Diagnosis of respiratory syncytial virus infection in children: comparison of viral antigen detection and serology.
Direct detection of viral antigen in nasopharyngeal secretion by radioimmunoassay was compared with serology by IgG antibody enzyme immunoassay for diagnostic efficacy in 77 children with clinically suspected respiratory syncytial virus (RSV) infections. Antigen detection gave a positive diagnosis in 26 of 33 (79%) children in whom RSV infection was diagnosed by any of the two methods. The diagnostic efficacy of antigen detection was dependent upon the interval after onset at which specimens were collected; 88% of specimens taken during the first 5 days and 50% of specimens taken 6-10 days after onset of illness were positive. It was also dependent on the age of the patients, the diagnostic efficacy being 88 and 76% in children under and over 6 months of age, respectively.


Intelligent Detection Platform for Simultaneous Detection of Multiple MiRNAs Based on Smartphone.
As a marker of malignant tumors, miRNA is closely related to the occurrence and metastasis of tumors. How to achieve rapid and sensitive real-time detection is important for clinical prevention and treatment of cancer. In this study, an intelligent detection platform based on smartphone image processing technology made point-of-care testing a reality. This new smart approach could detect multiple targets simultaneously and sensitively. Hydrogel microparticles of different coding modes (shapes, numbers) were prepared by flow lithography to detect different miRNAs. After sandwich immunoassays, different shapes of hydrogels showed different fluorescence intensities depending on their targets. Images were captured by a smartphone and then analyzed by image recognition processing software installed on the smartphone. The concentration of miRNA was obtained within 10 s. The entire reaction process did not exceed 2 h. This intelligent and portable detection platform for miRNAs was reliable and the limit of detection reached the femtomole level. This work provided a demonstration of intelligent, portable, real-time detection of tumor markers.


Effect of meteorological factors on Betula, Fraxinus and Quercus pollen concentrations in the atmosphere of Lublin and Szczecin, Poland.
The aim of the study was to compare the concentration of 3 allergenic taxa pollen (ash, birch and oak) in the cities of Lublin (eastern Poland) and Szczecin (western Poland) during the years 2004 and 2005 and examine correlations between weather factors and pollen concentration. The meteorological parameters analysed were maximum and mean air temperature, relative humidity, amount of precipitation and wind speed. Measurements were performed by the volumetric method (Lanzoni 2000 pollen sampler). Pollen seasons were defined as the period in which 95 % of the total catch occurred. The pollen seasons of the studied taxa started earlier in Szczecin than in Lublin. In both cities much higher Betula pollen concentration and slightly higher Fraxinus pollen concentration were recorded in 2004 compared to 2005. But for Quercus, higher concentrations were recorded in Lublin and in Szczecin in 2005. Annual totals and maximum daily pollen grain concentrations of the tree taxa in question were higher in Lublin than in Szczecin. In 2005, maximum Betula and Fraxinus pollen concentrations occurred in each of the cities at the same time: in Lublin on 18 April, in Szczecin on 16 April. Among the meteorological parameters analysed, maximum temperature and relative humidity belong to the most important factors which affect ash, birch and oak pollen concentrations in the air.


Practical issues in picture archiving and communication system and networking.
Picture Archiving and Communication System (PACS) is a key workflow tool in the functioning of radiology departments worldwide, today, and its utilization is rapidly growing in India. The key challenges in PACS implementation are related to vendor and feature selection, integration with the existing HIS, user training, maintenance and scalability to meet increasing demands. Additionally, the networking requirements that PACS imposes on hospital networks are not insignificant. This article attempts to review these issues from the standpoint of what a prospective or new user needs to know.


Widespread distribution of the major polypeptide component of MAP 1 (microtubule-associated protein 1) in the nervous system.
We prepared a monoclonal antibody to microtubule-associated protein 1 (MAP 1), one of the two major high molecular weight MAP found in microtubules isolated from brain tissue. We found that MAP 1 can be resolved by SDS PAGE into three electrophoretic bands, which we have designated MAP 1A, MAP 1B, and MAP 1C in order of increasing electrophoretic mobility. Our antibody recognized exclusively MAP 1A, the most abundant and largest MAP 1 polypeptide. To determine the distribution of MAP 1A in nervous system tissues and cells, we examined tissue sections from rat brain and spinal cord, as well as primary cultures of newborn rat brain by immunofluorescence microscopy. Anti-MAP 1A stained white matter and gray matter regions, while a polyclonal anti-MAP 2 antibody previously prepared in this laboratory stained only gray matter. This confirmed our earlier biochemical results, which indicated that MAP 1 is more uniformly distributed in brain tissue than MAP 2 (Vallee, R.B., 1982, J. Cell Biol., 92:435-442). To determine the identity of cells and cellular processes immunoreactive with anti-MAP 1A, we examined a variety of brain and spinal cord regions. Fibrous staining of white matter by anti-MAP 1A was generally observed. This was due in part to immunoreactivity of axons, as judged by examination of axonal fiber tracts in the cerebral cortex and of large myelinated axons in the spinal cord and in spinal nerve roots. Cells with the morphology of oligodendrocytes were brightly labeled in white matter. Intense staining of Purkinje cell dendrites in the cerebellar cortex and of the apical dendrites of pyramidal cells in the cerebral cortex was observed. By double-labeling with antibodies to MAP 1A and MAP 2, the presence of both MAP in identical dendrites and neuronal perikarya was found. In primary brain cell cultures anti-MAP 2 stained predominantly cells of neuronal morphology. In contrast, anti-MAP 1A stained nearly all cells. Included among these were neurons, oligodendrocytes and astrocytes as determined by double-labeling with anti-MAP 1A in combination with antibody to MAP 2, myelin basic protein or glial fibrillary acidic protein, respectively. These results indicate that in contrast to MAP 2, which is specifically enriched in dendrites and perikarya of neurons, MAP 1A is widely distributed in the nervous system.


'Click chemistry' for diagnosis: a patent review on exploitation of its emerging trends.
Click chemistry is the novel synthetic approach towards developing reactions with large thermodynamic driving forces to give almost complete conversion of new molecular reagents to a single product. Thus, click chemistry describes the chemistry for making carbon-heteroatom-carbon bonds in benign solvents, especially in water, and having a plethora of chemical and biological applications. This has played an important role in early detection of diseases, real-time monitoring of drug delivery and investigating the biomolecular functions in vivo. This review aims at highlighting the research advancements in click chemistry published in the patent literature and categorizing the patents according to the technological progress. An extensive search was carried out to collect and analyze the patent information claiming the use of click chemistry in biotechnology, especially for diagnosis. The study further concentrates on licensing of the click chemistry patents and defining the recent breakthroughs. Different databases like Espacenet, ISI Web of Science, Patbase and Thomson Innovation are used to compile the relevant literature. In recent years, considerable development in the click concept has encouraged researchers in using click reactions in almost every branch of industry that uses chemistry. Click chemistry for chemical ligation has been immensely explored in the field of biotechnology especially for detection, diagnosis and therapeutics.


Translational coupling during expression of the tryptophan operon of Escherichia coli.
E. coli trpE polar mutations are 10 time more polar on trpD gene expression than on downstream (trpC, B, or A) gene expression. This effects was shown to be the result of "translational coupling," in which efficient translation of trpE-trpD intercistronic punctuation region consists of overlapping stop and start codons, and the trpE and trpD gene products form a functional complex in the cell. In light observations and characteristics, several models for the mechanism of translational coupling are considered.


Large destructive facial hemangioma in PHACE syndrome.
We report an infant who presented with large facial hemangioma associated with Dandy-Walker cyst and atrial septal defect. This case is peculiar in that the large facial hemangioma in posterior fossa malformations, hemangiomas, arterial anomalies, coarctation of aorta and other cardiac defects (PHACE) syndrome resulted in massive tissue destruction.


Cytosolic calcium regulates phorbol diester binding affinity in intact phagocytes.
The mobilization of internally sequestered stores of Ca2+ and activation of protein kinase C appear to be involved in neutrophil activation. We have examined the inter-relationship of these two pathways by investigating the effects of modulating Ca2+ activity on the binding of [3H]phorbol 12,13-dibutyrate (PDBU) to protein kinase C in intact phagocytes. Differentiated HL-60 cells were equilibrated with [3H]PDBU prior to stimulation with various agents known to alter Ca2+ homeostasis in cells. Agents that elevated cytosolic Ca2+, such as f-Met-Leu-Phe and A23187, up-regulated radioligand binding by increasing the affinity of the PDBU/protein kinase C interaction. These effects were time- and agonist concentration-dependent and temperature-sensitive. The kinetics of the up-regulation of binding by f-Met-Leu-Phe coincided with the kinetics of Ca2+ mobilization (by quin2 fluorescence measurements). The putative intracellular Ca2+ antagonist 8-(N,N-diethylamino)-octyl 3,4,5-trimethoxybenzoate alone down-regulated [3H]PDBU binding and inhibited the up-regulation of ligand binding by f-Met-Leu-Phe and A23187. Low concentrations of La3+ (0.1-10 microM) also inhibited up-regulation of radioligand binding to f-Met-Leu-Phe and A23187, whereas higher concentrations (0.1-1 mM) alone increased [3H] PDBU binding and supported further up-regulation of ligand binding by the Ca2+-mobilizing agents. These data suggest a role for Ca2+ in the regulation of phorbol diester binding to protein kinase C in intact cells.


Lysophosphatidic acid receptors LPA1 and LPA3 promote CXCL12-mediated smooth muscle progenitor cell recruitment in neointima formation.
The chemokine CXCL12 (CXC motif ligand 12) and its receptor CXCR 4 (CXC motif receptor 4) direct the recruitment of smooth muscle progenitor cells (SPCs) in neointima formation after vascular injury. Lysophosphatidic acid (LPA) induces CXCL12 and neointimal accumulation of smooth muscle cells (SMCs) in uninjured arteries. Thus, we hypothesize that LPA may regulate CXCL12-mediated vascular remodelling. We evaluated the role of LPA receptors in initiating CXCL12-dependent vascular repair by SPCs. Wire-induced carotid injury was performed in apolipoprotein E(-/-) mice on western-type diet. LPA receptor expression was studied by immunostaining and quantitative RT-PCR. LPA receptors LPA(1) and LPA(3) were detected in the media of uninjured arteries and in the injury-induced neointima. LPA(3) mRNA was upregulated and LPA(1) mRNA downregulated at one week after injury. The LPA(1/3) antagonist Ki16425 inhibited neointima formation by 71% and reduced both relative neointimal SMCs and the macrophage content. Additionally, neointimal hypoxia-inducible factor-1alpha and CXCL12 expression, the injury-induced peripheral stem cell antigen-1 (Sca-1)(+)/Lin(-) SPC mobilization, and the neointimal recruitment of Sca-1(+)SMCs were inhibited by Ki16425. In wild type mice, LPA20:4 increased CXCL12 and hypoxia-inducible factor-1alpha expression in carotid arteries as early as 1 day following short-term endoluminal incubation. LPA20:4-induced SPC mobilization and neointima formation were blocked by Ki16425, LPA(1)- and LPA(3)-specific small interfering (si)RNA, and the CXCR4 antagonist POL5551. Ki16425 reduced LPA20:4-mediated neointimal recruitment of SPC as demonstrated by 2-photon microscopy in bone marrow chimeric mice after repopulation with SM22-LacZ transgenic, hematopoietic cells. Moreover, POL5551 decreased the neointimal accumulation of CXCR4(+) SMCs. LPA(1) and LPA(3) promote neointima formation through activation of CXCL12-mediated mobilization and recruitment of SPCs.


Association analysis of ADPRT1, AKR1B1, RAGE, GFPT2 and PAI-1 gene polymorphisms with chronic renal insufficiency among Asian Indians with type-2 diabetes.
To determine association of nine single nucleotide polymorphisms (SNPs) in ADP ribosyltransferase-1 (ADPRT1), aldo-keto reductase family 1 member B1 (AKR1B1), receptor for advanced glycation end-products (RAGE), glutamine:fructose-6-phosphate amidotransferase-2 (GFPT2), and plasminogen activator inhibitor-1 (PAI-1) genes with chronic renal insufficiency (CRI) among Asian Indians with type 2 diabetes; and to identify epistatic interactionss between genes from the present study and those from renin-angiotensin-aldosterone system (RAAS), and chemokine-cytokine, dopaminergic and oxidative stress pathways (previously investigated using the same sample set). Type 2 diabetes subjects with CRI (serum creatinine > or =3.0 mg/dl) constituted the cases (n = 196), and ethnicity and age matched individuals with diabetes for a duration of > or = 10 years, normal renal functions and normoalbuminuria recruited as controls (n = 225). Allelic and genotypic constitution of 10 polymorphisms (SNPs) from five genes namely--ADPRT1, AKR1B1, RAGE, GFPT2 and PAI-1 with diabetic CRI was investigated. The genetic associations were evaluated by computation of odds ratio and 95% confidence interval. Multiple logistic regression analysis was carried out to correlate various clinical parameters with genotypes, and to study epistatic interactions between SNPs in different genes. Single nucleotide polymorphisms -429 T>C in RAGE and rs7725 C>T SNP in 3' UTR in GFPT2 gene showed a trend towards association with diabetic CRI. Investigation using miRBase statistical tool revealed that rs7725 in GFPT2 was a perfect target for predicted miRNA (hsa miR-378) suggesting the presence of the variant 'T' allele may result in an upregulation of GFPT2 contributing to diabetic renal complication. Epistatic interaction between SNPs in transforming growth factor TGF-beta1 (investigated using the same sample set and reported elsewhere) and GFPT2 genotype was observed. Association of SNPs in RAGE and GFPT2 suggest that the genes involved in modulation of oxidative pathway could be major contributor to diabetic chronic renal insufficiency. In addition, GFPT2 mediated overproduction of TGF-beta1 leading to endothelial expansion and thereby CRI seems likely, suggested by our observation of a significant interaction between GFPT2 with TGF-beta1 genes. Further, identification of predicted miRNA targets spanning the associated SNP in GFPT2 implicates the rs7725 SNP in transcriptional regulation of the gene, and suggests GFPT2 could be a relevant target for pharmacological intervention. Larger replication studies are needed to confirm these observations.


In Vitro Evaluation of the Antioxidant, Cytoprotective, and Antimicrobial Properties of Essential Oil from Pistacia vera L. Variety Bronte Hull.
Although the chemical composition and biological properties of some species of the genus Pistacia has been investigated, studies on hull essential oil of Pistacia vera L. variety Bronte (HEO) are currently lacking. In this work, we have carried out an in-depth phytochemical profile elucidation by Gas Chromatography-Mass Spectrometry (GC-MS) analysis, and an evaluation of antioxidant scavenging properties of HEO, using several different in vitro methods, checking also its cytoprotective potential on lymphocytes treated with tert-butyl hydroperoxide. Moreover, the antimicrobial activity against Gram-positive and Gram-negative strains, both American Type Culture Collection (ATCC) and clinical isolates, was also investigated. GC-MS analysis highlighted the richness of this complex matrix, with the identification of 40 derivatives. The major components identified were 4-Carene (31.743%), α-Pinene (23.584%), d-Limonene (8.002%), and 3-Carene (7.731%). The HEO showed a strong iron chelating activity and was found to be markedly active against hydroxyl radical, while scarce effects were found against 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical. Moreover, pre-treatment with HEO was observed to significantly increase the cell viability, decreasing the lactate dehydrogenase (LDH) release. HEO was bactericidal against all the tested strains at the concentration of 7.11 mg/mL, with the exception of Pseudomonas aeruginosa ATCC 9027. The obtained results demonstrate the strong free-radical scavenging activity of HEO along with remarkable cytoprotective and antimicrobial properties.


Molecular diagnostics in medical microbiology: yesterday, today and tomorrow.
Clinical microbiology is clearly on the move, and various new diagnostic technologies have been introduced into laboratory practice over the past few decades. However, Henri D Isenberg recently stated that molecular biology techniques promised to revolutionise the diagnosis of infectious disease, but that, to date, this promise is still in its infancy. Molecular diagnostics have now surpassed these early stages and have definitely reached puberty. Currently, a second generation of automated molecular approaches is already within the microbiologists' reach. Quantitative amplification tests in combination with genomics, transcriptomics, proteomics and related methodologies will pave the way to further enhancement of innovative microbial detection and identification.


Spectral characteristics of autofluorescence and second harmonic generation from ex vivo human skin induced by femtosecond laser and visible lasers.
The spectral properties of one-photon, two-photon excited autofluorescence and second harmonic generation (SHG) from ex vivo human skin induced by a femtosecond (fs) laser and three visible lasers in backscattering geometry are systematically investigated. Our experimental results indicate that peak position of autofluorescence spectra from the dermis and epidermis shift toward long wavelengths, and the fluorescent intensity decreases when the excitation wavelength increases due to an effect of the excitation wavelength on autofluorescence signals. However, the intensity of the SHG signal in collagen has the maximal value of 800 nm excitation wavelength. This may be the result that the energy of the SHG signal is in resonance with an electronic absorption band. The two-photon excited autofluorescence and SHG intensity all obey a quadratical dependence on the excitation power. Compared with the two-photon excited fluorescence and SHG, the one-photon excited fluorescence in the dermis and epidermis exhibits different spectral characteristics. The investigation of the spectral characteristics of autofluorescence and SHG from ex vivo human skin can provide new insights into morphologic structures and biochemical components of tissues, which are vital for improving the application of laser-induced autofluorescence and SHG spectroscopy technique for noninvasive in vivo tissue diagnostics.


Mechanism of action of the antifugal agent polyoxin D.
The antibiotic polyoxin D was shown to inhibit the incorporation of (14)C-glucosamine into cell wall chitin in Neurospora crassa at levels which were comparable with those required for inhibition of fungal growth. At the same time, the antibiotic increased the accumulation of a nucleotide, which was identified as uridine diphosphate (UDP)-N-acetylglucosamine, indicating inhibition of chitin synthesis. Chitin synthetase (UDP-N-acetylglucosamine: chitin N-acetylglucosaminyl transferase, EC 22.214.171.124) of N. crassa was found to be strongly inhibited by polyoxin D, as determined by the transfer of (14)C-N-acetylglucosamine from (14)C-UDP-N-acetylglucosamine to the particulate fraction. The inhibition was competitive with respect to UDP-N-acetylglucosamine and specific for chitin synthetase. The K(i) for polyoxin D in the reaction was 1.40 x 10(-6)m, and the K(m) for UDP-N-acetylglucosamine was 1.43 x 10(-3)m. The formation of osmotically sensitive, protoplast-like structures, when the fungus Cochliobolus miyabeanus was grown in the presence of polyoxin D, also suggested that the primary site of action of polyoxin D was in the formation of cell wall structures.


Knowledge of memory aging across the lifespan.
The authors examined knowledge of normal and pathological memory aging in a lifespan sample of 198 individuals who ranged in age from 13 to 88 years. Participants completed the Knowledge of Memory Aging Questionnaire (Cherry, Brigman, Hawley, & Reese, 2003). The authors hypothesized that high school students would be less knowledgeable about memory aging issues than college students, middle-aged, and community-dwelling older adults. Consistent with this hypothesis, response accuracy was lower for high school students compared to their older counterparts. Follow-up analyses revealed that high school students' responses to a subset of questions that tap ageist views of adult cognition were less accurate than the other age groups, implying a response bias toward stereotypical images of memory aging. Implications for research and the design of instructional materials to increase people's knowledge about normative changes in adult cognition are discussed.


Straw-thawing method interacts with sire and extender to influence sperm motility and conception rates of dairy cows.
Influence of interactions of straw-thawing method with sire and extender type (milk or egg yolk-based) on postthaw sperm motility and conception rates of dairy cows was assessed. In experiment 1, sperm from 10 Holstein sires were frozen in egg yolk citrate and heated whole-milk extenders using a split-ejaculate technique. Straws were thawed in a 37 degrees C water bath with or without 3 min of exposure to a 37 degrees C warming plate while wrapped in a paper towel (air-thaw). Percentage of motile sperm was assessed after 1 min and 3 h of incubation at 37 degrees C. In experiment 2, sperm from 3 Holstein sires were frozen in egg-yolk citrate and a nonheated whole milk extender using a split-ejaculate technique. Straws were thawed and motility was assessed as in experiment 1. Conception rates (n = 475) were compared in a single herd of Holstein cows after thawing straws in 35 degrees C water for 45 s or after air-thawing by wiping straws with a paper towel upon removal from the storage vessel and placing directly into the insemination gun. In each experiment, interactions between thaw method and sire, extender type, or both, indicated that conditions may be created that facilitate sperm tolerance of air-thaw procedures. When a significant thaw method effect was detected in either experiment, air-thaw was consistently associated with the lesser measure of sperm motility, conception, or both. In conclusion, although some sire x extender combinations seem to be tolerant of air-thaw procedures, other combinations are more sensitive, resulting in reduced postthaw sperm survival, conception rates of cows, or both, in response to air-thaw.


Binding Affinity Characterization of Four Antennae-Enriched Odorant-Binding Proteins From Harmonia axyridis (Coleoptera: Coccinellidae).
Harmonia axyridis is an important natural enemy that consumes many agricultural and forestry pests. It relies on a sensitive olfactory system to find prey and mates. Odorant-binding proteins (OBPs) as the first-step of recognizing volatiles, transport odors through sensillum lymph to odorant receptors (ORs). However, little is known about the molecular mechanisms of H. axyridis olfaction. In this study, four H. axyridis antenna specific OBP genes, HaxyOBP3, 5, 12, and 15, were bacterially expressed and the binding features of the four recombinant proteins to 40 substances were investigated using fluorescence competitive binding assays. Three-dimensional structure modeling and molecular docking analysis predicted the binding sites between HaxyOBPs and candidate volatiles. Developmental expression analyses showed that the four HaxyOBP genes displayed a variety of expression patterns at different development stages. The expression levels of HaxyOBP3 and HaxyOBP15 were higher in the adult stage than in the other developmental stages, and HaxyOBP15 was significantly transcriptionally enriched in adult stage. Ligand-binding analysis demonstrated that HaxyOBP3 and HaxyOBP12 only combined with two compounds, β-ionone and p-anisaldehyde. HaxyOBP5 protein displayed binding affinities with methyl salicylate, β-ionone, and p-anisaldehyde (Ki = 18.15, 11.71, and 13.45 μM). HaxyOBP15 protein had a broad binding profile with (E)-β-farnesene, β-ionone, α-ionone, geranyl acetate, nonyl aldehyde, dihydro-β-ionone, and linalyl acetate (Ki = 4.33-31.01 μM), and hydrophobic interactions played a key role in the binding of HaxyOBP15 to these substances according to molecular docking. Taken together, HaxyOBP15 exhibited a broader ligand-binding spectrum and a higher expression in adult stage than HaxyOBP3, 5, and 12, indicating HaxyOBP15 may play a greater role in binding volatiles than other three HaxyOBPs. The results will increase our understanding of the molecular mechanism of H. axyridis olfaction and may also result in new management strategies (attractants/repellents) that increase the biological control efficacy of H. axyridis.


Idiopathic Spontaneous Intra-Abdominal Hemorrhage or Abdominal Apoplexy: A Rare Cause of Abdominal Pain.
Idiopathic spontaneous intra-abdominal hemorrhage (ISIH) is a rare condition that can be catastrophic if not diagnosed and treated promptly. Herein, we report a case of ISIH due to suspected hemorrhage of the proximal branch of the superior mesenteric artery, which caused epigastric pain.


Dynamic dialogue: application to generational diversity.
The complexity of the work environment demands a new level of creativity that goes beyond traditional organization development strategies. Dynamic Dialogue is a learning practice that provides the structure for divergent groups of people to develop greater understanding and appreciation for individual perspective, subsequently enhancing efficiency, satisfaction, and accomplishment in the work environment. This article presents how Dynamic Dialogue can be used to uncover the assumptions and beliefs regarding generational diversity (Generation X, Baby Boomers, and Matures).


[Biological effects of phenytoin on cultured human periodontal ligament fibroblasts in vitro].
To study the biological effects of phenytoin (PHT) on cultured human periodontal ligament fibroblasts (hPDLF), and explore the possibility of its accelerating periodontal regeneration. Increasing concentrations of PHT (1, 5, 20, 100, 500, 2 500 mg/L) were added into the medium of the fourth passage of cultured hPDLF, respectively. After co-incubated for 3 days, cell proliferation activity, the total amount of protein and alkaline phosphatase (ALP) activity were detected. Mineralized sodium and PHT (20, 100, 500 mg/L) were added into the medium of the fourth passage hPDLF. After co-incubated, the mineralized nodules formation were detected by Von Kossa staining. The third passage hPDLF were stimulated by PHT (20, 100 mg/L), bone morphogenetic protein-2 (BMP-2) concentration was analyzed by enzyme linked immunosorbent sandwich assay (ELISA). At the concentration of 20 or 100 mg/L, PHT significantly enhanced the proliferating activity and ALP activity of hPDLF (P<0.01). PHT at 100 mg/L could increase protein synthesis of hPDLF (P<0.05). The capability of mineralization and BMP-2 expression of hPDLF were increased significantly (P<0.01) in 100 mg/L group when compared with that in the control group. However, higher concentration (2 500 mg/L) not only changed cell morphology, but also significantly inhibited cell activity. The results suggested that proper doses of PHT could promote proliferation and biosynthesis and also enhance osteogenesis by increasing the differentiation, mineralization and BMP-2 expression of hPDLF while higher concentrations of PHT had cytotoxic effect.


Novel chlorinated and nitrogenated azaphilones with cytotoxic activities from the marine algal-derived fungus Chaetomium globosum 2020HZ23.
Two novel chlorinated and nitrogenated azaphilones, namely N-butyl-2-aza-2-deoxychaetoviridin A (1) and N-hexyl-2-aza-2-deoxychaetoviridin A (2), along with a previously identified analogue, chaetoviridin A (3), were successfully obtained from Chaetomium globosum 2020HZ23, a marine algal-sourced endophytic fungus. The planar structures as well as the absolute configurations of these new metabolites were determined utilizing a synergistic approach that involved both spectroscopic techniques (1D/2D NMR and HRESIMS) and Density Functional Theory (DFT) calculations. Each compound was subject to in vitro cytotoxicity evaluation toward the A549 cancer cell line. Both compounds 1 and 2 demonstrated significant cytotoxicity, as evidenced by their respective IC50 values of 13.6 and 17.5 μM. Furthermore, 1 and 2 demonstrated potent cell migration inhibition, which elevated with increasing dose concentration. In contrast, compound 3 exhibited less cytotoxic activity relative to 1 and 2, suggesting that the cytotoxic potency escalates with N-substitution at the C-2 position and the introduction of a side chain. This finding could offer implications for future studies aimed at designing and refining lead compounds within this class.


Sequential bilateral lesser trochanter avulsion fractures in an adolescent patient.
We report the rare case of a 15-year-old boy who sustained sequential bilateral lesser trochanter avulsion fractures over a 6-month period while playing football. No malignancy or associated metabolic bone disease was found. He subsequently made a full recovery with non-operative treatment.


Artificial Intelligence-Based Psoriasis Severity Assessment: Real-world Study and Application.
Psoriasis is one of the most frequent inflammatory skin conditions and could be treated via tele-dermatology, provided that the current lack of reliable tools for objective severity assessments is overcome. Psoriasis Area and Severity Index (PASI) has a prominent level of subjectivity and is rarely used in real practice, although it is the most widely accepted metric for measuring psoriasis severity currently. This study aimed to develop an image-artificial intelligence (AI)-based validated system for severity assessment with the explicit intention of facilitating long-term management of patients with psoriasis. A deep learning system was trained to estimate the PASI score by using 14,096 images from 2367 patients with psoriasis. We used 1962 patients from January 2015 to April 2021 to train the model and the other 405 patients from May 2021 to July 2021 to validate it. A multiview feature enhancement block was designed to combine vision features from different perspectives to better simulate the visual diagnostic method in clinical practice. A classification header along with a regression header was simultaneously applied to generate PASI scores, and an extra cross-teacher header after these 2 headers was designed to revise their output. The mean average error (MAE) was used as the metric to evaluate the accuracy of the predicted PASI score. By making the model minimize the MAE value, the model becomes closer to the target value. Then, the proposed model was compared with 43 experienced dermatologists. Finally, the proposed model was deployed into an app named SkinTeller on the WeChat platform. The proposed image-AI-based PASI-estimating model outperformed the average performance of 43 experienced dermatologists with a 33.2% performance gain in the overall PASI score. The model achieved the smallest MAE of 2.05 at 3 input images by the ablation experiment. In other words, for the task of psoriasis severity assessment, the severity score predicted by our model was close to the PASI score diagnosed by experienced dermatologists. The SkinTeller app has been used 3369 times for PASI scoring in 1497 patients from 18 hospitals, and its excellent performance was confirmed by a feedback survey of 43 dermatologist users. An image-AI-based psoriasis severity assessment model has been proposed to automatically calculate PASI scores in an efficient, objective, and accurate manner. The SkinTeller app may be a promising alternative for dermatologists' accurate assessment in the real world and chronic disease self-management in patients with psoriasis.


Neck node bolus technique in the treatment of Nasopharyngeal Carcinoma with Intensity-modulated radiotherapy.
To study the effect of bolus versus no bolus in the coverage of the nodal tumour volume with intensity-modulated radiotherapy (IMRT) for the treatment of nasopharyngeal carcinoma (NPC). This retrospective study used data from 5 consecutive patients with NPC who were treated with bolus for large neck nodes using IMRT from November 2011-January 2012 in our institute. All these patients were treated radically with IMRT according to our institution's protocol. Re-planning with IMRT without bolus for these patients with exactly the same target volumes were done for comparison. Comparison of the plans was done by comparing the V70 of PTV70-N, V66.5 of PTV70-N, V65.1 of PTV70-N and the surface dose of the PTV70-N. The mean size of the largest diameter of the enlarged lymph nodes for the 5 patients was 3.9 cm. The mean distance of the GTV-N to the skin surface was 0.6 cm. The mean V70 of PTV70-N for the 5 patients showed an absolute advantage of 10.8% (92.4% vs. 81.6%) for the plan with bolus while the V66.5 of PTV70-N had an advantage of 8.1% (97.0% vs. 88.9%). The mean V65.1 also had an advantage of 7.1% (97.6% vs. 90.5%). The mean surface dose for the PTV70-N was also much higher at 61.1 Gy for the plans with bolus compared to only 23.5 Gy for the plans without bolus. Neck node bolus technique should be strongly considered in the treatment of NPC with enlarged lymph nodes treated with IMRT. It yields a superior dosimetry compared to non-bolus plans with acceptable skin toxicity.


Clinical outcomes and Oncotype DX Breast Recurrence Score® in early-stage BRCA-associated hormone receptor-positive breast cancer.
BRCA-associated breast cancers tend to have distinctive features compared to sporadic breast cancers; further characterization can aid in optimizing treatment. The study evaluated a patient cohort with early-stage estrogen receptor positive, HER2 negative invasive breast cancer who had Oncotype DX Breast Recurrence Score® analysis and genetic testing for hereditary breast and ovarian cancer syndrome. Data on patients and their breast cancers with outcomes were collected and analyzed. 745 patients were included, of whom 33 had pathogenic BRCA mutations (8 BRCA1, 25 BRCA2). Patients with BRCA mutations were younger and received more adjuvant chemotherapy, but less endocrine therapy and radiation therapy. BRCA-associated breast cancers had less progesterone receptor expression, higher nuclear grade, and higher Oncotype DX Breast Recurrence Scores® with median Recurrence Score® 29, compared to 16 in cancers without mutations (p < 0.0001). Breast cancer recurrence developed in 18% of patients with BRCA mutations and 9% of patient without mutations, although multivariate analysis of relapse-free survival was not significant, HR 1.519 (95% confidence interval [CI] 0.64-3.58; p = 0.3401). After adjusting for Recurrence Score®, overall survival by BRCA status was improved HR 0.448 (95% CI 0.06-3.34; p = 0.4333). BRCA-associated early-stage hormone receptor-positive breast cancers have higher Oncotype DX Breast Recurrence Score® compared to those without mutations. BRCA status did not significantly impact relapse-free survival and overall survival. Larger clinical trials are needed to further assess the findings, and if confirmed, could impact clinical management of BRCA-associated breast cancers.


Disrupted-in-schizophrenia-1 (DISC1): a key susceptibility factor for major mental illnesses.
Here we overview Disrupted-in-Schizophrenia-1 (DISC1), a promising lead in studying the pathophysiology of major mental conditions. Genetic association studies reproducibly suggest involvement of DISC1 in both schizophrenia and bipolar disorder in several ethnic groups. Different from several other susceptibility genes for schizophrenia, such as neuregulin-1 and dysbindin, there are two independent pedigrees in which genetic variations of DISC1 directly segregate with major mental conditions. This uniqueness has facilitated neurobiology of DISC1, which may hopefully lead to an important breakthrough in understanding of pathophysiology of major mental conditions. DISC1 is a multifunctional protein that plays a role in neurodevelopment and cell signaling. In autopsied brains from patients with psychosis and substance abuse, change in subcellular distribution of DISC1 is observed. DISC1 interacts with phosphodiesterase (PDE) 4B that degrades cyclic AMP (cAMP), which may be a regulatory molecule for working memory in the prefrontal cortex. Knockdown expression of DISC1 in developing cerebral cortex in mouse brains leads to changes that resemble, at least in part, the pathology found in patients with schizophrenia. These results support involvement of DISC1 in the pathophysiology of major mental conditions, including schizophrenia, in several mechanisms.


Cavitary histoplasmosis occurring during two large urban outbreaks. Analysis of clinical, epidemiologic, roentgenographic, and laboratory features.
We have compared risk factors for cavitary histoplasmosis in 62 patients with that manifestation of the infection and in 679 patients with other forms of histoplasmosis, and we have evaluated the clinical and laboratory findings in 45 patients with cavitary histoplasmosis who were cared for at the Indiana University Medical Center hospitals during two large histoplasmosis outbreaks. Chronic obstructive lung disease and old age were the strongest risk factors for cavitary histoplasmosis but male sex, white race and immunosuppression were also important in certain patient groups. Fever, sweats, weight loss, productive cough, anemia, lymphopenia, and alkaline phosphatase elevation were common findings. The patients were occasionally incorrectly treated for presumed class 3 tuberculosis. Cultures were positive in 58% of patients, with sputum samples providing the highest yield (61%). Histoplasmal serologic tests provided useful clues to the diagnosis, positive in over 90% of cases. About one-third of patients recovered spontaneously while another 35% improved following treatment. About 4% developed chronic untreated cavitary histoplasmosis characterized by clinical and roentgenographic exacerbations and remissions. Of the deaths in four patients with untreated disease, one was caused by disseminated histoplasmosis while three died of other causes. Ketoconazole appeared effective in three of seven patients while its effect in three additional patients was uncertain. Toxicity precluded completion of ketoconazole therapy in one patient. Only amphotericin B has been proven to be effective therapy for cavitary histoplasmosis.


Mechanical factors in loosening of Christiansen and Charnley arthroplasties.
A series of 96 Christiansen and 23 Charnley hip arthroplasties, mainly for osteoarthrosis, were followed for an average of 40 (15-93) months. Radiolucent zones at the cement bone interface and resorption of the calcar were more frequent in the Christiansen than in the Charnley hips. Medial and axial migration, and cement fracture often occurred concurrently, with a total frequency of 27/96 in the Christiansen and 4/23 in the Charnley subseries. Wide radiolucent zones in the acetabular cement bone interface were more frequent in the Christiansen hips. Six acetabular protrusions were observed in the Christiansen hips against none in the Charnley hips. The average Harris' hip scores were significantly higher for the Charnley than for the Christiansen hips. Reoperation for loosening was performed in two Charnley hips and 19 Christiansen hips.


Prevention and management of panic in personnel facing a chemical threat--lessons from the Gulf War.
During the Gulf War a number of subjects presented with panic, hyperventilation, and inability to wear respirators when chemical alarms were sounded, despite a perceived real chemical threat. Twenty-five such sufferers were seen at the Psychiatric Department of 33 General (Surgical) Hospital. This paper considers the aetiology of such responses, describes a mode of treatment which can be used in the threat situation, and considers issues of future training.


Multiple myeloma cells recruit tumor-supportive macrophages through the CXCR4/CXCL12 axis and promote their polarization toward the M2 phenotype.
Multiple myeloma (MM) cells specifically attract peripheral-blood monocytes, while interaction of MM with bone marrow stromal cells (BMSCs) significantly increased monocyte recruitment (p<0.01). The CXCL12 chemokine, produced by both the MM and BMSCs, was found to be a critical regulator of monocyte migration. CXCL12 production was up-regulated under MM-BMSCs co-culture conditions, whereas blockage with anti-CXCR4 antibodies significantly abrogated monocyte recruitment toward a MM-derived conditioned medium (p<0.01). Furthermore, elevated levels of CXCL12 were detected in MM, but not in normal BM samples, whereas malignant MM cells often represented the source of increased CXCL12 in the BM. Blood-derived macrophages effectively supported MM cells proliferation and protected them from chemotherapy-induced apoptosis. Importantly, MM cells affected macrophage polarization, elevating the expression of M2-related scavenger receptor CD206 in macrophages and blocking LPS-induced TNFα secretion (a hallmark of M1 response). Of note, MM-educated macrophages suppressed T-cell proliferation and IFNγ production in response to activation. Finally, increased numbers of CXCR4-expressing CD163+CD206+ macrophages were detected in the BM of MM patients (n=25) in comparison to MGUS (n=11) and normal specimens (n=8). Taken together, these results identify macrophages as important players in MM tumorogenicity, and recognize the CXCR4/CXCL12 axis as a critical regulator of MM-stroma interactions and microenvironment formation.


Annulus Fibrosus Can Strip Hyaline Cartilage End Plate from Subchondral Bone: A Study of the Intervertebral Disk in Tension.
Study Design Biomechanical study on cadaveric spines. Objective Spinal bending causes the annulus to pull vertically (axially) on the end plate, but failure mechanisms in response to this type of loading are poorly understood. Therefore, the objective of this study was to identify the weak point of the intervertebral disk in tension. Methods Cadaveric motion segments (aged 79 to 88 years) were dissected to create midsagittal blocks of tissue, with ∼10 mm of bone superior and inferior to the disk. From these blocks, 14 bone-disk-bone slices (average 4.8 mm thick) were cut in the frontal plane. Each slice was gripped by its bony ends and stretched to failure at 1 mm/s. Mode of failure was recorded using a digital camera. Results Of the 14 slices, 10 failed by the hyaline cartilage being peeled off the subchondral bone, with the failure starting opposite the lateral annulus and proceeding medially. Two slices failed by rupturing of the trabecular bone, and a further two failed in the annulus. Conclusions The hyaline cartilage-bone junction is the disk's weak link in tension. These findings provide a plausible mechanism for the appearance of bone and cartilage fragments in herniated material. Stripping cartilage from the bony end plate would result in the herniated mass containing relatively stiff cartilage that does not easily resorb.


Training health workers to prevent and manage post-partum haemorrhage (PPH).
Post-partum haemorrhage (PPH) is the second greatest direct cause of maternal death in the United Kingdom, and rates of PPH continue to increase despite advances in clinical care. Training workers to manage PPH involves improvement of technical and non-technical skills in the context of a multidisciplinary team (MDT). Management of PPH should begin in the antenatal period, with identification of high-risk women and referral for multispecialty input. Training for the acute management of PPH should involve all members of the labour ward team and beyond, including haematology and non-clinical staff. Simulation-based training, didactic teaching and hybrid obstetric emergency courses are current options for training workers. Non-technical skills should also be taught, including specific training on communication, leadership, situational awareness and team-working skills. Improving management of obstetric emergencies requires thorough antenatal and intra-partum risk assessment, optimising knowledge and non-technical skills of individual members of the team, improving collaboration of the MDT, better simulation training and adjusting local infrastructure.


6-Hydroxy-5-nitrobenzo[d]oxazol-2(3H)-one-A degradable derivative of natural 6-Hydroxybenzoxazolin-2(3H)-one produced by Pantoea ananatis.
Pantoea ananatis is a bacterium associated with other microorganisms on Abutilon theophrasti Medik. roots. It converts 6-hydroxybenzoxazolin-2(3H)-one (BOA-6-OH), a hydroxylated derivative of the allelochemical benzoxazolin-2(3H)-one, into 6-hydroxy-5-nitrobenzo[d]oxazol-2(3H)-one. The compound was identified by NMR and mass spectrometric methods. In vitro synthesis succeeded with Pantoea protein, with isolated proteins from the Abutilon root surface or with horseradish peroxidase in the presence of nitrite and H2O2. Nitro-BOA-6-OH is completely degraded further by Pantoea ananatis and Abutilon root surface proteins. Under laboratory conditions, 6-hydroxy-5-nitrobenzo[d]oxazol-2(3H)-one inhibits Lepidium sativum seedling growth whereas Abutilon theophrasti is much less affected. Although biodegradable, an agricultural use of 6-hydroxy-5-nitrobenzo[d]oxazol-2(3H)-one is undesirable because of the high toxicity of nitro aromatic compounds to mammals.


Spared motivational modulation of cognitive effort in a maternal immune activation model of schizophrenia risk.
Maternal immune activation (MIA) during gestation is a significant risk factor for development of schizophrenia and other neurodevelopmental diseases. In animal models of this risk factor, MIA during pregnancy can produce offspring that recapitulate certain aspects of the behavioral and neurophysiological impairments seen in schizophrenia. Here, the authors tested the effect of polyinosinic-polycytidylic acid (poly I:C)-induced MIA in a task that explicitly assays the interaction between motivation and cognition. In our paradigm, discrimination accuracy during a sustained-attention task is differentially impacted by environmental cues that signal the probability of reward for accurate performance. Cognition-motivation interactions are implicated in producing functional impairments in patients. Therefore, to the extent that this MIA model recapitulates such impairments, the authors predicted impaired ability of reward-associated signals to modulate cognitive performance in MIA rat offpsring. Adult offspring of dams in which MIA was induced displayed impaired prepulse inhibition relative to controls, verifying a functional effect of poly I:C induction. Despite this deficit, there were no differences between MIA and control rats in any aspects of task learning or performance, including under extinction and reacquisition conditions. These results indicate that MIA spares functioning of some of the cognitive, motivational, and decision-making processes that are impacted in schizophrenia and suggest that MIA as an isolated manipulation does not model the full range and nuance of the cognitive and motivational impairments in the disease. The authors suggest that some aspects of the functional impairment in schizophrenia and other neurodevelopmental diseases may be better modeled using multiple "hit" models of disease risk. (PsycINFO Database Record


A super-resolution scanning algorithm for lensless microfluidic imaging using the dual-line array image sensor.
The lensless optical fluid microscopy is of great significance to the miniaturization, portability and low cost development of cell detection instruments. However, the resolution of the cell image collected directly is low, because the physical pixel size of the image sensor is the same order of magnitude as the cell size. To solve this problem, this paper proposes a super-resolution scanning algorithm using a dual-line array sensor and a microfluidic chip. For dual-line array sensor images, the multi-group velocity and acceleration of cells flowing through the line array sensor are calculated. Then the reconstruction model of the super-resolution image is constructed with variable acceleration. By changing the angle between the line array image sensor and the direction of cell flow, the super-resolution image scanning and reconstruction are achieved in both horizontal and vertical directions. In addition, it is necessary to study the row by row extraction algorithm for cell foreground image. In this paper, the dual-line array sensor is implemented by adjusting the acquisition window of the image sensor with a pixel size of 2.2μm. When the tilt angle is 21 degrees, the equivalent pixel size is 0.79μm, improved 2.8 times, and after de-diffraction its average size error was 3.249%. As the angle decreases, the image resolution is higher, but the amount of information is less. This super-resolution scanning algorithm can be integrated on the chip and used with a microfluidic chip to realize on-chip instrument.


The rheological properties of fluid denture-base resins.
The rheological properties of six commercial fluid denture resins were determined by rotational viscometry. Initial viscosity ranged from 67 to 575 centipoise at a rotational speed of 10 revolutions per minute. All resins showed initial non-Newtonian flow behavior and increased viscosity with time.


Longitudinal course of depression scores with and without insomnia in non-depressed individuals: a 6-year follow-up longitudinal study in a Korean cohort.
This is a population-based longitudinal study that followed insomnia symptoms over a 6-year period in non-depressed individuals. The purpose of the study was to (1) investigate the longitudinal course of depression based on number of insomnia episodes; and (2) describe longitudinal associations between insomnia and depression, and insomnia and suicidal ideation. Population-based longitudinal study. Community-based sample from the Korean Genome and Epidemiology Study (KoGES). 1,282 non-depressed individuals (44% male, mean age 52.3 ± 7.14 years). This study prospectively assessed insomnia, depression, and suicidal ideation with 4 time points. Individuals were classified into no insomnia (NI), single episode insomnia (SEI), and persistent insomnia (PI; ≥ insomnia at 2+ time points) groups based on number of times insomnia was indicated. Mixed effects modeling indicated that depression scores increased significantly faster in the PI group compared to the NI (P < 0.001) and SEI (P = 0.02) groups. Additionally, the PI group had significantly increased odds of depression as compared to NI or SEI (OR 2.44, P = 0.001) groups, with 18.7% meeting criteria for depression compared to the NI (5.3%) and SEI (11.6%) groups at end point. The PI group also had significantly increased odds of suicidal ideation as compared to NI or SEI (OR 1.86, P = 0.002) groups. Persistent insomnia significantly increases the rate in which depression occurs over time in non-depressed individuals, which ultimately leads to higher risk for depression. Additionally, having persistent insomnia also increased the risk of suicidal ideation. Suh S; Kim H; Yang HC; Cho ER; Lee SK; Shin C. Longitudinal course of depression scores with and without insomnia in non-depressed individuals: a 6-year follow-up longitudinal study in a Korean cohort. SLEEP 2013;36(3):369-376.


[Eurhytmy by Steiner].
According to Rudolph Steiner the aim of medical anthroposophy must be to revalue the soul-body intercourse as a function of recovery. To this purpose, along with mineral, organic and vegetable medicinal principles, of a particular importance is eurhythmy: a series of static postures and dancing shapes which encourage the course of selfeuring innate with man.


Getting entangled with body image: development and validation of a new measure.
Several studies have highlighted the role of cognitive fusion on human suffering and a wide range of psychopathological conditions. Namely, this process has been regarded as a core aspect in eating disorders. Nevertheless, the study of cognitive fusion on eating psychopathology is scarce and a measure that specifically concerns body image was still to be created. The present study aimed therefore at developing and validating such measure, the Cognitive Fusion Questionnaire - Body Image (CFQ-BI). The current study was conducted using different samples of both genders, collected in the general and student populations. The dimensionality of the CFQ-BI was tested through an exploratory factor analysis and a confirmatory factor analysis (CFA). The scale's internal reliability and other psychometric qualities were also analysed. The CFQ-BI's final structure was one-dimensional and comprised 10 items that assess body image-related cognitive fusion. This final structure explained a total of 73.41% of the variance. The adequacy of the questionnaire was corroborated through a CFA which revealed that CFQ-BI presents good global and local adjustment values and goodness-of-fit indices. Results also showed that the CFQ-BI holds a very good internal consistency (α = .96), convergent, divergent and temporal reliabilities, and is able to discriminate cases from non-cases of eating psychopathology. The CFQ-BI was thus established as a short, robust, and reliable measure of body image-related cognitive fusion. This new measure may correspond to a significant contribution to research and clinical practice in the field of body image and eating-related difficulties. A new measure of body image-related cognitive fusion (CFQ-BI) was developed. The CFQ-BI was proved to be a short, robust, and reliable measure. Body image-related cognitive fusion was strongly linked to eating psychopathology. CFQ-BI may be useful in eating psychopathology's research and clinical practice.


Is high-resolution ultrasonography suitable for the detection of temporomandibular joint involvement in children with juvenile idiopathic arthritis?
The purpose of this study was to determine the potential of high-resolution ultrasonography for the detection of temporomandibular joint (TMJ) changes in children with juvenile idiopathic arthritis (JIA). We investigated prospectively 20 children (17 female and 3 male; mean age 11.06 years, standard deviation 3.43 years) with TMJ disorders caused by JIA, over a period of 16 months. Using a 12 MHz array transducer, four images in each TMJ (160 images) were acquired. Each image was analysed with regard to five different aspects (condylar erosion, thickness of the condylar disc, synovial thickness, joint effusion and enlargement of the intra-articular space). Diagnosis of JIA was ensured for every child and involvement of the TMJ was proven by MRI. Overall 287 changes (35.9%) were detected by using high-resolution ultrasonography. On 124 images (77.5%) condylar erosions were diagnosed; on 55 images (34.4%) synovial thickness was abnormal; on 48 images (30%) we could see higher thickness of the condylar disc; on 40 images (25%) irregularities of the bony surface were detected; and on 20 images (12.5%) we found joint effusion. High-resolution ultrasonography could be a sufficient diagnostic method, especially for the detection of condylar involvement in children with JIA, even if not all parts of the TMJ are visible for ultrasonography. High-resolution ultrasonography is a valuable tool in particular situations: (i) when MRI examination is not available; (ii) when children fear MRI examination; (iii) in more advanced stages of JIA; and (iv) for monitoring the progression of TMJ involvement and response of therapy.


Trends in pediatric tuberculosis diagnosis utilizing xpert Mycobacterium tuberculosis/Rifampicin in a poor-resource, high-burden region: A retrospective, multicenter study.
The burden of tuberculosis (TB) in Nigeria remains high, and diagnosis in children, a challenge. We aimed to document yield from Xpert Mycobacterium tuberculosis/rifampicin (MTB/RIF) as a mode of diagnosis for children and the variables associated with a positive result. This was a retrospective review of TB treatment cards of children aged 0-15 years managed from January 2017 to December 2021 across six public tertiary institutions in Nigeria. The data obtained were analyzed using the descriptive and inferential statistics. Statistical significance was set at P < 0.05. Of 1489 children commenced on TB treatment, 1463 (97.9%) had sufficient data for analysis the median age of study participants was 60 months (interquartile range [IQR]: 24, 120), and 814 (55.6%) were males. Xpert MTB/RIF test was performed in 862 (59%) participants and MTB was detected in 171 (19.8%) participants, of which 6.4% (11/171) had RIF resistance reported. The use of Xpert MTB/RIF rose from 56.5% in 2017 to 64% in 2020 but fell to 60.9% in 2021. We found that older age (> 10 years), the presence of pulmonary TB (PTB), and a negative human immunodeficiency virus (HIV) status were associated with positive Xpert MTB/RIF tests (P = 0.002, 0.001, and 0.012, respectively). The utilization of Xpert MTB/RIF in children increased in the years before the COVID-19 pandemic. Factors associated with MTB detection by Xpert MTB/RIF include older age, the presence of PTB, and a negative HIV status. Clinical and radiological evaluation continues to play vital roles in the diagnosis of childhood TB in Nigeria.


Transverse Maxillary Deficiency Predicts Increased Upper Airway Collapsibility during Drug-Induced Sleep Endoscopy.
To examine the relationship between craniofacial skeletal anatomy and objective measures of pharyngeal collapse obtained during drug-induced sleep endoscopy. We hypothesized that transverse maxillary deficiency and an increased pharyngeal length will be associated with higher levels of pharyngeal collapsibility. Cross-sectional analysis in a prospective cohort. University Hospital. A cross-sectional analysis was conducted in a cohort of consecutive patients from the positive airway pressure (PAP) alternatives clinic who underwent computed tomography (CT) analysis and drug-induced sleep endoscopy for characterization of upper airway collapsibility. PAP titration was used to determine pharyngeal critical pressure (PCRIT ) and pharyngeal opening pressure (PhOP). CT metrics included: Transverse maxillary dimensions (interpremolar and intermolar distances) and pharyngeal length (posterior nasal spine to hyoid distance). The cohort (n = 103) of severe obstructive sleep apnea (Apnea and Hipopnea Index 32.1 ± 21.3 events/h) was predominantly male (71.8%), Caucasian (81.6%), middle-aged (54.4 ± 14.3 years), and obese (body mass index [BMI] = 30.0 ± 4.9 kg/m2 ). Reduced transverse maxillary dimensions were associated with higher PCRIT (intermolar distance: β [95% confidence interval, CI] = -.25 [-0.14, -0.36] cmH2 O/mm; p = .03) and PhOP (Interpremolar distance: β = -.25 [-0.14, -0.36] cmH2 O/mm; p = .02). Longer pharyngeal length was also associated with higher PCRIT (β = .11 [0.08, 0.14] cmH2 O/mm, p = .04) and PhOP (β [95% CI] = .06 [0.03, 0.09] cmH2 O/mm, p = .04). These associations persisted after adjustments for sex, age, height, and BMI. Our results further the concept that skeletal restriction in the transverse dimension and hyoid descent are associated with elevations in pharyngeal collapsibility during sleep, suggesting a role of transverse deficiency in the pathogenesis of airway obstruction.


Soft Listeria: actin-based propulsion of liquid drops.
We study the motion of oil drops propelled by actin polymerization in cell extracts. Drops deform and acquire a pearlike shape under the action of the elastic stresses exerted by the actin comet, a tail of cross-linked actin filaments. We solve this free boundary problem and calculate the drop shape taking into account the elasticity of the actin gel and the variation of the polymerization velocity with normal stress. The pressure balance on the liquid drop imposes a zero propulsive force if gradients in surface tension or internal pressure are not taken into account. Quantitative parameters of actin polymerization are obtained by fitting theory to experiment.


Identification and promoter analysis of PERV LTR subtypes in NIH-miniature pig.
Porcine endogenous retroviruses (PERVs) are integrated into the genomes of all pigs. Since some PERVs can also infect human cells, they represent a potential risk for xenotransplantation involving pig cells or organs. The long terminal repeat (LTR) elements of PERVs show promoter activity that can affect human functional genes; therefore, we examined these elements in this study. We detected several expressed LTRs in the NIH-miniature pig liver, among which we identified 9 different subtypes. When these LTRs were compared, distinct structures that contained several insertion and deletion (INDEL) events and tandem repeats were identified in the U3 region. The transcriptional activity of the 9 LTR subtypes was analyzed in the PK15 porcine cell line and in the HepG2 and Hep3B human liver cell lines, and transcriptional regulation was found to be different in the 3 cell lines. The D LTR subtype was found to have stronger promoter activity than all other types in 4 different human cell lines (HepG2, Hep3B, U251, and 293). Using computational approaches, the D type was shown to contain 4 transcription factor-binding sites distinct from those in the U3 regions of the other subtypes. Therefore, deletion mutants were constructed and examined by a transient transfection luciferase assay. The results of this analysis indicated that the binding site for the Hand1:E47 transcription factor might play a positive role in the transcriptional regulation of PERV LTR subtype D in human liver cell lines.


Cytoplasmic estradiol binding sites in testis of fertile and infertile men.
Free cytoplasmic estradiol receptor was determined in testicular biopsies from six adults showing various primary testicular disorders, and in testicular tissue obtained at autopsy from 18 males of various ages. Estradiol receptors were found in all cases examined. Receptor concentration varied during testicular maturation and from one patient to another. The presence of the receptor at an early stage of development and the changes observed in its concentration during testicular maturation and dysfunction support the idea that estradiol may play, through its receptor interaction, an important role in the regulation of testicular steroidogenesis during postnatal human development.


The use of categorical regression in the assessment of the risks of nutrient deficiency and excess
Exposure-response assessment methods have shifted towards more quantitative approaches, with health risk assessors exploring more statistically driven techniques. These assessments, however, usually rely on one critical health effect from a single key study. Categorical regression addresses this limitation by incorporating data from all relevant studies – including human, animal, and mechanistic studies – thereby including a broad spectrum of health endpoints and exposure levels for exposure-response analysis in an objective manner. Categorical regression requires the establishment of ordered response categories corresponding to increasingly severe adverse health outcomes and the availability of a comprehensive database that summarizes all data on different outcomes from different studies, including the exposure or dose at which these out-comes are observed and their severity. It has found application in the risk assessment of essential nutrients and trace metals. Since adverse effects may arise from either deficient or excess exposure, the exposure-response curve is U-shaped, which provides a basis for determining optimal intake levels that minimize the joint risks of deficiency and excess. This article provides an overview of the use of categorical regression fit exposure-response models incorporating data from multiple evidence streams. An extension of categorical regression that permits the simultaneous analysis of excess and deficiency toxicity data is presented and applied to comprehensive databases on copper and manganese. Future applications of cat-egorical regression will be able to make greater use of diverse data sets developed using new approach methodologies, which can be expected to provide valuable information on toxic responses of varying severity.


Is FCH PET able to identify foci of infection superiorly to FDG PET?
We report a case of a brain abscess identified on fluorine-18 choline (FCH) positron emission tomography (PET) scan, which was not identified on fluorodeoxyglucose (FDG) PET scan. To our knowledge, there are no previous case reports of incidental brain abscess identified by FCH PET imaging. A 51-year-old man, with liver cirrhosis complicated by hepatocellular carcinoma (HCC) was enrolled in a research trial comparing HCC detection in FCH PET versus FDG PET. During the course of the trial, he underwent radiofrequency ablation (RFA) for HCC. A repeat FCH PET scan post-RFA incidentally revealed a 2.5 cm lesion with avid uptake in the left occipital area of the brain. The patient was asymptomatic. MRI suggested this was an abscess. A craniotomy and drainage was performed, with culture of Streptococcus intermedius (Smilleri group) from the thick-walled collection, a causative organism for previous episode of pneumonia. He successfully completed a 6 week course of antibiotics.


The Forgotten Hemodynamic (PCO2 Gap) in Severe Sepsis.
Central venous-arterial carbon dioxide difference (PCO2 gap) can be a marker of cardiac output adequacy in global metabolic conditions that are less affected by the impairment of oxygen extraction capacity. We investigated the relation between the PCO2 gap, serum lactate, and cardiac index (CI) and prognostic value on admission in relation to fluid administration in the early phases of resuscitation in sepsis. We also investigated the chest ultrasound pattern A or B. We performed a prospective observational study and recruited 28 patients with severe sepsis and septic shock in a mixed ICU. We determined central venous PO2, PCO2, PCO2 gap, lactate, and CI at 0 and 6 hours after critical care unit (CCU) admission. The population was divided into two groups based on the PCO2 gap (cutoff value 0.8 kPa). The CI was significantly lower in the high PCO2 gap group (P=0.001). The high PCO2 gap group, on admission, required more administered fluid and vasopressors (P=0.01 and P=0.009, respectively). There was also a significant difference between the two groups for low mean pressure (P=0.01), central venous O2 (P=0.01), and lactate level (P=0.003). The mean arterial pressure was lower in the high PCO2 gap group, and the lactate level was higher, indicating global hypoperfusion. The hospital mortality rate for all patients was 24.5% (7/28). The in-hospital mortality rate was 20% (2/12) for the low gap group and 30% (5/16) for the high gap group; the odds ratio was 1.6 (95% CI 0.5-5.5; P=0.53). Patients with a persistent or rising PCO2 gap larger than 0.8 kPa at T = 6 and 12 hours had a higher mortality change (n = 6; in-hospital mortality was 21.4%) than patients with a PCO2 gap of less than 0.8 kPa at T = 6 (n = 1; in-hospital mortality was 3%); this odds ratio was 5.3 (95% CI 0.9-30.7; P=0.08). The PCO2 gap had no relation with the chest ultrasound pattern. The PCO2 gap is an important hemodynamic variable in the management of sepsis-induced circulatory failure. The PCO2 gap can be a marker of the adequacy of the cardiac output status in severe sepsis. A high PCO2 gap value (>0.8 kPa) can identify situations in which increasing CO can be attempted with fluid resuscitation in severe sepsis. The PCO2 gap carries an important prognostic value in severe sepsis.


Extended Gibbs Free Energy and Laplace Pressure of Ordered Hexagonal Close-Packed Spherical Particles: A Wettability Study.
The wetting property of spherical particles in a hexagonal close-packed (HCP) ordering from extended Gibbs free energy (GFE) and Laplace pressure view points is studied. A formalism is proposed to predict the contact angle (θ) of a droplet on the HCP films and penetration angle (α) of the liquid on the spherical particles. Then, the extended Laplace pressure for the layered HCP ordering is calculated and a correlation between the wetting angle, sign of pressure, and pressure gradient is achieved. Our results show that the sign and the slope of pressure are important criteria for determining the wettability state and it is found that the contact angle is independent of the particle radius, as supported by various experimental reports. The pressure gradient for the HCP films with Young contact angle higher than (lower than) a critical contact angle, 135° (45°), is positive (negative), indicating the superhydrophobicity (superhydrophilicity) state of the surface. To validate the proposed formulation, theoretical calculations are compared with the reported experimental measurements, showing a good agreement.


Mpox (Monkeypox) Infection During Pregnancy.
An mpox (formerly "monkeypox") outbreak began in 2022, leading to infection in special populations, including pregnant individuals. We present a case of an individual who presented with a labial ulcer and subsequent papular rash at 31 weeks of gestation. She was diagnosed with mpox infection and was treated with tecovirimat. She had an uncomplicated induction of labor at 39 2/7 weeks of gestation and delivered a healthy neonate. The neonate had a positive immunoglobulin G test result for orthopoxvirus but did not have skin lesions or positive molecular test results suggestive of infection. Transplacental transmission of mpox is possible, but, in this case, the neonate did not have clinical findings suggestive of active or antenatal mpox infection. Treatment with tecovirimat in gestational cases of mpox may be beneficial.


Insights into the structure and function of GABA-benzodiazepine receptors: ion channels and psychiatry.
As a result of combined biophysical and molecular biological studies, important insights into the structure and function of gamma-aminobutyric acid (GABA) receptors have been achieved. These insights have helped to define the role of GABA receptors in synaptic inhibition and the ion channel mechanisms by which different neuropsychiatric drugs work. The authors' goal is to describe the actions of GABA as a neurotransmitter and discuss the modulation of receptor function by different drugs. The authors focus on more recent studies of the structure and physiology of the receptor-ion channel complex and the relevance of these studies to psychiatry. The CNS effects of benzodiazepines, barbiturates, and alcohol have been linked to the GABA-chloride channel receptor complex. Multiple subunits of this complex have been cloned, sequenced, and expressed in heterologous systems. The results of cloning studies, coupled with membrane biophysics, have provided important insights into the structure and function of GABA receptors and their modulation by psychopharmacological agents. Future understanding of disease states, drug effects, and therapeutic successes and failures may be expressed in terms of differences in the structure and function of specific receptors and their associated ion channels. Furthermore, the ability to describe the molecular function of receptor subtypes offers the ability to tailor drug specificity by developing agents directed against a given receptor subtype. The current GABA studies also have important implications for the understanding of how neurotransmitter systems may be involved in illness.


Hypoplastic Left Heart Syndrome: A Review.
Hypoplastic left heart syndrome is a rare and poorly understood congenital disorder featuring a univentricular myocardium, invariably resulting in early childhood death if left untreated. The process to palliate this congenital cardiomyopathy is of high complexity and may include invasive interventions in the first week of life. The preferred treatment strategy involves a staged correction with 3 surgical procedures at different points in time. The Norwood procedure is usually performed within the first weeks of life and aims to increase systemic circulation and relieve pulmonary vascular pressure. This procedure is followed by the bidirectional Glenn and the Fontan procedures in later life, which offer to decrease stress in the ventricular chamber. The prognosis of children with this disease has greatly improved in the past decades; however, it is still largely driven by multiple modifiable and nonmodifiable variables. Novel and clever alternatives have been proposed to improve the survival and neurodevelopment of these patients, although they are not used as standard of care in all centers. The neurodevelopmental outcomes among these patients have received particular attention in the last decade in light to improve this very limiting associated comorbidity that compromises quality of life.


The value of electronic health records in solo or small group practices.
We conducted case studies of fourteen solo or small-group primary care practices using electronic health record (EHR) software from two vendors. Initial EHR costs averaged $44,000 per full-time-equivalent (FTE) provider, and ongoing costs averaged $8,500 per provider per year. The average practice paid for its EHR costs in 2.5 years and profited handsomely after that; however, some practices could not cover costs quickly, most providers spent more time at work initially, and some practices experienced substantial financial risks. Policies should be designed to provide incentives and support services to help practices improve the quality of their care by using EHRs.


The effect of the NMDA receptor antagonist MK-801 on the acquisition and extinction of learned fear in the developing rat.
Recent findings reveal qualitative developmental differences in extinction of learned fear. The present study explored potential developmental differences in the role of NMDA in acquisition and extinction. Rats were injected with MK-801 prior to fear conditioning or extinction training. Acquisition was found to be NMDA dependent in both age groups, whereas extinction was found to be NMDA dependent in 23-day-old rats, but NMDA independent in 16-day-old rats. These results illustrate another fundamental developmental difference in extinction as well as a dissociation in the role of NMDA in the acquisition and extinction of fear early in development.


Application of characteristic fragment filtering with ultra high performance liquid chromatography coupled with high-resolution mass spectrometry for comprehensive identification of components in Schisandrae chinensis Fructus.
An integrated strategy of characteristic fragment filtering combined with target database screening based on ultra-high-performance liquid chromatography coupled with high-resolution mass spectrometry was proposed for comprehensive profiling of components in Schisandrae chinensis Fructus. The strategy consisted of following five steps: (1) Representative standards were analyzed by ultra high performance liquid chromatography coupled with linear ion trap-Orbitrap mass spectrometer for characteristic fragments and fragmentation rules of each structure type. (2) The raw data of 70% methanol extract was collected by ultra high performance liquid chromatography quadrupole time-of-flight tandem mass spectrometry. (3) The chemical components database that consisted of names, chemical formulas and structures of potential components in Schisandrae chinensis Fructus was established by summarizing previous literature to screen the collected liquid chromatography with mass spectrometry data and obtain matched compounds. (4) Characteristic fragments, literature, and reference standards were used to verify the matches. (5) Characteristic fragment filtering combined with online database querying was used to deduce potential new compounds. As a result, a total of 94 compounds were identified or characterized and 16 of them were potential new compounds. The study provided a reference for comprehensive characterization of ingredients in herbal medicine and formed the foundation for pharmacodynamic study of Schisandrae chinensis Fructus.


Association of partial pressure of carbon dioxide in expired gas and arterial blood at three different ventilation states in apneic chickens (Gallus domesticus) during air sac insufflation anesthesia.
To test whether partial pressure of CO2 in expired gas (PĒCO2) predicts the partial pressure of CO2 in arterial blood (PaCO2) in apneic chickens during air sac insufflation anesthesia at three different ventilation states. To determine the PĒCO2 at which apnea occurs during air sac insufflation anesthesia. Randomized cross-over study. Twenty-three healthy male white leghorn chickens. Chickens were anesthetized via mask with isoflurane in oxygen and an air sac cannula was placed in the right abdominal air sac. Delivery of isoflurane in O2 was transferred from the mask to the air sac cannula. The birds were maintained at a surgical plane of anesthesia and apnea was induced by adjusting gas flow; the PĒCO2 at apnea was recorded. The birds were then paralyzed and gas flow was adjusted to achieve three different PĒCO2 s in random order: 43 mmHg (5.6 kPa) [hypoventilation]; 33 mmHg (4.3 kPa) [normoventilation]; and 23 mmHg (3.0 kPa) [hyperventilation]. After maintaining the target expired isoflurane concentration (EIso; 1.85 or 1.90%) and PĒCO2 for 15 minutes, arterial blood gas analysis was performed to determine the PaCO2 . The chickens were euthanized at the end of the experiment. Based on Bland-Altman comparisons, PĒCO2 was not strongly associated with PaCO2 during the three ventilation states. The PĒCO2 at which apnea occurred varied {median (minimum, maximum): 35 (30, 48) mmHg [4.6 (3.9, 6.2) kPa]}. Measured PĒCO2 cannot be used in a simple linear fashion to predict PaCO2 in birds during air sac insufflation anesthesia. The PĒCO2 at which apnea occurs during air sac insufflation anesthesia is not predictable. Arterial blood gases should be used to monitor CO2 during air sac insufflation anesthesia to verify appropriate patient ventilation.


Cranial CT for diagnosis of intracranial complications in adult and pediatric patients during ECMO: Clinical benefits in diagnosis and treatment.
To evaluate the clinical utility of cranial computed tomography (CT) in pediatric and adult patients during ongoing extracorporeal membrane oxygenation (ECMO) treatment from acute respiratory failure and to assess the frequency of intracranial hemorrhage (ICH) and infarction during the treatment. The medical records of 123 consecutive patients, 54 children (ages 3 months-17 years) and 69 adults (ages 18-62 years), treated with ECMO over a 10-year period were searched for cranial CT performed during ECMO. Indications for CT, CT findings, impact on clinical management, and patient outcome were noted. In addition, all CT scans were reviewed for the frequency of ICH or infarction. Seventy-eight patients had cranial CT while on ECMO. ICH or cerebral infarction were detected in 45 (37%) of the 123 patients. Eighteen patients (15%) had focal hemorrhage, 11 (9%) focal infarction, and 16 (13%) general brain edema. In 16 of the 45 patients, the CT findings were decisive to withdraw the ECMO treatment. Five patients were weaned from ECMO, and in four patients the findings motivated cranial surgery during ECMO. In the remaining 20 patients with less extended intracranial pathology, the ECMO treatment was continued with high survival. Cranial CT has an important role during ECMO treatment to reveal or exclude severe intracranial complications where ECMO treatment should be discontinued. Less severe complications have a favorable prognosis with continued treatment. Our study suggests an underreporting of intracranial complications in adults and pediatric patients on ECMO because of low utilization of neuroimaging.


In Vitro Synthesis of Connectin in an Extract of Chicken Embryo Muscles.
Incorporation of 35S-methionine into connectin during protein synthesis in an extract from chicken embryo muscles was detected by autoradiography after immunoprecipitation with anti-connectin antibodies followed by SDS gel electrophoresis. Any radioactivity of peptides smaller than connectin but larger than actin was not detected with anti-connectin antibodies reacted samples. On the other hand, incorporation of radioactive methionine into nebulin was not observed.


Rasmussen and the boundaries of empirical evaluation.
In this special issue, many of the papers focus on Rasmussen's analytic contributions to the understanding of work in complex sociotechnical systems. Work is analysed for the purpose of developing new designs that can improve the nature of that work. The evaluation of such designs was a key part of Rasmussen's program, yet he was often sceptical of the claims made for the generalizability of empirical studies. To tackle this problem, he extended his work analysis framework to provide a way of thinking about empirical evaluation. As authors of this paper, we come from two different backgrounds-systems engineering in the case of Burns, and engineering psychology in the case of Sanderson-and over the decades of our respective research programs, we have both performed many empirical investigations: field investigations, simulation studies, and behavioural laboratory experiments. Rasmussen's scepticism-and his writings on the issue-have stimulated and shaped our own research. In this brief paper we present our interpretation of Rasmussen's perspective, we provide examples how our research sits within Rasmussen's framework of constraints defining boundary conditions for experiments, and we draw conclusions for the future.


Acute obstructive hydrocephalus due to an unruptured basilar bifurcation aneurysm associated with bilateral internal carotid occlusion--a case report.
A patient with a higherly positioned and large basilar bifurcation aneurysm associated with bilateral internal carotid occlusion was described. A 63 year-old man was admitted to Yokokura Hospital with disturbed consciousness and mild left hemiparesis. On admission, an initial plain CT-scan showed an acute obstructive hydrocephalus with periventricular lucency caused by an abnormal lesion in the anterior part of the third ventricle. An emergency ventriculo-peritoneal shunt was inserted. The postoperative course was uneventful. The patient regained his consciousness with normal motor function by the following day. Postoperative cerebral angiography disclosed a large basilar bifurcation aneurysm at a higher position, 19 mm from the dorsum sellae. Bilateral internal carotid occlusion had occurred, but rich collateral blood supply from the vertebro-basilar artery via the bilaterally enlarged posterior communicating arteries to the anterior circulation was observed. This rich collateral blood supply to the vertebrobasilar artery might be responsible for the development of the aneurysmal formation due to the increased hemodynamic stress.


Specific PCR detection of Fusarium oxysporum f. sp. raphani: a causal agent of Fusarium wilt on radish plants.
Fusarium oxysporum, a causal agent of Fusarium wilt, is one of the most important fungal pathogens worldwide, and detection of F. oxysporum DNA at the forma specialis level is crucial for disease diagnosis and control. In this study, two novel F. oxysporum f. sp. raphani (For)-specific primer sets were designed, FOR1-F/FOR1-R and FOR2-F/FOR2-R, to target FOQG_17868 and FOQG_17869 ORFs, respectively, which were selected based on the genome comparison of other formae speciales of F. oxysporum including conglutinans, cubense, lycopersici, melonis, and pisi. The primer sets FOR1-F/FOR1-R and FOR2-F/FOR2-R that amplified a 610- and 425-bp DNA fragment, respectively, were specific to For isolates which was confirmed using a total of 40 F. oxysporum isolates. From infected plants, the FOR2-F/FOR2-R primer set directly detected the DNA fragment of For isolates even when the radish plants were collected in their early stage of disease development. Although the loci targeted by the For-specific primer sets were not likely involved in the pathogenesis, the primer set FOR2-F/FOR2-R is available for the determination of pathogenicity of radish-infecting F. oxysporum isolates. This study is the first report providing novel primer sets to detect F. oxysporum f. sp. raphani. Because plant pathogenic Fusarium oxysporum has been classified into special forms based on its host specificity, identification of F. oxysporum usually requires a pathogenicity assay as well as knowledge of the morphological characteristics. For rapid and reliable diagnosis, this study provides PCR primer sets that specifically detect Fusarium oxysporum f. sp. raphani (For) which is a devastating pathogen of radish plants. Because one of the primer sets directly detected the DNA fragment of For isolates from infected plants, the specific PCR method demonstrated in this study will provide a foundation for integrated disease management practices in commodity crops.


Molecular design, synthesis and cell based HCV replicon assay of novel benzoxazole derivatives.
Hepatitis C virus inhibitors based on benzoxazole scaffold were designed based on molecular modeling simulation study including docking into the NS5B polymerase active site. Several compounds showed significant high simulation docking scores relative to the assigned benzimidazole lead compound. The designed compounds were synthesized, structurally elucidated and their antiviral activity was evaluated through cell-based replicon in cultured Huh 5-2 cells. A number of the synthesized compounds showed significant inhibitory activity ranging from (52.2% inhibition up to 98% at<50 µg/mL). N-Benzyl-2-phenylbenzo[1,3]oxazole-5-carboxamide (8b) and N-Phenethyl-2-phenylbenzo[1,3] oxazole-5-carboxamide (8c) demonstrated genuine HCV inhibitory activity with EC50 values of 41.6 and 24.5 µg/mL respectively.


Energetics of hydrogen bonds in peptides.
Hydrogen bonds and their relative strengths in proteins are of importance for understanding protein structure and protein motions. The correct strength of such hydrogen bonds is experimentally known to vary greatly from approximately 5-6 kcal/mol for the isolated bond to approximately 0.5-1.5 kcal/mol for proteins in solution. To estimate these bond strengths, here we suggest a direct novel kinetic procedure. This analyzes the timing of the trajectories of a properly averaged dynamic ensemble. Here we study the observed rupture of these hydrogen bonds in a molecular dynamics calculation as an alternative to using thermodynamics. This calculation is performed for the isolated system and contrasted with results for water. We find that the activation energy for the rupture of the hydrogen bond in a beta-sheet under isolated conditions is 4.76 kcal/mol, and the activation energy is 1.58 kcal/mol for the same beta-sheet in water. These results are in excellent agreement with observations and suggest that such a direct calculation can be useful for the prediction of hydrogen bond strengths in various environments of interest.


Mislocalization of membrane proteins associated with multidrug resistance in cisplatin-resistant cancer cell lines.
The accumulation of [(14)C]carboplatin and [(3)H]methotrexate is reduced in single-step KB epidermoid adenocarcinoma (KB-CP) cells, which are cross-resistant to carboplatin, methotrexate, and sodium arsenite. In these KB-CP cells, multidrug resistance is accompanied by mislocalization of multidrug resistance associated protein (MRP) 1 and other membrane proteins such as folate-binding protein. MRP1 was not decreased in amount in single-step variants but accumulates in a cytoplasmic fraction, and its apparent molecular weight was altered probably because of reduced glycosylation in resistant cells. This low-density compartment was partially labeled with antibodies to lectin-GSII (a Golgi marker) and Bip/GRP78 (an endoplasmic reticulum marker). Pulse-chase labeling of MRP1 with (35)S-methionine and (35)S-cysteine and pulse-chase biotinylation of cell surface MRP1 suggests that membrane protein mislocalization is caused mainly by a defect of plasma membrane protein recycling, manifested also as a defect in acidification of lysosomes. The reduced accumulation of cytotoxic compounds in the KB-CP cells is presumed to result from the failure of carrier proteins and/or transporters to localize to the plasma membrane.


Dinitramidoborates: A Fascinating Case of Competing Oxygen and Nitrogen Donors and Tautomerism.
Reactions of the BH4- anion with equimolar amounts of HN(NO2 )2 or of BH3 ⋅THF with K[N(NO2 )2 ]- produced a mono-substituted [BH3 N(NO2 )2 ]- anion, which contains a B-N connected dinitramido ligand. The reaction of BH4- with two equivalents of HN(NO2 )2 afforded the di-substituted borate anion consisting of two isomers, one with both nitramido ligands attached to B through N and the other one with one ligand attached through N and the other one through O. The disubstituted dinitramidoborates are marginally stable under ambient conditions, and the isomer with two N-connected ligands was characterized by its crystal structure. A tri-substituted borate was tentatively identified by NMR in the reaction of BH4- with a large excess of HN(NO2 )2 . All of the anions are highly energetic. Theoretical calculations show that the energy differences between the B-N and B-O tautomers are small, explaining the formation of both.


Current Status of Marine-Derived Compounds as Warheads in Anti-Tumor Drug Candidates.
In this review, we have attempted to describe all of the antibody-drug conjugates using a marine-derived compound as the "warhead", that are currently in clinical trials as listed in the current version of the NIH clinical trials database (clinicaltrials.gov). In searching this database, we used the beta-test version currently available, as it permitted more specific search parameters, since the regular version did not always find trials that had been completed in the past with some agents. We also added small discussion sections on candidates that are still at the preclinical stage, including a derivative of diazonamide that has an unusual interaction with tubulin (DZ-23840), which may also be a potential warhead in the future.


Genetic analysis of the VP4/VP2 coding region in human rhinovirus species C in patients with acute respiratory infection in Japan.
Detailed genetic analysis was carried out of the VP4/VP2 coding region in human rhinovirus species C (HRV-C) strains detected in patients with acute respiratory infection in Japan. Phylogenetic trees were constructed by the neighbour-joining (NJ) and maximum-likelihood (ML) methods. The NJ phylogenetic tree assigned 11 genotypes to the present strains, whilst the ML tree showed that the strains diversified sometime in the early 1870 s. Moreover, the pairwise distance among the present strains was relatively long, and the rate of molecular evolution of the coding region was rapid (3.07 × 10(-3) substitutions per site per year). The results suggest that the present HRV-C strains have a wide genetic divergence and a unique evolutionary timescale.


Panton-Valentine leukocidin positive sequence type 80 methicillin-resistant Staphylococcus aureus carrying a staphylococcal cassette chromosome mec type IVc is dominant in neonates and children in an Algiers hospital.
Methicillin-resistant Staphylococcus aureus (MRSA) is a major antimicrobial drug-resistant pathogen causing serious infections. It was first detected in healthcare settings, but in recent years it has also become disseminated in the community. Children and young adults are most susceptible to infection by community-acquired (CA) MRSA strains. In this study 25 MRSA isolates implicated in infections of neonates and children admitted to an Algiers hospital during an 18 month period were characterized by molecular methods including staphylococcal cassette chromosome (SCC) mec typing, PCR amplification of pvl genes, pulsed field gel electrophoresis (PFGE) and multilocus sequence typing (MLST). Fifteen out of 25 isolates were from hospital-acquired infections. Twenty-four isolates carried SCCmec type IVc and belonged to the sequence type (ST) 80, one isolate carried SCCmec type II and was ST 39. Twenty-two out of 24 ST80-MRSA-IVc isolates carried pvl genes. Our results suggest that the Panton-Valentine leukocidin positive ST80- MRSA-IVc is the dominant MRSA clone causing disease in neonates and children in Algiers.


In the Zzz zone: the effects of Z-drugs on human performance and driving.
Despite their improved pharmacokinetic profile, the Z-drugs, zolpidem, zopiclone, and zaleplon, have a spectrum of adverse effects comparable to benzodiazepines. This review focuses on the impairment from Z-drugs on cognition, behavior, psychomotor performance, and driving ability. Z-drugs are short-acting GABA agonists that reduce sleep latency without disturbing sleep architecture. Bizarre behavioral effects have prompted warnings on the prescription, dispensation, and use of Z-drugs. Psychomotor impairment, falls, and hip fractures are more likely to occur with Z-drugs that have longer half-lives, that are taken at higher-than-recommended doses and when mixed with other psychoactive substances including alcohol. Zopiclone and higher doses of zolpidem are more likely to cause anterograde amnesia than zaleplon. Z-drugs, especially zolpidem, are associated with complex behaviors such as sleepwalking, sleep-driving, and hallucinations. Patients taking zopiclone and zolpidem have an increased risk of motor vehicle collisions, over double that of unexposed drivers. Driving impairment occurs with zopiclone and higher doses of zolpidem but is unlikely to occur after 4 h post-zaleplon administration. The residual effect of Z-drugs on next-day cognitive and psychomotor performance has significant impact on lifestyle, safety, and occupational considerations, including motor vehicle and machine operation. The risk-benefit analysis of Z-drugs in the treatment of insomnia, particularly in the elderly, may not favor treatment due to the increased risks of falls and motor vehicle collisions. Prescribers should warn patients taking Z-drugs of minimum time thresholds before they operate machinery or drive motor vehicles.


Effect of process parameters on catalytic incineration of solvent emissions.
Catalytic oxidation is a feasible and affordable technology for solvent emission abatement. However, finding optimal operation conditions is important, since they are strongly dependent on the application area of VOC incineration. This paper presents the results of the laboratory experiments concerning four most central parameters, that is, effects of concentration, gas hourly space velocity (GHSV), temperature, and moisture on the oxidation of n-butyl acetate. Both fresh and industrially aged commercial Pt/Al(2)O(3) catalysts were tested to determine optimal process conditions and the significance order and level of selected parameters. The effects of these parameters were evaluated by computer-aided statistical experimental design. According to the results, GHSV was the most dominant parameter in the oxidation of n-butyl acetate. Decreasing GHSV and increasing temperature increased the conversion of n-butyl acetate. The interaction effect of GHSV and temperature was more significant than the effect of concentration. Both of these affected the reaction by increasing the conversion of n-butyl acetate. Moisture had only a minor decreasing effect on the conversion, but it also decreased slightly the formation of by products. Ageing did not change the significance order of the above-mentioned parameters, however, the effects of individual parameters increased slightly as a function of ageing.


Microtubules in Candida albicans hyphae drive nuclear dynamics and connect cell cycle progression to morphogenesis.
Candida albicans is an opportunistic fungal pathogen whose virulence is related to its ability to switch between yeast, pseudohyphal, and true-hyphal morphologies. To ask how long-distance nuclear migration occurs in C. albicans hyphae, we identified the fundamental properties of nuclear movements and microtubule dynamics using time-lapse microscopy. In hyphae, nuclei migrate to, and divide across, the presumptive site of septation, which forms 10 to 15 microm distal to the basal cell. The mother nucleus returns to the basal cell, while the daughter nucleus reiterates the process. We used time-lapse microscopy to identify the mechanisms by which C. albicans nuclei move over long distances and are coordinated with hyphal morphology. We followed nuclear migration and spindle dynamics, as well as the time and position of septum specification, defined it as the presumptum, and established a chronology of nuclear, spindle, and morphological events. Analysis of microtubule dynamics revealed that premitotic forward nuclear migration is due to the repetitive sliding of astral microtubules along the cell cortex but that postmitotic forward and reverse nuclear migrations are due primarily to spindle elongation. Free microtubules exhibit cell cycle regulation; they are present during interphase and disappear at the time of spindle assembly. Finally, a growth defect in strains expressing Tub2-green fluorescent protein revealed a connection between hyphal elongation and the nuclear cell cycle that is coordinated by hyphal length and/or volume.