Traumatic abdominal wall hernia--four cases and a review of the literature.
To review blunt traumatic abdominal wall hernias (TAWHs) in our institution. Retrospective review of blunt abdominal trauma cases over a 6-month period. Four patients with TAWH were identified. The mean age was 36 years. Three had been involved in vehicular collisions, and 1 had been assaulted with a large stone. All were diagnosed on presentation, 3 by computed tomography scan and 1 clinically. Two were repaired as emergencies, and 1 was repaired after 4 months. The 4th patient refused surgery. This uncommon injury requires a high index of suspicion and a low threshold for intervention. CT scan offers the best imaging potential.


Cytologic grading of canine and feline spindle-cell sarcomas of soft tissues and its correlation with histologic grading.
In humans, soft tissue spindle cell sarcomas (STSCS) grading is considered a useful parameter in determining prognosis and therapy, and it is recognized as an important prognostic factor in canine STSCS. The purpose of this study was to assess the utility and the accuracy of a cytologic grading system on fine needle aspiration cytology (FNAC) smears of canine and feline cutaneous and subcutaneous STSCS .Thirty-three cases of cytologically diagnosed STSCS were included. The smears and their tumour sections were cytologically and histologically graded, according to established methods in human oncology.Canine STSCS showed a cyto/histologic concordance in 12/20 cases (60%). Concordance was observed in 4/8 (50%) of grade 1, in 8/12 (67%) of grade 2, and in 0 cases of grade 3. Feline STSCS showed concordance in 11/13 cases (85%). Concordance was observed in 5/6 (83%) of grade 1, in 4/4 (100%) of grade 2, and in 2/3 (66.6%) of grade 3 cases. The overall concordance in the entire canine and feline population was 70%. The gradewise concordance was 65% in grade 1, 75% in grade 2, and 66% in grade 3 cases. The overall concordance is similar to that reported in humans. Although a wider population is required to strengthen our findings, these results suggest that cytologic grading of STSCSs may be a useful tool for therapeutic and prognostic evaluations in dogs and cats.


Respiratory virus RNA is detectable in airborne and droplet particles.
Aerosol transmission routes of respiratory viruses have been classified by the WHO on the basis of equilibrium particle size. Droplet transmission is associated with particles sized >5 µm in diameter and airborne transmission is associated with particles sized ≤5 µm in diameter. Current infection control measures for respiratory viruses are directed at preventing droplet transmission, although epidemiological evidence suggests concurrent airborne transmission also occurs. Understanding the size of particles carrying viruses can be used to inform infection control procedures and therefore reduce virus transmission. This study determined the size of particles carrying respiratory viral RNA produced on coughing and breathing by 12 adults and 41 children with symptomatic respiratory infections. A modified six-stage Andersen Sampler collected expelled particles. Each stage was washed to recover samples for viral RNA extraction. Influenza A and B, parainfluenza 1, 2 and 3, respiratory syncytial virus (RSV), human metapneumovirus and human rhinoviruses (hRV) were detected using RT-PCR. On breathing, 58% of participants produced large particles (>5 µm) containing viral RNA and 80% produced small particles (≤5 µm) carrying viral RNA. On coughing, 57% of participants produced large particles containing viral RNA and 82% produced small particles containing viral RNA. Forty five percent of participants produced samples positive for hRV viral RNA and 26% of participants produced samples positive for viral RNA from parainfluenza viruses. This study demonstrates that individuals with symptomatic respiratory viral infections produce both large and small particles carrying viral RNA on coughing and breathing.


The phylogenetic relationships of Eeniella nana Smith, Batenburg-van der Vegte et Scheffers based on the partial sequences of 18S and 26S ribosomal RNAs (Candidaceae).
Two strains of Eeniella nana were examined for their partial base sequences of 18S and 26S rRNAs. In the partial base sequences of 18S rRNA (positions 1451 through 1618, 168 bases) the strains of E. nana have five, five, four and eleven base differences with those of Dekkera bruxellensis (type species), D. anomala (and Brettanomyces anomalus), D. naardenensis and D. custersiana, respectively. In the 26S rRNA partial base sequencings (positions 1611 through 1835, 225 bases and positions 493 through 622, 130 bases) the base differences were 46, 43, 34 and 40 and the percent similarities were 53-54, 51-54, 56-57 and 51-53, respectively. The sequence data obtained are discussed phylogenetically and taxonomically, especially on retention of the generic name Eeniella.


Prurigo Nodularis: A Review of IL-31RA Blockade and Other Potential Treatments.
Prurigo nodularis (PN), or chronic prurigo, is a distinct disease characterized by the presence of chronic pruritus and multiple localized or generalized pruriginous lesions. While there are few epidemiologic studies describing the prevalence of PN, it is thought to be relatively rare, but is likely underdiagnosed and underrecognized. Management of PN is challenging, and there are no approved drugs that can relieve the distress as well as signs and symptoms caused by PN and its pruritus. Improved understanding of the neuroimmune pathways involved in management of PN have led to discovery and trial of emerging treatments for PN. This publication provides an overview of PN and discusses several of the most promising treatments that are undergoing evaluation.


A developmental approach to severe depression.
Reduced rapid-eye-movement (REM) sleep latency and increased REM sleep activity are associated not only with increased risk of recurrent depressive episodes but also with shortened time to the onset of subsequent episodes. Increased REM sleep activity might be a sign of attempt to excite the photic-responsive brain regions during the night, and there is a negative correlation between regional blood flow in the dorsolateral prefrontal cortex and REM sleep. The relative deactivation of the dorsolateral prefrontal cortex as a result of a developmental abnormality could explain the increased REM sleep activity during the first half of the night and the subsequent terminal insomnia among depressed subjects.


Characterization of the cholesterol biosynthetic pathway in Dioscorea transversa.
Cholesterol is the precursor of bioactive plant metabolites such as steroidal saponins. An Australian plant, Dioscorea transversa, produces only two steroidal saponins: 1β-hydroxyprotoneogracillin and protoneogracillin. Here, we used D. transversa as a model in which to elucidate the biosynthetic pathway to cholesterol, a precursor to these compounds. Preliminary transcriptomes of D. transversa rhizome and leaves were constructed, annotated, and analyzed. We identified a novel sterol side-chain reductase as a key initiator of cholesterol biosynthesis in this plant. By complementation in yeast, we determine that this sterol side-chain reductase reduces Δ24,28 double bonds required for phytosterol biogenesis as well as Δ24,25 double bonds. The latter function is believed to initiate cholesterogenesis by reducing cycloartenol to cycloartanol. Through heterologous expression, purification, and enzymatic reconstitution, we also demonstrate that the D. transversa sterol demethylase (CYP51) effectively demethylates obtusifoliol, an intermediate of phytosterol biosynthesis and 4-desmethyl-24,25-dihydrolanosterol, a postulated downstream intermediate of cholesterol biosynthesis. In summary, we investigated specific steps of the cholesterol biosynthetic pathway, providing further insight into the downstream production of bioactive steroidal saponin metabolites.


Dynamic Quantitative Iodine Myocardial Perfusion Imaging with Dual-Layer CT using a Porcine Model.
Ischemic heart disease is the globally leading cause of death. When using coronary CT angiography, the functional hemodynamics within the myocardium remain uncertain. In this study myocardial CT perfusion imaging using iodine contrast agent demonstrated to strongly improve the assessment of myocardial disorders. However, a retrieval of such dynamics using Hounsfield units from conventional CT poses concerns with respect to beam-hardening effects and low contrast-to-noise ratio (CNR). Dual-energy CT offers novel approaches to overcome aforementioned limitations. Quantitative peak enhancement, perfusion, time to peak and iodine volume measurements inside the myocardium were determined resulting in 0.92 mg/ml, 0.085 mg/ml/s 17.12 s and 29.89 mg/ml*s, respectively. We report on the first extensive quantitative and iodine-based analysis of myocardial dynamics in a healthy porcine model using a dual-layer spectral CT. We further elucidate on the potential of reducing the radiation dose from 135 to 18 mGy and the contrast agent volume from 60 to 30 mL by presenting a two-shot acquisition approach and measuring iodine concentrations in the myocardium in-vivo down to 1 mg/ml, respectively. We believe that dynamic quantitative iodine perfusion imaging may be a highly sensitive tool for the precise functional assessment and monitoring of early myocardial ischemia.


Contraction induced by antibodies to paramyosin in glycerinated fibers of Barnacle giant muscle in an ATP-deficient medium: a possible function of paramyosin.
Glycerinated giant muscle fibers of the barnacle Balanus rostratus in an ATP-deficient solution respond to antibodies to paramyosin (aPM) by an isometric tension development followed by an immediate spontaneous relaxation. The aPM presence does not affect the subsequent contraction and relaxation of the fibers in suitable ATP-containing media. The effects of ATP and aPM present together in a contracting medium are additive. The aPM effect is caused assumedly by a sudden shortening of some highly elastic connecting filaments which are linked in a stretched and strained state to the thick filament by its paramyosin, aPM dissociates this link. Possible specific functions of paramyosin in various types of muscles are discussed.


Interpersonal Musical Synchronization and Prosocial Behavior in Children: No Effects in a Controlled Field Experiment.
Prosocial effects of music have recently attracted increased attention in research and media. An often-cited experiment, carried out by Kirschner and Tomasello in 2010 under laboratory conditions, found that children at the age of four years were more willing to help each other after they had engaged in synchronous musical activities. The aim of the current study was to replicate this research under controlled field conditions in the children's social environment, and to disentangle the musical synchronization effect by introducing a verbal interaction (singing together) and a motor interaction (tapping together) task, contrasted by an asynchronous control condition. In a between-participants design, no effects of musical synchronization nor the children's gender were found. Furthermore, age was not related to prosocial behavior. Explanations are systematically discussed, yet it remains possible that the original effect found in 2010 might be overestimated and less consistently reproducible as previously assumed.


Species difference in brain penetration of P-gp and BCRP substrates among monkey, dog and mouse.
The brain penetration of 19 drugs, including P-glycoprotein (P-gp) and/or breast cancer resistance protein (BCRP) substrates, was compared among mice, cynomolgus monkeys and beagle dogs. The brain-to-plasma concentration ratios (Kp,brain) of the tested compounds in monkey and dog showed good correlation, whereas species differences were observed between non-rodents (monkey/dog) and rodents (mouse). In particular, the Kp,brain values of 7 compounds out of 12 P-gp substrates (Kp,brain ratio in P-gp knockout mice versus wild-type mice ≥3) in monkey and dog were more than three-fold higher than those in mice and a similar trend was observed in the brain-to-plasma unbound concentration ratios (Kp,uu,brain). The cerebral spinal fluid (CSF) drug concentrations (CCSF), a surrogate for unbound brain concentration (Cu,brain), were also compared between dog and monkey, and the CSF-to-plasma unbound concentration ratios (Kp,uu,CSF) of BCRP substrates in dog were notably higher than those in monkey, although non-bcrp substrates showed good correlation. Also, the Kp,uu,CSF values of BCRP substrates in dog were clearly higher than the Kp,uu,brain values, indicating that the dog CCSF of BCRP substrates was not suitable as a surrogate of Cu,brain. These observations should be useful when selecting the appropriate animal models for CNS drug discovery.


A randomised controlled trial of bilateral dual transversus abdominis plane blockade for laparoscopic appendicectomy.
We investigated the effects of pre-operative ultrasound-guided bilateral dual transversus abdominis plane blocks on pain when sitting up and pain at rest after laparoscopic appendicectomy. We allocated 28 participants to injection with 60 ml ropivacaine 0.375% and 28 participants to 60 ml isotonic saline. The median (IQR [range]) cumulative pain scores during the first 12 postoperative hours were less after ropivacaine than saline (maximum 120): on sitting, 34 (19-46 [0-59]) vs 50 (30-59 [0-97]), respectively, p = 0.009; and at rest, 25 (10-33 [0-49]) vs 31 (24-43 [0-72]), respectively, p = 0.035. There were no differences in morphine consumption, nausea, vomiting, time in recovery or time to walk.


Exploring the indirect effect of loneliness in the association between problematic use of social networks and cognitive function in Lebanese adolescents.
Problematic use of social networks is a widespread problem that may exert deleterious impacts on cognitive functions. Moreover, studies have added an important link between loneliness and its harmful effect on cognitive functions. Other studies have also revealed that problematic use of social networks among teenagers has a pejorative influence on their social interactions, leading to increased social isolation. Therefore, the goal of our research was to investigate the link between problematic use of social networks and cognitive function in a group of Lebanese adolescents while also taking into consideration the indirect role of loneliness in this relationship. This cross-sectional study, which was carried out between January and April 2022, included 379 teenagers (aged between 13 and 17 years), from all Lebanese governorates. The PROCESS SPSS Macro version 3.4, model four was used to compute three pathways. Pathway A determined the regression coefficient for the effect of problematic use of social networks on loneliness; Pathway B examined the association between loneliness and cognitive function, and Pathway C' estimated the direct effect of problematic use of social networks on cognitive function. Higher negative social comparison, addictive consequences of problematic use of social networks, and loneliness were significantly associated with worse cognitive function. Loneliness mediated the association between negative social comparison and worse cognitive function, as well as between addictive consequences of problematic use of social networks and worse cognitive function. In addition, higher financial burden was significantly correlated with worse cognitive function, whereas higher physical activity was related to better cognitive function. In sum, the current study supports that problematic use of social networks is negatively associated with adolescents' cognitive function, where loneliness seems to play a pivotal role in this equation. The results thus endorse the importance of helping Lebanese adolescents to overcome problematic use of social networks and recover from their loneliness, to achieve a better cognitive/academic performance.


The fungicide "fluopyram" promotes pepper growth by increasing the abundance of P-solubilizing and N-fixing bacteria.
Fluopyram, as a reasonably good fungicide and nematicide, is widely used to control agricultural pests worldwide. However, its effects on soil microbial communities and plant growth remain controversial. Therefore, in this study, we investigated the effects of three concentrations (0.5, 1.5, and 5.0 mg/kg) of the fluopyram (Lufuda 41.7% a.i., suspension concentrate, SC) on the pepper rhizosphere microorganisms and pepper seedlings growth in a plant growth room. Moreover, we also investigated the dissipation of fluopyram in the soil, pepper roots, and leaves across a time interval of 45 days. The results showed that fluopyram application increased the number of pepper rhizosphere phosphate (P)-solubilizing bacteria, the abundance of nitrogen (N)-fixing nifH genes, and the pepper seedling growth. The results of terminal restriction fragment length polymorphism (T-RFLP) analysis demonstrated that fluopyram did not alter rhizosphere bacterial community structure and diversity. However, fluopyram did increase the relative abundances of 138 bp and 400 bp T-RFs closely representing Bacillus and Rhizobium genera that were known as efficient plant growth promoting bacteria with P-solubilization and N-fixation properties. Corresponding to the increase of plant growth and beneficial microbes, the half-lives of fluopyram in soil and plant tissues also decreased that nevertheless suggested the role of plant-microbe interactions in the faster removal of fluopyram after application. Our results suggest that short-lived and easily degradable pesticides may have less toxicological effects on soil health while their judicious use may reshape plant-microbe interactions in favor of the plant growth.


Patient predictors of histopathologic response after photodynamic therapy of Barrett's esophagus with high-grade dysplasia or intramucosal carcinoma.
Photodynamic therapy (PDT) has been used extensively for endoscopic ablation of Barrett's esophagus with high-grade dysplasia (HGD) or intramucosal carcinoma. To identify patient variables that influence the likelihood of response to PDT. A retrospective cohort study. Tertiary-referral center. A total of 116 patients with Barrett's esophagus and with HGD, intramucosal carcinoma, or T1 cancer. PDT with porfimer sodium. (1) Ablation of HGD and/or intramucosal carcinoma and (2) eradication of all Barrett's epithelium. Of the patients, 51% underwent treatment for HGD and 49% of patients had intramucosal carcinoma or T1 cancer. At 12-month follow-up, ablation of HGD and/or cancer was observed in 70% of patients, and ablation of all Barrett's epithelium was observed in 39%. In multivariate analysis, the pretreatment length of Barrett's esophagus was inversely correlated with successful ablation of all Barrett's epithelium. Patients with Barrett's esophagus length more than 3 cm were less likely to experience complete ablation compared with patients with Barrett's esophagus length 3 cm or less (odds ratio [OR] 0.15 [95% CI, 0.04-0.50]). Patients with intramucosal carcinoma were not significantly less likely to experience elimination of HGD and/or cancer (OR 0.77 [95% CI, 0.30-2.00]) or ablation of all Barrett's epithelium (OR 0.82 [95% CI, 0.32-2.07]) compared with patients with HGD alone. Retrospective study, limited sample size without a control group for comparison. PDT of Barrett's esophagus with HGD, intramucosal carcinoma, or T1 cancer can result in ablation of dysplasia and/or eradication of all Barrett's epithelium. Factors associated with the likelihood of response include length of Barrett's esophagus. The presence of intramucosal carcinoma or T1 cancer was not associated with higher likelihood of treatment failure.


Down-regulation of c-jun N-terminal kinase-activator protein-1 signaling pathway by Ginkgo biloba extract in human peripheral blood T cells.
The activation of T lymphocytes contributes to inflammatory process of cardiovascular and cerebrovascular diseases. We investigated the effects of the extract of Ginkgo biloba (EGb), an ancient plant preserving antioxidant property, on phorbol 12-myristate 13-acetate+ionomycin or anti-CD3+anti-CD28 monoclonal antibodies-activated T cells. Human peripheral blood T cells were negatively selected from whole blood. Cytokines were measured by ELISA, cell surface markers by flow cytometry and the activities of transcription factors and kinases were determined by electrophoresis mobility shift assays, kinase assays and transfection assays. We showed that EGb inhibited several cytokines, including tumor necrosis factor-alpha, interleukin (IL)-2, IL-4 and interferon-gamma production from activated T cells. Electrophoresis mobility shift assay analysis indicated that EGb down-regulated activator protein-1 (AP-1) but not nuclear factor kappa B DNA-binding activity. In addition, EGb inhibited c-jun N-terminal kinase but not extracellular signal regulated protein kinase activity. The inhibitory specificity on AP-1 by EGb was also demonstrated in transfection assays. The inhibition of AP-1 signaling pathway in T cells by EGb provides a support for its efficacy in cardiovascular and cerebrovascular diseases and raises a therapeutic potential for this drug in activated T cell-mediated pathologies.


Low molecular weight GTP-binding proteins in cardiac muscle. Association with a 32-kDa component related to connexins.
Low molecular weight GTP-binding proteins and their cellular interactions were examined in cardiac muscle. Heart homogenate was separated into various subcellular fractions by differential and sucrose density gradient centrifugation. Various fractions were separated by sodium dodecyl sulfate-gel electrophoresis, blotted to nitrocellulose, and GTP-binding proteins detected by incubating with [alpha-32]GTP. Three polypeptides of M(r) 23,000, 26,000, and 29,000 were specifically labeled with [alpha-32P]GTP in all the fractions examined and enriched in sarcolemmal membranes. The 23-kDa polypeptide was labeled to a higher extent with [alpha-32P]GTP than the 26- and 29-kDa polypeptides. A polypeptide of M(r) 40,000 was weakly labeled with [alpha-32P]GTP in the sarcolemmal membrane and tentatively identified as Gi alpha by immunostaining with anti-Gi alpha antibodies. Cytosolic GTP-binding proteins were labeled with [alpha-32P]GTP and their potential sites of interaction investigated using the blot overlay approach. A polypeptide of 32 kDa present in sarcolemmal membranes, intercalated discs, and enriched in heart gap junctions was identified as a major site of interaction. The low molecular weight GTP-binding proteins associated with the 32-kDa polypeptide through a complex involving cytosolic components of M(r) 56,000, 36,000, 26,000, 23,000, and 12,000. A monoclonal antibody against connexin 32 from liver strongly recognized the 32-kDa polypeptide in heart gap junctions, whereas polyclonal antibodies only weakly reacted with this polypeptide. The low molecular weight GTP-binding proteins associated with a 32-kDa polypeptide in liver membranes that was also immunologically related to connexin 32. These results indicate the presence of a subset of low molecular weight GTP-binding proteins in a membrane-associated and a cytoplasmic pool in cardiac muscle. Their association with a 32-kDa component that is related to the connexins suggests that these polypeptides may be uniquely situated to modulate communication at the cell membrane.


GSH-depleting and H2O2-self-supplying hybrid nanozymes for intensive catalytic antibacterial therapy by photothermal-augmented co-catalysis.
Nanozyme-based chemodynamic therapy (CDT) has shown tremendous potential in the treatment of bacterial infections. However, the CDT antibacterial efficacy is severely limited by the catalytic activity of nanozymes or the infection microenvironments such as insufficient hydrogen peroxide (H2O2) and overexpressed glutathione (GSH). Herein, a versatile hybrid nanozyme (MoS2/CuO2) is rationally constructed by simply decorating ultrasmall CuO2 nanodots onto lamellar MoS2 platelets of hydrangea-like MoS2 nanocarrier via a covalent Cu-S bond. The MoS2/CuO2 nanozyme exhibits the peroxidase-mimic activity for catalytically converting H2O2 produced by acid-triggered decomposition of the decorated CuO2 into hydroxyl radical (•OH). Meanwhile, the MoS2/CuO2 can consume GSH overexpressed in the infection sites via redox reaction mediated by polyvalent transition metal ions (Cu2+ and Mo6+) for enhanced CDT. More importantly, MoS2 support can promote the conversion of Cu2+ to Cu+ by a co-catalytic reaction based on the Mo4+/Mo6+ redox couples, and provide photonic hyperthermia (PTT) to augment the peroxidase-mimic activity. The developed MoS2/CuO2 nanozymes possesses a desirable catalytic property, as well as a remarkably improved antibacterial efficiency both in vitro and in vivo. Taken together, this study proposes a synergetic multiple enhancement strategy to successfully construct the versatile hybrid nanozymes for intensive in vivo PTT/CDT dual-mode anti-infective therapy. STATEMENT OF SIGNIFICANCE: Chemodynamic therapy (CDT) has shown great potentialities in the treatment of bacterial infections, while its therapeutic efficiency is severely limited by the infection microenvironments such as insufficient hydrogen peroxide (H2O2) and overexpressed glutathione (GSH). Here, we rationally construct a hybrid nanozyme (MoS2/CuO2) with peroxidase-like activity that can enhance CDT by regulating local microenvironments, that is, simultaneously self-supplying H2O2 and consuming GSH. Importantly, MoS2 support can promote the conversion of Cu2+ to Cu+ by the Mo4+/Mo6+ redox couples, and provide photonic hyperthermia (PTT) to augment the peroxidase-mimic activity. The developed MoS2/CuO2 shows desirable PTT/CDT dual-mode antibacterial efficacy both in vitro and in vivo. This study proposes a versatile hybrid nanozyme with multiple enhancement effects for intensive in vivo anti-infective therapy.


Effect of medium osmolality on the growth of murine continuous marrow cultures.
The effect of medium osmolality was examined in primary, continuous bone-marrow cultures established from TO strain mice. The non-adherent cell population increased exponentially between weeks 2 and 5 and thereafter declined steadily. The number of CFU-GM followed a similar pattern but showed greater variability. The optimum osmolality in 4 week old cultures was found to be about 345 mosmol/kg which was higher than the plasma osmolality (n = 20; mean = 323.3 mosmol/kg; range = 313-331). Maximum non-adherent cell numbers were found at about 345 mosmol/kg (better than half-maximum between 320 and 370 mosmol/kg). CFU-GM numbers in the culture supernatant were maximal at about 355 mosmol/kg (better than half-maximum between 320 and 400 mosmol/kg). An adherent layer developed over a wider range of osmolality than supported granulopoiesis (better than half-maximum between 258 and 402 mosmol/kg). It was necessary to increase the osmolality of Fischer's medium in order to obtain maximum growth.


Impact of waste management among Industry 4.0 and sustainable development.
The study is aimed at investigating the impact of waste management in the context of Industry 4.0 and sustainable development. Data were collected from 257 production managers in the industrial sector using a survey questionnaire and analyzed using SPSS and PLS-SEM. The findings indicated that Industry 4.0 and waste management significantly contribute to achieving sustainable development. The integration of Industry 4.0 technologies and effective waste management practices can help organizations implement sustainable development goals. Practical implications include assisting organizations in implementing Industry 4.0 technologies and waste management strategies based on the 3Rs principle. This can lead to reduced environmental impacts and improved resource efficiency, contributing to sustainable development. Policymakers can also benefit from the study's insights to address waste management challenges and promote sustainable development. The study's originality lies in its incorporation of the cyber-physical system and niche theory to explore how Industry 4.0 can facilitate sustainable waste management. It highlights the transformative potential of Industry 4.0 in the industrial sector, particularly in developing countries. Overall, this research offers a unique contribution to understanding waste management within the context of Industry 4.0 and sustainable development.


Theoretical study of two-photon absorption properties and up-conversion efficiency of new symmetric organic π-conjugated molecules for photovoltaic devices.
Organic material with high intensity of two-photon absorption (TPA) induced fluorescence can be used as the frequency up-converter materials for improving efficiency of the solar cells. In this work, the organic molecular structures were designed by symmetrically grafting two elongated conjugated linkers on a conjugated core and then adding donor groups at both terminals. Fluorene derivatives as a core acceptor, phenylethynyl as the conjugated linker and diphenylamino or methyl-9H-carbozole as the donor end groups were selected. Quantum mechanical modeling techniques were applied to investigate the molecular electronic structure and properties. Absorption properties of these novel π-conjugated organic molecules were studied. The TPA cross-sections of these derivatives were calculated using few-states models, respectively. The effects of donor and acceptor groups on the TPA behaviors of these designed molecules were investigated. The up-conversion efficiency of designed molecules was also calculated.


Functional characterization of the promoter of the human glucose transporter 10 gene.
The human SLC2A10 gene encodes the high-affinity glucose transporter 10 (GLUT10) and is widely expressed in adult tissues, including organs which play major roles in glucose homeostasis. Its function and genomic location in a region linked to Type 2 diabetes susceptibility are consistent with a potential role in Type 2 diabetes. Analysis of the CpG-rich promoter revealed the presence of two major transcription start points with differential use in tissues and cell lines. Mapping of transcriptionally active regions in the 5' flanking sequence identified a region, located between nucleotides -70 and -14 (relative to the major transcription start point) as the SLC2A10 basal promoter. This sequence harbors consensus binding sites for Sp, AP2alpha, and other transcription factors. A juxtaposed Sp/AP2alpha motif located between -25 and -11 is critical for core promoter function. In cells expressing Sp and AP2 factors, the two motifs are required for maximal activation of the basal promoter. In cells lacking AP2alpha, transcription is dependent on the integrity of the Sp site. Using electrophoresis mobility shift assays, we demonstrate that Sp1 and Sp3 bind to the GC-box in site 5 forming specific complexes. In addition, a silencer region is present upstream of -696 which down-regulates SLC2A10 promoter activity independently of its distance to the transcript start site.


Comparison of commercial peroxidases for removing phenol from water solutions.
This paper describes a comparison between horseradish peroxidase (HRP) and soybean peroxidase (SBP), the two most widely used commercial peroxidases for the removal of phenol from wastewater. Both enzymes achieve maximal removal efficiency in a neutral pH medium although they are still quite active in a pH range of between 6.0 and 8.0. The fact that both enzymes show similar phenol elimination levels at any temperature between 25 and 40 degrees C is also of interest. Studies were carried out in the absence and presence of different concentrations of a stabilisation additive, polyethylene glycol (PEG), in an attempt to optimise the phenol elimination procedure. The final choice of peroxidase will depend on the characteristics of the effluent, operational requirements and on economic considerations. Our findings show that HRP acts faster than SBP but is more susceptible to inactivation, although it is better protected by PEG. In consequence HRP will be the most suitable choice but the addition of a sufficient amount of PEG is critical.


Expression of microRNAs in basal cell carcinoma.
Perturbations in the expression profiles of microRNAs (miRNAs) have been reported for a variety of different cancers. Differentially expressed miRNAs have not been systematically evaluated in basal cell carcinoma (BCC) of the skin. To initiate a microarray-based miRNA profiling study to identify specific miRNA candidates that are differentially expressed in BCC. Patients with BCC (n = 7) were included in this study. Punch biopsies were harvested from the tumour centre (lesional, n = 7) and from adjacent nonlesional skin (intraindividual control, n = 7). Microarray-based miRNA expression profiles were obtained on an Agilent platform using miRBase 16 screening for 1205 Homo sapiens (hsa)-miRNA candidates. To validate the microarray data, the expression of seven dysregulated miRNAs was measured by TaqMan quantitative real-time reverse transcription polymerase chain reaction. We identified 16 significantly upregulated (hsa-miR-17, hsa-miR-18a, hsa-miR-18b, hsa-miR-19b, hsa-miR-19b-1*, hsa-miR-93, hsa-miR-106b, hsa-miR-125a-5p, hsa-miR-130a, hsa-miR-181c, hsa-miR-181c*, hsa-miR-181d, hsa-miR-182, hsa-miR-455-3p, hsa-miR-455-5p and hsa-miR-542-5p) and 10 significantly downregulated (hsa-miR-29c, hsa-miR-29c*, hsa-miR-139-5p, hsa-miR-140-3p, hsa-miR-145, hsa-miR-378, hsa-miR-572, hsa-miR-638, hsa-miR-2861 and hsa-miR-3196) miRNAs in BCC compared with nonlesional skin. Data mining revealed connections to many tumour-promoting pathways, such as the Hedgehog and the mitogen-activated protein kinase/extracellular signal-regulated kinase signalling cascades. This study identified several miRNA candidates that may play a role in the molecular pathogenesis of BCC.


Polydom/SVEP1 binds to Tie1 and promotes migration of lymphatic endothelial cells.
Polydom is an extracellular matrix protein involved in lymphatic vessel development. Polydom-deficient mice die immediately after birth due to defects in lymphatic vessel remodeling, but the mechanism involved is poorly understood. Here, we report that Polydom directly binds to Tie1, an orphan receptor in the Angiopoietin-Tie axis, and facilitates migration of lymphatic endothelial cells (LECs) in a Tie1-dependent manner. Polydom-induced LEC migration is diminished by PI3K inhibitors but not by an ERK inhibitor, suggesting that the PI3K/Akt signaling pathway is involved in Polydom-induced LEC migration. In line with this possibility, Akt phosphorylation in LECs is enhanced by Polydom although no significant Tie1 phosphorylation is induced by Polydom. LECs also exhibited nuclear exclusion of Foxo1, a signaling event downstream of Akt activation, which was impaired in Polydom-deficient mice. These findings indicate that Polydom is a physiological ligand for Tie1 and participates in lymphatic vessel development through activation of the PI3K/Akt pathway.


Wastewater treatment using hybrid treatment schemes based on cavitation and Fenton chemistry: a review.
Advanced oxidation processes such as cavitation and Fenton chemistry have shown considerable promise for wastewater treatment applications due to the ease of operation and simple reactor design. In this review, hybrid methods based on cavitation coupled with Fenton process for the treatment of wastewater have been discussed. The basics of individual processes (Acoustic cavitation, Hydrodynamic cavitation, Fenton chemistry) have been discussed initially highlighting the need for combined processes. The different types of reactors used for the combined processes have been discussed with some recommendations for large scale operation. The effects of important operating parameters such as solution temperature, initial pH, initial pollutant concentration and Fenton's reagent dosage have been discussed with guidelines for selection of optimum parameters. The optimization of power density is necessary for ultrasonic processes (US) and combined processes (US/Fenton) whereas the inlet pressure needs to be optimized in the case of Hydrodynamic cavitation (HC) based processes. An overview of different pollutants degraded under optimized conditions using HC/Fenton and US/Fenton process with comparison with individual processes have been presented. It has been observed that the main mechanism for the synergy of the combined process depends on the generation of additional hydroxyl radicals and its proper utilization for the degradation of the pollutant, which is strongly dependent on the loading of hydrogen peroxide. Overall, efficient wastewater treatment with high degree of energy efficiency can be achieved using combined process operating under optimized conditions, as compared to the individual process.


Call for next-generation drugs that remove the uptake barrier to combat antibiotic resistance.
Existing antibacterial agents can be categorized into two generations, but bacterial insensitivity towards both of these generations poses a serious public health challenge worldwide. Thus, novel approaches and/or novel antibacterials are urgently needed to maintain a concentration of antibacterials that is lethal to bacteria that are resistant to existing antibiotic treatments. Metabolite(s)-based adjuvants that promote antibiotic uptake and enhance antibiotic efficacy are an effective strategy that is unlikely to develop resistance. Thus, we propose a metabolite(s)-based approach, in which metabolites and antibacterials are combined, as a promising strategy for the development of next-generation agents to combat a variety of antibiotic-resistant pathogens.


The effect of placebo and tricyclic antidepressants on cortical evoked potentials in depressed patients.
Cortical evoked potentials in depressives were recorded in order to study stimulus intensity control in this group, and also to study the effect of treatment. In a sample of 33 psychiatric patients, the amplitudes of visual and auditory evoked potentials were found to be significantly greater during depression, than at recovery. The changes which appeared to be due to recovery were found not only in patients treated with tricyclic antidepressants (n = 22), but in those who had recovered following treatment with placebo (n = 11). The changes were most evident in the auditory system. In addition, no diagnostic predictors differentiated depressed patients who subsequently recovered on placebo from those who did not. It is concluded that: (i) cortical evoked potentials may change in amplitude with emotional state; (ii) placebo may have physiological consequences usually attributed to drugs alone.


Basic features of the ancestral chordate brain: a protochordate perspective.
Basic features of the anterior nerve cord in amphioxus larvae are summarized to highlight its essential similarity with the vertebrate brain. Except for a pineal homolog, the amphioxus brain consists of a much simplified version of the ventral brainstem, including a region probably homologous with the hypothalamus, and a locomotory control center roughly comparable to the vertebrate tegmentum and reticulospinal system. Amphioxus has direct pathways for activating its locomotory circuits in response to mechanical stimuli via epithelial sensory cells, but this response is evidently modulated by inputs from diverse sensory-type cells located in the putative hypothalamic homolog, and from the lamellar body, the pineal homolog. This implies that a basic function of the amphioxus brain is to switch between locomotory activities, of which there are several, and the principal non-locomotory one, namely feeding. A similar involvement in switching between behavioral modes may thus have been a core brain function in ancestral chordates. Currently, however, incomplete knowledge of the physiology and behavior of amphioxus limits how effectively it can be used as an evolutionary model. Eye evolution is briefly discussed to illustrate how a better understanding of living forms can inform the evolutionary debate. An account of recent data on dorsoventral inversion is also included, as this bears directly on the question of where the chordate brain originated in relation to other structures. It now appears likely that key components of the ancestral brain were originally located around the mouth. A secondary repositioning of the latter would therefore have been required before a unitary brain could be assembled and internalized. This association between the mouth and the evolving brain reinforces the idea of a fundamental early connection between core brain structures and the control of feeding activity.


Highly efficient intracellular transduction in three-dimensional gradients for programming cell fate.
Fundamental behaviour such as cell fate, growth and death are mediated through the control of key genetic transcriptional regulators. These regulators are activated or repressed by the integration of multiple signalling molecules in spatio-temporal gradients. Engineering these gradients is complex but considered key in controlling tissue formation in regenerative medicine approaches. Direct programming of cells using exogenously delivered transcription factors can by-pass growth factor complexity but there is still a requirement to deliver such activity spatio-temporally. We previously developed a technology termed GAG-binding enhanced transduction (GET) to efficiently deliver a variety of cargoes intracellularly using GAG-binding domains to promote cell targeting, and cell penetrating peptides (CPPs) to allow cell entry. Herein we demonstrate that GET can be used in a three dimensional (3D) hydrogel matrix to produce gradients of intracellular transduction of mammalian cells. Using a compartmentalised diffusion model with a source-gel-sink (So-G-Si) assembly, we created gradients of reporter proteins (mRFP1-tagged) and a transcription factor (TF, myogenic master regulator MyoD) and showed that GET can be used to deliver molecules into cells spatio-temporally by monitoring intracellular transduction and gene expression programming as a function of location and time. The ability to spatio-temporally control the intracellular delivery of functional proteins will allow the establishment of gradients of cell programming in hydrogels and approaches to direct cellular behaviour for many regenerative medicine applications. Regenerative medicine aims to reform functional biological tissues by controlling cell behaviour. Growth factors (GFs) are soluble cues presented to cells in spatio-temporal gradients and play important roles programming cell fate and gene expression. The efficient transduction of cells by GET (Glycosaminoglycan-enhanced transducing)-tagged transcription factors (TFs) can be used to by-pass GF-stimulation and directly program cells. For the first time we demonstrate diffusion of GET proteins generate stable protein transduction gradients. We demonstrated the feasibility of creating spatio-temporal gradients of GET-MyoD and show differential programing of myogenic differentiation. We believe that GET could provide a powerful tool to program cell behaviour using gradients of recombinant proteins that allow tissue generation directly by programming gene expression with TFs.


Chemically shifted singlet oxygen spectrum.
The estimated light emission spectrum was determined for a singlet oxygen (1O2)-producing system, NaOCl + H2O2, alone and in the presence of tryptophan and bovine serum albumin. Tryptophan and bovine serum albumin caused a decrease in the red emission of 1O2 and an increase in the amount of shorter wavelength light. This effect was due to chemiluminescence rather than fluorescence. Arachidonic acid caused a similar spectral shift, while guanosine demonstrated a late chemiluminescent reaction of predominantly short wavelength light in the presence of 1O2.


Invasive candidiasis during granulocytopenia.
Candidiasis remains the most frequently encountered fungal infection in patients with profound granulocytopenia and appears to be increasing in frequency. In addition, Candida infections are occurring earlier during remission induction chemotherapy and can be caused by a variety of species such as C. albicans, C. tropicalis, and C. krusei. The most frequent source of disseminated infection is the gastrointestinal tract, as the integrity of the epithelium is disrupted by chemotherapeutic agents. The spectrum of disseminated candidiasis comprises both an acute and a chronic presentation (also known in the literature as hepatosplenic candidiasis). The management of disseminated infection consists of early empiric antifungal therapy with a standard agent, amphotericin B. Unfortunately, responses in the setting of profound granulocytopenia appear to be poor. Other agents that appear to be useful in the management of disseminated candidiasis include 5-flucytosine and fluconazole. Based on animal experimentation, it appears that the combination of these three classes of agents might produce superior results compared with amphotericin B alone. Removal of the central venous catheter does not appear warranted in the setting of profound granulocytopenia, and the role of colony stimulating factors needs to be defined. Given the severity and high mortality associated with disseminated candidiasis in patients with hematologic malignancies, antifungal prophylaxis appears warranted.


Severe cutaneous zygomycosis due to Basidiobolus ranarum in a young infant.
Basidiobolomycosis classically presents as a noninflammatory, nonulcerated, nontender woody indurated mass without much contiguous spread. It is almost always seen in an immunocompetent host younger than 20. We report a case of a 9-month-old baby with a rapidly expanding malignant presentation of basidiobolomycosis with nonhealing ulcers and spread to underlying muscles, mimicking lymphoma. She responded poorly to itraconazole alone but showed dramatic improvement with a combination therapy of itraconazole and potassium iodide. The case also highlights an early acquisition of the infection at 1 month of age.


Effects of taurolidine and octreotide on port site and liver metastasis after laparoscopy in an animal model of pancreatic cancer.
Port site metastasis is a dreadful event following laparoscopy; however, the exact pathomechanism is still unknown. In order to prevent trocar metastasis we determined the effects of intraperitoneal lavage with either taurolidine or octreotide on port site and liver metastasis after laparoscopy in a chemically induced, solid pancreatic adenocarcinoma. Pancreatic adenocarcinoma was induced in 60 Syrian hamsters by weekly injection of 10 mg/kg body weight N-nitrosobis-2-oxopropylamine s.c. for 10 weeks. Six weeks later, a laparoscopic pancreatic biopsy was performed by the use of a pneumoperitoneum with carbon dioxide (12 mm Hg), followed by an abdominal irrigation with 5 ml normal saline (group 1, n = 20), 5 ml 0.5% taurolidine (group 2, n = 20) or 5 ml octreotide (20 mg/ml) (group 3, n = 20). After 8 weeks, all hamsters were sacrificed and histopathologically examined. There was only one macroscopic visible primary tumor in the taurolidine group (5.9%), compared to 42.1% in the saline group and 62.5% in the octreotide group (P < 0.05). The size of carcinomas was smaller in the saline group than after octreotide irrigation (median 6, range 2-25 vs. median 70, range 40-160 mm2, P < 0.05). The number of liver metastases per animal was increased after saline irrigation (median 4, range 2-6), compared to taurolidine (median 2, range 1-3) or octreotide (median 2.5, range 2-4) (P < 0.05). Port site metastases were found in 36.8% after saline, in 37.5% after octreotide and in 0% after taurolidine irrigation (P < 0.05). Thus port site metastasis was effectively prevented by taurolidine irrigation after staging-laparoscopy in pancreatic cancer.


Salicylates increase insulin secretion in healthy obese subjects.
Conflicting results on the effects of salicylates on glucose tolerance in subjects with normal glucose tolerance or type 2 diabetes have been reported. The objective of the study was to investigate the effects of a salicylate derivative (triflusal) on insulin sensitivity and insulin secretion. This was a double-blind, randomized, crossover study with three treatment periods corresponding to two dose levels of triflusal and placebo in healthy obese subjects. Insulin sensitivity and insulin secretion, evaluated through frequently sampled iv glucose tolerance test that was performed after each treatment period, were measured. Insulin secretion was also evaluated in vitro in mice and human islets of Langerhans. The administration of triflusal led to decreased fasting serum glucose concentration in the study subjects. Insulin sensitivity did not significantly change after each treatment period. Insulin secretion, however, significantly increased in a dose-dependent fashion after each triflusal treatment period. The administration of 800 mum of the main triflusal metabolite to whole mice islets of Langerhans led to a sustained increase in intracellular calcium concentration level. This was followed by a significantly increase in insulin secretion. In human islets, 200 mum of 2-hydroxy-4-trifluoromethylbenzoic acid was sufficient to increase insulin release. The administration of a salicylate compound led to lowering of serum glucose concentration. We suggest that this effect was mediated through increased insulin secretion induced by salicylate directly on the beta-cell.


Interaction between microRNA expression and classical risk factors in the risk of coronary heart disease.
The aim of this study was to identify the synergistic effect of microRNA expression with classical risk factors of coronary heart disease (CHD) and to explore their diagnostic value for coronary stenotic lesions in subjects with CHD. Plasma samples were obtained from 66 subjects with CHD and from 58 control individuals. A quantitative reverse-transcription PCR (RT-qPCR) assay was conducted to confirm the relative expressions of the known CHD-related miRNAs. The severity of coronary atherosclerosis was based on the Gensini scoring system. The expression of miR-125b in plasma of the CHD group was lower than that of the non-CHD group (0.14 ± 0.09 vs. 0.18 ± 0.10, p = 0.055), and the miR-125b levels significantly decreased following an increasing Gensini score (P = 0.037). Spearman correlation analyses indicated the Gensini score was negatively associated with miR-125b (r = -0.215, p = 0.017). Of all the miRNAs, miR-125b showed the lowest AUC (0.405; 95% CI: 0.305 ~ 0.506, p = 0.070). We found several synergistic effects between miR-125b and classical risk factors, such as age, sex, CR, FBG and HDL-C; the proportion of CHD attributable to the interaction of miR-125b and age was as high as 80%. Therefore, miR-125b was shown to play an important role in individual's susceptibility to developing CHD.


Pharmacokinetic evidence for improved ophthalmic drug delivery by reduction of instilled volume.
The bioavailability of topically applied pilocarpine nitrate was studied as a function of instilled volume. As the instilled volume decreased, the fraction of dose absorbed increased. The relationship between fraction absorbed and instilled volume was not direct, but appropriate adjustment of instilled volume and concentration should permit substantial dosage reductions without sacrifice of drug concentration in the eye. The implications of these findings from both a therapeutic and toxicity standpoint are discussed.


Impact of distance between donor and recipient hospitals on cadaveric kidney transplantation outcomes.
The impact of distance between donor and recipient hospitals on outcomes in cadaveric kidney transplantations is unknown. We investigated the association between inter-hospital distance and outcomes in cadaveric kidney transplantations in Japan. We retrospectively analyzed 363 cadaveric kidney transplantations between 2002 and 2017 in Japan. Inter-hospital distance, graft transport time, total ischemic time (TIT), and graft survival were compared between our hospital and national transplantation cohort in Japan. Estimated glomerular filtration rate (eGFR) 1 month and 1 year after transplantation was compared between cadaveric and living-donor kidney transplantations in our hospitals. Additionally, inter-hospital distances among the seven geographical regions in Japan were assessed. There were 12 and 351 cadaveric kidney transplantations at our hospital and in Japan, respectively. Mean inter-hospital distance at our hospital (217 ± 121 km) was significantly longer than that of the national cohort (53 ± 80 km; P < 0.001). Mean TIT and graft survival for our hospital and national cohort were 539 ± 200 min and 91% and 491 ± 193 min and 81%, respectively. Mean eGFRs 1 year after cadaveric and living-donor transplantations at our hospitals were comparable (47 ± 16 vs. 47 ± 15 mL/min/1.73 m2). The comparison among seven regions in Japan indicated a regional difference in inter-hospital distance with an association between area (km2) and inter-hospital distance (km). Despite the longer inter-hospital distance at our hospital, TIT and transplant outcomes were acceptable in our cases. In addition, geographical inequity in graft allocation in Japan was suggested.


National Pediatric Palliative Care Needs from Hospital Deaths.
The objective of this study was to estimate palliative care needs and to describe the cohort of children with life-limiting illnesses (LLI) dying in hospitals. This study was a retrospective cohort study. The national hospital admissions database was reviewed and children who had died who had life-limiting illnesses were identified. This study was conducted at Ministry of Health hospitals, Malaysia. Children aged 18 years and below who had died between January 1, 2012 and December 31, 2014. Life-limiting diagnoses based on Hain et al.'s directory of LLI or the ACT/RCPCH categories of life-limiting disease trajectories. There were 8907 deaths and 3958 (44.4%) were that of children with LLI. The majority, 2531 (63.9%) of children with LLI were neonates, and the most common diagnosis was extreme prematurity <28 weeks with 676 children (26.7%). For the nonneonatal age group, the median age at admission was 42 months (1-216 months). A majority, 456 (32.0%) had diagnoses from the ICD-10 chapter "Neoplasms" followed by 360 (25.3%) who had a diagnoses from "Congenital malformations, deformations, and chromosomal abnormalities" and 139 (9.7%) with diagnoses from "Disease of the nervous system." While a majority of the terminal admissions were to the general ward, there were children from the nonneonatal age group, 202 (14.2%) who died in nonpediatric wards. Understanding the characteristics of children with LLI who die in hospitals could contribute toward a more efficient pediatric palliative care (PPC) service development. PPC service should include perinatal and neonatal palliative care. Palliative care education needs to extend to nonpediatric healthcare providers who also have to manage children with LLI.


Prediction models of human plasma protein binding rate and oral bioavailability derived by using GA-CG-SVM method.
In this study, support vector machine (SVM) method combined with genetic algorithm (GA) for feature selection and conjugate gradient (CG) method for parameter optimization (GA-CG-SVM), has been employed to develop prediction models of human plasma protein binding rate (PPBR) and oral bioavailability (BIO). The advantage of the GA-CG-SVM is that it can deal with feature selection and SVM parameter optimization simultaneously. Five-fold cross-validation as well as independent test set method were used to validate the prediction models. For the PPBR, a total of 692 compounds were used to train and test the prediction model. The prediction accuracy by means of 5-fold cross-validation is 86% and that for the independent test set (161 compounds) is 81%. These accuracies are markedly higher over that of the best model currently available in literature. The number of descriptors selected is 29. For the BIO, the training set is composed of 690 compounds and external 76 compounds form an independent validation set. The prediction accuracy for the training set by using 5-fold cross-validation and that for the independent test set are 80% and 86%, respectively, which are better than or comparable to those of other classification models in literature. The number of descriptors selected is 25. For both the PPBR and BIO, the descriptors selected by GA-CG method cover a large range of molecular properties which imply that the PPBR and BIO of a drug might be affected by many complicated factors.


Complex carbohydrates in shell precursor globules of the vitellarium and at the eggshell of Hymenolepis microstoma (Cestoda).
The vitellocytes of Hymenolepis microstoma contain protein globules as building material for the shell of egg cocoons. Complex carbohydrates were detected as an additive component, dispersed in the matrix of the shell globules. Similar glycans were found at newly formed shells, suggesting that these molecules are provided by the vitellocytes. The glycans remained associated with the surface of mature eggs. Carbohydrate residues, characterized using gold-labeled lectins, were N-acetylglucosamine, galactose, or the N-acetyllactosamine sequence of these residues and N-acetylgalactosamine, whereas glucose, mannose, and fucose were not demonstrable. The glycans scarcely stained with periodic acid-Schiff and, thus, seem to have few diols, and they did not bind cationic dye, indicating that they are not glycosaminoglycans. Since they occur in significant amounts, the glycans may have fundamental, as yet undetermined function(s) in the formation of the shells and/or interactions of the cocoons with the host.


Deposition of genetically engineered human antibodies into the egg yolk of hens.
To determine if human immunoglobulins (hIg) are capable of being transported into the hen's egg, 10 microg each of purified hIgG and hIgA were intravenously injected into SC Hyline(TM) hens and their presence in egg yolk and egg white was determined by ELISA. In both cases deposition into the egg yolk was observed and in the case of hIgA, deposition was also observed in the egg white. Two stably transfected DT40 cell lines secreting recombinant human IgG3 and IgA (rhIgG3 and rhIgA) were injected into laying hens. The DT40 cells colonized the host and rhIgG3 and rhIgA were deposited in egg yolk. Deposition of rhIgA was also observed in the egg white. These data demonstrate that human immunoglobulins and other foreign proteins may be targeted to the chicken's egg. In view of the high rate of reproduction, the short generation interval, the high rates of egg production and the extensive infrastructure to fractionate egg yolk proteins, it should be possible to produce large amounts of foreign protein in the eggs of transgenic chickens.


Young women who develop anorexia nervosa exhibit a persistently low premorbid body weight on average: A longitudinal investigation of an important etiologic clue.
test whether (1) young women who subsequently show onset of anorexia nervosa (AN) exhibit persistently lower average premorbid BMI than those who subsequently show onset of bulimia nervosa (BN), binge eating disorder (BED), purging disorder (PD), or no eating disorder; (2) a proximal spike in other risk factors occurs immediately before AN emergence; and (3) psychological and behavioral factors differentiate youth who show persistently low BMI from those who do not. Data from a sample (N = 1952) of young women at high-risk for eating disorders followed for 3 years and a socioethno-racially representative sample (N = 496) of adolescent girls followed for 8 years were used to address these aims. Participants who developed AN exhibited significantly lower average measured premorbid BMI over repeated assessments than those who showed onset of other or no eating disorders. Dietary restraint, negative affect, and eating affect regulation expectancies significantly increased immediately before AN onset. Youth who showed persistently low BMI reported lower pressure for thinness, body dissatisfaction, and dieting at baseline, implying that elevations in these factors did not drive the low BMI. The evidence that young women who subsequently show AN onset exhibit a low premorbid BMI on average is novel and suggests that etiologic models should incorporate this finding and selective prevention programs should target low-BMI adolescent girls. The finding that dieting, negative affect, affect-regulation eating expectances spiked immediately before emergence of AN is also novel and suggests that it might be useful for selective prevention programs to target these factors. (PsycInfo Database Record (c) 2022 APA, all rights reserved).


Serum gastrin and chromogranin A levels in patients with fundic gland polyps caused by long-term proton-pump inhibition.
Use of proton-pump inhibitors (PPIs) causes hypergastrinemia, and it is well known that gastrin has a trophic effect on the oxyntic mucosa. Some PPI users develop fundic gland polyps. The purpose of this study was to determine whether patients developing fundic gland polyps have a more pronounced gastric hypoacidity, hypergastrinemia or increased serum chromogranin A (CgA), which is an enterochromaffin-like (ECL) cell marker. Five PPI users who developed multiple fundic gland polyps during PPI use were included in the study. PPI users without fundic gland polyps (n = 6) as well as healthy individuals (n = 6) were used as controls. In PPI users, we measured 24-h gastric pH, serum gastrin and CgA during one day, with standardized meals, whereas only gastrin and CgA were measured in the healthy individuals. Helicobacter pylori status was determined. Gastric pH, serum gastrin and CgA did not differ significantly between PPI users with and those without fundic gland polyps. All patients with fundic gland polyps were H. pylori negative, whereas 4 out of 6 PPI users without fundic gland polyps were H. pylori positive. Fasting CgA levels were elevated in all PPI users, and CgA more than doubled during the day in all groups. Fundic gland polyps induced by PPIs are not related to the level of hypergastrinemia. Serum CgA is markedly affected by meals and should be measured in samples from fasting patients.


Cardiac Arrhythmias Related to Sodium Channel Dysfunction.
The voltage-gated cardiac sodium channel (Nav1.5) is a mega-complex comprised of a pore-forming α subunit and 4 ancillary β-subunits together with numerous protein partners. Genetic defects in the form of rare variants in one or more sodium channel-related genes can cause a loss- or gain-of-function of sodium channel current (INa) leading to the manifestation of various disease phenotypes, including Brugada syndrome, long QT syndrome, progressive cardiac conduction disease, sick sinus syndrome, multifocal ectopic Purkinje-related premature contractions, and atrial fibrillation. Some sodium channelopathies have also been shown to be responsible for sudden infant death syndrome (SIDS). Although these genetic defects often present as pure electrical diseases, recent studies point to a contribution of structural abnormalities to the electrocardiographic and arrhythmic manifestation in some cases, such as dilated cardiomyopathy. The same rare variants in SCN5A or related genes may present with different clinical phenotypes in different individuals and sometimes in members of the same family. Genetic background and epigenetic and environmental factors contribute to the expression of these overlap syndromes. Our goal in this chapter is to review and discuss what is known about the clinical phenotype and genotype of each cardiac sodium channelopathy, and to briefly discuss the underlying mechanisms.


Evidence for a membrane exchangeable glucose pool in the functioning of rat liver glucose-6-phosphatase.
We have investigated the kinetics of tracer uptake into rat liver microsomes in relation to [14C]glucose 6-phosphate (Glu-6-P) hydrolysis by glucose 6-phosphatase (Glu-6-Pase). 1) The steady-state levels of intravesicular tracer accumulated during the rapid (AMP1) and slow (AMP2) phases of uptake both demonstrate Michaelis-Menten kinetics relative to outside Glu-6-P concentrations with Km values similar to those observed for the initial burst (Vi) and steady-state (VSS) rates of Glu-6-P hydrolysis. 2) The AMP1/AMP2 ratio is constant (mean value = 0.105 +/- 0.018) over the whole range of outside Glu-6-P concentrations and is equal to the AMP1max/AMP2max ratio (0.109 +/- 0.032). 3) Linear relationships are observed between the initial rates of glucose transport during the slow uptake phase (V alpha 2) and [AMP1], and between [VSS] and [AMP2]. 4) The value of Vss max exceeds by more than 10-fold that of V alpha 2 max. 5) It is concluded that the substrate transport model is incompatible with those results and that AMP1 represents a membrane exchangeable glucose pool. 6) We propose a new version of the conformational model in which the catalytic site lies deep within a hydrophilic pocket of an intrinsic membrane protein and communicates with the extra- and intravesicular spaces through channels with different glucose permeabilities.


An efficient strategy of phosphorus recovery: Electrochemical pretreatment enhanced the anaerobic fermentation of waste activated sludge.
The anaerobic fermentation (AF) of waste activated sludge (WAS) with an electrochemical pretreatment (EPT) was investigated to determine its correlation with the release of phosphorus and the disintegration of WAS. The sludge was pretreated by holding under 4.5 V for 60 min, followed by AF for 9 days. Untreated sludge was used as the control group (no-EPT). Results showed that, with pretreatment, the total dissolved P (TDP), orthophosphate (PO43--P) and organic P (OP) reached the maximum values of 7.30 mg/L, 4.77 mg/L and 2.35 mg/L on day 8, respectively, which were approximately 5.3, 9.2 and 2.7 times greater than that in the control group. The analysis of soluble chemical oxygen demand (SCOD), protein and polysaccharides showed that the EPT promoted the disintegration of sludge, thereby enhancing the P release. The SCOD reached 1625 mg/L on day 6 in pretreatment experiment, which was about 9.8 times greater than that in control group. Additionally, the EPT contributed to fewer metal ions in sludge supernatant. This mechanism might have been due to the anions accumulating in the supernatant from the greater degree of sludge collapse after EPT, which caused the released metal ions to combine with anions to form insoluble compounds. In conclusion, EPT could be a promising method for the dissolution of sludge and the recovery of phosphorus from WAS under AF. Besides, the economic benefit evaluation showed the potential value of EPT for P recovery.


NES1/KLK10 gene represses proliferation, enhances apoptosis and down-regulates glucose metabolism of PC3 prostate cancer cells.
The normal epithelial cell-specific-1 (NES1) gene, also named as KLK10, is recognised as a novel putative tumour suppressor in breast cancer, but few studies have focused on the function of KLK10 in human prostate cancer. Our study confirms that the expression of KLK10 in prostate cancer tissue and cell lines (PC3, DU145, and LNCaP clone FGC) is low. Given that the androgen-independent growth characteristic of the PC3 cell line is more similar to clinical castration-resistant prostate cancer, we studied the role of KLK10 in PC3. In vitro and in vivo assays showed that over-expressing KLK10 in PC3 could decelerate tumour proliferation, which was accompanied with an increase in apoptosis and suppression of glucose metabolism. The related proteins, such as Bcl-2 and HK-2, were down-regulated subsequently. Furthermore, by up-regulating Bcl-2 or HK-2 respectively in the PC3-KLK10 cell line, we observed a subsequent increase of cell proliferation and a synchronous up-regulation of HK-2 and Bcl-2. Besides, KLK10 expression was also increased by Bcl-2 and HK-2, which suggests that there is a negative feedback loop between KLK10 and Bcl-2/HK-2. Thus, our results demonstrated that KLK10 may function as a tumour suppressor by repressing proliferation, enhancing apoptosis and decreasing glucose metabolism in PC3 cells.


Cleavage activation of human-adapted influenza virus subtypes by kallikrein-related peptidases 5 and 12.
A critical step in the influenza virus replication cycle is the cleavage activation of the HA precursor. Cleavage activation of influenza HA enables fusion with the host endosome, allowing for release of the viral genome into the host cell. To date, studies have determined that HA activation is driven by trypsin-like host cell proteases, as well as yet to be identified bacterial proteases. Although the number of host proteases that can activate HA is growing, there is still uncertainty regarding which secreted proteases are able to support multicycle replication of influenza. In this study, we have determined that the kallikrein-related peptidases 5 and 12 are secreted from the human respiratory tract and have the ability to cleave and activate HA from the H1, H2, and H3 subtypes. Each peptidase appears to have a preference for particular influenza subtypes, with kallikrein 5 cleaving the H1 and H3 subtypes most efficiently and kallikrein 12 cleaving the H1 and H2 subtypes most efficiently. Cleavage analysis using HA cleavage site peptide mimics revealed that the amino acids neighboring the arginine cleavage site affect cleavage efficiency. Additionally, the thrombolytic zymogens plasminogen, urokinase, and plasma kallikrein have all been shown to cleave and activate influenza but are found circulating mainly as inactive precursors. Kallikrein 5 and kallikrein 12 were examined for their ability to activate the thrombolytic zymogens, and both resulted in activation of each zymogen, with kallikrein 12 being a more potent activator. Activation of the thrombolytic zymogens may therefore allow for both direct and indirect activation of the HA of human-adapted influenza viruses by kallikrein 5 and kallikrein 12.


Peripheral 3-hydroxybutyrate and food intake in a model of dietary-fat induced obesity: effect of vagotomy.
We have examined the effect of peripheral 3-hydroxybutyrate injections on food intake and the contribution of the vagus nerve in the resistance to dietary fat-induced obesity in a rodent model. S 5B/Pl rats, which are resistant to dietary-fat induced obesity, and Osborne-Mendel rats, which are sensitive, were adapted to reverse light cycle. Food intake was measured for 24 h following the injection of 3-hydroxybutyrate, lactate, or glycerol (all 5 mMol/kg0.75, SC) at the onset of dark. Three-hydroxybutyrate reduced food intake (p < 0.0001) in S 5B/Pl rats only. Lactate reduced food intake slightly (p < 0.009) in both strains and glycerol had no effect on food intake. In a second experiment, S 5B/Pl and Osborne-Mendel rats were adapted to a high-fat diet and were then subjected to either selective hepatic vagotomy or sham operation. Vagotomy had no effect on weight gain of Osborne-Mendel rats but allowed weight gain in S 5B/Pl rats (p < 0.0001). Even in vagotomized S 5B/Pl rats, however, blood 3-hydroxybutyrate levels were inversely associated (r = -0.50) with food intake. These data suggest that the hepatic vagus nerve may contribute to the resistance of S 5B/Pl rats to dietary-fat induced obesity, but the data do not rule out a strictly central role for the regulation of food intake by 3-hydroxybutyrate in this strain.


Chemokine gene transfection into tumour cells reduced tumorigenicity in nude mice in association with neutrophilic infiltration.
To study the effect of localised secretion of chemokines on tumour growth, the genes for human (hu) interleukin 8 (IL-8), hu-MCP-1 (MCAF), hu-MIP-1 alpha (LD78), murine (mu)-MCP-1 (JE), mu-MIP-1 alpha or mu-MIP-2 were introduced, via mammalian expression vectors, into Chinese hamster ovary (CHO) cells, and the ability of transfected cells to form tumours in vivo was evaluated. The production of hu-IL-8, hu-MIP-1 alpha or mu-MIP-1 alpha by transfected clones did not influence the growth rate in vitro, but drastically suppressed tumour growth when injected subcutaneously (s.c.) into nude mice. However, clones transfected with hu-MCP-1, mu-MCP-1 or mu-MIP-2 did not show any significant difference in growth rate in vivo compared with clones transfected with vector alone. Histological examination of the site of injection of CHO clones transfected with hu-IL-8, hu-MIP-1 alpha or mu-MIP-1 alpha showed predominantly neutrophilic infiltration. These results indicate that chemokines have potent anti-tumour activity when released, even at low doses, at the tumour site, which may be mediated by recruitment and targeting of neutrophilic granulocytes to chemokine-releasing cells. Our studies highlight the potential usefulness of localised chemokine secretion in inducing potent host anti-tumour defensive responses.


Role of phosphoinositides at the neuronal synapse.
Synaptic transmission is amongst the most sophisticated and tightly controlled biological phenomena in higher eukaryotes. In the past few decades, tremendous progress has been made in our understanding of the molecular mechanisms underlying multiple facets of neurotransmission, both pre- and postsynaptically. Brought under the spotlight by pioneer studies in the areas of secretion and signal transduction, phosphoinositides and their metabolizing enzymes have been increasingly recognized as key protagonists in fundamental aspects of neurotransmission. Not surprisingly, dysregulation of phosphoinositide metabolism has also been implicated in synaptic malfunction associated with a variety of brain disorders. In the present chapter, we summarize current knowledge on the role of phosphoinositides at the neuronal synapse and highlight some of the outstanding questions in this research field.


Rhode Island's child protective service system.
Rhode Island has found that an adaptation of the Illinois child protective services system has successfully enabled it to improve its protective service, giving primacy to children's rights while minimizing intrusion on family privacy.


Degradation of STAT1 and STAT2 by the V proteins of simian virus 5 and human parainfluenza virus type 2, respectively: consequences for virus replication in the presence of alpha/beta and gamma interferons.
Human cell lines were isolated that express the V protein of either simian virus 5 (SV5) or human parainfluenza virus type 2 (hPIV2); the cell lines were termed 2f/SV5-V and 2f/PIV2-V, respectively. STAT1 was not detectable in 2f/SV5-V cells, and the cells failed to signal in response to either alpha/beta interferons (IFN-alpha and IFN-beta, or IFN-alpha/beta) or gamma interferon (IFN-gamma). In contrast, STAT2 was absent from 2f/PIV2-V cells, and IFN-alpha/beta but not IFN-gamma signaling was blocked in these cells. Treatment of both 2f/SV5-V and 2f/PIV2-V cells with a proteasome inhibitor allowed the respective STAT levels to accumulate at rates similar to those seen in 2fTGH cells, indicating that the V proteins target the STATs for proteasomal degradation. Infection with SV5 can lead to a complete loss of both phosphorylated and nonphosphorylated forms of STAT1 by 6 h postinfection. Since the turnover of STAT1 in uninfected cells is longer than 24 h, we conclude that degradation of STAT1 is the main mechanism by which SV5 blocks interferon (IFN) signaling. Pretreatment of 2fTGH cells with IFN-alpha severely inhibited both SV5 and hPIV2 protein synthesis. However, and in marked contrast, pretreatment of 2fTGH cells with IFN-gamma had little obvious effect on SV5 protein synthesis but did significantly reduce the replication of hPIV2. Pretreament with IFN-alpha or IFN-gamma did not induce an antiviral state in 2f/SV5-V cells, indicating either that the induction of an antiviral state is completely dependent on STAT signaling or that the V protein interferes with other, STAT-independent cell signaling pathways that may be induced by IFNs. Even though SV5 blocked IFN signaling, the addition of exogenous IFN-alpha to the culture medium of 2fTGH cells 12 h after a low-multiplicity infection with SV5 significantly reduced the subsequent cell-to-cell spread of virus. The significance of the results in terms of the strategy that these viruses have evolved to circumvent the IFN response is discussed.


Bcl-2 inhibits the caspase-dependent apoptosis induced by SARS-CoV without affecting virus replication kinetics.
Vero cells transfected with either neo- or bcl-2-plasmid were infected with SARS-CoV at a high multiplicity of infection. Apoptosis appeared after the onset of CPE and completion of virus replication, and could be prevented by Bcl-2 expression. Apoptosis is likely mediated by the mitochondrial pathway, as demonstrated by its inhibition using Bcl-2, and by the activation of the caspase cascade, resulting in PARP cleavage. Prevention of apoptosis did not affect susceptibility to infection, kinetics and extent of viral replication and release, thus implying that apoptosis is not involved in facilitating release and/or dissemination of SARS-CoV in Vero cells.


High-pressure liquid chromatography of drugs. An evaluation of an octadecylsilane stationary phase.
The performance of a commonly used high-pressure liquid chromatographic stationary phase, octadecylsilane, has been evaluated for 30 compounds selected as representative of a wide variety of drug substances. Chromatographic behavior is found to be highly predictable on the basis of pKa and partition coefficient, and the stationary phase should be especially valuable for the separation of acidic and neutral drugs. For basic drugs, however, the column efficiency is poor, detracting from the overall usefulness.


Human skeletal muscle myosin function at physiological and non-physiological temperatures.
The aim of the study was to assess the function of human skeletal muscle myosin across a wide range of temperatures, including physiological. We used a single fibre in vitro motility assay. The in vitro motility speed of actin filaments propelled by myosin extracted from fibres expressing type I myosin heavy chain (MyHC; n = 9), IIa MyHC (n = 6), IIax MyHC (n = 4) and I/IIa MyHC (n = 1) was measured at 15, 20, 25, 30 and 35 degrees C. The motility speed between groups of fibres expressing different MyHC differed significantly (P << 0.001). The increase in motility speed with an increase in temperature was statistically significant (P << 0.001) between all temperatures. The relative difference in motility speed between the slow type I and the fast IIax MyHC fibres decreased with increasing temperature, i.e. a 7.5-fold difference at 15 degrees C was reduced to twofold at 35 degrees C. Furthermore, the twofold difference in motility speed between type IIa and IIax MyHC at 15 degrees C disappeared completely at 35 degrees C. The activation energy, E(A), and temperature coefficient, Q(10), over the 15-35 degrees C temperature range was higher for type I MyHC, 54.47 +/- 4.37 kJ mol(-1) and 2.09 +/- 0.12, respectively, than for type IIa MyHC, 45.41 +/- 3.12 kJ mol(-1) (P < 0.001) and 1.85 +/- 0.08 (P < 0.001), or IIax MyHC, 34.71 +/- 1.75 kJ mol(-1) (P << 0.001) and 1.60 +/- 0.04 (P << 0.001). The present results suggest a significantly reduced difference in shortening velocity between different human muscle fibre types at physiological temperature than previously reported at lower temperatures (12 or 15 degrees C) with implications for human in vivo muscle function.


Promising aberrant DNA methylation marker to predict gastric cancer development in individuals with family history and long-term effects of H. pylori eradication on DNA methylation.
It remains unknown whether individuals with a family history (FH) of gastric cancer (GC) are associated with aberrant DNA methylation. The aim of this study was to investigate the association between aberrant DNA methylation and FH of GC. Using quantitative MethyLight assay, MOS, miR124a-3, NKX6-1, EMX1, CDH1, and TWIST1 methylation levels in the noncancerous gastric mucosa was compared between subjects with and without FH based on GC and Helicobacter pylori (Hp) infection. Changes in the methylation levels were evaluated over time after Hp eradication. In Hp-positive GC patients, MOS (P < 0.001), CDH1 (P < 0.001), and TWIST1 (P = 0.004) methylation were decreased in subjects with FH (n = 64) than in those without FH (n = 58). In Hp-positive controls, MOS methylation was lower in subjects with FH (n = 73) than in those without FH (n = 50) (P = 0.042), while miR124a-3 (P = 0.006), NKX6-1 (P < 0.001), and CDH1 (P < 0.001) methylation were higher in subjects with FH. CDH1 methylation constantly decreased from 2 years in GC patients and 3-4 years in controls after Hp eradication (all P < 0.001). A persistent decrease in methylation over time was not observed in other genes after eradication. The methylation of MOS and CDH1 provided an association between aberrant DNA methylation and gastric carcinogenesis in FH of GC, a useful marker for GC risk in individuals with FH. Furthermore, CDH1 methylation decreased after Hp eradication.


Effect of transcription peptide inhibitors on HIV-1 replication.
HIV-1 manipulates cellular machineries such as cyclin dependent kinases (cdks) and their cyclin elements, to stimulate virus production and maintain latent infection. Specifically, the HIV-1 viral protein Tat increases viral transcription by binding to the TAR promoter element. This binding event is mediated by the phosphorylation of Pol II by complexes such as cdk9/Cyclin T and cdk2/Cyclin E. Recent studies have shown that a Tat 41/44 peptide derivative prevents the loading of cdk2 onto the HIV-1 promoter, inhibiting gene expression and replication. Here we show that Tat peptide analogs computationally designed to dock at the cyclin binding site of cdk2 have the ability to bind to cdk2 and inhibit the association of cdk2 with the HIV promoter. Specifically, the peptide LAALS dissociated the complex and decreased kinase activity in vitro. We also describe our novel small animal model which utilizes humanized Rag2(-/-)gamma(c)(-/-) mice. This small peptide inhibitor induces a decrease in HIV-1 viral transcription in vitro and minimizes viral loads in vivo.


Interference from haloacetamides during the determination of haloacetic acids using gas chromatography.
Haloacetic acids (HAAs) are the second largest class of disinfection by-products (DBPs) by weight in water and are more cytotoxic and genotoxic to mammalian cells than trihalomethanes, the first largest class of DBPs. Gas chromatography (GC) is the most widely used technique for determining HAAs. Due to their polar nature, derivatization prior to GC analysis is required. Typically, derivatization is undertaken with acidic methanol, which converts HAAs to the corresponding methyl ester (haloacetic acid methyl esters, abbreviated as HAAMEs), and HAAs are quantified by measuring HAAMEs. In this study, the interference from two other groups of DBPs, the haloacetonitriles (HANs) and haloacetamides (HAMs), on the determination of HAAs was investigated. HANs and HAMs at a range of concentrations (0, 20, 40, 60, 80, and 100 µg/L) were subjected to the same derivatization and analytical procedures as HAAs. The stability of HANs and HAMs under strongly acidic conditions was assessed and the operative mechanism of interference was investigated. The results showed that HAMs significantly interfered with the determination of the corresponding HAAs and the transformation rates of HAMs (representing the extent of HAMs transforming to corresponding HAAMEs) ranged from 6.5 to 45.7%, while the impact of HANs can be neglected. The stability of HANs and HAMs under strongly acidic conditions indicated that hydrolysis was not the cause of the interference. Instead, it was proposed that HAMs react with methyl alcohol, to generate the same corresponding HAAMEs that was generated when HAAs reacted with methyl alcohol. A method for revising HAA concentrations in the presence of HAMs is suggested.


Arsenic in waters, soils, sediments, and biota from Mexico: An environmental review.
We reviewed over 226 studies dealing with arsenic (As) in water bodies (124 sites or regions; 5,834 samples), soils (44; 2,700), sediments (56; 765), rocks (6; 85), mine waste (25; 582), continental plants (17 (77 species); 571), continental animals (10 (32 species); 3,525) and aquatic organisms (27 (100 species) 2,417) in Mexico. In general, higher As concentrations were associated with specific regions in the states of Hidalgo (21 sites), San Luis Potosi (SLP) (19), Baja California Sur (15), Zacatecas (5), and Morelos (4). High As levels have been detected in drinking water in certain locations of Coahuila (up to 435 μg L-1) and Sonora (up to 1004 μg L-1); in continental surficial water in Puebla (up to 780 μg L-1) and Matehuala, SLP (up to 8684 μg L-1); in groundwater in SLP (up to 16,000 μg L-1) and Morelia, Michoacán (up to 1506,000 μg L-1); in soils in Matehuala, SLP (up to 27,945 μg g-1) and the Xichú mining area, Guanajuato (up to 62,302 μg g-1); and in sediments in Zimapán, Hidalgo (up to 11,810 μg g-1) and Matehuala, SLP (up to 28,600 μg g-1). In contaminated arid and semi-arid areas, the plants P. laevigata and A. farnesiana exhibit the highest As levels. These findings emphasize the human and environmental risks associated with the presence of As in such regions. A synthesis of the available techniques for the removal of As in water and the remediation technologies for As contaminated soils and sediments is given. The As occurrence, origin (geogenic, thermal, mining and anthropogenic) and evolution in specific regions is summarized. Also, the mobilization and mechanisms to explain the As variability in continental environments are concisely given. For future research, a stratified regional sampling is proposed which prioritizes critical sites for waters, soils and sediments, and biota, considering the subpopulation of foods from agriculture, livestock, and seafood. It is concluded that more detailed and comprehensive studies concerning pollution levels, as well as As trends, transfer, speciation, and toxic effects are still required.


RNA-seq analysis provides insight into molecular adaptations of Andrias davidianus.
The Chinese giant salamander Andrias davidianus is regarded as an ideal model for studying local adaptations, such as longevity, tolerance to starvation, and cutaneous respiration. Transcriptome analysis is useful for studying the large and complex genomes of amphibians. Based on the coding gene set of adult A. davidianus, dozens of A. davidianus-specific genes were identified and three signaling pathway (JAK-STAT, HIF-1, and FoxO) genes were expanded as compared with other amphibians. The results of the pathway analysis of A. davidianus-specific genes indicated that the molecular adaptation of A. davidianus may have required a more rapid evolution of the immune system. Additionally, for the first time, the gene expressions in different parts of the skin tissue were compared. The results of the comparison analysis demonstrated that lateral skin could be more focused on mucus secretion, dorsal skin on immunity and melanogenesis, and abdominal skin on water and salt metabolism. This study provides the first insight into studying longevity and starvation tolerance in A. davidianus, and offers a basis for further investigation of the molecular mechanisms of adaptations in amphibians.


Intervention Studies in Humans.
Intervention studies in humans provide the highest level of evidence in the assessment of the effect of nutrients or bioactive food components on human health /disease. There are different intervention study designs, and their selection depends on the objectives of the study. Here we present the main designs and the factors that should be considered when selecting and developing them.


Constrictive amniotic band syndrome (CABS) is a rare condition which occurs sporadically and should not be compared with a syndrome as it is known from genetics. However, since the pathogenesis is not yet fully understood, some theories suggest genetics playing a role. Even though CABS is rare it is associated with a high risk of foetal death as seen in 1/70 of these cases. The diagnostics start with ultrasound of the pregnant woman, and if this leads to suspicion of CABS it is possible to supplement with 3D ultrasound or MRI to verify. The treatment involves either in utero or postnatal surgery depending on the case, as argued in this review.


Association between atherogenic dyslipidemia and recurrent stroke risk in patients with different subtypes of ischemic stroke.
The association between atherogenic dyslipidemia and stroke recurrence remains unclear, and may be influenced by different subtypes of ischemic stroke. We aimed to investigate whether atherogenic dyslipidemia contributed to stroke recurrence in ischemic stroke patients and in those with certain subtypes of ischemic stroke. We conducted a prospective hospital-based study enrolling patients with acute ischemic stroke. Atherogenic dyslipidemia was defined as high-density lipoprotein cholesterol <40 mg/dl and triglycerides ≥200 mg/dl. Ischemic stroke subtypes were classified according to the Trial of Org 10172 in Acute Stroke Treatment criteria. The patients were followed up at 3, 6, 12 and 24 months after stroke onset. The association between atherogenic dyslipidemia and stroke recurrence was analyzed by using multivariable Cox regression model. In the 510 ischemic stroke patients, 64 patients (12·5%) had atherogenic dyslipidemia, and 66 patients (12·9%) experienced stroke recurrence events within 24 months. Kaplan-Meier analysis revealed that stroke recurrence rate was significantly higher in patients with atherogenic dyslipidemia than those without in all the stroke patients (20·3% vs. 11·9%; P = 0·048), and more evident in those of large-artery atherosclerosis subtype (31·0% vs. 14·1%; P = 0·014), but not in the other subtypes. Multivariable Cox regression analysis revealed that atherogenic dyslipidemia was associated with higher stroke recurrence risk among stroke patients of large-artery atherosclerosis subtype (hazard ratio, 2·79; 95% confidence interval, 1·24-6·28), but not significant in all the stroke patients (hazard ratio, 1·69; 95% confidence interval, 0·85-3·37). Atherogenic dyslipidemia is associated with higher risk of stroke recurrence in ischemic stroke patients. Such association might be more pronounced in large-artery atherosclerosis subtype and needs further investigation to establish such relationship.


Short-term stimulatory effect of Sertoli cell conditioned medium on Leydig cell steroidogenesis is not mediated by inhibin.
Addition of concentrated rat Sertoli cell conditioned medium (rSCCM) to isolated Leydig cells from immature rats stimulated steroid production more than 13-fold within 4 h. LH-stimulated steroidogenesis was not enhanced by addition of rSCCM. The biological activity of the concentrated rSCCM was higher after incubation of Sertoli cells with FSH, whereas FSH alone did not stimulate steroid production. This effect of rSCCM was not due to inhibin, since highly purified 32 kDa rat inhibin, in doses equivalent to those present in rSCCM, had no effect on steroidogenesis during the 4 h incubation period. Furthermore, inhibin could be separated from the Leydig cell stimulating factor by anion-exchange chromatography. These results indicate a short-term paracrine control of Leydig cell steroidogenesis by Sertoli cell derived factors, which differ from inhibin.


Non-invasive cardiovascular imaging for evaluating subclinical target organ damage in hypertensive patients: A consensus paper from the European Association of Cardiovascular Imaging (EACVI), the European Society of Cardiology Council on Hypertension, and the European Society of Hypertension (ESH).
Arterial hypertension (HTN) accounts for the largest amount of attributable cardiovascular (CV) mortality worldwide, and risk stratification in hypertensive patients is of crucial importance to manage treatment and prevent adverse events. Asymptomatic involvement of different organs in patients affected by HTN represents an independent determinant of CV risk and the identification of target organ damage (TOD) is recommended to further reclassify patients' risk. Non-invasive CV imaging is progressively being used and continues to provide new technological opportunities to TOD evaluation at early stage. The aim of this article is to provide the community of cardiology with an update on appropriate and justified use of non-invasive imaging tests in the growing population of hypertensive patients.


Stabilization of flat anterior chamber after trabeculectomy with Healon5.
A 64-year-old phakic patient had a trabeculectomy complicated by complete shallowing of the anterior chamber 10 days postoperatively. Despite repair of a conjunctival wound dehiscence and reformation of the anterior chamber with sodium hyaluronate 3.0%-chondroitin sulfate 4.0% (Viscoat), he had a flat anterior chamber again the following day with 360 degrees of pupillary synechias and lens-to-cornea touch. Sodium hyaluronate 2.3% (Healon5) instilled through a paracentesis at the slitlamp lysed the synechias, stabilized the anterior chamber, facilitated filtration, and prevented complications from hypotony. The unique properties of Healon5 allowed for a conservative and less invasive approach in the management of this particular complication.


Dentoalveolar Distraction Osteogenesis for Rapid Maxillary Canine Retraction: An Overview of Technique, Treatment, and Outcomes.
Patients and orthodontists seek to reduce treatment time in braces. Rapid canine retraction through dentoalveolar distraction osteogenesis is one of several treatment approaches to reduce treatment in braces. This article provides an overview of technique of dentoalveolar distraction osteogenesis to accomplish rapid canine retraction and associated outcomes. When this treatment protocol is implemented well, rapid canine retraction is achieved predictably with minimal side effects. Although current evidence suggests that adverse sequelae, such as root resorptions and pulp devitalization, are rare, prospective clinical studies that are adequately powered and documenting long-term follow-up of these outcomes are lacking.


Methods used for the detection and subtyping of Listeria monocytogenes.
Listeria monocytogenes is an important foodborne pathogen responsible for non-invasive and invasive diseases in the elderly, pregnant women, neonates and immunocompromised populations. This bacterium has many similarities with other non-pathogenic Listeria species which makes its detection from food and environmental samples challenging. Subtyping of L. monocytogenes strains can prove to be crucial in epidemiological investigations, source tracking contamination from food processing plants and determining evolutionary relationships between different strains. In recent years there has been a shift towards the use of molecular subtyping. This has led to the development of new subtyping techniques such as multi-locus variable number tandem repeat analysis (MLVA) and multi-locus sequence based typing (MLST). This review focuses on the available methods for Listeria detection including immuno-based techniques and the more recently developed molecular methods and analytical techniques such as matrix-assisted laser desorption/ionisation time-of-flight based mass spectrometry (MALDI-TOF MS). It also includes a comparison and critical analysis of the available phenotypic and genotypic subtyping techniques that have been investigated for L. monocytogenes.


Predicting outcome after acute ischemic stroke: an external validation of prognostic models.
To externally validate two prognostic models predicting functional outcome and survival 100 days after acute ischemic stroke. Using prospectively collected data from 1,470 patients, the authors evaluated two previously developed models. Model I predicts incomplete functional recovery (Barthel Index <95) vs complete functional recovery with 11 variables, whereas model II predicts mortality vs survival with 3 variables. On admission to a participating hospital, patients were registered prospectively and included according to defined criteria. Within 72 hours, predictive variables under investigation were assessed. Follow-up was performed 100 days after the event. Model I correctly predicted 68.1% of the patients who had incompletely recovered or had died and 85.7% of the completely recovered patients, model II 46.9% of the patients who had died and 95.9% of the surviving patients. Both models performed better than the treating physicians' predictions made within 72 hours after admission. The resulting prognostic models are useful to correctly stratify treatment groups in clinical trials and to accurately predict the distribution of endpoint variables.


Control of gene expression in the P2-related temperate coliphage 186. VI. Sequence analysis of the early lytic region.
We have completed the sequence of the 186 early lytic region and established that this region encodes the four genes CP75, CP76, CP77 and CP78, with CP79 the first gene of the next region. Functions have been assigned to the four early genes.