Defective lysosomal exocytosis and plasma membrane repair in Chediak-Higashi/beige cells.
Plasma membrane resealing is a Ca(2+)-dependent process that involves the exocytosis of intracellular vesicles next to the wound site. Recent studies revealed that conventional lysosomes behave as Ca(2+)-regulated secretory compartments and play a central role in membrane resealing. These findings raised the possibility that the complex pathology of lysosomal diseases might also include defects in plasma membrane repair. Here, we investigated the capacity for lysosomal exocytosis and membrane resealing of fibroblasts derived from Chediak-Higashi syndrome (CHS) patients, or from beige-J mice. By using a sensitive electroporation/fluorescence-activated cell sorter-based assay, we show that lysosomal exocytosis triggered by membrane wounding is impaired in both human Chediak-Higashi and mouse beige-J fibroblasts. Lysosomal exocytosis increased when the normal size of lysosomes was restored in beige-J cells by expression of the CHS/Beige protein. A similar effect was seen when the lysosomal enlargement in beige-J cells was reversed by treatment with E64d. In addition, the survival of Chediak-Higashi and beige-J fibroblasts after wounding was reduced, indicating that impaired lysosomal exocytosis inhibits membrane resealing in these mutant cells. Thus, the severe symptoms exhibited by CHS patients may also include defects in the ability of cells to repair plasma membrane lesions.


Effect of continuous renal replacement therapy on kidney injury molecule-1 and neutrophil gelatinase-associated lipocalin in patients with septic acute kidney injury.
Kidney injury molecule-1 (Kim-1) and neutrophil gelatinase-associated lipocalin (NGAL) have been investigated as biomarkers for acute kidney injury (AKI). However, they are seldom investigated in patients with septic AKI treated with continuous renal replacement therapy (CRRT). The aim of the present study was to investigate the therapeutic effectiveness and possible mechanisms of CRRT in septic AKI by observing the changes in Kim-1 and NGAL levels. A group of 38 patients with septic AKI was randomly divided into the conventional drug treatment group (group A) and the CRRT group (group B). All patients were treated with standard antisepsis agents, and group B was additionally submitted to CRRT for 24 h. The levels of Kim-1 and NGAL in serum, urine and the ultrafiltrate of CRRT were measured prior to and at 12, 24, and 48 h after treatment. In group A, urinary Kim-1 (uKim-1) levels at 12, 24 and 48 h were lower than prior to treatment (P<0.05), whereas urinary NGAL (uNGAL) showed no difference among the various time points (P>0.05). In group B, uKim-1 was decreased at 24 and 48 h compared with before treatment (all P<0.05), whereas uNGAL was decreased at 48 h (P<0.05). Serum Kim-1 did not change with time in groups A and B (P>0.05), whereas serum NGAL was increased after treatment in group A (P<0.05) but did not change in group B (P>0.05). Kim-1 and NGAL were not detected in the ultrafiltrate of CRRT. uKim-1 and uNGAL decreased significantly after CRRT, and therefore may be used to reflect the change of renal function during CRRT and to evaluate the therapeutic effectiveness of the method.


Consensus Statement on Ethical & Safety Practices for Conducting Digital Monitoring Studies with People at Risk of Suicide and Related Behaviors.
Digital monitoring technologies (e.g., smart-phones and wearable devices) provide unprecedented opportunities to study potentially harmful behaviors such as suicide, violence, and alcohol/substance use in real-time. The use of these new technologies has the potential to significantly advance the understanding, prediction, and prevention of these behaviors. However, such technologies also introduce myriad ethical and safety concerns, such as deciding when and how to intervene if a participant's responses indicate elevated risk during the study? We used a modified Delphi process to develop a consensus among a diverse panel of experts on the ethical and safety practices for conducting digital monitoring studies with those at risk for suicide and related behaviors. Twenty-four experts including scientists, clinicians, ethicists, legal experts, and those with lived experience provided input into an iterative, multi-stage survey, and discussion process. Consensus was reached on multiple aspects of such studies, including: inclusion criteria, informed consent elements, technical and safety procedures, data review practices during the study, responding to various levels of participant risk in real-time, and data and safety monitoring. This consensus statement provides guidance for researchers, funding agencies, and institutional review boards regarding expert views on current best practices for conducting digital monitoring studies with those at risk for suicide-with relevance to the study of a range of other potentially harmful behaviors (e.g., alcohol/substance use and violence). This statement also highlights areas in which more data are needed before consensus can be reached regarding best ethical and safety practices for digital monitoring studies.


Pediatric soft-tissue tumors.
Soft-tissue tumors in children (<18 years) are a heterogeneous group of lesions. Masses may be asymptomatic or associated with pain or discomfort. Although most lesions are benign, developing an appropriate differential diagnosis requires knowledge of the clinical and radiographic characteristics of tumors and tumorlike conditions in children. A thorough history and physical examination, followed by appropriate imaging studies, when indicated, can establish a correct diagnosis and help determine appropriate treatment recommendations.


Glucose utilization in relation to insulin secretion in NZO and C57Bl mouse islets.
Further studies of insulin secretion from isolated pancreatic islets of the NZO strain of obese hyperglycemic mouse have shown markedly impaired insulin secretory responses to D-glucose in islets from fasted or fed mice. NZO islets at a low glucose concentration (3.3 mM) showed a significant insulin secretory response to 0.5 mM 3-isobutyl-1-methylxanthine (IBMX), a phosphodiesterase inhibitor, but in the presence of this agent showed no significant additional response to increased glucose concentration. This contrasted with the situation in islets from an arbitrarily chosen control strain of mouse (C57Bl) which showed a small or insignificant response to 0.5 mM IBMX at a low glucose concentration, but a greatly enhanced response to glucose in the presence of IBMX. In contrast to the relative refractoriness of the NZO islets to glucose, they showed a large response to D,L-glyceraldehyde, at least equal to that found in the control islets. Glucose utilization was studied by measuring the conversion of D-[5-3H]glucose to [3H]H2O. In islets from both fasted and fed NZO mice, glucose utilization, when calculated on the basis of islet DNA content, was markedly reduced at high glucose concentrations compared to that in islets from the control strain. It is concluded that the relative unresponsiveness of NZO islets to glucose is associated with, and perhaps due to, a decreased rate of glucose utilization. The preserved responsiveness to glyceraldehyde suggests that the reduced glucose utilization may be due to a partial metabolic block before the triose phosphate step in the islet glycolytic pathway.


[Molecular biology diagnosis of tumors of the musculoskeletal system].
It is sometimes difficult to make an unequivocal diagnosis of tumours of bone and soft tissue based upon classical morphology alone, which has led to an increased use of additional diagnostic tools. In the past decade new techniques have become available, based on tumour specific genetic alterations, for instance chromosomal translocations. With the cloning of the translocation breakpoints and the identification of the genes involved, the reverse transcriptase polymerase chain reaction (RT-PCR) detection of the fusion gene has become an important diagnostic test. Also, non-tumour specific genetic alterations with prognostic value can be detected.


Studies of Angular Resolution for Acoustic Arc Arrays.
Currently, phased arrays are increasingly used in ultrasonic nondestructive testing. One of the most important parameters of ultrasonic nondestructive testing with the application of phased arrays is the angular resolution. This paper presents the results of studies of the angular resolution of concave and convex acoustic arrays in ultrasonic testing with the application of the total focusing method. Computer modeling of concave and convex acoustic arrays consisting of 16, 32 and 64 elements with distances between elements of 0.5 and 1 mm and arc radii of 30 and 60 mm have been performed. The results obtained by computer modeling were confirmed via in situ experiments.


Detection of genetic variation with radioactive ligands. I. Electrophoretic screening of plasma proteins with a selected panel of compounds.
To detect new genetic variation in human plasma proteins, a panel of 63 radioactive substances were screened as potential radioligands using polyacrylamide gel electrophoresis (PAGE) and autoradiography. Vitamins, hormones, drugs, amino acids, purines, pyrimidines, sugars and lipids labeled with 14C or other radionuclides were among those substances tested. A majority bound to albumin and a smaller fraction to prealbumins and lipoproteins. Several vitamins and hormones bound to specific alpha and beta globulins. (1) Electrophoretic polymorphisms of vitamin D-binding protein (group-specific component), a vitamin B12-binding protein (transcobalamin II), and thyroxine-binding alpha-globulin are described elsewhere. (2) Testosterone-binding beta-globulin (TeBG) showed an electrophoretic polymorphism in Caucasians and a possible deficiency allele. (3) Transcortin showed an electrophoretic doublet in all persons tested but no electrophoretic variation. (4) A protein binding derivative of norepinephrine or epinephrine was identified as transferrin. (5) A nonpolymorphic protein running cathodal to albumin and binding a derivative of riboflavin was tentatively identified as a fraction of albumin with mobility altered as a result of interaction with the ligand.


ePharmer: An integrated and graphical software for pharmacophore-based virtual screening.
Pharmacophore-based virtual screening (VS) has emerged as an efficient computer-aided drug design technique when appraising multiple ligands with similar structures or targets with unknown crystal structures. Current pharmacophore modeling and analysis software suffers from inadequate integration of mainstream methods and insufficient user-friendly program interface. In this study, we propose a stand-alone, integrated, graphical software for pharmacophore-based VS, termed ePharmer. Both ligand-based and structure-based pharmacophore generation methods were integrated into a compact architecture. Fine-grained modules were carefully organized into the computing, integration, and visualization layers. Graphical design covered the global user interface and specific user operations including editing, evaluation, and task management. Metabolites prediction analysis with the chosen VS result is provided for preselection of wet experiments. Moreover, the underlying computing units largely adopted the preliminary work of our research team. The presented software is currently in client use and will be released for both professional and nonexpert users. Experimental results verified the favorable computing capability, user convenience, and case performance of the proposed software.


PBSword: a web server for searching similar protein-protein binding sites.
PBSword is a web server designed for efficient and accurate comparisons and searches of geometrically similar protein-protein binding sites from a large-scale database. The basic idea of PBSword is that each protein binding site is first represented by a high-dimensional vector of 'visual words', which characterizes both the global and local shape features of the binding site. It then uses a scalable indexing technique to search for those binding sites whose visual words representations are similar to that of the query binding site. Our system is able to return ranked results of binding sites in short time from a database of 194 322 domain-domain binding sites. PBSword supports query by protein ID and by new structures uploaded by users. PBSword is a useful tool to investigate functional connections among proteins based on the local structures of binding site and has potential applications to protein-protein docking and drug discovery. The system is hosted at http://pbs.rnet.missouri.edu.


Treatment of varicose and telangiectatic leg veins: double-blind prospective comparative trial between aethoxyskerol and sotradecol.
One hundred twenty-nine patients were treated with either polidocanol (POL) or sodium tetradecyl sulfate (STS) to compare the efficacy and adverse sequelae of each agent. To determine the safety and efficacy of two sclerosing solutions. Each patient's leg veins that did not have incompetence from the saphenofemoral junction (SFJ) were divided into three categories by size (<1 mm, 1-3 mm, 3-6 mm). Each leg was randomly treated with either 0.25%, 0.5%, or 1.5% of STS or 0.5%, 1.0%, or 3% of POL respective of size. An independent, three-panel, blindly randomized photographic examination was obtained pretreatment and at 4 and 16 weeks. Patient satisfaction index and overall clinical improvement assessment were also obtained. All patients had an average of 70% improvement and were 70-72% satisfied in all vein categories treated with either solution. There was no significant difference in adverse effects between each group except for a decrease in ulcerations and swelling in the POL group. Both STS and POL are safe and effective sclerosing solutions for varicose and telangiectatic leg veins.


Stress responses to repeated exposure to a combined physical and social evaluative laboratory stressor in young healthy males.
Repeated exposure to homotypic laboratory psychosocial stressors typically instigates rapid habituation in hypothalamic-pituitary-adrenal (HPA) axis-mediated stress responses in humans. However, emerging evidence suggests the combination of physical stress and social evaluative threat may be sufficient to attenuate this response habituation. Neuroendocrine, cardiovascular and subjective stress responses following repeated exposure to a combined physical and social evaluative stress protocol were assessed to examine the habituation response dynamic in this context. The speech task of the Trier social stress test (TSST; Kirschbaum et al., 1993) and the socially evaluated cold pressor task (SECPT; Schwabe et al., 2008) were administered in a combined stressor protocol. Salivary cortisol, cardiovascular and subjective stress responses to a non-stress control and repeat stressor exposure separated by six weeks were examined in males (N=24) in a crossover manner. Stressor exposure resulted in significant elevations in all stress parameters. In contrast to the commonly reported habituation in cortisol response, a comparable post-stress response was demonstrated. Cortisol, heart rate and subjective stress responses were also characterised by a heightened response in anticipation to repeated stress exposure. Blood pressure responses were comparatively uniform across repeated exposures. Findings suggest a combined physical and social evaluative stressor is a potentially useful method for study designs that require repeated presentation of a homotypic stressor.


TMD prevalence in rural and urban Native American populations.
The purpose of this study was to assess the prevalence of TMD in a consecutive sample of 102 subjects from the Native American population living in an urban setting and 90 subjects living in a rural setting. The study utilized a clinical examination and standardized questionnaires. The sample age ranged from five to 84 years of age. The subjects were asked to estimate pain frequency, severity and daily pattern of jaw pain, difficulty in opening, joint clicking, and sleeping problems. Examination was performed on joint, masticatory, and cervical muscles, as well as occlusion. Data was collected and statistically analyzed. Statistically significant differences were found; however, the only statistically significant difference that might have clinical significance was more facial pain in the urban population.


Tetramethylammonium hydroxide (TMAH) thermochemolysis for probing in situ softwood lignin modification in each gut segment of the termite.
Termites are highly effective in lignocellulose degradation; however, the process of lignin deconstruction along the alimentary canal is not well understood. In this study, the wood metabolites in each gut segment were tentatively analyzed using pyrolysis-gas chromatography-mass spectrometry in the presence of tetramethylammonium hydroxide. Collectively, the significant differences in the pyrolysate distribution among each sample established (1) conservation of the major β-O-4' bonds of lignin during termite digestion, although a selective lignin substructure modification was observed across the whole gut; (2) initiation of lignin-polysaccharide dissociation, aliphatic oxidation/carboxylation, phenolic dehydroxylation in the foregut, and linkage modification of the 5-5', β-5', and β-1' substructures; (3) the continuation of foregut reactions into the midgut with further phenolic carboxylation/demethoxylation/carbonylation; and (4) phenolic/aliphatic esterifications in the hindgut. Overall, elucidation of the stepwise lignin unlocking mechanism in termites provides a valuable insight for understanding plant cell wall structure and its recalcitrance.


Modulation of HT-29 human colonic cancer cell differentiation with calmidazolium and 12-O-tetradecanoylphorbol-13-acetate.
The effects of a protein kinase C activator, 12-O-tetradecanoylphorbol-13-acetate (TPA), and of a calmodulin antagonist calmidazolium (CZ), on a human colonic cancer cell line HT-29 were analyzed. HT-29 cells are undifferentiated in standard culture conditions (HT-29 G+) and display an enterocytic differentiation when cultured in glucose-deprived medium (HT-29 G-). Early effects of TPA and CZ on the localization of cytoskeletal proteins (caldesmon, alpha-actinin and vinculin) and on cell proliferation were examined. Differentiation of the cells was assessed after 4 weeks on the basis of ultrastructural and functional characteristics of enterocytic polarity, presence of apical brush borders, expression of brush border membrane antigens (Caco 5/50 and sucrase-isomaltase), and segregation of calmodulin to the brush border cytoskeleton. TPA treatment of HT-29 G+ or G- cells induced early morphological and cytoskeletal alterations: the cells rounded up and lost their stress fibers with the associated caldesmon, alpha-actinin, and vinculin. TPA did not modify the differentiation of G- cells, but induced in G+ cells the expression, although limited, of enterocytic differentiation characteristics. Addition of CZ to HT-29 G- cells enhanced their differentiation state but did not provoke any early morphological or cytoskeletal alterations. No effects of CZ on HT-29 G+ cells were obvious. The results suggest that protein kinase C, the TPA receptor, is involved in the triggering of HT-29 G+ cell differentiation whereas calmodulin-dependent functions would be implicated in HT-29 G- cell maturation.


Acute confusional States in the elderly--diagnosis and treatment.
Delirium is common, has multiple causes and causes distress to numerous patients and their relatives. Selective review of the literature in PubMed and PsycINFO, with reference to selected national and international guidelines. The hypoactive subtype of delirium is commoner than the hyperactive type, and often overlooked. Delirium in an elderly individual is associated with an additional burden, a possible loss of potential for rehabilitation, and a marked increase in mortality. The diagnosis of delirium is primarily clinical. All professionals involved in patient care must be able to recognize the features of delirium. Dementia, dehydration and polypharmacy are particularly strongly associated, in the elderly. A careful history and examination with appropriate investigation allows underlying causes to be detected and treated. Rehabilitation strategies should be initiated without delay. Neuroleptics and benzodiazepines have an established role in the pharmacological treatment even of the hyperactive subtype. Non-pharmacological treatments include the creation of a calm and patient centred environment, and the involvement of relatives. In many cases, delirium can be diagnosed and treated in good time. Prevention is preferable to treatment.


Phonetic processing in children with cochlear implants: an auditory event-related potentials study.
To investigate the effect of increasing acoustic-phonetic difficulty in children with cochlear implants (CI) by means of auditory event-related potentials (AERPs). AERPs were recorded from a group of ten 9- to 14-year-old prelingually deafened children who exhibited open-set speech recognition, using the Nucleus 22 CI for at least 5 years. AERPs were recorded in sound field while children were performing oddball discrimination tasks with increasing acoustic-phonetic demand. The tasks consisted pairs of naturally produced stimuli that differed by one phonetic feature: vowel place (/ki/ versus/ku/), vowel height (/ki/ versus /ke/), voicing (/ka/ versus /ga/), and place of articulation (/ka/ versus /ta/). Using a repeated measure design, the effect of increasing acoustic-phonetic difficulty on P3 latency, amplitude, and scalp distribution as well as on the simultaneously obtained behavioral measures, performance accuracy, and reaction time was evaluated. AERPs elicited in the range of 350 msec poststimulus onset were contaminated by the CI stimulus artifact, thus enabling reliable identification of the P3 component only. Increasing acoustic-phonetic difficulty was manifested in all measures in a hierarchical manner: P3 latency and reaction time increased, whereas P3 amplitude and performance accuracy decreased. The correlations, however, between behavioral and electrophysiological measures were not significant. Further support for P3 sensitivity to increasing acoustic-phonetic demand was its absence in four of the 10 children, but only in the most difficult place of articulation task. P3 amplitude was maximal at the midline parietal cite, with equal amplitudes over the right and left scalp regardless of side of implant. The results underscore the significant value of the P3 potential as a sensitive neural index of speech-sound processing in children with CI. The similar hierarchy of acoustic-phonetic demand manifested in both behavioral and electrophysiological measures suggests that speech perception performance relates to neurophysiologic responses at cortical levels of the auditory system. Thus, recording the P3 potential to distinct phonetic contrasts may be useful for studying accessibility and neural encoding at the cortical level in CI recipients.


Open versus laparoscopic radical prostatectomy.
Expert laparoscopic surgeons have demonstrated that laparoscopic radical prostatectomy with or without robotic assistance can be performed with excellent results. There is no evidence that laparoscopic radical prostatectomy with or without robotic assistance offers any clinically relevant advantage over open radical prostatectomy. Laparoscopic radical prostatectomy with or without robotic assistance requires a significant learning curve, is a longer surgical procedure, carries greater costs, and requires an expanded operating room team. The literature suggests that laparoscopic radical prostatectomy is associated with more intraoperative complications and higher positive surgical margins. The lesser amount of postoperative bleeding associated with laparoscopic radical prostatectomy is not clinically relevant. Laparoscopic radical prostatectomy is not associated with less pain and does not facilitate earlier urinary catheter removal. The best way to improve overall outcomes after radical prostatectomy is to direct patients to expert open or laparoscopic surgeons.


Purification of filaggrin from human epidermis and measurement of antifilaggrin autoantibodies in sera from patients with rheumatoid arthritis by an enzyme-linked immunosorbent assay.
The so-called antikeratin antibody (AKA) and the antiperinuclear factor (APF) that recognize proteins related to human epidermal filaggrin belong to the most specific serological markers of rheumatoid arthritis (RA). However, assays for the detection of AKA and APF are currently based on immunofluorescence, a method that is subject to arbitrary interpretation and inadequate standardization of the substrates. Proteins extracted from human epidermis were separated by reversed-phase high-performance liquid chromatography (HPLC). Filaggrin-containing fractions, identified in immunoblotting by monoclonal antifilaggrin antibodies, were then subjected to gel filtration HPLC and, finally, to a second reversed-phase HPLC step. Tryptic digestion, amino acid sequencing and mass spectrometry were used to confirm the identity of the purified protein. Filaggrin was used as antigen in enzyme-linked immunosorbent assay (ELISA) to measure IgG class antifilaggrin antibodies. The filaggrin preparation obtained gave a single band in sodium dodecyl sulfate-polyacrylamide gel electrophoresis, binding monoclonal antifilaggrin antibody in immunoblotting. Amino acid sequences of all 10 tryptic peptides analyzed were shown to originate from human filaggrin. Antifilaggrin antibody levels exceeded the 99th percentile level of 100 middle-aged blood donors in 26/55 (47%) RA sera. At a similar cutoff level 28/55 (51%) of the RA sera were positive in the AKA test. Of the 26 antifilaggrin-positive sera, 21 were also AKA-positive. Human filaggrin can be purified by standard biochemical techniques, despite the heterogeneity of the protein, and used in ELISA for testing autoantibodies to filaggrin. The sensitivity of the assay equals that of the AKA test.


Communication Matters-Pitfalls and Promise of Hightech Communication Devices in Palliative Care of Severely Physically Disabled Patients With Amyotrophic Lateral Sclerosis.
Amyotrophic lateral sclerosis (ALS) is the most common motor neuron disease, leading to progressive paralysis, dysarthria, dysphagia, and respiratory disabilities. Therapy is mostly focused on palliative interventions. During the course of the disease, verbal as well as nonverbal communicative abilities become more and more impaired. In this light, communication has been argued to be "the essence of human life" and crucial for patients' quality of life. High-tech augmentative and alternative communication (HT-AAC) technologies such as eyetracking based computer devices and brain-computer-interfaces provide the possibility to maintain caregiver-independent communication and environmental control even in the advanced disease state of ALS. Thus, they enable patients to preserve social participation and to independently communicate end-of-life-decisions. In accordance with these functions of HT-AAC, their use is reported to strengthen self-determination, increase patients' quality of life and reduce caregiver burden. Therefore, HT-AAC should be considered as standard of (palliative) care for people with ALS. On the other hand, the supply with individually tailored HT-AAC technologies is limited by external and patient-inherent variables. This review aims to provide an overview of the possibilities and limitations of HT-AAC technologies and discuss their role in the palliative care for patients with ALS.


Exosomal MFI2-AS1 sponge miR-107 promotes non-small cell lung cancer progression through NFAT5.
Non-small cell lung cancer is a heterogeneous disease driven by extensive molecular alterations. Exosomes are small vesicles with diameters ranging from 30 to 150 nm released by various cell types and are important mediators of information transmission in tumor cells. Exosomes contain proteins, lipids, and various types of nucleic acids, including miRNAs and even DNA and RNA. MFI2 Antisense RNA 1 (MFI2-AS1) is a long noncoding RNA known to promote cell proliferation, metastasis and invasion in a variety of malignancies. The relative expression of MFI2-AS1 in NSCLC tissues was examined using RNA fluorescence in situ hybridization (FISH) staining. Transwell migration and wound healing assays were used to analyze cell migration and invasion abilities. Tube formation is used to assess angiogenic capacity. CCK8 was used to assess cell proliferation ability. RNA immunoprecipitation (RIP) experiments confirmed that MFI2-AS1 acts as a competing endogenous RNA (ceRNA) for miR-107. Dual-luciferase reporter assays were used to identify potential binding between MFI2-miRNA and target mRNA. In vivo experiments were performed by injecting exosomes into subcutaneous tumors to establish animal models. Exosomal MFI2-AS1 increases NFAT5 expression by sponging miR-107, which in turn activates the PI3K/AKT pathway. We found that the MFI2-AS1/miR-107/NFAT5 axis plays an important role in exosome-mediated NSCLC progression, is involved in pre-metastatic niche formation, and can be used as a blood-based biomarker for NSCLC metastasis. We demonstrate that MFI2-AS1 is upregulated in exosomes secreted by metastatic NSCLC cells and can be transferred to HUVECs, promoting angiogenesis and migration.


Proliferation and migration of hepatoblastoma cells are mediated by IRS-4 via PI3K/Akt pathways.
Levels of IRS-4 (insulin receptor substrate-4) in hepatoblastoma cells from the patients, HepG2 and HuH-6 cell lines were measured by Western Blot analysis, and they were all found significantly higher than those of normal hepatic cells. When the HepG2 and HuH-6 cells cultivated in vitro were treated with IRS-4 and infected with recombinant adenovirus containing IRS-4 gene, the proliferation and migration of the cells were significantly improved. Meanwhile, the expressions of PI3K (phosphatidylinositol 3'-kinase), pS473 Akt (Protein Kinase B) and pThr308 Akt were positively regulated by IRS-4 overexpression. These results indicated that IRS-4 was very likely to be involved in PI3K/Akt path way, which was further confirmed by the fact that the PI3K/Akt blocker LY294002 attenuated the proliferation and migration of the hepatoblastoma cells. In conclusion, IRS-4 enhanced the proliferation and migration of the hepatoblastoma cells via PI3K/Akt pathways.


Immunological monitoring in lung cancer: use of the leukocyte migration inhibition assay.
The agarose microdroplet leukocyte migration inhibition assay has been applied to the management of patients with lung cancer. Sera of patients with various stages of the disease were assayed in the indirect LMI system for their influence on the LIF production of normal leukocytes. A probably cell-mediated immunity blocking activity could be detected both in the serum of patients with inoperable tumours and in that of operable patients before and two weeks after surgery. The activity, however, disappeared in two thirds of the cases in about 6 months after surgery. The immune competence of patients with inoperable tumours was investigated before and during combined chemotherapy. A positive correlation was established between the tuberculin skin reactions and the leukocyte migration inhibition obtained in the direct LMI assay against PPD, but only in the presence of autologous serum. Sera of patients were also tested for putative in vivo LIF activity by their effect on the migration of autologous leukocytes. A significant correlation between anergy to PHA, as evaluated by skin testing, and the migration inhibition caused by sera was found. When, however, sera from healthy persons and from patients with chronic bronchitis or lung cancer were compared for their effect on the migration of normal leukocytes, no difference could be detected among the three groups. Single doses of the drugs temporarily weakened the skin reactions to PHA and the migration inhibition to PPD in autologous serum, but activity was restored when the drug influence had ceased.


Profiling of Chlorogenic Acids from Bidens pilosa and Differentiation of Closely Related Positional Isomers with the Aid of UHPLC-QTOF-MS/MS-Based In-Source Collision-Induced Dissociation.
Bidens pilosa is an edible herb from the Asteraceae family which is traditionally consumed as a leafy vegetable. B. pilosa has many bioactivities owing to its diverse phytochemicals, which include aliphatics, terpenoids, tannins, alkaloids, hydroxycinnamic acid (HCA) derivatives and other phenylpropanoids. The later include compounds such as chlorogenic acids (CGAs), which are produced as either regio- or geometrical isomers. To profile the CGA composition of B. pilosa, methanol extracts from tissues, callus and cell suspensions were utilized for liquid chromatography coupled to mass spectrometric detection (UHPLC-QTOF-MS/MS). An optimized in-source collision-induced dissociation (ISCID) method capable of discriminating between closely related HCA derivatives of quinic acids, based on MS-based fragmentation patterns, was applied. Careful control of collision energies resulted in fragment patterns similar to MS2 and MS3 fragmentation, obtainable by a typical ion trap MSn approach. For the first time, an ISCID approach was shown to efficiently discriminate between positional isomers of chlorogenic acids containing two different cinnamoyl moieties, such as a mixed di-ester of feruloyl-caffeoylquinic acid (m/z 529) and coumaroyl-caffeoylquinic acid (m/z 499). The results indicate that tissues and cell cultures of B. pilosa contained a combined total of 30 mono-, di-, and tri-substituted chlorogenic acids with positional isomers dominating the composition thereof. In addition, the tartaric acid esters, caftaric- and chicoric acids were also identified. Profiling revealed that these HCA derivatives were differentially distributed across tissues types and cell culture lines derived from leaf and stem explants.


[Corrigendum] Downregulation of cytokeratin 18 is associated with paclitaxel‑resistance and tumor aggressiveness in prostate cancer.
After the publication of the article, the authors noted that they would like to add Dr Robert H. Getzenberg's name to the authors' list and as a co-corresponding author, upon the agreement of all the authors. The correct author list should be as follows: BO YIN1, MO ZHANG1, YU ZENG2,3*, YOUQIANG LI3, CHAO ZHANG1, ROBERT H. GETZENBERG3* and YONGSHENG SONG1* 1Department of Urology, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004; 2Department of Urology, The First Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China; 3James Buchanan Brady Urological Institute, The Johns Hopkins University School of Medicine, Baltimore, MD 21087, USA Correspondence should now be addressed to: Correspondence to: Dr Yongsheng Song, Department of Urology, Shengjing Hospital of China Medical University, 36 Sanhao Street, Shenyang, Liaoning 110004, P.R. China E-mail: email@example.com Dr Robert H. Getzenberg, James Buchanan Brady Urological Institute, The Johns Hopkins University School of Medicine, Baltimore, MD 21087, USA E-mail: firstname.lastname@example.com *Contributed equally [the original article was published in the International Journal of Oncology 48: 1730-1736, 2016; DOI: 10.3892/ijo.2016.3396].


Improved Discrimination of Myocardial Perfusion Defects at Low Energy Levels Using Virtual Monochromatic Imaging.
The aim of this study was to explore the diagnostic performance of dual-energy computed tomography perfusion (DE-CTP) at different energy levels. Patients with known or suspected coronary artery disease underwent stress and rest DE-CTP and single-photon emission computed tomography. Images were evaluated using monochromatic data, and perfusion defects were initially identified in a qualitative manner and subsequently confirmed using attenuation levels. Thirty-six patients were included. Sensitivity, specificity, positive predictive value, and negative predictive value of DE-CTP for the identification of perfusion defects were 84.1%, 94.2%, 77.3%, and 96.2%, respectively. Perfusion defects showed significantly lower attenuation than normal segments, with the largest differences among low energy levels (sensitivity of 96% and specificity of 98% using a cutoff value ≤ 153 Hounsfield units at 40 keV), progressively declining at the higher levels (P < 0.001). Dual-energy CTP at the lowest energy levels allowed improved discrimination of perfusion defects compared with higher energy levels.


The regulation of oxytocin and oxytocin receptor in human placenta according to gestational age.
Oxytocin (OXT) is a peptide hormone that plays a central role in the regulation of parturition and lactation. OXT signaling is mediated by OXT receptor (OXTR), which shows species- and tissue-specific expressions and gene regulation. In the present study, we examined the synthesis of OXT and OXTR in human placenta tissue according to gestational age. A total of 48 placentas were divided into early preterm, late preterm and term groups depending on gestational age, and expression of OXT and OXTR was evaluated. First, OXT and OXTR mRNA and protein were detected in normal placenta tissue via Q-PCR, Dot-blot and Western blot assay. Both OXT and OXTR levels in normal placenta increased gradually in the late stage of pregnancy, suggesting that local OXT may play a critical role in the function of the placenta. To determine the regulatory mechanism of OXT, placental BeWo cells were administrated estrogen (E2) or progesterone (P4), and expression of OXT and OXTR was tested. The mRNA and protein levels of OXT and OXTR were upregulated by E2 but blocked by co-treatment with P4 In order to confirm the estrogen receptor (ESR)-mediated signaling, we administrated ESR antagonists together with E2 to BeWo cells. As a result, both OXT and OXTR were significantly altered by ESR1 antagonist (MPP) while moderately regulated by ESR2 antagonist (PHTPP). These results suggest that OXT and OXTR are controlled mainly by E2 in the placenta via ESR1 and thus may play physiological functions in the human placenta during the late stage of pregnancy.


Disruption of the ECM33 gene in Candida albicans prevents biofilm formation, engineered human oral mucosa tissue damage and gingival cell necrosis/apoptosis.
In this study we demonstrated that ΔCaecm33 double mutant showed reduced biofilm formation and causes less damage to gingival mucosa tissues. This was confirmed by the reduced level of necrotic cells and Bax/Bcl2 gene expression as apoptotic markers. In contrast, parental and Caecm33 mutant strains decreased basement membrane protein production (laminin 5 and type IV collagen). We thus propose that ECM33 gene/protein represents a novel target for the prevention and treatment of infections caused by Candida.


Preliminary Study of UAS Equipped with Thermal Camera for Volcanic Geothermal Monitoring in Taiwan.
Thermal infrared cameras sense the temperature information of sensed scenes. With the development of UASs (Unmanned Aircraft Systems), thermal infrared cameras can now be carried on a quadcopter UAV (Unmanned Aircraft Vehicle) to appropriately collect high-resolution thermal images for volcanic geothermal monitoring in a local area. Therefore, the quadcopter UAS used to acquire thermal images for volcanic geothermal monitoring has been developed in Taiwan as part of this study to overcome the difficult terrain with highly variable topography and extreme environmental conditions. An XM6 thermal infrared camera was employed in this thermal image collection system. The Trimble BD970 GNSS (Global Navigation Satellite System) OEM (Original Equipment Manufacturer) board was also carried on the quadcopter UAV to gather dual-frequency GNSS observations in order to determine the flying trajectory data by using the Post-Processed Kinematic (PPK) technique; this will be used to establish the position and orientation of collected thermal images with less ground control points (GCPs). The digital surface model (DSM) and thermal orthoimages were then produced from collected thermal images. Tests conducted in the Hsiaoyukeng area of Taiwan's Yangmingshan National Park show that the difference between produced DSM and airborne LIDAR (Light Detection and Ranging) data are about 37% between -1 m and 1 m, and 66% between -2 m and 2 m in the area surrounded by GCPs. As the accuracy of thermal orthoimages is about 1.78 m, it is deemed sufficient for volcanic geothermal monitoring. In addition, the thermal orthoimages show some phenomena not only more globally than do the traditional methods for volcanic geothermal monitoring, but they also show that the developed system can be further employed in Taiwan in the future.


Selection of developmentally competent human oocytes aspirated during cesarean section.
To evaluate the efficiency/safety of Brilliant Cresyl Blue (BCB) staining as a selection method of developmentally competent immature human oocytes. Immature oocytes of 32 pregnant women were recovered during cesarean section (CS). After retrieval, 92 oocytes were randomly divided into two groups: control (directly disposed to in vitro maturation - IVM) and treated - exposed to BCB 26 μM during 60 min. After staining, the treated group was classified as cytoplasm coloration, BCB positive (blue) or negative (colorless), and then disposed to IVM. Nuclear status was checked after 24 and 48 h of IVM. Nuclear maturation (polar body extrusion), meiosis resumption (absence of germinal vesicle) and degeneration rates were evaluated among the three groups (control, BCB positive and BCB negative) using Generalized Estimating Equations, followed by Bonferroni's correction for multiple comparisons. Nuclear maturation was higher in BCB positive compared to BCB negative, after 24 and 48 h of IVM (p = .004 and p = .032). The control group was equal to BCB positive. There was no difference among groups analyzing meiosis resumption and degeneration rates. The BCB test can be a good marker in pre-selection procedures of developmentally competent human oocytes aspirated during CS.


Bacterial biofilms: an emerging link to disease pathogenesis.
The role of biofilms in the pathogenesis of some chronic human infections is now widely accepted. However, the criteria used to determine whether a given infection is caused by biofilms remain unclear. In this chapter we discuss three infections that are caused by biofilms--infectious kidney stones, bacterial endocarditis, and cystic fibrosis lung infections--and focus on the role of the biofilm in disease pathogenesis. Biofilms are also important as environmental reservoirs for pathogens, and the biofilm growth mode may provide organisms with survival advantages in natural environments and increase their virulence. The consequences of pathogens living in environmental biofilms and an analysis of some specific environmental biofilm systems are presented.


Access and Benefit Sharing Under the Nagoya Protocol-Quo Vadis? Six Latin American Case Studies Assessing Opportunities and Risk.
Global challenges related to access and benefit sharing (ABS) of biological resources have become a key concern in the area of research on herbal medicines, ethnopharmacology, drug discovery, and the development of other high value products for which Intellectual Property protection can be secured. While the Convention on Biological Diversity (CBD, Rio 1992) has been recognized as a huge step forward, the implementation of the Nagoya Protocol (NP) and of new forms of collaboration often remain unresolved, especially in the context of "the fair and equitable sharing of benefits arising from the utilization of genetic resources" (Convention on Biological Diversity, 2011). The vision and the specific implementation of this international treaty vary from country to country, which poses additional challenges. Using a case study approach, in this analysis we aim at understanding the specific opportunities and challenges for implementing international collaborations regarding ABS in six Latin American countries-Chile, Colombia, Guatemala, México, Panama, and Peru. Based on that analysis, we provide recommendations for the path ahead regarding international collaborations under ABS agreements in ethnopharmacological research. The implementation of the NP varies in the six countries; and while they are all rich in biodiversity, access and benefit sharing mechanisms differ considerably. There is a need to engage in a consultation process with stakeholders, but this has often come to a halt. Institutional infrastructures to implement national policies are weak, and the level of knowledge about the NP and the CBD within countries remains limited. Different policies in the six countries result in very diverse strategies and opportunities relating to the equitable use of biodiversity. A long-term strategy is required to facilitate a better understanding of the treaties and the resulting opportunities for a fairer development and implementation of transparent national polices, which currently differ in the six countries. So far, the benefits envisioned by the CBD and the NP remain unfulfilled for all stakeholders involved including local communities.


Iodinated contrast media induced Kounis syndrome during coronary angiogram: a life-threatening clinical dilemma.
Kounis syndrome (KS) is a well-documented hypersensitivity vasospastic reaction induced by a variety of triggers. Clinical presentation ranges from non-specific symptoms such as dizziness and nausea to myocardial infarction. Many cases of KS were reported after the use of iodinated contrast media, mainly during radiological procedures. This report describes the case of a 46-year-old man developing coronary vasospasm and anaphylactic shock at the end of percutaneous coronary intervention. Occurrence of such pathology while performing coronary angiogram is a tricky situation for the invasive cardiologist. It requires recognising a rare syndrome and interrupting the procedure to avoid extra use of contrast media even in presence of severe coronary lesions due to vasospasm. Every interventionalist should be aware of such a presentation to recognise and react promptly when facing a potentially life-threatening clinical dilemma.


Computational model of the complex between GR113808 and the 5-HT4 receptor guided by site-directed mutagenesis and the crystal structure of rhodopsin.
A computational model of the transmembrane domain of the human 5-HT4 receptorcomplexed with the GR113808 antagonist was constructed from the crystal structure of rhodopsin and the putative residues of the ligand-binding site, experimentally determined by site-directed mutagenesis. The recognition mode of GR113808 consist of: (i) the ionic interaction between the protonated amine and Asp3.32; (ii) the hydrogen bond between the carbonylic oxygen and Ser5.43; (iii) the hydrogen bond between the ether oxygen and Asn6.55; (iv) the hydrogen bond between the C-H groups adjacent to the protonated piperidine nitrogen and the pi electrons of Phe6.51; and (v) the pi-sigma aromatic-aromatic interaction between the indole ring and Phe6.52. This computational model offers structural indications about the role of Asp3.32, Ser5.43, Phe6.51, Phe6.52, and Asn6.55 in the experimental binding affinities. Asp3.32Asn mutation does not affect the binding of GR113808 because the loss of binding affinity from an ion pair to a charged hydrogen bond is compensated by the larger energetical penalty of Asp to disrupt its side chain environment in the ligand-free form, and the larger interaction between Phe6.51 and the piperidine ring of the ligand in the mutant receptor. In the Phe6.52Val mutant the indole ring of the ligand replaces the interaction with Phe6.52 by a similarly intense interaction with Tyr5.38, with no significant effect in the binding of GR113808. The mutation of Asn6.55 to Leu replaces the hydrogen bond of the ether oxygen of the ligand from Asn6.55 to Cys5.42, with a decrease of binding affinity that approximately equals the free energy difference between the SH...O and NH...O hydrogen bonds. Because these residues are also present in the other members of the neurotransmitter family of G protein-coupled receptors, these findings will also serve for our understanding of the binding of related ligands to their cognate receptors.


Targeted Therapy in Patients with Metastatic Male Germ Cell Tumors.
Ten to fifteen percent of patients with metastatic testis cancer (mGCT) will develop chemorefractory disease of which about 50% will die. We report on the integration of next generation sequencing in daily clinical practice to identify druggable mutations in metastatic lesions of 3 patients with mGCT. Mutational analysis revealed KIT D820G, TP53, and NPM1 mutations as well as mismatch repair deficiency with loss of MSH2 and MSH6 proteins so that targeted therapy with sunitinib (n = 2) or pembrolizumab (n = 1) was initiated resulting in remarkable partial remissions for 9, 12+, and 15 months.


[Performance indicators: the role of 'task uncertainty'].
In recent years, quality of care has occupied a prominent place in health care. Different performance indicators are used to assess the quality of care. There is some debate about the value of outcome versus process indicators in measuring aspects of quality of care. Van de Geer et al. carried out a field study in a medical rehabilitation centre in the Netherlands in which four low task uncertainty teams ('hand trauma', 'heart failure', 'amputation', 'chronic pain'), and four high task uncertainty teams ('children with developmental coordination disorder', 'Parkinson disease', 'young children (aged 1-4 years) with developmental disorders', 'acquired brain injuries') participated in the development of performance indicators. They concluded that task uncertainty is an important factor to be considered in the development of indicators, and in the choice between the use of process and outcome indicators. Notably, outcome indicators are only useful in health problems with little variation and little task uncertainty, while many tasks are complex and uncertain. The participation of health care professionals in the development of quality indicators is, therefore, very important.


There is an Association of Synovial Interleukin-6 Levels With Chondral Damage in Anterior Cruciate Ligament-Deficient Knees.
Background: Osteoarthritis (OA) in the anterior cruciate ligament (ACL)-deficient knee is seen in approximately 50% of affected patients. Possible causes include biochemical or biomechanical changes. Purpose: We sought to study the correlation between inflammatory cytokines and chondral damage in ACL-deficient knees. Methods: Seventy-six male patients who underwent ACL reconstruction were enrolled in a cross-sectional study. Synovial fluid was aspirated before surgery and analyzed for levels of the inflammatory cytokines tumor necrosis factor-α, interleukin-1 (IL-1), and interleukin-6 (IL-6). At the time of ACL reconstruction, the severity of chondral damage was documented as described by the Outerbridge classification. Results: Patients with grade 2 or higher chondral damage were observed to have elevated IL-6 levels when compared to patients who had no chondral damage. Interleukin-6 levels had no correlation with the duration of injury. Conclusion: Elevated levels of IL-6 in synovial fluid were associated with chondral damage in ACL-deficient knees. Further study is warranted to determine whether inflammatory cytokines contribute to the development of OA of the knee after ACL injury.


Ultrathin g-C3 N4 Nanosheets Coupled with AgIO3 as Highly Efficient Heterostructured Photocatalysts for Enhanced Visible-Light Photocatalytic Activity.
The photocatalytic activity of graphite-like carbon nitride (g-C3 N4 ) could be enhanced by heterojunction strategies through increasing the charge-separation efficiency. As a surface-based process, the heterogeneous photocatalytic process would become more efficient if a larger contact region existed in the heterojunction interface. In this work, ultrathin g-C3 N4 nanosheets (g-C3 N4 -NS) with much larger specific surface areas are employed instead of bulk g-C3 N4 (g-C3 N4 -B) to prepare AgIO3 /g-C3 N4 -NS nanocomposite photocatalysts. By taking advantage of this feature, the as-prepared composites exhibit remarkable performances for photocatalytic wastewater treatment under visible-light irradiation. Notably, the optimum photocatalytic activity of AgIO3 /g-C3 N4 -NS composites is almost 80.59 and 55.09 times higher than that of pure g-C3 N4 -B towards the degradation of rhodamine B and methyl orange pollutants, respectively. Finally, the stability and possible photocatalytic mechanism of the AgIO3 /g-C3 N4 -NS system are also investigated.


Associations between perceived everyday discrimination and health among college students at a Hispanic-serving institution.
Despite efforts by universities to promote racial/ethnic, gender, and socioeconomic diversity, college students continue to report discrimination. In two studies, we examined the frequency, predictors, and health consequences of experiencing everyday discrimination at a Hispanic-Serving Institution. Findings show the majority of students reported experiencing discrimination at the university, with most experiences attributed to their gender and aspects of their physical appearance. More frequent discrimination was associated with poorer physical and psychological health. Furthermore, most participants cited other students as the source of their discrimination. These findings offer important insight into students' experiences of everyday discrimination at a diverse setting.


Regulation of methane oxidation in the facultative methanotroph Methylocella silvestris BL2.
The molecular regulation of methane oxidation in the first fully authenticated facultative methanotroph Methylocella silvestris BL2 was assessed during growth on methane and acetate. Problems of poor growth of Methylocella spp. in small-scale batch culture were overcome by growth in fermentor culture. The genes encoding soluble methane monooxygenase were cloned and sequenced, which revealed that the structural genes for soluble methane monooxygenase, mmoXYBZDC, were adjacent to two genes, mmoR and mmoG, encoding a sigma54 transcriptional activator and a putative GroEL-like chaperone, located downstream (3') of mmoC. Transcriptional analysis revealed that the genes were all cotranscribed from a sigma54-dependent promoter located upstream (5') of mmo X. The transcriptional start site was mapped. Transcriptional analysis of soluble methane monooxygenase genes and expression studies on fermentor grown cultures showed that acetate repressed transcription of sMMO in M. silvestris BL2. The possibility of the presence of a particulate, membrane-bound methane monooxygenase enzyme in M. silvestris BL2 and the copper-mediated regulation of soluble methane monooxygenase was investigated. Both were shown to be absent. A promoter probe vector was constructed and used to assay transcription of the promoter of the soluble methane monoxygenase genes of M. silvestris BL2 grown under various conditions and with different substrates. These data represent the first insights into the molecular physiology of a facultative methanotroph.


Autologous stem cell transplantation in the treatment of adults with acute myeloid leukaemia.
Most adult patients under 60 years with acute myeloid leukaemia (AML) who achieve a complete remission after induction chemotherapy will relapse if they do not receive further therapy. Consolidation treatment with autologous stem cell transplantation (SCT) is one option that has been studied extensively. High-dose cytotoxic therapy followed by autologous SCT or intensive cycles of chemotherapy furnish overall approximately similar probabilities of survival when applied in first remission. Here, we present a concise update regarding the place of autologous SCT in the treatment of AML. Particular issues discussed are the value of autologous SCT in different prognostic subsets of AML and the value of autologous mobilised peripheral blood stem cell transplants, which offer a much faster haematopoietic recovery.


[Functional nutriments in diet].
Functional nutriments contribute to improve one's health or to reduce the risk of suffering diseases, but they are not cures by themselves. They are not indispensable in the balanced diet of a healthy person, who already ingests all the nutrients which are needed. These may supplement the needs of some nutriments under special circumstances, but some of the substances considered beneficial can be prejudicial if taken in excess. The authors analyze the most common of these functional nutriments and they evaluate their advantages and inconveniences; furthermore, the authors analyze those cases in which the use of these nutriments is deemed adequate.


Personalized treatment of adult depression: medication, psychotherapy, or both? A systematic review.
Personalized medicine aims to identify which characteristics of an individual predict the outcome of a specific treatment, in order to get a better match between the individual and the treatment received. We conducted a systematic review and meta-analysis of randomized trials comparing two treatments directly in a group of patients with a specific characteristic. We searched relevant studies from bibliographical databases and included trials comparing (1) medication with psychotherapy, (2) medication with combined treatment, and (3) psychotherapy with combined treatment, in specific target groups (a) with a predefined sociodemographic characteristic, (b) a specific type of depression, (c) a comorbid mental or somatic disorder, or (d) from a specific setting (outpatients, primary care). We included 52 studies with 4,734 depressed patients. In these studies, 20 characteristics of the target groups were examined. The results showed that medication is probably the best treatment for dysthymia, and combined treatments are more effective in depressed outpatients, as well as in depressed older adults. However, in order to examine the 20 characteristics in the three categories of comparisons, 254 studies would be needed for having sufficient statistical power to show an effect size of g = 0.5. Currently, only 20.1% of these studies have been conducted. Although a considerable number of studies have compared medication, psychotherapy, and combined treatments, and some preliminary results are useful for deciding which treatment is best for which patient, the development of personalized treatment of depression has only just begun.


Automaticity and cognitive control: Effects of cognitive load on cue-controlled reward choice.
The extent to which human outcome-response (O-R) priming effects are automatic or under cognitive control is currently unclear. Two experiments tested the effect of cognitive load on O-R priming to shed further light on the debate. In Experiment 1, two instrumental responses earned beer and chocolate points in an instrumental training phase. Instrumental response choice was then tested in the presence of beer, chocolate, and neutral stimuli. On test, a Reversal instruction group was told that the stimuli signalled which response would not be rewarded. The transfer test was also conducted under either minimal (No Load) or considerable (Load) cognitive load. The Non-Reversal groups showed O-R priming effects, where the reward cues increased the instrumental responses that had previously produced those outcomes, relative to the neutral stimulus. This effect was observed even under cognitive load. The Reversal No Load group demonstrated a reversed effect, where response choice was biased towards the response that was most likely to be rewarded according to the instruction. Most importantly, response choice was at chance in the Reversal Load condition. In Experiment 2, cognitive load abolished the sensitivity to outcome devaluation that was otherwise seen when multiple outcomes and responses were cued on test. Collectively, the results demonstrate that complex O-R priming effects are sensitive to cognitive load, whereas the very simple, standard O-R priming effect is more robust.


Glutathione-S-transferase P1, early exposure to mould in relation to respiratory and allergic health outcomes in children from six birth cohorts. A meta-analysis.
There are conflicting study results regarding the association of exposure to visible mould and fungal components in house dust with respiratory and allergic diseases in children. It has been suggested that functional polymorphisms of the GSTP1 gene may influence the risk for allergic disorders through an impaired defence against oxidant injury. We examined in six birth cohorts of over 14 000 children whether the association between early exposure to reported mould at home in relation to respiratory and allergic diseases is modified by a single nucleotide polymorphism of the GSTP1 gene. We observed a positive association of mould exposure with nasal symptoms (2-10 year) aOR: 1.19 (1.02-11.38). Further, there was a borderline significant increased risk of rhinoconjunctivitis (6-8 year) in children homozygous for the minor allele Val/Val, aOR: 1.25 (0.98-1.60). In stratified analyses, subjects homozygous for the minor allele and exposed to mould at home were at increased risk for early wheezing aOR: 1.34 (1.03-1.75), whereas the major allele may confer susceptibility for later nasal outcomes, (6-8 year) aOR: 1.20 (1.00-1.45) and (2-10 year) aOR: 1.30 (1.04-1.61), respectively. For none of the health outcomes studied, we found gene by environment interactions. A genetic influence of the GSTP1 gene cannot be ruled out, but the magnitude of the effect is a matter of further research. In conclusion, the interplay between gene and environments is complex and remains subject of further study.


Ocular changes in Takayasu's arteritis in India.
Twenty-seven patients (ages 13-55 years) with Takayasu's arteritis (TA) underwent a detailed ophthalmological examination which included a history of visual symptoms, recording of visual acuity, slit-lamp examination, examination of retina (direct fundoscopy and rapid sequence fluorescein angiography) and estimation of retinal haemodynamics. Arterial hypertension was the commonest (77%) presentation of TA. Sixty-six percent of the patients had one or more ocular change. Sixteen (33%) of the 54 eyes tested had Takayasu's retinopathy (TR), 20 eyes (37%) had hypertensive retinopathy (HR) and the retina was normal (NR) in 18 eyes (33%). Two patients with advanced TR had bilateral cataract. The arm-to-retina circulation time in eyes with TR (16.4 +/- 2.66 seconds) was prolonged as compared to the eyes with HR (10.9 +/- 1.63 seconds, P < 0.01) and NR (9.6 +/- 2.37 seconds, P < 0.01). The arteriovenous filling time in eyes with TR was also significantly prolonged. The intraocular pressure (mmHg) in eyes with TR (9.3 +/- 3.6) was lower (P < 0.001) than that in eyes with HR (14.4 +/- 4.1 mmHg) and NR (14.2 +/- 2.6). Central retinal artery pressure recorded in 8 eyes with TR was less than 35 mmHg in spite of the systemic hypertension. The retinal haemodynamics suggest that the carotid artery involvement leading to diminished retinal blood flow is the pathogenetic mechanism of TR.


Association of a novel single nucleotide polymorphism of the prostacyclin synthase gene with myocardial infarction.
Myocardial infarction (MI) is a complex multifactorial and polygenic disorder that is thought to result from an interaction between an individual's genetic makeup and various environmental factors. The purpose of this study was to investigate the association between a novel single nucleotide polymorphism in the prostacyclin synthase gene and MI. By the use of polymerase chain reaction-single-strand conformation polymorphism analysis, we identified a single nucleotide polymorphism, C1117A, in exon 8. This nucleotide change did not cause an amino acid change in codon 373. We performed an association study of the polymorphism in 138 patients and 130 healthy control subjects. Multiple logistic linear regression analysis showed the genotype distributions were significantly different between the control group and the MI group (odds ratio, 2.12; 95% CI, 1.47-3.05, P =.04). The C/C genotype was found more frequently in the MI group than in the control group. We conclude that the C1117A polymorphism in exon 8 is associated with risk for MI and may be a genetic marker of MI in Japanese persons.


Comparison of palonosetron with combined palonosetron and midazolam for preventing postoperative nausea and vomiting after laparoscopic cholecystectomy.
Postoperative nausea and vomiting (PONV) is an undesirable complication in patients undergoing general anesthesia. Combination therapy via different mechanisms of action for antiemetic prophylaxis has been warranted for effective treatment of PONV. This study was designed to compare the prophylactic antiemetic effect between midazolam combined with palonosetron (group MP) and palonosetron alone (group P) after laparoscopic cholecystectomy surgeries. A prospective randomized controlled trial was investigated in non-smoking female. Eighty-eight patients were randomly divided into 2 groups with 44 patients each. Group MP received 0.05 mg/kg of midazolam intravenously before induction of anesthesia whereas group P received the same volume of normal saline. Immediately after anesthetic induction, 0.075 mg of palonosetron was administered to both the groups. The incidence and severity of PONV were assessed during 2 time intervals (0-2 hours, 2-24 hours), postoperatively. The incidence of PONV during 24 hours after surgery was lower in group MP as compared to group P. There was also a significant difference in the use of rescue antiemetics. The severity of nausea was significantly lower in group MP as compared to group P, in the initial 2 hours after surgery. The incidence of side effects was similar between the 2 groups. In the prevention of PONV, midazolam combined with palonosetron, administered during induction of anesthesia was more effective as compared to palonosetron alone.


Identification and characterization of two cysteinyl-leukotriene high affinity binding sites with receptor characteristics in human lung parenchyma.
We report the characterization of two distinct binding sites with receptor characteristics for leukotriene (LT)D4 and LTC4 in membranes from human lung parenchyma. The use of S-decyl-glutathione allowed us to characterize a previously unidentified high affinity binding site for LTC4. Computerized analysis of binding data revealed that each leukotriene interacts with two distinct classes of binding sites (Kd = 0.015 and 105 nM for LTC4 and 0.023 and 230 nM for LTD4) and that despite cross-reactivity, the two high affinity sites are different entities. LTD4 binding sites displayed features of G protein-coupled receptors, whereas LTC4 binding sites did not show any significant modulation by guanosine-5'-(beta, gamma-imido)triphosphate or stimulation of GTPase activity. The antagonists ICI 198,615 and SKF 104353 were unselective for the high and low affinity states of LTD4 receptor, whereas only SKF 104353 was able to recognize the two [3H]LTC4 binding sites although with different affinities. These data indicate that in human lung parenchyma, LTD4 and LTC4 recognize two different binding sites; these binding sites are different entities; and for LTD4, the two binding sites represent the interconvertible affinity states of a G protein-coupled receptor, whereas for LTC4, the high affinity site is likely to be a specific LTC4 receptor.


Tracking Internal Electron Shuttle Using X-ray Spectroscopies in La/Zr Hydroxide for Reconciliation of Charge-Transfer Interaction and Coordination toward Phosphate.
Metallic hydroxides have been applied as the adsorbents of oxyanion contaminants, with the oxygen-bonded metal (M-O) considered as the core site for adsorption. For enhanced adsorption toward oxyanions, multimetallic modification of M-O is a promising approach for high removal performance. Here, bimetallic La/Zr hydroxides were prepared via a solvothermal route with varying La/Zr dosages. Bimetallic La/Zr hydroxides exhibited higher oxyanion adsorption capacity than La or Zr hydroxide. A maximum phosphate adsorption capacity of ∼160 mg g-1 was achieved under the La/Zr atomic ratio of 1:1, representing a new record among comparable adsorbents. X-ray photoelectron spectroscopy and X-ray absorption near-edge structure (XANES) spectroscopy showed that the incorporation of [LaO6] and [ZrO6] can induce an internal charge shuttle owing to the electronegativity difference of La and Zr. The charge transfers from La to Zr through the surrounding O 2p ligand, where the electrons in the highest occupied molecular orbitals of the [LaO6] octahedron filled unoccupied π orbitals of [ZrO6]. The as-induced internal electron shuttle in the bimetallic hydroxides primarily strengthened the formation of [MO6]···PO4 species (backdonation interaction). Further, the σP-O donation interaction between [LaO6] and [PO4] was clearly increased via intensification of the covalent coordination with O, as confirmed by the P K-edge XANES spectra for the as-used samples.


Solute descriptors for phenoxide anions and their use to establish correlations of rates of reaction of anions with iodomethane.
Partition coefficients from water to organic solvents for phenoxide anions have been obtained using a method based on the variation of pK(a) of phenols with solvent. From these partition coefficients, the Abraham descriptors for phenoxide anions, on the same scale as descriptors for neutral molecules, have been obtained. Equations have been constructed for the prediction of descriptors, and values of the Abraham descriptors E, S, A (equal to zero for the phenoxide anions we have studied), B, V, and J(-) have been determined or estimated for some 60 substituted phenoxide anions. These anions are characterized by very large values of the dipolarity/polarizability descriptor S and the hydrogen bond basicity descriptor B. In order to show the utility of the obtained phenoxide descriptors, we demonstrate that they can be combined with descriptors for carboxylate anions and permanent anions to yield equations for the Finkelstein reaction of anions with iodomethane in methanol, N,N-dimethylformamide, and water.


Axonal outgrowth stimulation after alginate/mesenchymal stem cell therapy in injured rat spinal cord.
Despite strong efforts in the field, spinal cord trauma still belongs among the untreatable neurological conditions at present. Given the complexity of the nervous system, an effective therapy leading to complete recovery has still not been found. One of the potential tools for supporting tissue regeneration may be found in mesenchymal stem cells, which possess anti‑inflammatory and trophic factor‑producing properties. In the context of transplantations, application of degradable biomaterials which could form a supportive environment and scaffold to bridge the lesion area represents another attractive strategy. In the present study, through a combination of these two approaches we applied both alginate hydrogel biomaterial alone or allogenic transplants of MSCs isolated from bone marrow seeded in alginate biomaterial into injured rat spinal cord at three weeks after spinal cord compression performed at Th8‑9 level. Following three‑week survival, using immunohistochemistry we studied axonal growth (GAP‑43 expression) and both microglia (Iba‑1) and astrocyte (GFAP) reactions at the lesion site and in the segments below and above the lesion. To detect functional improvement, during whole survival period we performed behavioral analyses of locomotor abilities using a classical open field test (BBB score) and a Catwalk automated gait analyzing device (Noldus). We found that despite the absence of locomotor improvement, application of both alginate and MSCs caused significant increase in the number of GAP‑43 positive axons.


Sirtuin 2 enhances allergic asthmatic inflammation.
Allergic eosinophilic asthma is a chronic condition causing airway remodeling resulting in lung dysfunction. We observed that expression of sirtuin 2 (Sirt2), a histone deacetylase, regulates the recruitment of eosinophils after sensitization and challenge with a triple antigen: dust mite, ragweed, and Aspergillus fumigatus (DRA). Our data demonstrate that IL-4 regulates the expression of Sirt2 isoform 3/5. Pharmacological inhibition of Sirt2 by AGK2 resulted in diminished cellular recruitment, decreased CCL17/TARC, and reduced goblet cell hyperplasia. YM1 and Fizz1 expression was reduced in AGK2-treated, IL-4-stimulated lung macrophages in vitro as well as in lung macrophages from AGK2-DRA-challenged mice. Conversely, overexpression of Sirt2 resulted in increased cellular recruitment, CCL17 production, and goblet cell hyperplasia following DRA challenge. Sirt2 isoform 3/5 was upregulated in primary human alveolar macrophages following IL-4 and AGK2 treatment, which resulted in reduced CCL17 and markers of alternative activation. These gain-of-function and loss-of-function studies indicate that Sirt2 could be developed as a treatment for eosinophilic asthma.


Quality assessment in personal anaesthetic practice.
Continuing education can improve anaesthetic practice if it is relevant to an individual's work and complications. A practice profile delineates the significance of untoward events. A personal audit of consecutive anaesthetics and associated complications is presented as a first step to checking one's competence over the course of years.


Endoscopic submucosal tunnel dissection of upper gastrointestinal submucosal tumors: A comparative study of hook knife vs hybrid knife.
To compare the efficacy and safety of a hook knife (HO) with a hybrid knife (HK) during endoscopic submucosal tunnel dissection (ESTD) procedure. Between August 2012 and December 2015, the ESTD procedure was performed for 83 upper GI submucosal lesions, which originated from the muscularis propria layer identified by upper endoscopy and endoscopic ultrasonography. Of these, 34 lesions were treated by a HO, whereas 49 lesions were treated by a HK. Data regarding age, gender, presenting symptoms, tumor location and size, procedure time, complications, en bloc resection rate and others were analyzed and compared between the two groups. There were no significant differences in the age, gender, presenting symptoms and tumor location between the two groups. ESTD was successfully completed in all the patients, and no case was converted to laparoscopy. The mean procedure time was significantly shorter in the HK group than in the HO group (41.3 ± 20.3 min vs 57.2 ± 28.0 min, P = 0.004). The mean frequency of device exchange was 1.4 ± 0.6 in the HK group and significantly less than 3.3 ± 0.6 in the HO group (P < 0.001). The differences in tumor size and histopathological diagnoses were not significant between the two groups (P = 0.813, P = 0.363, respectively). Both groups had an equal en bloc resection rate and complete resection rate. Additionally, the complication rate was similar between the two groups (P = 0.901). During the follow-up, no recurrence occurred in either group. We demonstrate for the first time that HO and HK do not differ in efficacy or safety, but HK reduces the frequency of device exchange and procedure time.


Clinical and laboratory diagnosis of invasive candida infection in neutropenic patients.
Cancer patients, especially those with acute leukaemia, represent a group that has the greatest risk for deep fungal infection. Almost no cases were seen before the advent of modern chemotherapy, and prior to the availability of antibacterial agents, less than 5% of patients with acute leukaemia died of fungal infection. These infections are now responsible for 40% or more of the deaths at some institutions. Candida species continues to be the most common fungal pathogen. Rapid and specific diagnosis of invasive candiosis enabling early effective therapy is therefore an important measure for reducing mortality in patients. Here the current status of clinical and laboratory diagnosis of invasive candida infection in neutropenic patients is discussed and recommendations made as to future development programmes.


Inhibition of VEGF receptors induces pituitary apoplexy: An experimental study in mice.
Anti-vascular endothelial growth factor (VEGF) therapy has been developed for the treatment of a variety of cancers. Although this therapy may be a promising alternative treatment for refractory pituitary adenomas and pituitary carcinomas, the effects of anti-VEGF agents on the pituitary gland are not yet well understood. Here, we found that mice administered with OSI-930, an inhibitor of receptor tyrosine kinases including VEGF receptor 1 and 2, frequently exhibited hemorrhage in the pituitary gland. This is the first report that anti-VEGF therapy can cause pituitary apoplexy. C57BL/6 mice were daily injected intraperitoneally with 100 mg/kg body weight of OSI-930 for one to six days. Pituitary glands were immunohistochemically examined. Four of six mice treated for three days and all of five mice treated for six days exhibited hemorrhage in the pituitary gland. In all cases, the hemorrhage occurred just around Rathke's cleft. In OSI-930-administered mice, the vascular coverage and branching were reduced in the anterior lobe, and capillary networks were also decreased in the intermediate lobe in a treatment-day dependent manner. Few blood vessels around Rathke's cleft of the intermediate lobe express VE-cadherin and are covered with platelet-derived growth factor receptor-β (PDGFR-β)-positive cells, which suggests that capillaries around Rathke's cleft of the intermediate lobe were VE-cadherin-negative and not covered with pericytes. The reduction of capillary plexus around Rathke's cleft was observed at the site where hemorrhage occurred, suggesting a causal relationship with the pathogenesis of pituitary hemorrhage. Our study demonstrates that anti-VEGF agents have a risk of pituitary apoplexy. Pituitary apoplexy should be kept in mind as an adverse effect of anti-VEGF therapy.


Design criteria for percutaneous devices.
A theoretical model of a percutaneous device is described. The model is split into several components, each with its own function. Special structures such as horns, hair, feathers, fingernails, hoofs , teeth, and antlers are taken as examples where nature has solved the problems of "percutaneous devices." These structures have been regarded in relation to dimensional and structural differences of epidermis, dermis, and subcutis. Theoretical guidelines are described for the design of a prosthetic percutaneous device.


Surgical treatment patterns and clinical outcomes of patients treated for expanding aneurysm sacs with type II endoleaks after endovascular aneurysm repair.
Persistent type II endoleaks (T2ELs) after endovascular aneurysm repair (EVAR) with sac growth have been associated with adverse events, including rupture. Whereas intervention in the presence of aneurysm growth has become an accepted treatment paradigm for T2ELs, the efficacy and clinical success of such interventions remain unclear. Therefore, we examined the treatment patterns and clinical outcomes of patients undergoing T2EL interventions after EVAR. We performed a retrospective review of all patients treated for expanding aneurysm sacs with T2ELs after EVAR at an academic medical center between 2006 and 2017. The primary outcomes assessed were need for repeated intervention; intervention types; and achievement of clinical success, defined as stable aneurysm sac size on computed tomography angiography after treatment. Fifty-six patients underwent 119 interventions, of which 107 (90%) were technically successful. The median time from EVAR to index T2EL procedure was 37 months (interquartile range, 17-56 months), and the median follow-up time from first T2EL procedure was 27 months (interquartile range, 10-51 months). The most common index procedure was transarterial lumbar embolization (64%), followed by transarterial inferior mesenteric artery (20%), transcaval (14%), and translumbar embolization (1.8%). Thirty-three (59%) patients required further procedures for persistent aneurysm sac expansion. For subsequent T2EL interventions, the most common endovascular procedure was transarterial lumbar embolization (21%), followed by transcaval (21%), translumbar (11%), and transarterial inferior mesenteric artery embolization (8.6%). Twelve patients (21%) were found to have loss of proximal or distal seal on subsequent imaging and required graft extensions to stabilize aneurysm sac size. Ten patients (18%) ultimately underwent graft explantation or sacotomy with oversewing of the endoleak source. Freedom from any endoleak-related reintervention was 57% at 1 year and 36% at 3 years. Freedom from open treatment was 93% at 1 year and 82% at 3 years. Of the 44 patients with ≥6-month follow-up, 39 (89%) achieved clinical success. However, only 11 patients (25%) achieved clinical success without any further reintervention, and 29 patients (66%) achieved clinical success without open treatment. Despite high technical success, endoleak recurrence after T2EL treatment is common, and multiple interventions are often needed to stabilize aneurysm sac size in patients diagnosed with T2EL-associated sac growth. Notably, one in five patients treated for T2ELs was discovered, on further evaluation, to have proximal or distal seal zone loss that necessitated repair to achieve sac stability. Thus, thorough assessment of all endoleak types should be performed in patients with T2ELs associated with sac growth before T2EL treatment to ensure appropriate care and to minimize ineffective interventions.


Analysis of mismatch repair gene mutations in Turkish HNPCC patients.
Hereditary non-polyposis colorectal cancer (HNPCC or Lynch syndrome) is caused by the inheritance of a mutant allele of a DNA mismatch repair gene. We aimed to investigate types and frequencies of mismatch repair (MMR) gene mutations in Turkish patients with HNPCC and to identify specific biomarkers for early diagnosis of their non-symptomatic kindred's. The molecular characteristics of 28 Turkish colorectal cancer patients at high-risk for HNPCC were investigated by analysis of microsatellite instability (MSI), immunohistochemistry and methylation-specific PCR in order to select tumors for mutation analysis. Ten cases (35.7%) were classified as MSI (+). Lack of expression of the main MMR proteins was observed in MSI (+) tumors. Hypermethylation of the MLH1 promoter region was observed in one tumor. Nine Lynch syndrome cases showed novel germ-line alterations of the MMR gene: two frame-shifts (MLH1 c.1843dupC and MLH1 c.1743delG) and three missense mutations (MLH1 c.293G>C, MLH1 c.954_955delinsTA and MSH2 c.2210G>A). Unclassified variants were evaluated as likely to be pathogenic by using the in-silico analyses. In addition, the MSH2 c.2210G>A alteration could be considered as a founder mutation for the Turkish population due to its identification in five different Lynch syndrome families and absence in control group. The present study adds new information about MMR gene mutation types and their role in Lynch syndrome. This is the first detailed research on Turkish Lynch syndrome families.


Design, synthesis and biological evaluation of gentiopicroside derivatives as potential antiviral inhibitors.
Based on classical drug design theory, a novel series of gentiopicroside derivatives was designed and synthesized. All synthesized compounds were then biologically evaluated for their inhibition of influenza virus and anti-HCV activity in vitro. Some of the gentiopicroside derivatives, such as 11a, 13d and 16 showed interesting anti-influenza virus activity with IC50 at 39.5 μM, 45.2 μM and 44.0 μM, respectively. However, no significant anti-HCV activity was found for all of gentiopicroside derivatives. The preliminary results indicate that modification of the sugar moiety on gentiopicroside was helpful for enhancing the anti-influenza activities. Our works demonstrate the importance of secoiridoid natural products as new leads in the development of potential antiviral inhibitors.


[Importance of water-soluble vitamins as regulatory factors of genetic expression].
Among nutrients, the role of water-soluble vitamins as genetic expression modulators has not been exhaustively stu-died. Relevant information is shown herein on the present state of the art in this field. For example, vitamin C deficiency leads to a decrease in mRNA levels of apolipoprotein A1 (Apo A1) in liver. Biotin participates in the regulation, both at mRNA and protein level, of the enzymes that participate in its own metabolic cycle and of enzymes that contribute to glucose metabolism. Thiamine regulates the expression of some genes that code for enzymes using thiamine diphosphate as cofactor. Thiamine deficiency diminishes the mRNA levels of transketolase and pyruvate dehydrogenase. It has been shown in riboflavin-deficient rats that FAD regulates some acetyl CoA dehydrogenases, producing a marked increase in mRNA levels. Nicotinamide positively regulates glyceraldehyde-3-phosphate dehydrogenase when NADH is added. Vitamin B6 modulates the expression of a variety of genes that respond to hormones. Vitamin B12 increases concentrations of the enzymatic protein methionine synthetase and doe not affect mRNA levels, which implies that this protein is regulated by its cofactor post-transcriptionally. Most mechanisms involved in these regulation examples are not known, which opens new research areas for the future.


Correlated morphological and physiological studies on isolated single muscle fibers. I. Fine structure of the crayfish muscle fiber.
Single fibers isolated from walking leg muscles of crayfish have 8- to 10-micro sarcomeres which are divided into A, I, and Z bands. The H zone is poorly defined and no M band is distinguishable. Changes in the width of the I band, accompanied by change in the overlap between thick and thin myofilaments, occur when the length of the sarcomere is changed by stretching or by shortening the fiber. The thick myofilaments (ca. 200 A in diameter) are confined to the A band. The thin myofilaments (ca. 50 A in diameter) are difficult to resolve except in swollen fibers, when they clearly lie between the thick filaments and run to the Z disc. The sarcolemma invaginates at 50 to 200 sites in each sarcomere. The sarcolemmal invaginations (SI) form tubes about 0.2 micro in diameter which run radially into the fiber and have longitudinal side branches. Tubules about 150 A in diameter arise from the SI and from the sarcolemma. The invaginations and tubules are all derived from and are continuous with the plasma membrane, forming the transverse tubular system (TTS), which is analogous with the T system of vertebrate muscle. In the A band region each myofibril is enveloped by a fenestrated membranous covering of sarcoplasmic reticulum (SR). Sacculations of the SR extend over the A-I junctions of the myofibrils, where they make specialized contacts (diads) with the TTS. At the diads the opposing membranes of the TTS and SR are spaced 150 A apart, with a 35-A plate centrally located in the gap. It appears likely that the anion-permselective membrane of the TTS which was described previously is located at the diads, and that this property of the diadic structures therefore may function in excitation-contraction coupling.


[Streptococcus suis infection, a zoonosis we should have in mind--2 case reports].
Streptococcus suis is primarily pig's pathogen, but can cause disease in a man exposed to contact with pigs (butchers, abatoir workers, farmers). Infection in man is most frequently manifested as purulent meningitis, with deafness and ataxia, but there are rare reports on septic shock with multiple organ failure and death. We report two patients with Streptococcus suis type 1 infection, treated in "Dr Josip Bencević" General Hospital, Slavonski Brod. The first patient suffered a very abrupt and severe illness, with septic shock, multiple organ failure and lethal outcome. The second patient had purulent meningitis with deafness. Both of them had a defect in immunologic function before infection. They were probably infected during manipulation with pork meat at home. Our patients had infection with Streptococcus suis type 1, contrary to reports on prevalent human infection with type 2. It is necessary to make epidemiologic survey on human infection with that pathogen, especially in those professionally exposed to pigs and pork meat.


[Diagnosis and treatment of Zollinger-Ellison syndrome].
An analysis of data concerning 37 patients with the Zollinger-Ellison syndrome (ZES) has been made, 36 of them were operated upon. Gastrinoma was found in 21 patients. Diagnosis of ZES was made in two steps: the first one is fulfilled in general medical institutions, the second one-in specialized clinics. The diagnosis of ZES must be either confirmed or rejected with certainty. When choosing the method of operative treatment several groups of patients must be born in mind: ZES without a gastrinoma detected, ZES with a gastrinoma, ZES with malignant ulcerogenic tumour. The main operation for ZES remains to be gastrectomy.


Anterior tibial compartment syndrome following rupture of a popliteal cyst.
Abstract A ruptured popliteal cyst usually results in calf pain and swelling. We report the case of a patient with rheumatoid arthritis who developed anterior compartment syndrome of the leg following rupture of a popliteal cyst. Since acute compartment syndrome requires prompt treatment, clinicians should be aware of this rare complication.


Methyltransferases of gentamicin biosynthesis.
Gentamicin C complex from Micromonospora echinospora remains a globally important antibiotic, and there is revived interest in the semisynthesis of analogs that might show improved therapeutic properties. The complex consists of five components differing in their methylation pattern at one or more sites in the molecule. We show here, using specific gene deletion and chemical complementation, that the gentamicin pathway up to the branch point is defined by the selectivity of the methyltransferases GenN, GenD1, and GenK. Unexpectedly, they comprise a methylation network in which early intermediates are ectopically modified. Using whole-genome sequence, we have also discovered the terminal 6'-N-methyltransfer required to produce gentamicin C2b from C1a or gentamicin C1 from C2, an example of an essential biosynthetic enzyme being located not in the biosynthetic gene cluster but far removed on the chromosome. These findings fully account for the methylation pattern in gentamicins and open the way to production of individual gentamicins by fermentation, as starting materials for semisynthesis.


Expression of a cyclophilin OsCyp2-P isolated from a salt-tolerant landrace of rice in tobacco alleviates stress via ion homeostasis and limiting ROS accumulation.
Cyclophilins are a set of ubiquitous proteins present in all subcellular compartments, involved in a wide variety of cellular processes. Comparative bioinformatics analysis of the rice and Arabidopsis genomes led us to identify novel putative cyclophilin gene family members in both the genomes not reported previously. We grouped cyclophilin members with similar molecular weight and subtypes together in the phylogenetic tree which indicated their co-evolution in rice and Arabidopsis. We also characterized a rice cyclophilin gene, OsCyp2-P (Os02g0121300), isolated from a salinity-tolerant landrace, Pokkali. Publicly available massively parallel signature sequencing (MPSS) and microarray data, besides our quantitative real time PCR (qRT-PCR) data suggest that transcript abundance of OsCyp2-P is regulated under different stress conditions in a developmental and organ specific manner. Ectopic expression of OsCyp2-P imparted multiple abiotic stress tolerance to transgenic tobacco plants as evidenced by higher root length, shoot length, chlorophyll content, and K(+)/Na(+) ratio under stress conditions. Transgenic plants also showed reduced lipid peroxidase content, electrolyte leakage, and superoxide content under stress conditions suggesting better ion homeostasis than WT plants. Localization studies confirmed that OsCyp2-P is localized in both cytosol and nucleus, indicating its possible interaction with several other proteins. The overall results suggest the explicit role of OsCyp2-P in bestowing multiple abiotic stress tolerance at the whole plant level. OsCyp2-P operates via reactive oxygen species (ROS) scavenging and ion homeostasis and thus is a promising candidate gene for enhancing multiple abiotic stress tolerance in crop plants.


Strategies toward High-Performance Solution-Processed Lateral Photodetectors.
Due to their low cost and ease of integration, solution-processed lateral photodetectors (PDs) are becoming an important device type among the PD family. In recent years, enormous effort has been devoted to improving their performances, and great achievements have been made. A summary of the core progress, especially from the perspective of design principles and device physics, is necessary to further the development of the field, but is currently lacking. Here, to address this need, first, the working mechanism of PDs and the device figures-of-merit are introduced. Second, by classifying the active materials into four categories, including inorganic, organic, hybrid, and perovskite, the developed strategies toward high performance are discussed respectively. To close, the common physical rules behind all these strategies are generalized, and suggestions for future development are given accordingly.


Thyroid hypoplasia of the left lobe in two girls affected by Williams syndrome.
Williams syndrome is a well-recognized disorder, having an incidence of 1 in 20,000 live births. However, thyroid function in these patients is rarely studied. This paper reports thyroid hypoplasia of the left lobe in two girls affected by Williams syndrome, suggesting that it may be a feature of this syndrome.


4D in vivo ultrafast ultrasound imaging using a row-column addressed matrix and coherently-compounded orthogonal plane waves.
4D ultrafast ultrasound imaging was recently shown using a 2D matrix (i.e. fully populated) connected to a 1024-channel ultrafast ultrasound scanner. In this study, we investigate the row-column addressing (RCA) matrix approach, which allows a reduction of independent channels from N × N to N + N, with a dedicated beamforming strategy for ultrafast ultrasound imaging based on the coherent compounding of orthogonal plane wave (OPW). OPW is based on coherent compounding of plane wave transmissions in one direction with receive beamforming along the orthogonal direction and its orthogonal companion sequence. Such coherent recombination of complementary orthogonal sequences leads to the virtual transmit focusing in both directions which results into a final isotropic point spread function (PSF). In this study, a 32 × 32 2D matrix array probe (1024 channels), centered at 5 MHz was considered. An RCA array, of same footprint with 32 + 32 elements (64 channels), was emulated by summing the elements either along a line or a column in software prior to beamforming. This approach allowed for the direct comparison of the 32 + 32 RCA scheme to the optimal fully sampled 32 × 32 2D matrix configuration, which served as the gold standard. This approach was first studied through PSF simulations and then validated experimentally on a phantom consisting of anechoic cysts and echogenic wires. The contrast-to-noise ratio and the lateral resolution of the RCA approach were found to be approximately equal to half (in decibel) and twice the values, respectively, obtained when using the 2D matrix approach. Results in a Doppler phantom and the human humeral artery in vivo confirmed that ultrafast Doppler imaging can be achieved with reduced performances when compared against the equivalent 2D matrix. Volumetric anatomic Doppler rendering and voxel-based pulsed Doppler quantification are presented as well. OPW compound imaging using emulated RCA matrix can achieve a power Doppler with sufficient contrast to recover the vein shape and provides an accurate Doppler spectrum.


Placenta accreta spectrum: treatment consensus in a resource-limited setting.
Management options for placenta accreta spectrum disorder are multiple, without a clear picture of which one is superior. Management guidelines describe the use of a wide range of human and technological resources that are not always available in resource-limited settings. This consensus seeks agreement on general guidelines that facilitate the management of placenta accreta spectrum in low- and middle-income countries. Consensus was developed using the modified Delphi methodology, incorporating 3 successive rounds in which 6 dimensions of placenta accreta spectrum treatment were discussed: pathway for placenta accreta spectrum care, roles at different levels of care, organization of the interdisciplinary teams at the reference hospitals, training interdisciplinary teams, placenta accreta spectrum surgical treatment, and management of placenta accreta spectrum patients without prenatal diagnosis. Consensus was achieved on all questions on placenta accreta spectrum management. Specific low- and middle-income countries problems were addressed, trying to establish guidelines for the construction of trained placenta accreta spectrum interdisciplinary teams, as well as the rational use of the different therapeutic options available in a limited resources setting. In addition, it is highlighted the need to facilitate contact between patients affected by this disease and the interdisciplinary groups, overcoming administrative barriers typical of some health systems. We present a consensus on the treatment of placenta accreta spectrum in a low- and middle-income countries, based on local experts' opinions. Construction of high-quality scientific evidence is essential in settings with limited resources.