonic development suggests that Emx could be one factor that regulates correct expression of Mitf by inhibiting its activation in neuroepithelial derivatives other than melanocytes.


MRI in the assessment of congenital vaginal anomalies.
To assess accuracy of magnetic resonance imaging (MRI) for the delineation of morphological abnormalities of the vagina in patients with congenital anomalies of the genito-urinary tract. Fifty-one patients (median age 19 years; range 12-40 years) were studied. All were consecutively referred for MRI to assess genital tract anatomy, between 1996 and 2004, from a clinic specializing in congenital abnormalities of the urogenital tract. All patients were assessed clinically and underwent MRI. Images were reviewed retrospectively by an experienced radiologist. Where there was discordance between clinical and radiological findings a consensus diagnosis was achieved by the gynaecologists and radiologists reviewing all of the clinical and radiological evidence together, including assessment of vaginal length. The clinical data were incomplete for five women and the images non-diagnostic in two cases; consequently, 44 of 51 women had complete datasets and could be evaluated. Vaginas were abnormal in 30 of the 44 patients. There was discordance between the clinical and imaging findings at the initial review in three of the 44 cases (6.8%). After consensus review, and with the inclusion of measurement of the vaginal length on MRI, the MRI and clinical findings were concordant in all cases. The initial discordance was due to two vaginal dimples not being appreciated on MRI and one case in which presence of vaginal tissue proximal to a mid-segment obstruction was not appreciated clinically. MRI is an accurate method of imaging vaginal anomalies. However, to achieve reliable results the radiologist requires details of previous surgery and the vaginal length must be measured.


Interaction between von Hippel-Lindau Protein and Fatty Acid Synthase Modulates Hypoxia Target Gene Expression.
Hypoxia-inducible factors (HIFs) play a central role in the transcriptional response to changes in oxygen availability. Stability of HIFs is regulated by multi-step reactions including recognition by the von Hippel-Lindau tumour suppressor protein (pVHL) in association with an E3 ligase complex. Here we show that pVHL physically interacts with fatty acid synthase (FASN), displacing the E3 ubiquitin ligase complex. This results in HIF-α protein stabilization and activation of HIF target genes even in normoxia such as during adipocyte differentiation. 25-hydroxycholesterol (25-OH), an inhibitor of FASN expression, also inhibited HIF target gene expression in cultured cells and in mouse liver. Clinically, FASN is frequently upregulated in a broad variety of cancers and has been reported to have an oncogenic function. We found that upregulation of FASN correlated with induction of many HIF target genes, notably in a malignant subtype of prostate tumours. Therefore, pVHL-FASN interaction plays a regulatory role for HIFs and their target gene expression.


SARC-F has low correlation and reliability with skeletal muscle mass index in older gastrointestinal cancer patients.
The evaluation of function and muscle mass in older cancer patients is essential to reduce comorbidities. We hypothesized that Simple Questionnaire to Rapidly Diagnose Sarcopenia (SARC-F) questionnaire is useful to assessment the muscle function, but not muscle mass. Thus, the purpose of this study was to evaluate the correlation and reliability between the SARC-F and skeletal muscle mass index (SMI) in older gastrointestinal cancer patients. A cross-sectional observational study enrolled 108 (63.55 ± 8.9 y) gastrointestinal cancer patients. The patients were evaluated using the SARC-F questionnaire and the muscle mass index (SMI). SMI was calculated using Lee's equation: the appendicular muscle mass (ASM) was divided by height. Pearson's correlation was used to examine the correlation between SARC-F and SMI. The Bland-Altman plot and Cohen's kappa coefficient were used to determine the concordance and reliability between them. Statistical difference was set at p < 0.05. The Bland-Altman plot showed that the difference between methods were within agreement (±1.96; p = 0.001). However, SARC-F has low concordance (κ = 0.20; standard error = 0.14) and correlation (r = -0.303; p = 0.0014) with SMI. In older cancer outpatients, we found that SARC-F has low correlation and reliability with SMI.


Sonic hedgehog maintains survival and growth of chronic myeloid leukemia progenitor cells through β-catenin signaling.
Sonic hedgehog (Shh) signaling plays an important role in many human cancers and cancer stem cells. Here we investigate the activity and functional role of Shh signaling in chronic myeloid leukemia (CML) and leukemia progenitor cells. Differential activation of Shh signaling was found in about 50% CML chronic phase samples, about 70% of CML accelerated phase samples, and >80% CML blast crisis phase samples. Deregulated activation of Shh signaling was observed in CD34(+) and c-kit(+) leukemia progenitor cells. Stimulation of Shh signaling with exogenous Shh peptide induced expansion of CD34(+) and c-kit(+) progenitor cells (p < 0.05), inversely, blocking the pathway with signal inhibitor induced cell apoptosis (p < 0.05). Low level of Shh protein was observed in CML bone marrow stromal cells, and CD34(+) progenitor cells are less sensitive to exogenous Shh peptide and more sensitive to cyclopamine than CD34(-) cells (p < 0.05), implying cell-autonomous activation of Shh signaling play a predominant role in progenitor cells. Coactivation of Shh and β-catenin signaling was found in CD34(+) and c-kit(+) progenitor cells. Administration of Shh-neutralizing antibody or Wnt3a-neutralizing antibody in c-kit(+) progenitor cells induced cell apoptosis; however, Wnt3a peptide could salvage cell apoptosis, while Shh peptide failed to revert anti-Wnt3a-induced cell apoptosis. C-MYC, GLI1, BCL-2, and P21 were also found to be downstream targets of Shh signaling, mediating apoptosis or G(2)/M cell cycle arrest of progenitor cells. Our results demonstrate that autoactivated Shh signaling provides survival and proliferative cues in CML progenitor cells through downstream β-catenin signaling, suggesting a novel therapeutic approach in CML.


Clopidogrel: review of bioanalytical methods, pharmacokinetics/pharmacodynamics, and update on recent trends in drug-drug interaction studies.
Clopidogrel, owing to its excellent inhibitory property of platelet aggregation, is used to reduce the cardiovascular risks in patients with multiple co-morbid conditions such as stroke, myocardial infarction and atherosclerosis. The current review focuses distinctly on three aspects: (a) an in-depth coverage on the bioanalytical methods for the quantification of clopidogrel and its inactive carboxylic acid metabolite as well as the active metabolite in pre-clinical and clinical samples; (b) an overview of the pharmacokinetic/pharmacodynamic aspects of clopidogrel; and (c) enumerating the key findings from drug-drug interaction studies of clopidogrel with various co-substrates such as lanzoprazole, fluvastatin, atorvastatin, pravastatin, digoxin, ketoconazole, donezepil and theophylline.


Simultaneous quantitation of acrylamide, 5-hydroxymethylfurfural, and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine using UPLC-MS/MS.
A robust and sensitive isotope dilution UPLC-MS/MS method was established for the simultaneous analysis of acrylamide (AA), 5-hydroxymethylfurfural (HMF), and 2-amino-1-methyl-6-phenylimidazo[4,5-b]-pyridine (PhIP). A fairly good separation of three analytes was achieved within 4.5 min. High correlation coefficients (R2 > 0.9998) of the three compounds were obtained in their respective linear ranges. This method demonstrated low limits of detection (1.57 μg/L for AA, 0.61 μg/L for HMF, and 0.02 μg/L for PhIP) and limits of quantification (5.22 μg/L for AA, 2.03 μg/L for HMF, and 0.05 μg/L for PhIP). This method also demonstrated excellent quantification accuracy (99.02%-101.12%), precision (RSD < 6%), and recovery (82.83-119.92%) in the Maillard model systems and deep-fried meatballs. This work develops a fundamental method for the rapid simultaneous determination of AA, HMF, and PhIP in thermally processed foods that are both carbohydrates-rich and protein-rich, meanwhile providing technical support for the generation mechanism of various hazards.


[Effect of the nitrogen components of a peptide diet and the analogous amino acids on pancreatic secretion in the human].
In healthy volunteers (n = 10), the exocrine pancreatic secretion was studied after intragastric administration of a peptid solution which corresponded to the nitrogen component of a commercially available peptid diet, and of a solution of the analogous amino acids. Both test solutions were emptied out of the stomach in the same time interval and evoked a comparably high pancreatic secretion of volume, amylase, lipase, trypsin and chymotrypsin. These findings are discussed in regard to recommendations to apply elemental diets for treatment of complicated pancreatitis.


Increased antigen-induced local and systemic mediator release in rhinitis subjects with pulmonary symptoms in the pollen season.
In order to delineate parameters that might discriminate between allergic subjects who develop R or R-P symptoms during natural antigen exposure, 26 subjects allergic to grass or ragweed pollen were classified into R or R-P groups, and then the antigen sensitivity and degree of in vivo mediator release were compared. Antigen-skin sensitivity was quantitated by dilutional skin-test titration, and bronchial sensitivity was quantitated by the amount of inhaled antigen required to receive the FEV1 by 20%. Mediator release was determined by measuring the amount of histamine that was released into skin chambers during antigen incubation and the rise in plasma histamine and serum NCA during antigen-induced bronchospasm. Compared to the 13 R subjects, the 13 R-P subjects were: (1) more sensitive to antigen by both skin-test and inhalation challenge, (2) responded to inhalation of antigen with a greater fall in FEV1 and a greater rise in serum NCA and plasma histamine, and (3) released more histamine into skin chambers after antigen incubation. Even when R and R-P subjects were matched by comparing only subjects with equal skin sensitivity to antigen, greater increases in serum NCA and plasma histamine occurred after inhalation of antigen in the R-P subjects. These data are consistent with the hypothesis that allergic rhinitis subjects who develop pulmonary symptoms during natural pollen exposure are more sensitive to antigen and release more mediators in response to antigen administration. It is therefore possible that the degree of mediator release may be an important factor in determining the pattern of clinical responses to antigen exposure.


Pediatric hydatid cyst with ventricular aneurysm and surgical treatment with dor procedure, case report.
Cardiac involvement of hydatid cyst disease (HCD) is a rare presentation but may lead to life-threatening complications such as cyst rupture and should be treated surgically. A 10-year-old male patient with cranial and complicated cardiac HCD lesions that caused lower extremity peripheral arterial occlusion and aneurysmatic dilatation in the left ventricular apex is presented. Although the patient was in the pediatric age group, the Dor procedure was successfully applied to preserve the ventricular geometry. The Dor procedure for a ventricular aneurysm caused by a cardiac hydatid cyst (CHC) was rarely applied in the pediatric age group. In conclusion, this case differs from other CHCs previously reported in the literature due to the advanced stage of the disease, atypical clinical presentation, and rare complications despite the young age of the case. The surgical method used in treating the patient makes the subject more interesting.


Teaching methods in anatomy courses in North American medical schools the role of radiology.
We sought to determine the current and anticipated future status of anatomy education in medical schools in North America, with particular emphasis on the role of radiologists and imaging in the curriculum. A Web-based survey was sent to all schools identified using the AAMC Web site to find e-mail addresses for deans and course directors. Responses were obtained from approximately 50% of schools. Most courses are taught over a semester, and most are directed by anatomists. Only one is directed by a radiologist. Dissection is still the major teaching method, with radiologic anatomy averaging about 5% of total teaching time. Most directors anticipate a decrease in teaching time over the next 5 years and an increase in use of digital methods and teaching of radiologic anatomy. The role of radiologists will probably increase in future teaching of anatomy.


Initial Approach to Patients with a Newly Diagnosed Solitary Brain Metastasis.
Solitary brain metastasis is defined by a single metastatic brain lesion as the only site of metastasis. The initial approach to this condition consists of radiographical evaluation to establish diagnosis, followed by assessment of functional and prognostic status. Neurologic symptom management consists of using dexamethasone and antiepileptic medications. Treatment consists of a combination of surgical and radiation therapy. Surgical treatment is indicated where there is a need for tissue diagnosis or immediate alleviation of neurologic symptoms and mass effect. Stereotactic radiosurgery has become an effective treatment modality. Whole-brain radiation therapy may have a role as an adjunctive therapy.


Strategies for Increasing the Rate of Defect Annihilation in the Directed Self-Assembly of High-χ Block Copolymers.
Directed self-assembly (DSA) of high-χ block copolymer thin films is a promising approach for nanofabrication of features with length scale below 10 nm. Recent work has highlighted that kinetics are of crucial importance in determining whether a block copolymer film can self-assemble into a defect-free ordered state. In this work, different strategies for improving the rate of defect annihilation in the DSA of a silicon-containing, high-χ block copolymer film were explored. Chemo-epitaxial DSA of poly(4-methoxystyrene-block-4-trimethylsilylstyrene) with 5× density multiplication was implemented on 300 mm wafers by using production level nanofabrication tools, and the influence of different processes and material parameters on dislocation defect density was studied. It was observed that only at sufficiently low χN can the block copolymer assemble into well-aligned patterns within a practical time frame. In addition, there is a clear correlation between the rate of the lamellar grain coarsening in unguided self-assembly and the rate of dislocation annihilation in DSA. For a fixed chemical pattern, the density of kinetically trapped dislocation defects can be predicted by measuring the correlation length of the unguided self-assembly under the same process conditions. This learning enables more efficient screening of block copolymers and annealing conditions by rapid analysis of block copolymer films that were allowed to self-assemble into unguided (commonly termed fingerprint) patterns.


Identifying prognostic parameters related to surgical technique in patients treated by robotic radical prostatectomy.
The most frequently studied factors in patients treated by robotic radical prostatectomy are PSA and pathological features of the biopsy and prostatectomy specimen. Studies on the factors associated with the surgical technique are scarce and with controversial results. The objective is to identify all possible surgical factors and their relationship with disease-free and metastasis-free survival. Prospective study approved by the Ethics Committee, including patients who underwent robotic radical prostatectomy since January 2009 with a minimum follow-up of 5 years. Surgeon, surgical time, blood loss, fascial access, continence techniques, preservation of the fascia, neurovascular bundles, bladder neck, urethra, learning curve and surgical complications, were analyzed as possible prognostic factors. We performed univariate and matched comparisons of survival using Kaplan-Meier estimation and long-rank tests. The significance level for multiple comparisons was established with False Discovery Rate-adjustment (adjusted p). Cohort of 667 patients with a median follow-up of 69 months. In univariate analysis, surgeon (adjp=0.018), preservation of puboprostatic ligaments (adjp=0.02), preservation of endopelvic fascia (adjp=0.001) and performing periurethral suspension (adjp<0.001) are poor prognostic factors for disease-free survival. Fascia preservation also negatively affects metastasis-free survival (adjp=0.04). Previous abdominal surgeries, prostate, surgical time, blood loss, type of residual urethra, middle lobe, fascial access, fascia or bladder neck preservation, have no statistical significance. The surgeon and specific aspects of the surgical technique are determining factors in disease-free survival. Preservation of the fascia is the only factor that negatively affects metastasis-free survival.


Disclosing a diagnosis of autism spectrum disorder without intellectual disability to pediatric patients in Japan in early diagnostic stages and associated factors: a cross-sectional study.
With a recent increase in the prevalence of autism spectrum disorder (ASD), an important issue has emerged in clinical practice regarding when and how patients themselves should be given explanations following a diagnosis of ASD. The clinical guidelines of the UK National Institute for Health and Care Excellence state that children diagnosed with ASD should receive an explanation about what ASD is and how it affects their development and functioning-"if appropriate". However, the guidelines do not provide any specifics regarding what constitutes "appropriate" situations METHODS: We conducted an anonymous self-administered postal questionnaire survey targeting all members of the Japanese Society for Child and Adolescent Psychiatry (n=1,995). The analysis included only physicians who had newly diagnosed pediatric patients with ASD in the past year. We imposed a limit of one year because diagnoses further back than that are difficult to recall; in other words, this would enhance the recall bias RESULTS: The recovery rate was 30.8%, and the rate of diagnosis disclosure to patients themselves without intellectual disability was 15.3%. We asked 361 physicians who responded that "deciding on a case-by-case basis" was the ideal way to disclose an ASD diagnosis about 20 items prioritized by physicians at the time of diagnosis disclosure and extracted three factors through exploratory factor analysis. Multiple logistic regression analysis was performed with physician attributes, awareness of ASD as a disorder or personality, and the three extracted factors as explanatory variables; diagnosis disclosure was the dependent variable. The patient age group and only one of the three factors (i.e., "factor related to readiness to accept diagnosis") showed a significant association with disclosure of the diagnosis to the individual. Items included in the "factor related to readiness to accept diagnosis" were as follows: the degree of parental understanding, relationship of the patient with their parents/physician, agreement in opinion between parents, parental consent, "sufficient" patient understanding, symptom stabilization, and a guarantee of sufficient time required to explain the diagnosis to the patient CONCLUSION: In clinical settings, disclosing an ASD diagnosis with the consideration of patient/parent readiness toward accepting the diagnosis could help to guide physicians in determining an ideal timing for disclosure. Future studies are needed to establish detailed and concrete guidelines regarding disclosure of an ASD diagnosis to patients.


The physiological assessment of acid-base balance.
Acid-base terminology including the sue of SI units is reviewed. The historical reasons why nomograms have been particularly used in acid-base work are discussed. The theoretical basis of the Henderson-Hasselbalch equation is considered. It is emphasized that the solubility of CO2 in plasma and the apparent first dissociation constant of carbonic acid are not chemical constants when applied to media of uncertain and varying composition such as blood plasma. The use of the Henderson-Hasselbalch equation in making hypothermia corrections for PCO2 is discussed. The Astrup system for the in vitro determination of blood gases and derived parameters is described and the theoretical weakness of the base excess concept stressed. A more clinically-oriented approach to the assessment of acid-base problems is presented. Measurement of blood [H+] and PCO2 are considered to be primary data which should be recorded on a chart with in vivo CO2-titration lines (see below). Clinical information and results of other laboratory investigations such as plasma bicarbonate, PO2,P50 are then to be considered together with the primary data. In order to interpret this combined information it is essential to take into account the known ventilatory response to metabolic acidosis and alkalosis, and the renal response to respiratory acidosis and alkalosis. The use is recommended of a chart showing the whole-body CO2-titration points obtained when patients with different initial levels of non-respiratory [H+] are ventilated. A number of examples are given of the use of this [H+] and PCO2 in vivo chart in the interpretation of acid-base data. The aetiology, prognosis and treatment of metabolic alkalosis is briefly reviewed. Treatment with intravenous acid is recommended for established cases. Attention is drawn to the possibility of iatrogenic production of metabolic alkalosis. Caution is expressed over the use of intravenous alkali in all but the severest cases of metabolic acidosis. The role of 2,3-diphosphoglycerate on tissue oxygenation is stressed and use of intravenous sodium phosphate as an alternative to intravenous bicarbonate is mentioned.


The levels of bioactive compounds found in raw and cooked Canadian pulses.
The effect of cooking on the levels of bioactive compounds (oligosaccharides, polyphenols and saponins, and vicine/convicine for faba bean only) were examined in a wide range of Canadian pulses. The total oligosaccharide concentrations were reduced ∼40% for chickpea, 11-81% for lentils, 41-43% for faba beans, 10-51% for beans, and 20-44% for peas. Individual oligosaccharides, raffinose, ciceritol, stachyose and verbascose, increased or decreased in the cooked samples depending on each pulse sample. Cooking reduced the total polyphenol content by 13-25% for chickpeas, 0-83% for lentils, 47-54% for faba beans, 47-54% for beans, and 48-70% for peas. And, the total saponin concentrations were reduced by 11-30% for chickpeas, 0-40% for lentils, 32-46% for beans, 14-30% for peas and increased by 8-26% in faba bean. The vicine and convicine levels in faba bean were reduced by 26-38% with cooking. The reduction in bioactive compounds after cooking depended on the specific compound and specific type of pulse. This large analyses of 20 different pulse samples allows for comparison between and within different types of pulses.


Antimutagenicity of components of dairy products.
This paper reports the potential antimutagenicity of some components of dairy products. For both milk and fermented milk, Bifidobacterium sp. Bio (strain Danone 173010), casein and calcium showed a dose-dependent antimutagenic activity against benzo[a]pyrene mutagenicity in the Ames test using Salmonella typhimurium TA98. Fatty compounds present in milk had no antimutagenic effect. At the level occurring in cultured or uninoculated milks, and even more, the bifidobacteria, casein and calcium showed less antimutagenic activity than fermented and uninoculated milks. So, the mix of all these components must contribute to the total protective effect of dairy products against induced mutagenicity, and this does not rule out the possibility of contribution of other unknown substances. The total antimutagenicity of uninoculated skim milk corresponds to the additional activity of casein and calcium. The observed antimutagenic activity of fermented skim milk remains lower than expected.


[Personal experience with surgical treatment of hyperparathyroidism in chronic kidney failure. I. Etiopathogenesis of secondary hyperparathyroidism, preoperative findings, indications for parathyroidectomy].
The authors give an account of the fundamental relations of the calcium-phosphate metabolism in conjunction with the development of secondary HPT in chronic renal failure. The authors analyzed a group of 20 patients operated on account of secondary and tertiary forms of HPT as regards preoperative findings. The analysis comprised the clinical condition, biochemical, radiological and histological findings pertaining to bone, along with evidence of enlarged parathyroid glands by computed tomography and ultrasonography. The mentioned findings supplemented by some findings from the literature are the sum of indications for PTE. From the practical aspect they are indicators of the affection, of a high total ALP blood level and X-ray evidence of subperiostal absorption.


Prospective development of a patient-reported outcomes instrument for desmoid tumors or aggressive fibromatosis.
Desmoid tumors (or aggressive fibromatosis) are locally infiltrative connective-tissue tumors that can arise in any anatomic location; they can be asymptomatic, or they can result in pain, deformity, swelling, and loss of mobility and/or threaten visceral organs with bowel perforation, hydronephrosis, neurovascular damage, and other complications. Existing clinical trial endpoints such as the Response Evaluation Criteria in Solid Tumors (version 1.1) and progression-free survival are inadequate in capturing treatment efficacy. This study was designed to develop a novel clinical trial endpoint by capturing patient-reported outcomes (PROs). Following best practices in qualitative methodology, this study used concept elicitation (CE) interviews to explore desmoid patients' perspectives on key disease-related symptoms and impacts. Qualitative analysis was performed to determine the relative frequency and disturbance of symptoms and impacts as well as other characteristics of these concepts. A draft PRO scale was then developed and tested with cognitive interviewing. Information from the interviews was subsequently incorporated into the refined PRO scale. CE interviews with desmoid patients (n = 31) helped to identify salient concepts and led to a draft scale that included symptom and impact scales. Cognitive interviews were completed with additional patients (n = 15) across 3 phases. Patient input was used to refine instructions, revise and/or remove items, and modify the response scale. This resulted in an 11-item symptom scale and a 17-item impact scale. This is the first disease-specific PRO instrument developed for desmoid tumors. The instrument is available as an exploratory endpoint in clinical trials. This study highlights the feasibility and challenges of developing PRO instruments for rare diseases.


Synthesis of Amphiphilic Statistical Copolymers Bearing Methoxyethyl and Phosphorylcholine Groups and Their Self-Association Behavior in Water.
Biocompatible amphiphilic statistical copolymers P(MEA/MPCm) composed of 2-methoxyethyl acrylate (MEA) and 2-methacryloyloxyethyl phosphorylcholine (MPC) were prepared with three different mol% of the hydrophilic unit MPC (m = 6, 12 and 46 mol%). The monomer reactivity ratios of MEA (rMEA) and MPC (rMPC) were 0.53 and 2.21, respectively. The rMEA × rMPC value of 1.17 demonstrated that statistical copolymerization was successful. P(MEA/MPC12) and P(MEA/MPC46) copolymers did not undergo aggregation in water, whereas the P(MEA/MPC6) copolymer formed micelles in water with a hydrodynamic radius (Rh) of 96.9 nm and a critical aggregation concentration, which was determined using pyrene fluorescence, at 0.0082 g/L. The restricted motion of the protons in the hydrophobic MEA units in the micelles' cores provided additional evidence of self-association in P(MEA/MPC6).


Immune cells within the tumor microenvironment: Biological functions and roles in cancer immunotherapy.
The immune cells within the tumor microenvironment (TME) play important roles in tumorigenesis. It has been known that these tumor associated immune cells may possess tumor-antagonizing or tumor-promoting functions. Although the tumor-antagonizing immune cells within TME tend to target and kill the cancer cells in the early stage of tumorigenesis, the cancer cells seems to eventually escape from immune surveillance and even inhibit the cytotoxic function of tumor-antagonizing immune cells through a variety of mechanisms. The immune evasion capability, as a new hallmark of cancer, accidently provides opportunities for new strategies of cancer therapy, namely harnessing the immune cells to battle the cancer cells. Recently, the administrations of immune checkpoint modulators (represented by anti-CTLA4 and anti-PD antibodies) and adoptive immune cells (represented by CAR-T) have exhibited unexpected antitumor effect in multiple types of cancer, bringing a new era for cancer therapy. Here, we review the biological functions of immune cells within TME and their roles in cancer immunotherapy, and discuss the perspectives of the basic studies for improving the effectiveness of the clinical use.


Findings from the first colorectal cancer screening among 103 542 individuals in Vietnam with systematic review of colorectal cancer screening programs in Asia-Pacific region.
Colorectal cancer is a leading cancer incidence and cause of death worldwide and in Vietnam. Although screening is considered an effective measure to prevent and control colorectal cancer, there is no such effort in Vietnam. Between 01 January 2018 and 31 October 2019, a population-based colorectal cancer screening program was conducted in Hanoi, Vietnam. A health advocacy campaign and follow-up phone calls were used to enroll residents aged ≥40 years old to complete an immunochemical-fecal occult blood testing. Positive immunochemical-fecal occult blood testing was followed by a colonoscopy. We also conducted a systematic review of the colorectal cancer screening programs in the Asia-Pacific region that used similar approach by searching Ovid Medline and PubMed databases. During study period, 103 542 individuals among 672 742 eligible residents attended the screening of whom 81.5% participants finished immunochemical-fecal occult blood testing test and the positive rate was 6.1%. The coverage rate for immunochemical-fecal occult blood testing test was 11.9%. Among 2278 individuals who underwent colonoscopy, 3.5% were histologically diagnosed with cancer, 17.8% with advanced adenomas, and 23.1% with non-advanced adenomas. Males had significantly higher detection rate of advanced adenomas, cancer or ≥ two polyps/tumor than females (P < 0.0001). The systematic review showed that in two-step modality (i.e. immunochemical-fecal occult blood testing/fecal immunochemical test and colonoscopy), the test positive was from 4.1 to 10.6%. Once colonoscopy was performed subsequently, the rate of cancer among positive participants was from 1.7 to 16.4% and that of advanced adenomas was from 7.1 to 23.1%. We showed that the two-step modality is a promising strategy for colorectal cancer screening in Vietnam that might apply to similar settings with limited resources.


Alloxan-induced diabetes mellitus in pregnant sheep and chronic fetal catheterization.
25 female sheep of the Texel breed were made hyperglycaemic by administration of alloxan monohydrate (ALX) in early pregnancy and 15 ewes served as controls. Average venous glucose levels (mean +/- standard deviation) increased from 3.5 +/- 0.2 to 14.0 +/- 1.8 mmol/l. All hyperglycaemic sheep were treated with long-acting insulin in doses adjusted individually (0.2-1.0 U/kg per day) to keep glucose levels above 8 mmol/l. After a temporary significant increase, maternal venous concentrations of urea and creatinine returned to normal levels. One sheep died on day 6 after administration of ALX. Another hyperglycaemic sheep died at induction of anaesthesia. Eight hyperglycaemic ewes aborted between days 90 and 128 of gestation. Between days 103 and 135 of gestation the remaining hyperglycaemic (n = 15) and control (n = 15) ewes were operated upon and the fetuses were provided with EEG, nuchal EMG and ECG electrodes and catheters in the trachea, amniotic fluid, jugular vein and carotid artery. Use of the chronic sheep preparation for the study of diabetes mellitus and fetal reactions was successful in 10 out of 25 cases, as in the diabetic group postoperative intra-uterine fetal survival varied between 2 and 19 days and in 10 cases was at least 5 days. Postoperative intrauterine fetal survival in the controls was significantly longer and varied between 4 and 28 days, and in 13 cases was at least 5 days. A highly significant correlation (P less than 10-6) between maternal and fetal blood glucose levels was seen.(ABSTRACT TRUNCATED AT 250 WORDS)


Reduction of human fecal markers and enteric viruses in Sydney estuarine waters receiving wet weather overflows.
The current microbial source tracking (MST) study tracked the reduction of the culturable fecal indicator bacteria enterococci, four human fecal markers (Bacteroides HF183, Lachnospiraceae Lachno3, cross-assembly phage (CrAssphage) and pepper mild mottle virus (PMMoV)) along with four enteric viruses - human adenovirus 40/41 (HAdV 40/41), enterovirus (EV), human norovirus GI (HNoV GI) and GII (HNoV GII) post wet weather overflows (WWOs) at two estuarine water sites from two depths under separate six-day sampling campaigns over seven and 12 days in Sydney, NSW, Australia. Neither HNoV GI nor GII was detected, while 13.9 % (10/72) of estuarine water samples had detections of EV. Quantifiable concentrations (0.64 to 2.00 log10 gene copies (GC)/100 mL) for HAdV 40/41 were returned from 65.2 % (47/72) of samples collected across the two sites and two depths with 30 quantifications recorded in the surface layer samples. In contrast the presence of HF183, Lachno3, CrAssphage, and PMMoV markers was observed in all 36 (100 %) estuarine water samples collected from the surface layer from both sites. Detection frequencies of these markers were slightly lower at 1 m above the bottom surface. The concentrations of the human fecal markers were compared to established gastrointestinal (GI) risk benchmarks. The concentrations of HF183, Lachno3 and CrAssphage marker only exceeded the GI risk benchmark until day 3, while concentrations of PMMoV marker were indicative of exceedance of the GI risk benchmark on day 7 post WWOs that was much longer than indicated by culturable enterococci concentrations that were within this GI risk benchmark by day 2 and day 4 for the two sites, respectively.


Optimizing the role of FDG PET-CT for potentially operable metastatic colorectal cancer.
Recent treatment advances now allow a realistic chance of cure in selected patients with metastatic colorectal carcinoma (CRC). Accurate pre-treatment staging is crucial to ensure appropriate management by identification of patients with more advanced disease who will not benefit from surgery. (18)Fluorine 2-fluoro-2-deoxy-D-glucose positron emission tomography-computed tomography (PET-CT) has a firmly established role in staging, restaging, and recurrence detection of a range of tumors. This article will review the role of PET-CT in patients with CRC with a particular emphasis on optimizing the technique in patients with potentially operable metastatic disease.


Genotypic variability of carotenoids in traditional tomato cultivars.
Traditional varieties constitute a wide source of genetic variation that can be used per se or to obtain new cultivars with high consumer appeal and nutritional value. This work focuses on the carotenoid and chlorophyll profiles and contents of 53 traditional tomato cultivars, paying particular attention to compounds with recognized health-promoting properties. The study includes fruits with different shapes (oblate, slightly flattened, rounded, heart-shaped, long oblong and pyriform), colors (yellow, pink and red) and sizes (very small to very large). In addition, black colored tomato fruits with yellow, pink or red background color were studied. The highest concentrations of lycopene, β-carotene, phytoene and phytofluene were found in pink and red tomatoes, while the highest concentrations of lutein, violaxanthin, neoxanthin and chlorophylls were found in fruits with a dark coloration, regardless of their background coloration. Finally, the highest concentrations of the studied compounds as a whole (except β-carotene) were found in red- and pink-black varieties. Findings will hopefully contribute to recovering many tomato traditional varieties for use, directly in the field or as donor parents for breeding programs, to increase the nutraceutical properties of commercial varieties.


Enhancement of cytokine expression in transiently transfected cells by magnetoliposome mediated hyperthermia.
We investigated the enhancement of cytokine expression by heat treatment in transiently transfected glioma cells. The cells were transfected with plasmid bearing the interferon (IFN)-β gene under control of the MMTV promoter, which is inducible by glucocorticoid (dexamethasone). Then magnetite particles (10 nm diameter) as intracellular heating material were incorporated to the cells as the form of magnetoliposome. After 5 hours of incorporation, alternative magnetic field (384Oe, 118kHz) was applied for intracellular heating. IFN-β secreted in the medium was assayed and its concentration was compared to the extracellular heating induced expression, both in the presence and absence of dexamethasone. Higher IFN-β concentration was detected in intracellular heating even at lower temperature, 39 °C, than 43 °C in extracellular heating. The IFN-β expression level reached in the presence of dexamethasone was about three times higher than in the absence of inducer. In intracellular heating of 60 min, the surviving cell number reduced until 20%.


Effects of resistance exercise alone or with caffeine on hemodynamics, autonomic modulation and arterial stiffness in resistance-trained women.
Both an acute bout of resistance exercise (RE) and caffeine consumption can significantly alter hemodynamics, autonomic modulation, and arterial stiffness, which may correlate with adverse cardiovascular events. However, effects of an acute bout of RE and caffeine are unclear in resistance-trained women. The purpose of this study was to compare the effects of an acute bout of RE with repetitions to failure on squat and bench press, with or without caffeine, on performance, resting and recovery measures of hemodynamics, autonomic modulation, as well as arterial stiffness in resistance-trained women. Eleven women participated in a double-blind, placebo controlled cross-over design in which they consumed caffeine (4 mg/kg) or placebo at least 72 h apart. Sixty minutes following ingestion, participants performed two sets of 10 repetitions followed by a third set to failure on squat and bench press. Hemodynamics, autonomic modulation, and arterial stiffness were measured at rest, 60 min post-ingestion, and three minutes and 10 min following RE. Data demonstrated caffeine has no additive effects on performance, hemodynamics, autonomic modulation, or arterial stiffness (p > 0.05) before or following an acute bout of RE in resistance-trained women compared to a placebo. Resistance-trained women may not observe any alteration to RE performance on the squat and bench press in terms of repetitions to failure following caffeine ingestion. In addition, the data from the present study suggests that there may also not be any further negative effects on the cardiovasculature if caffeine is consumed prior to the RE bout.


Effect of a triacontanol-rich biostimulant on the ripening dynamic and wine must technological parameters in Vitis vinifera cv. 'Ribolla Gialla'.
Biostimulants are organic compounds which can influence the biochemical activity of the whole plant. Lately, great attention has been focused on the possibility of using these stimulants in the viticulture sector. Due to this, the aim of this work was to investigate the foliar application of a biostimulant made by Fabaceae tissue, rich in amino acids and peptides along with the high presence of natural triacontanol (C30H62O) (>6 mg kg-1), previously reported in many crops as chemicals able to stimulate different yield components, the technological composition of musts still having an effect on some of the microbial population of different fruits/crops. Hence, this research was conducted during the growing seasons 2020 and 2021 in a commercial vineyard of the 'Ribolla Gialla' grapevine (Vitis vinifera, L.), in the Friuli Venezia Giulia Region (North-Eastern Italy), in order to understand the effect on this woody perennial crop not yet investigated. After a two-year-study, a physiological response occurred, as ripening and veraision were brought forward in the treated plants as well as the harvest time, having higher enological parameters (sugars, total titrable acidity and citric acid content) than the non-treated at every stage. Thus, grapes in the treated plants reached a full technological maturity earlier than the non-treated, in both study years. There was a positive effect on must microbial ecology important for winemaking, hence, the biostimulant have promoted the growth of the microbial community on berry skin translating into what found in the must.


Single-cell analysis defines the lineage plasticity of stem cells in cervix epithelium.
Information about the dynamic change and post-injury regeneration of cervical epithelium is relatively rare, even though it is tightly related to gynecologic malignancy. Here, using a feeder cell-based culturing system, we stably cloned mouse and human P63 and KRT5 expressing cells from the adult cervix as putative cervical stem/progenitor cells (CVSCs). When subjected to differentiation, the cultured cells gave rise to mature cervical epithelium by differentiating into squamous or glandular cells. The ability of endogenous mouse CVSCs to reconstitute cervical epithelium after injury was also evident from the genetic lineage tracing experiments. Single-cell transcriptomic analysis further classified the CVSCs into three subtypes and delineated their bi-lineage differentiation roadmap by pseudo-time analysis. We also tracked the real-time differentiation routes of two representing single CVSC lines in vitro and found that they recapitulated the predicted roadmap in pseudo-time analysis. Signaling pathways including Wnt, TGF-beta, Notch and EGFR were found to regulate the cervical epithelial hierarchy and implicated the different roles of distinct types of cells in tissue homeostasis and tumorigenesis. Collectively, the above data provide a cloning system to achieve stable in vitro culture of a bi-lineage stem/progenitor cell population in the cervix, which has profound implications for our understanding of the cervix stem/progenitor cell function in homeostasis, regeneration, and disease and could be helpful for developing stem cell-based therapies in future.


Clustering of features of von Hippel-Lindau syndrome: evidence for a complex genetic locus.
von Hippel-Lindau syndrome (HLS), an autosomal-dominant inherited disease, was studied in 92 affected subjects from 29 kindreds. In an initial survey to identify HLS gene carriers, all patients treated at the University of Freiburg for angiomatosis retinae (22), haemangioblastoma of the central nervous system (CNS) (63), and phaeochromocytoma (54) were examined as potential HLS gene carriers. HLS was diagnosed in 86% of the patients with angiomatosis retinae, 19% of the patients with haemangioblastoma of the CNS, and 19% of the patients with phaeochromocytoma. Based on these and on an additional 49 newly diagnosed cases (24 by clinical examination and 25 by pedigree analysis), the calculated prevalence of the disease in the district of Freiburg, Germany, with a population of 1.909 million is 1/38 951. There was a striking tendency for familial clustering of HLS features in affected kindreds. Both angiomatosis retinae and haemangioblastoma of the CNS occurred in most families, whereas renal lesions and/or pancreatic cysts and phaeochromatocytoma were mutually exclusive. This finding suggests that HLS is caused by different mutations within a complex genetic locus, or additional genetic lesions, which cooperate with the HLS gene on chromosome 3p. The data point to a linear sequence of features as follows: phaeochromocytoma, angiomatosis retinae, haemangioblastoma of the CNS, renal lesions, pancreatic cysts, and epididymal cystadenoma.


LPS induced hypothermia in pregnant rats: a regulated thermoregulatory response.
Intraperitoneal administration of E. coli LPS in doses that elicit half-maximal (EC50 - 20 ug/kg) and maximal (EC100 - 160 ug/kg) febrile responses in nonpregnant rats produce hypothermia in near-term pregnant rats. The present experiments have been carried out to determine if the hypothermia results from a "regulated" or "forced" thermoregulatory response. Chronically-instrumented pregnant rats were allocated to one of two experimental groups depending upon whether they were studied in an experimental apparatus configured as a metabolic chamber with a uniform ambient temperature of 25 degrees C or configured as a thermocline with a linear temperature gradient ranging from 10 degrees C to 40 degrees C. The pregnant rats developed hypothermia following intraperitoneal administration of 160 ug/kg of E. coli LPS when they were studied in the thermal gradient as well as when they were studied in the uniform thermoneutral environment. They did not attempt to prevent the hypothermia following administration of bacterial pyrogen by moving to a warmer region of the thermocline. Thus, our data provide evidence that the hypothermia which occurs following intraperitoneal administration of an EC100 dose of E. coli LPS results from a regulated rather than a forced thermoregulatory response. The mechanism and consequences of this pregnancy-induced thermoregulatory response to bacterial pyrogen are unknown.


[Ultrastructural study of carcinoembryonic antigen (CEA) using the peroxidase-antiperoxidase (PAP) complex technic in patients with breast cancer].
In the studied material taken from 70 patients with the mammary carcinoma was tried to discover the presence of the CEA antigen in the cells on the ultrastructural level. In studies was used peroxidase-antiperoxidase method (PAP). The product of the immunocytochemical reaction was found on the surface of cell membrane. In 42 patients (60%) positive reaction was observed and in 28 (40%) reaction with PAP complex was negative. Just in 3 cases intracytoplasmic reaction was observed.


Educational interventions--computers for delivering education to children with respiratory illness and to their parents.
Educational interventions for children with asthma can result in both clinical and psychological improvements. However, traditional education programs have been hampered by lack of resources and doubts concerning long-term benefits. Researchers have looked to computer technology to overcome some of these obstacles and respiratory conditions have been the focus for a number of educational computer programs. Computer education packages should have a robust theoretical basis. Many programs aim to improve children's confidence, self-esteem and feelings of control, all of which are linked to compliance and positive health behaviours. The specific skills and knowledge needed for effective self-management also need to be taught in order to equip the child for future independent self-care. Programs tend to be either a stand-alone game, promoting self-regulation and practicing of skills, or an internet-enabled package, which may provide a link to their healthcare provider and/or other people with a similar condition. Computer technology is flexible, can be tailored to individuals' information needs, provides ongoing educational support and promotes active learning. However, there can be problems around accessibility, both in terms of computer ownership and technological literacy. Furthermore, internet sites are largely unregulated and of variable quality. It is essential that educational computer interventions are evidence-based and rigorously evaluated to identify who will benefit most from these packages.


Simplified uniform theory of diffraction.
Simple exponential functions that approach zero for reflection and shadow boundaries are considered to cancel the infinite values of diffraction coefficients at these regions. This method is applied to a wedge diffraction coefficient, and the resultant uniform coefficient is compared with the exact diffracted fields numerically.


Impact of transcutaneous interferential electrical stimulation for management of primary bladder neck dysfunction in children.
Several studies have revealed that electrical stimulation is an effective modality for treatment of lower urinary tract (LUT) dysfunction via raising the capacity or compliance of the bladder or maybe by pelvic floor relaxation and reducing detrusor pressure as well. This study aimed to assess the efficacy of transcutaneous interferential (IF) electrical stimulation on LUT symptoms as well as urine flow parameters in children with primary bladder neck dysfunction (PBND). We reviewed the charts of all children with persistent LUT symptoms who underwent IF electrical stimulation between 2010 and 2017. Twenty-three neurologically and anatomically normal children (mean age: 7.7 years, range: 5-13) with LUT symptoms were included in this study. Children had different LUT symptoms such as hesitancy, straining, urinary incontinence and constipation with no sufficient response to medical treatment (α -blocker) for at least 6 months. IF electrical stimulation was performed for 15 sessions, two times per week. All children were symptomatic and had abnormal urine flow pattern with an electromyographic (EMG) lag time of more than 6 s on uroflowmetry with EMG. A voiding chart, uroflowmetry with EMG and kidney and bladder ultrasounds were performed before and after the treatment for all children. Maximum and average urine flow rates, EMG lag time and postvoid residual volume were analyzed. In addition, alpha blocker therapy was continued during IF therapy. Mean maximum and average urine flow rates improved from 14.1 to 7.6-19.7 ml/s and 9.5 ml/s, respectively, while mean EMG lag time decreased from 11.7 to 5.2 s after the treatment (all P < 0.05). Also postvoid residual volume decreased significantly from 35.6 to 7.6 ml at the end of treatment courses. Pelvic floor EMG lag time, a documented parameter on uroflowmetry with EMG, defined as the time from the start of pelvic floor relaxation during a volitional voiding effort (the first stage of normal voiding) to the start of urine flow. Results showed that IF therapy decreased pelvic floor EMG lag time in children with PBND. In addition, increase in mean maximum and average urine flow rates in our patients indicated that pelvic IF therapy and behavioral modification improved voiding dysfunction in most of the patients and probably decreased bladder neck activity during voiding. Future studies with larger sample size are needed to support this finding. IF therapy appears safe, effective and reproducible in improvement of PBND in children.


Identification of precipitation trend and landslide susceptibility analysis in Miandoab County using MATLAB.
Iranian plateau is a seismically active region. Within this region, northwestern Iran is of high importance. Before proper planning for mitigating the earthquake-induced hazards can be achieved, it is necessary to identify high-risk areas in terms of susceptibility to earthquakes. In this study, landslide susceptibility in Miandoab Country was modeled using the so-called random forest algorithm (RFA) in MATLAB based on records acquired at 67 earthquake hotspots considering 9 factors affecting the earthquake occurrence (i.e., height, slope, direction, distance from fault, distance from river, distance from road, land use, geology, and precipitation). Predictive power of the model and validity of its results were evaluated using relative operating characteristic (ROC) curve and area under the curve (AUC). The assessment results showed very good accuracy of the model (0.97). It was further found that digital height layer, geology, and distance from fault impose the largest contributions into earthquake potential. The results also showed that 53%, 8.3%, and 38.4% of the study area were classified as being at low risk, moderate risk, and high risk of earthquake. Among other climatic elements, the precipitation exhibits the largest fluctuations; we proceeded to evaluate precipitation trends in the study area for a statistical period of 30 years. This was practiced by implementing Mann-Kendall nonparametric test in MATLAB. This subject-matter is especially important in Iran where the annual precipitation level is as low as 250 mm. The results showed that the precipitation follows an increasing trend in the region.


Cascade damming impacts on microbial mediated nitrogen cycling in rivers.
Rivers display essential role in nitrogen (N) cycling in terrestrial and aquatic ecosystems, but now they are suffering from damming worldwide, especially from cascade damming. Despite of the importance of microorganisms in biogeochemical nutrient cycling, little attention has been paid to microbial functional biogeography under damming disturbances. Here, the Geochip microarray was applied to investigate the microbial mediated N cycling across the single-dammed Yarlung Tsangpo-Brahmaputra River and the cascade-dammed Lancang-Mekong River in southwest China. Our results showed that the N cycling processes (nitrogen fixation, ammonification, denitrification, nitrification and anammox) were stimulated in reservoirs in both rivers and the enhancement was inversely coupled with hydraulic retention time, but the recovery of N-cycling gene abundance in downstream of dam was intervened by cascade damming. Moreover, N-cycling gene composition was significantly altered in the single-dammed river, while no remarkable change was found in the cascade-dammed reaches. However, different from the unvaried gene composition, cascade damming intervened the recovery of N-cycling gene flow connectivity and resulted in the continuous decrease of connectivity in cascade damming reaches. In addition, in the single-dammed river, nutrients were the important drivers for variation in gene abundance, while they did not influence gene composition. Meanwhile, the abundance and composition of N-cycling genes in the cascade-dammed river were both significantly correlated to geographical parameters and water physical characteristics. Therefore, our study has vital implications for anticipating microbial functional response and biogeochemical feedback to ongoing cascade damming, contributing to the protection of river ecosystems under river regulation.


An exploration of Operating Department Practice students' experiences of placement support during their first perioperative clinical placement.
National and International research shows student anxiety and stress levels are high during times of clinical practice, especially during initial placement allocations. Current literature stresses the importance of preparing students for clinical placements but it is not clear what information students require to adequately prepare them. This study explored Operating Department Practice students' experiences during their first placement. A focus group approach was used to explore the experiences of Operating Department Practice students immediately following their first clinical placements. Following pilot study work a small focus group study was conducted. Data were analysed thematically providing a large amount of in-depth rich data. Three main themes were identified; information, placement and learning experience. Students highlighted inconsistencies in their mentoring, exacerbated by inaccurate information provided by the university. Students felt confused as a result. It was found important for students to feel welcomed and supported by the mentoring processes in order to foster a sense of belonging. Information given by the university should be accurate and effective. This can only be achieved by closer collaboration between the university and practice providers.


Two-cusp plasty for the right ventricular outflow tract in complete repair of tetralogy of Fallot.
A procedure termed two-cusp plasty, which prevents pulmonary regurgitation in complete repair of tetralogy of Fallot, is described.


The function of Wls in ovarian development.
WNT ligand transporter Wls is essential for the WNT dependent developmental and pathogenic processes. The spatiotemporal expression pattern of Wls was investigated in this study. Immature female mice (21-22 days old) were treated with 5 IU, pregnant mare's serum gonadotrophin (PMSG) to stimulate follicular development, followed 48 h later by injection with 5 IU, human chorionic gonadotrophin (hCG) to induce ovulation. The expression of Wls was stimulated in granulosa cells and the forming corpus luteum after hCG administration. To study the function of Wls, the Amhr2tm3(cre)Bhr strain was used to target deletion of Wls in granulosa cells. The deletion of Wls caused a significant decrease in the fertility of WlsAmhr2-Cre female mice. In female WlsAmhr2-Cre mice, decreased ovarian size and number of antral follicles were found. The number of corpus luteum in immature PMSG/hCG primed WlsAmhr2-Cre mice was much less than that in the control group. Compared with control animals, WlsAmhr2-Cre mice have lower serum progesterone levels. RNA sequencing was used to identify genes regulated by Wls after hCG treatment. Several genes known to be critical for follicle development and steroidogenesis were significantly down-regulated, such as Fshr, Lhcgr, Sfrp4, Inhba, Cyp17a1, Hsd3b1, and Hsd17b7. The expression of WNT signaling downstream target genes, Bmp2 and Cyp19a1, also decreased significantly in WlsAmhr2-Cre ovary. In summary, the findings of this study suggest that Wls is critical for female fertility and luteinization.


A translocation t(6;14) in two cases of leiomyosarcoma: Molecular cytogenetic and array-based comparative genomic hybridization characterization.
Leiomyosarcomas are malignant mesenchymal tumors that recapitulate smooth muscle cell differentiation. Tumors are characterized by a genetic heterogeneity with complex karyotypes without a tumor-specific genetic aberration. Their pathobiology is still poorly understood and no specific targeted treatment is currently available for these aggressive tumors. For six leiomyosarcomas, cells were cultured and analyzed by combined binary ratio labeling fluorescence in situ hybridization (COBRA-FISH) karyotyping. A t(6;14) was identified in two cases. FISH breakpoint mapping of case L1339 reveals a breakpoint at chromosome 6p21.31 close to HMGA1, and a small deletion was observed on the distal side of the gene. A small homozygous deletion was also found in the breakpoint region of chromosome 14q24.1 involving ACTN1. The second case revealed a der(6)t(6;14)(p21.1;q21.3), with a duplication adjacent to the breakpoint at chromosome 6. Confirmatory FISH revealed a second leiomyosarcoma with an aberration at 14q24.1. Alterations at this locus were found in 5% (2 of 39) of the leiomyosarcomas in this study. The other identified breakpoints appeared to be non-recurrent, because they were not detected in other leiomyosarcomas, uterine leiomyomas, undifferentiated spindle cell sarcomas, or undifferentiated pleomorphic sarcomas.


A comparison between genetically humanized and chimeric liver humanized mouse models for studies in drug metabolism and toxicity.
Mice that have been genetically humanized for proteins involved in drug metabolism and toxicity and mice engrafted with human hepatocytes are emerging and promising in vivo models for an improved prediction of the pharmacokinetic, drug-drug interaction and safety characteristics of compounds in humans. The specific advantages and disadvantages of these models should be carefully considered when using them for studies in drug discovery and development. Here, an overview on the corresponding genetically humanized and chimeric liver humanized mouse models described to date is provided and illustrated with examples of their utility in drug metabolism and toxicity studies. We compare the strength and weaknesses of the two different approaches, give guidance for the selection of the appropriate model for various applications and discuss future trends and perspectives.


Fenton oxidation treatment of oxytetracycline fermentation residues: Harmless performance and bioresource properties.
The pharmaceutical factories of oxytetracycline (OTC) massively produce OTC fermentation residues (OFRs). The high content of residual OTC and antibiotic resistance genes in OFRs must to be considered and controlled at an acceptable level. This study therefore investigated the applicability of Fenton oxidation in OTC degradation and resistant gene inactivation of OFRs. The results revealed that Fe2+ as catalyzer could very rapidly activate H2O2 to produce HO•, leading to instantaneous degradation of OTC. The optimum conditions for OTC removal were 60 mM H2O2 and 140 mg/L Fe2+ under pH 7. After Fenton oxidation treatment, the release of water-soluble polysaccharides, NO3-N, and PO4-P was enhanced, whereas for proteins and NH3-N were reduced. Three soluble fluorescence components (humic, tryptophan-like, and humic acid-like substances) were identified through fluorescence spectra with parallel factor analysis, and their reduction exceeded 50% after Fenton oxidation. There were twelve intermediates and three degradation pathways of OTC in OFRs during Fenton process. According to toxicity prediction, the comprehensive toxicity of OTC in OFRs was alleviated via Fenton oxidation treatment. In addition, Fenton oxidation showed the ability to reduce antibiotic resistance genes and mobile genetic elements, and even tetO, tetG, intI1, and intI2 were eliminated completely. These results suggested that Fenton oxidation treatment could be an efficient strategy for removing OTC and resistance genes in OFRs.


Hepatic tumours and radiotherapy.
We present the update of the recommendations of the French society of oncological radiotherapy on hepatic tumours. Recent technological progress led to develop the concept of focused liver radiation therapy. We must distinguish primary and secondary tumours, as the indications are restricted and must be discussed as an alternative to surgical or medical treatments. The tumour volume, its liver location close to the organs at risk determine the irradiation technique (repositioning method, total dose delivered, dose fractionation regimens). Tumour (and liver) breathing related motions should be taken into account. Strict dosimetric criteria must be observed with particular attention to the dose-volume histograms of non-tumoral liver as well as of the hollow organs, particularly in case of hypofractionated high dose radiotherapy "under stereotaxic conditions". Stereotactic body radiotherapy is being evaluated and is often preferred to radiofrequency for primary or secondary tumours (usually less than 5cm). An adaptation can be proposed, with a conformal fractionated irradiation protocol with or without intensity modulation, for hepatocellular carcinomas larger than 5cm.


Alteration of erythrocyte membrane fluidity by heavy metal cations.
Fluorescence polarization measurements were carried out on erythrocyte ghosts treated with heavy metal cations. Membranes labelled with the fluorescent lipid probe all-trans 1,6-diphenyl-1,3, 5-hexatriene (DPH) had increased DPH polarization (P) values, consistent with increased membrane lipid viscosity, when treated with 10(-3)-10(-2) M of the chloride salts of cadmium, zinc or lead for 1 hour at 37 degrees C, but not with calcium. Using cadmium as a prototype heavy metal, additional studies showed that exposure of ghosts to cadmium also increased the native protein fluorescence polarization. These increases in P values were observed at temperatures ranging from 15-40 degrees C. These data suggest that interaction of cadmium and other heavy metals with cellular membranes may alter membrane lipid and possibly membrane protein fluidity, which may contribute to abnormal cellular function.


Ganglioside content and composition of cells from normal and atherosclerotic human aorta.
The ganglioside content and composition of cells obtained by enzyme digestion of 2 layers of human aortic intima were investigated. Five gangliosides were identified in cells isolated from the external musculo-elastic intimal layer adjacent to the media: GM3, GM1, GD3, GD1a, and GT1b. The same gangliosides plus ganglioside Gx, the chromatographic mobility of which corresponded to the mobility of ganglioside GD1b from human brain, were found in cells from the internal elastic-hyperplastic intimal layer adjacent to the vessel lumen. In both layers, the major cellular ganglioside was GM3 which represented 60% of the total cellular ganglioside content. The ganglioside content was lower in cells obtained from fatty streaks compared to cells isolated from unaffected intima. The amount of di- and trisialogangliosides in atherosclerotic plaque cells was lower, and that of monosialogangliosides higher than in cells isolated from unaffected intima. The amount of GM3 was mainly responsible for the difference in the total ganglioside content of cells obtained from different lesion types. On the whole, cells from fatty streaks contained smaller amounts of total gangliosides, whereas cells from plaques had greater total ganglioside content, than cells from unaffected intima.


Acute hyperosmolar hyperglycaemic state in cystic fibrosis-related diabetes caused by glucocorticoid and itraconazole interaction.
Hyperosmolar hyperglycaemic state (HHS) has not previously been reported in cystic fibrosis-related diabetes (CFRD). We report the case of a 15-year old boy with stable CFRD who developed acute HHS after treatment with glucocorticoids and itraconazole for presumed allergic broncho-pulmonary aspergillosis (ABPA). This case highlights the dangerous and preventable combination of high glucose intake, glucocorticoids and itraconazole inhibition of CYP3A4 (with resultant glucocorticoid accumulation) that can result in a state of life- threatening HHS in an adolescent with previously stable CFRD.


Pinopodes: Recent advancements, current perspectives, and future directions.
Successful embryo implantation is a complex and highly regulated process involving precise synchronization between the fetal-derived trophoblast cells and maternal uterine luminal epithelium. Multiple endocrine-driven factors are important for controlling the timely receptivity of the uterus, and this complexity underscores implantation failure as a major cause of recurrent infertility associated with assisted reproductive technologies. One particular cellular structure often hypothesized to promote receptivity is the pinopode or uterodome - a hormonally regulated, large cellular protrusion on the uterine epithelial surface. Recent clinical studies associate pinopodes with favorable fertility outcomes in women, and because they are directly linked to an increase in progesterone levels, the potential utility of these hormone-regulated cell biological structures in predicting or improving implantation in a clinical setting holds promise. In this review, we aim to generate interest in pinopodes from the broader cell biology and endocrinology communities, re-examine methodologies in pinopode research, and identify priorities for future investigation of pinopode structure and function in women's reproductive health.


Abdominal compression: a new technique for improved computed tomographic images.
A technique utilizing abdominal compression during CT scanning with resultant improvement in image quality is described. Advantages included decrease or elimination of streak artifacts; differentiation of nonopacified bowel from other soft tissue densities; and better delineation of tissue planes.


Validation of Opportunistic Artificial Intelligence-Based Bone Mineral Density Measurements in Coronary Artery Calcium Scans.
Previously we reported a manual method of measuring thoracic vertebral bone mineral density (BMD) using quantitative CT in noncontrast cardiac CT scans used for coronary artery calcium (CAC) scoring. In this report, we present validation studies of an artificial intelligence-based automated BMD measurement (AutoBMD) that recently received FDA approval as an opportunistic add-on to CAC scans. A deep learning model was trained to detect vertebral bodies. Subsequently, signal processing techniques were developed to detect intervertebral discs and the trabecular components of the vertebral body. The model was trained using 132 CAC scans comprising 7,649 slices. To validate AutoBMD, we used 5,785 cases of manual BMD measurements previously reported from CAC scans in the Multi-Ethnic Study of Atherosclerosis. Mean ± SD for AutoBMD and manual BMD were 166.1 ± 47.9 mg/cc and 163.1 ± 46 mg/cc, respectively (P = .006). Multi-Ethnic Study of Atherosclerosis cases were 47.5% male and 52.5% female, with age 62.2 ± 10.3. A strong correlation was found between AutoBMD and manual measurements (R = 0.85, P < .0001). Accuracy, sensitivity, specificity, positive predictive value and negative predictive value for AutoBMD-based detection of osteoporosis were 99.6%, 96.7%, 97.7%, 99.7% and 99.8%, respectively. AutoBMD averaged 15 seconds per report versus 5.5 min for manual measurements (P < .0001). AutoBMD is an FDA-approved, artificial intelligence-enabled opportunistic tool that reports BMD with Z-scores and T-scores and accurately detects osteoporosis and osteopenia in CAC scans, demonstrating results comparable to manual measurements. No extra cost of scanning and no extra radiation to patients, plus the high prevalence of asymptomatic osteoporosis, make AutoBMD a promising candidate to enhance patient care.


Rich resource environment of fish farms facilitates phenotypic variation and virulence in an opportunistic fish pathogen.
Phenotypic variation is suggested to facilitate the persistence of environmentally growing pathogens under environmental change. Here, we hypothesized that the intensive farming environment induces higher phenotypic variation in microbial pathogens than natural environment, because of high stochasticity for growth and stronger survival selection compared to the natural environment. We tested the hypothesis with an opportunistic fish pathogen Flavobacterium columnare isolated either from fish farms or from natural waters. We measured growth parameters of two morphotypes from all isolates in different resource concentrations and two temperatures relevant for the occurrence of disease epidemics at farms and tested their virulence using a zebrafish (Danio rerio) infection model. According to our hypothesis, isolates originating from the fish farms had higher phenotypic variation in growth between the morphotypes than the isolates from natural waters. The difference was more pronounced in higher resource concentrations and the higher temperature, suggesting that phenotypic variation is driven by the exploitation of increased outside-host resources at farms. Phenotypic variation of virulence was not observed based on isolate origin but only based on morphotype. However, when in contact with the larger fish, the less virulent morphotype of some of the isolates also had high virulence. As the less virulent morphotype also had higher growth rate in outside-host resources, the results suggest that both morphotypes can contribute to F. columnare epidemics at fish farms, especially with current prospects of warming temperatures. Our results suggest that higher phenotypic variation per se does not lead to higher virulence, but that environmental conditions at fish farms could select isolates with high phenotypic variation in bacterial population and hence affect evolution in F. columnare at fish farms. Our results highlight the multifaceted effects of human-induced environmental alterations in shaping epidemiology and evolution in microbial pathogens.


Characteristics of antibiotic resistance genes and microbial community distribution in Wanfeng Lake, upper Pearl River, China.
Wanfeng Lake, a highland lake in the upper part of the Pearl River Basin, China, has long been disturbed by aquaculture and human activities, resulting in the accumulation of antibiotics and antibiotic resistance genes (ARGs), which pose a major threat to humans and animals. In this study, 20 antibiotics, 9 ARGs, 2 mobile genetic elements (intl1 and intl2), and microbial community structure were investigated in Wanfeng Lake. The results of the study showed that the total concentration of antibiotics in surface water was 372.72 ng/L, with ofloxacin (OFX) having the highest concentration (169.48 ng/L), posing a high ecological risk to aquatic organisms. The total concentration of antibiotics in sediments was 235.86 ng/g, with flumequine (FLU) having the highest concentration (122.54 ng/g). This indicates that the main type of antibiotics in Wanfeng Lake are quinolones. QPCR analysis results of the relative abundance of ARGs in both surface water and sediments showed that sulfonamide resistance genes > macrolide resistance genes > tetracycline resistance genes > quinolone resistance genes, indicating that sulfonamide resistance genes were the dominant type. The metagenomic results showed that the predominant microorganisms in the sediment under the phylum level were Planctomycetes, Proteobacteria, Euryarchaeota, and Chloroflexi. Pearson's correlation analysis showed a significantly positive correlation between antibiotics and environmental factors with ARGs in Wanfeng Lake and a significant positive correlation between antibiotics and ARGs with microorganisms in sediments. This suggests that there is a potential pressure of antibiotics on ARGs, while microorganisms provide the driving force for the evolution and spread of ARGs. This study provides a basis for further research on the occurrence and spread of antibiotics and ARGs in Wanfeng Lake. A total of 14 antibiotics were detected in surface water and sediments. OFX poses a high ecological risk in all points of surface water. Antibiotics and ARGs were significantly positively correlated in Wanfeng Lake. Antibiotics and ARGs in sediments were positively correlated with microorganisms.


Usefulness of specific IgE antibodies to ω-5 gliadin in the diagnosis and follow-up of Japanese children with wheat allergy.
Gliadins have been implicated in IgE-mediated allergy to ingested wheat. ω-5 gliadin seems to be a clinically relevant allergen component in children with immediate wheat allergy (WA), but contradictory results have been published. To investigate whether specific IgE (sIgE) antibodies to recombinant ω-5 gliadin could be used as a marker for oral wheat challenge outcome in wheat-sensitized children and to study whether measurements of sIgE to ω-5 gliadin are useful in monitoring children with WA to assess whether the allergy is outgrown or persistent. Eighty-eight serum samples from children sensitized to wheat were collected consecutively. sIgE to ω-5 gliadin was related to a physician's diagnosis of WA. Sixty-seven of 88 children sensitized to wheat were diagnosed as having WA. The geometric mean concentrations of sIgE to ω-5 gliadin were 2.04 kU(A)/L (range, <0.35-100 kU(A)/L) in children with WA and 0.40 kU(A)/L (range, <0.35-1.8 kU(A)/L) in children without WA. At follow-up, after being on a wheat-free diet for approximately 2 years, the sIgE titers to ω-5 gliadin were below 0.35 kU(A)/L (mean, 0.34 kU(A)/L; range, 0.34-2.3 kU(A)/L) in 10 of 15 children with outgrown WA. Conversely, in 12 of 14 children with persistent WA, the sIgE titers to ω-5 gliadin were still elevated (mean, 5.89 kU(A)/L; range, 0.34-16.3 kU(A)/L). sIgE to ω-5 gliadin can be used as an accurate alternative to potentially dangerous wheat food challenges in monitoring WA.


Impacts of viaduct and geometry configurations on the distribution of traffic-related particulate matter in urban street canyon.
Viaduct is a ubiquitous transportation infrastructure in the congested megacities worldwide to improve the accessibility and capacity of urban transportation network. However, there is a lack of understanding of the impacts of the interplay between viaduct-ground emissions and viaduct-canyon configurations on the particle distribution in urban street canyon. To fill the research gap, we conducted vertical measurements of particle number concentrations (PNCs) at different heights of "street canyon along a viaduct" to reveal effect of viaduct on the vertical distribution of PNCs in street canyon. Observation results indicated that the vertical profiles of PNCs exhibited bimodal distribution patterns, which were more significant for coarse particles than fine particles. The one peak appeared at ground level and the other at the viaduct height, indicating the impacts of "double" emission sources (i.e., the emissions on the ground and viaduct) and the hindrance of viaduct to particle diffusion. We further modelled the role of viaduct in street canyon through Computational Fluid Dynamics (CFD) simulations to reveal the vertical distribution of particles under different viaduct-canyon configurations and discern the contributions of viaduct and ground emissions to the particle distribution. Simulation results showed that viaduct changed airflow field and turbulence structure and elevated particle concentrations in street canyon while the optimized viaduct-canyon configurations including higher viaduct height (12 > 10 > 8 m), smaller aspect ratio (0.5 > 0.67 > 1), and shorter centerline distance (0 > 1 > 2 m) between canyon and viaduct could bring better dispersion conditions and lower particle concentrations. Additionally, ground emissions contributed more to the vertical distribution of particles on the leeward side of street canyon than viaduct emissions while the windward side displayed the opposite characteristics to the leeward side. These findings revealed the general patterns of particle diffusion in viaduct-canyon configurations and provided implications into viaduct design and traffic management to alleviate local particulate pollution.


Synthesis and Optoelectronic Properties of Thiophene Donor and Thiazole Acceptor Based Blue Fluorescent Conjugated Oligomers.
We report on the synthesis and characterization of low band gap, blue light emitting and thermal stable conjugated oligomer by Wittig condensation. Thiophene and thiazole type of donor-acceptor based series of conjugated oligomers, Oligo-4,5-bis-[2-[5-[2-thiophene-2-yl-vinyl]thiophene-2-yl]-vinyl]-thiazole (OBTV-TZ) and Oligo-2,4,5-Tris-[2-[5-[2-thiophene-2-yl-vinyl]thiophene-2-yl]-vinyl]-thiazole (OTTV-TZ) were synthesized. These oligomers were confirmed by FT-IR and (1)H-NMR and LC/MS analysis. The effect of the number of thiophene rings on the optical, electrochemical, thermal and morphological properties of the oligomers were systematically investigated. Both oligomers were exhibited almost same absorption wavelength in methanol solution (λmax = 365 nm and 369 nm) which indicates both oligomers illustrate similar intra molecular charge transfer (ICT). In solid state, the oligomers were exhibited broadening peaks with higher onset absorptions (λmax = 600 nm and 580 nm). The photoluminescence absorption spectrum of the oligomers was observed at 433 nm and 434 nm respectively in methanol solution with blue emission. The electrochemical band gap ([Formula: see text]) of the OBTV-TZ was 1.55 eV (low band gap) and OTTV-TZ was exhibited greater highest occupied molecular orbital (HOMO) value (E HOMO = -6.6 eV). Moreover morphological parameters of both oligomer film of 2D and 3D diagrams were observed by using AFM studies.