Ataxia telangiectasia: the effects of chemical mutagens and x-rays on sister chromatid exchanges in blood lymphocytes.
It is now possible to examine in detail exchanges between sister chromatids (SCEs) and to attempt to investigate the relationships of such exchanges to aberration formation and DNA-repair mechanisms. The frequency of SCEs is dramatically increased by chemical mutagens and may reflect the level of DNA damage. Lymphocytes from patients with ataxia telangiectasis (AT) show high levels of spontaneous chromosome damage and are hypersentive to ionising radiations and it was of interest to examine the levels of SCE induced in these cells by various mutagens. The frequencies of SCE after treatment with X=rays or three chemical mutagens were equivalent to those in normal cells. The effects of fluorodeoxyuridine and deoxycytidine on SCE frequencies were also tested.


Intravascular Volume Profiles in Patients With Class I and II Systolic Heart Failure: Heterogeneity and Volume Overload Are Common Even in Mild Heart Failure.
Although volume overload is a commonly described clinical feature of advanced heart failure (HF), less is known regarding volume profiles of patients with less severe class I and II HF. Intravascular volume was quantitated by radiolabeled-albumin indicator-dilution technique in clinic outpatients. Forty-six patients (age 61 ± 13years, left ventricular ejection fraction 30 ± 8%) were prospectively evaluated with 28 undergoing repeat evaluations at 1 year. There was no difference in averaged total blood volume (TBV) at baseline between class I (N = 26) and II (N = 20) patients (5.6 ± 1.6vs 6.0 ± 1.3 L, P = .368) and at 1-year of follow-up. However, there was marked heterogeneity in plasma volume (-13% to +69% of normal) and red cell mass (RBCM -31% to +50%) profiles with TBV expansion identified in 46% of the cohort, whereas only 48% had a normal TBV. RBCM deficit (true anemia) was common (39%), but a low hemoglobin concentration was accurate in identifying anemia in only 11% of the cohort. RBCM excess (polycythemia) also was identified in 20% of the cohort. Marked heterogeneity in plasma volume and RBCM volume profiles is present even in mild HF, and identifying volume overload, which was common in early HF, has the potential to help guide therapy in the reduction of HF progression. Intravascular volume as a modifiable risk factor in early HF warrants further study.


Pathological findings in patients with low anterior inferior iliac spine impingement.
Femoroacetabular impingement (FAI) has been well described in recent years as one of the major causes of hip pain potentially leading to acetabular labral tears and cartilage damage, which may in turn lead to the development of early degenerative changes. More recently, extra-articular patterns of impingement such as the anterior inferior iliac spine (AIIS)/subspine hip impingement have gained focus as a cause of hip pain and limitation in terminal hip flexion and internal rotation. The purpose of this study was to evaluate the prevalence of low AIIS in patients undergoing hip arthroscopy and to characterize the concomitant intra-articular lesions. Between November 2011 and April 2013, 100 consecutive patients underwent hip arthroscopy for various diagnoses by a single surgeon. After intra-operative diagnosis of low AIIS was made, a comprehensive review of the patients' records, preoperative radiographs, and intra-operative findings was conducted to document the existence and location of labral and chondral lesions. Twenty-one (21 %) patients had low AIIS. There were 13 males (mean age 38.4 years) and eight females (mean age 35.5 years). Eight patients had pre-operative radiographic evidence of low AIIS. All patients had a labral tear anteriorly, at the level of the AIIS; 17 had chondrolabral disruption and 17 had chondral lesions in zone two (antero-superior); and four patients had lesion in zones two and three. Low AIIS is a common intra-operative finding in hip arthroscopy patients. Characteristic labral and chondral lesions are routinely found in a predictable location that effaces the low AIIS. Level of Evidence-Level IV, Case Series.


Is radiation-induced degranulation of mast cells in salivary glands induced by substance P?
Although DNA is the critical target for the lethal effects of irradiation, the precise mechanisms by which irradiation causes damage in tissues and biological systems is not fully understood. In the present study, the number of mast cells and the expression of the neuropeptide substance P (SP) in salivary glands were examined 10 days after a regimen of irradiation. The irradiation was given as a single dose or 5 consecutive days with daily doses of 7 Gy up to a total dose of 35 Gy. In addition, the number of mast cells and the expression of SP were examined 2 and 24 h after a single dose of 7 Gy. Immunohistochemical staining for 5-hydroxytryptamine (5-HT) and staining with avidin peroxidase and toluidine blue were used to detect mast cells. At examination 2 and 24 h after irradiation treatment, no change in the number of mast cells and the pattern of SP expression was observed. Ten days after irradiation there was a remarkable reduction in the number of mast cells in all the three glands, but there was a marked increase in the number of nerve fibers showing SP-like immunoreactivity in the parenchyme. The results show that early time-dependent alterations in the density of mast cells occur in response to irradiation, and that these changes occur concomitantly with changes in the expression of SP. Since the peripheral nervous system is a main regulator of salivary gland function, it is tempting to speculate that the nervous system interacts with mast cells via SP in modulating irradiation provoked tissue responses in salivary glands.


Yeast associated with spontaneous fermentations of white wines from the "Txakoli de Bizkaia" region (Basque Country, North Spain).
The microbiota of eight spontaneous fermentation of white wine from different grape varieties and different wineries from the "Txakoli de Bizkaia" region (Basque country, North Spain), in 1996 and 1997 campaigns was studied. The yeast population was higher in grapes harvested in 1997, in which late summer and early autumn was warmer and drier. Eight species belonging to five genera were identified in total. The most frequent genera in grapes were Rhodotorula in 1996 and Kloeckera in 1997. Saccharomyces bayanus was the most frequent species during vigorous and final fermentation, and it was occasionally isolated from grapes and must. Only another Saccharomyces spp., i.e., S. kluyvery, was identified in some samples from 1997.


Induction of long-term depression and phosphorylation of the delta2 glutamate receptor by protein kinase C in cerebellar slices.
The phosphorylation of ionotropic glutamate receptors (iGluRs) by protein kinases plays a crucial role in synaptic plasticity. In the cerebellum, protein kinase C (PKC) activation is required for the induction of long-term depression (LTD) at parallel fibre-Purkinje cell synapses. Although delta2 glutamate receptors (GluRdelta2), expressed predominantly in Purkinje cells, are essential for cerebellar LTD, little is known about the mechanism by which GluRdelta2 participates in LTD or its relationship with PKC activation pathways. We found that a PKC activator, phorbol ester, induced postsynaptic LTD in Purkinje cells in mouse cerebellar slice preparations without significantly changing the presynaptic properties. Under this condition, the GluRdelta2 prepared from the cerebellar slices was significantly phosphorylated. Indeed, the C-terminus of the GluRdelta2 fused with glutathione-S-transferase (GST) was directly phosphorylated by purified PKC at a specific serine residue. In addition, two-dimensional phosphopeptide mapping analysis indicated that the major phosphorylation site of the GST-fusion protein containing the C-terminus of GluRdelta2 was identical to that of GluRdelta2 prepared from cerebellar slices. Therefore, GluRdelta2 is phosphorylated by PKC in vitro and by an LTD-inducing stimulus in slice preparations. Because this region of GluRdelta2 is known to associate with certain intracellular molecules, the PKC phosphorylation status of the C-terminus of GluRdelta2 may be involved in new signaling pathways during LTD.


Transplanted Moss Hylocomium splendens as a Bioaccumulator of Trace Elements from Different Categories of Sampling Sites in the Upper Silesia Area (SW Poland): Bulk and Dry Deposition Impact.
Concentrations of Cd, Co, Cr, Cu, Ni, K, Fe, Mn, Pb, V and Zn in transplants of Hylocomium splendens (Hedw.) Schimp. were compared with bulk deposition and dust samples from three different categories of sites: industrial, residential and their surroundings and rural (15 in total). Mosses were transplanted for 90 days to severely polluted areas of Upper Silesia, and samples of precipitation and dust were collected during the same period. Most of the significant correlations between element concentrations in mosses and bulk deposition (Cd, Ni, Pb and Zn) were found for industrial sites. In this study dry deposition carried higher element concentrations than bulk deposition, which may result in the higher passive capture of particulate matter by mosses.


Evaluation of the efficacy of intravenous acetaminophen in the treatment of acute migraine attacks: a double-blind, placebo-controlled parallel group multicenter study.
The efficacy of intravenous acetaminophen (1000mg) in the treatment of acute migraine attacks as an alternative to parenteral application of lysine acetylsalicylate or triptans was investigated, using a multi-center, randomized, double-blind, placebo controlled study design. Migraine diagnosis was made according to the International Headache Society Classification. Sixty patients were included in three headache outpatient centers (Neurology Departments of the Universities of Regensburg, Münster and München). In the acute migraine attack patients were treated intravenously with either 1000mg paracetamol (acetaminophen) or placebo. The primary end point was pain-free after 2h. Secondary efficacy criteria were pain-free after 24h or pain relief after 2hours and after 24hours. With regard to the efficacy criteria, 37% of patients reported pain relief or painfree after two hours, 12 patients after treatment with acetaminophen and 10 patients after treatment with placebo. Out of these, 3 patients in the acetaminophen and 4 patients in the placebo group were painfree. After 24hours 86% of the patients reported pain relief: 24 treated with acetaminophen and 27 treated with placebo. The results indicate, that 1000mg intravenous acetaminophen is not superior to placebo in treating severe acute migraine attacks.


[Diagnostic image (148). A man in coma after a traffic accident. Pneumocephaly].
A 73-year-old man developed extended pneumocephaly due to a skull fracture after a severe traffic accident.


Elution countercurrent distribution.
The single withdrawal technique, here called elution countercurrent distribution, was applied for the first time on aqueous two-phase systems. The modifications necessary for elution countercurrent distribution of a thin-layer countercurrent distribution apparatus are described. The results from a test run with sulfuric acid showed good agreement between the experimental and the theoretical curves for elution countercurrent distribution. Thylakoid membrane vesicles from spinach chloroplasts were subjected to the elution countercurrent distribution. A gradient of NaCl in the eluting upper phase was used to elute the different fractions in order of their affinity for the moving upper phase. Inside-out thylakoid vesicles were resolved into two major and several minor fractions having different chlorophyll a/b ratios. Sonicated inside-out thylacoid vesicles were resolved into at least five different fractions with different chlorophyll a/b ratios. An increased resolution is obtained with elution countercurrent distribution compared to the fundamental process.


Determination of precise gamma-ray emission probabilities for 88Rb.
Precise gamma-ray emission probabilities of 88Rb have been measured by 4pi beta-gamma coincidence using a live-timed two-dimensional data-acquisition system. The absolute emission probabilities of the 898.1, 1836.1 and 2677.9 keV gamma rays were determined from the absolute gamma-ray intensities and the disintegration rates to be 14.68+/-0.13%, 22.73+/-0.15% and 2.123+/-0.021%, respectively. The relative intensities were measured for the weak gamma rays by a gamma-ray spectrometer, and the 88Rb decay scheme was determined from these results.


[Culture of rabbit parotid acinar cells and evaluation of its excretion function in vitro].
To obtain a large number of rabbit parotid acinar cells with excretion function in vitro. Rabbit parotid acinar cells were cultured in the reformed DMEM; The shape and structure of cultured cells were observed with phase contrast microscope; Pan cytokeratin(PCK), alpha-amylase and actin of the cultured parotid acinar cells were examined with immunocytochemical SP technique; the secretion of different generations was evaluated with positive expression status of alpha-amylase. SPSS10.0 software package for windows was used for Student's t test. The acinar cells had the ability of proliferation, they could pass 4 generations and survive for 4 weeks. The specific immunocytochemical staining for PCK and alpha-amylase could be seen in the plasm and (or) membrane of parotid acinar cells, but not for actin. The positive expression of alpha-amylase in the primary generation, generation 1, 2 and 3 was 79.6%, 76%, 47.7% and 2.4%, respectively, which decreased gradually. There was a significant difference between the second generation and two earlier generations(P<0.05). The primary and first generations of parotid acinar cells maintain their characteristics and proliferation in vitro,which is very useful for further experiment.


Platelet interactions in thrombosis.
Patho/physiological platelet aggregate (thrombus) formation is initiated by engagement of platelet surface receptors, glycoprotein (GP)Ib-IX-V and GPVI that bind von Willebrand factor or collagen. Although beneficial in response to vascular injury by preventing blood loss (haemostasis), platelet aggregation in a sclerotic coronary artery or other diseased blood vessel (thrombosis) can cause thrombotic diseases like heart attack and stroke. At the molecular level, ligand interactions with GPIb-IX-V or GPVI trigger signalling responses, including elevation of cytosolic Ca2+, dissociation of calmodulin from their cytoplasmic domains, cytoskeletal actin-filament rearrangements, activation of src-family kinases or PI 3-kinase, and 'inside-out' activation of the integrin, alphaIIbbeta3 (GPIIb-llla), that binds von Willebrand factor or fibrinogen and mediates platelet aggregation. Furthermore, emerging evidence supports a topographical co-association of these receptors of the leucine-rich repeat family (GPIb-IX-V) and immunoglobulin superfamily (GPVI) in an adhesive cluster or 'adhesosome'. This arrangement may underlie common mechanisms of initiating thrombus formation in haemostasis or thrombotic disease.


Characterization of left ventricular mechanical function during arrhythmias by two-dimensional echocardiography. II. Location of the site of onset of premature ventricular systoles.
Two-dimensional echocardiography was applied experimentally in a closed chest dog model with intact pericardium to determine the location, magnitude and extent of contractile response during pacing from discrete ventricular sites. Midventricular short-axis tomographic images obtained during regular sinus rhythm and subsequent premature ventricular beats provided comparative measurements of global and segmental systolic changes of cross-sectional luminal areas and myocardial wall thickness. Computer-assisted standardized analysis of segmental systolic fractional area change and wall thickening was used to map left ventricular contraction during normal rhythm and premature beats of 70% coupling interval, induced alternately from anterior and lateral aspects of the mid-left ventricular short-axis cross-sectional plane. A characteristic pattern consisting of early systolic contraction and wall thickening was followed by paradoxical motion and wall thinning in late systole in segments corresponding to the region of direct electrical stimulation. Statistical analysis of segment by segment function indicated a maximal amount of premature beat contractile derangement at the site of the stimuli. Pacing from a right ventricular wall site in the midventricular plane caused a similar premature beat response at the anterior aspect of the interventricular septum. It is concluded that two-dimensional echographic analysis of segmental ventricular function can identify the location of electrical stimuli, and thus might noninvasively characterize regional patterns of contraction associated with ectopic foci during arrhythmias.


Molecular phylogeny of leader proteinase gene of type A of Foot-and-mouth disease virus from India.
We previously demonstrated the presence of three genotypes (IV, VI and VII) of type A (subtype A22) of Foot-and-mouth disease virus (FMDV) in India based on 1D gene sequence analysis. In the present study, the leader proteinase (L(pro)) gene sequences of 35 type A FMDV field isolates sampled over a period of 24 years (1977-2000) have been analyzed. Maximum-likelihood (ML) phylogenetic analysis revealed four distinct genetic lineages (A-D), indicating high divergence in L gene of type A FMDV. Lineages A and D correspond to the earlier genotypes IV, and VII, respectively. The genotype VI isolates were divided into two separate lineages (B and C) in the tree with high confidence values (96-99%). One isolate (IND 21/90) showed incongruous grouping between the (1D and L) gene-based analyses, which could be due to intergenotypic recombination. The ML molecular clock hypothesis was easily rejected on the data set studied indicating the absence of clock-like evolution in the L gene. ML codon-substitution models identified positive selection in the amino acid site 194 of C-terminal extension of the Lb(pro) with high posterior probability (>99%). The catalytic triad of the L(pro) at C-51, H-148 and D-163 were conserved across all the Indian isolates studied. Finally, amino acid differences between the lineages have been discussed briefly.


Biodegradable mulch films improve yield of winter potatoes through effects on soil properties and nutrients.
Biodegradable mulch films are recognized as a promising substitute of polyethylene (PE) films to alleviate the "white pollution". Biodegradable mulch films with optimum degradation rates increase crop yield even compared to PE films. However, the mechanisms underlying this yield-increasing effect remains elusive. In this study, three biodegradable film treatments (BFM1, BFM2 and BFM3) and one PE film treatment (PFM) were used to evaluate their effects on soil and winter potatoes, and a partial least squares path model (PLS-PM) was constructed to investigate their relationships. The degradation rates of films under different treatments were ranked as BFM3 > BFM2 >BFM1 > PFM, and presented distinctive effects on soil properties and nutrients, structure of soil bacterial community, and yield traits of winter potatoes. The PLS-PM showed that mulch treatments affected potato yield through effects on soil properties (soil water and temperature) and soil nutrients (TOC, DOC, TN and NO3--N). The disintegration of the biodegradable films decreased soil water content and temperature, and reduced the loss of soil nutrients in the topsoil at the later growth stage of winter potatoes compared to PE films. Additionally, the elevated content of soil TN and NO3--N under treatment BFM1 may play a key role in its yield-increasing effect on potatoes compared to treatments PFM and BFM2. Thus, biodegradable mulch films with proper degradation rates regulate soil TN and NO3--N through their effects on soil water and temperature, and subsequently improve the yield of winter potatoes compared to PE mulch films.


Adrenomedullary hyperplasia and phaeochromocytoma. DNA cytophotometric findings in 47 cases.
Fifty adrenalectomy specimens containing normal (n = 3), hyperplastic (n = 4) or neoplastic (n = 43) medullary tissue were subjected to quantitative cytophotometric measurements of DNA content. Differing evaluation schemes were applied for interpretation of DNA distribution patterns. Of the 43 phaeochromocytomas (PCC), 16 were inherited as part of the syndrome of multiple endocrine neoplasia type 2a (MEN 2a). Five of 27 sporadic PCCs followed a malignant course. Three benign and three malignant PCCs lacked endocrine activity. In normal medulla and in adrenomedullary hyperplasia, diploid or euploid DNA distributions were found. In contrast, 87% (33/38) of the benign and all 5 malignant PCCs exhibited non-diploid or aneuploid DNA histograms. No differences in DNA content existed between functioning and non-functioning PCCs or between sporadic and hereditary tumours. In this study, in contrast to earlier communications, DNA cytophotometry did not discriminate between benign and malignant adrenomedullary tumours. In addition, as opposed to the findings in a variety of other endocrine tumours, DNA measurements did not appear to be a useful tool to assess the prognosis of an individual malignant PCC.


Infective endocarditis caused by Capnocytophaga canimorsus; a case report.
Capnocytophaga canimorsus is a gram-negative bacterium and an oral commensal in dogs and cats, but occasionally causes serious infections in humans. Septicemia is one of the most fulminant forms, but diagnosis of C. canimorsus infection is often difficult mainly because of its very slow growth. C. canimorsus infective endocarditis (IE) is rare and is poorly understood. Since quite a few strains produce β-lactamase, antimicrobial susceptibility is pivotal information for adequate treatment. We herein report a case with C. canimorsus IE and the results of drug susceptibility test. A 46-year-old man had a dog bite in his left hand 3 months previously. The patient was referred to our hospital for fever (body temperature > 38 °C), visual disturbance, and dyspnea. Echocardiography showed aortic valve regurgitation and vegetation on the leaflets. IE was diagnosed, and we initially administered cefazolin and gentamycin assuming frequently encountered microorganisms and the patient underwent aortic valve replacement. C. canimorsus was detected in the aortic valve lesion and blood cultures. It was also identified by 16S ribosome DNA sequencing. Ceftriaxone were started and continued because disk diffusion test revealed the isolate was negative for β-lactamase and this case had cerebral symptoms. The patient successfully completed antibiotic treatment following surgery. We diagnosed C. canimorsus sepsis and IE by extended-period blood cultures and 16S ribosome DNA sequencing by polymerase chain reaction, and successfully identified its drug susceptibility.


Surgical management of proboscoid herniae.
The management of a large proboscoid umbilical hernia presents challenging problems to the surgeon. As children and parents are concerned with the appearance of the actual hernia they are also intensely interested in the postsurgical result. Presented is a simple one-stage umbilicoplasty that allows repair of the fascial defect and the management of the redundant skin in such a way as to produce a "scarless" and natural-appearing umbilicus.


Characterization of a thermophilic ATP-dependent DNA ligase from the euryarchaeon Pyrococcus horikoshii.
Archaea encode a DNA ligase composed of a C-terminal catalytic domain typical of ATP-dependent ligases plus an N-terminal domain similar to that found in eukaryotic cellular and poxvirus DNA ligases. All archaeal DNA ligases characterized to date have ATP-dependent adenylyltransferase and nick-joining activities. However, recent reports of dual-specificity ATP/NAD+ ligases in two Thermococcus species and Pyrococcus abyssi and an ATP/ADP ligase in Aeropyrum pernix raise the prospect that certain archaeal enzymes might exemplify an undifferentiated ancestral stage in the evolution of ligase substrate specificity. Here we analyze the biochemical properties of Pyrococcus horikoshii DNA ligase. P. horikoshii ligase catalyzes auto-adenylylation and nick sealing in the presence of a divalent cation and ATP; it is unable to utilize NAD+ or ADP to promote ligation in lieu of ATP. P. horikoshii ligase is thermophilic in vitro, with optimal adenylyltransferase activity at 90 degrees C and nick-joining activity at 70 to 90 degrees C. P. horikoshii ligase resembles the ligases of Methanobacterium thermautotrophicum and Sulfolobus shibatae in its strict specificity for ATP.


Decolorization of anthraquinone dye by Shewanella decolorationis S12.
A new species of genus Shewanella, Shewanella decolorationis S12, from activated sludge of a textile-printing wastewater treatment plant, can decolorize Reactive Brilliant Blue K-GR, one kind of anthraquinone dye, with flocculation first. Although S. decolorationis displayed good growth in an aerobic condition, color removal was the best in an anaerobic condition. For color removal, the most suitable pH values and temperatures were pH 6.0-8.0 and 30-37 degrees C under anaerobic culture. More than 99% of Reactive Brilliant Blue K-GR was removed in color within 15 h at a dye concentration of 50 mg/l. Lactate was the suitable carbon source for the dye decolorization. A metal compound, HgCl(2), had the inhibitory effect on decolorization of Reactive Brilliant Blue K-GR, but a nearly complete decolorization also could be observed at a HgCl(2) concentration of 10 mg/l. The enzyme activities, which mediate the tested dye decolorization, were not significantly affected by preadaptation of the bacterium to the dye.


Cell Composition of Central and Peripheral Lymphoid Organs of Wistar Rats Treated with a Biomedical Cell Product.
We studied the effect of a biomedical cell product (bone marrow multipotent mesenchymal stromal cells and products secreted by these cells in conditioned medium) on subpopulation composition of lymphoid cells of central and peripheral lymphoid organs of Wistar rats under normal conditions. Changes in the subpopulation composition of lymphoid organs depended on the route of administration of biomedical cell product.


Use of multistage models to infer stage affected by carcinogenic exposure: example of lung cancer and cigarette smoking.
Statistical methods based on the Armitage-Doll mathematical model of the carcinogenic process are presented for analyzing epidemiologic case-control studies of cancer. These methods are proposed to provide inferences regarding the stage(s) in the cancer process at which the exposure of interest acts. An example of these methods is given which shows evidence that carcinogens in cigarette smoke appear to affect the transition rates for two separate stages in the development of lung cancer, and the relative magnitudes of these effects are estimated. The data for this analysis came from a European multi-center case-control study of lung cancer. The results of the analysis show that: (1) the relative risk of lung cancer among continuing smokers compared to nonsmokers of the same age decreases as the age started smoking increases, while the rate of smoking stays fixed, a result which indicates a carcinogenic effect on an early stage in the process; and (2) the relative risk among ex-smokers compared to continuing smokers having the same duration and rate of smoking decreases with time since smoking stopped, a result which indicates a carcinogenic effect on a late stage in the process. Both results are shown to be best described by the hypothesis that cigarette smoking affects two stages. The estimated relative magnitudes of cigarettes' carcinogenic effects on the two stages indicate that the largest proportion of the total lifetime lung cancer risk among continuing smokers is due to its late stage effect, and that the proportion of risk due to causes other than smoking varies from 23% among men smoking 1-10 cigarettes per day to 6% among those smoking greater than 30 cigarettes per day. These findings imply that preventive measures directed toward inducing smokers to stop would have a potentially substantial payoff in reducing future lung cancer mortality.


Cypermethrin Impairs Hippocampal Neurogenesis and Cognitive Functions by Altering Neural Fate Decisions in the Rat Brain.
Neurogenesis is a developmental process that involves fine-tuned coordination between self-renewal, proliferation, and differentiation of neural stem cells (NSCs) into neurons. However, early-life assault with environmental toxicants interferes with the regular function of genes, proteins, and other molecules that build brain architecture resulting in attenuated neurogenesis. Cypermethrin is a class II synthetic pyrethroid pesticide extensively used in agriculture, veterinary, and residential applications due to its low mammalian toxicity, high bio-efficacy, and enhanced stability. Despite reports on cypermethrin-mediated behavioral and biochemical alterations, till now, no study implicates whether cypermethrin exposure has any effect on neurogenesis. Therefore, the present study was undertaken to comprehend the effects of cypermethrin treatment on embryonic and adult neurogenesis. We found that cypermethrin exposure led to a considerable decrease in the BrdU/Sox-2+, BrdU/Dcx+, and BrdU/NeuN+ co-labeled cells indicating that cypermethrin treatment decreases NSC proliferation and generation of mature and functional neurons. On the contrary, the generation of BrdU/S100β+ glial cells was increased resulting in neurogliogenesis imbalance in the hippocampus. Further, cypermethrin treatment also led to an increased number of BrdU/cleaved caspase-3+ and Fluoro-Jade B+ cells suggesting an induction of apoptosis in NSCs and increased degeneration of neurons in the hippocampus. Overall, these results explicate that cypermethrin exposure not only reduces the NSC pool but also disturbs the neuron-astrocyte ratio and potentiates neurodegeneration in the hippocampus, leading to cognitive dysfunctions in rats.


Biolayer interferometry provides a robust method for detecting DNA binding small molecules in microbial extracts.
DNA replication is an exceptional point of therapeutic intervention for many cancer types and several small molecules targeting DNA have been developed into clinically used antitumor agents. Many of these molecules are naturally occurring metabolites from plants and microorganisms, such as the widely used chemotherapeutic doxorubicin. While natural product sources contain a vast number of DNA binding small molecules, isolating and identifying these molecules is challenging. Typical screening campaigns utilize time-consuming bioactivity-guided fractionation approaches, which use sequential rounds of cell-based assays to guide the isolation of active compounds. In this study, we explore the use of biolayer interferometry (BLI) as a tool for rapidly screening natural product sources for DNA targeting small molecules. We first verified that BLI robustly detected DNA binding using designed GC- and AT-rich DNA oligonucleotides with known DNA intercalating, groove binding, and covalent binding agents including actinomycin D (1), doxorubicin (2), ethidium bromide (3), propidium iodide (4), Hoechst 33342 (5), and netropsin (6). Although binding varied with the properties of the oligonucleotides, measured binding affinities agreed with previously reported values. We next utilized BLI to screen over 100 bacterial extracts from our microbial library for DNA binding activity and found three highly active extracts. Binding-guided isolation was used to isolate the active principle component from each extract, which were identified as echinomycin (8), actinomycin V (9), and chartreusin (10). This biosensor-based DNA binding screen is a novel, low-cost, easy to use, and sensitive approach for medium-throughput screening of complex chemical libraries. Graphical abstract.


NMR structural studies of the myristoylated N-terminus of ADP ribosylation factor 6 (Arf6).
Arf proteins are guanine nucleotide binding proteins that are implicated in endocytotic pathways and vesicle trafficking. The two widely studied isoforms of Arf proteins (Arf1 and Arf6) have different cellular functions and localizations but similar structures. Arf proteins have an N-terminal helix with a covalently bound myristoyl group. Except structural models, there are no three dimensional structures of the myristoylated N-terminal peptide or the intact myristoylated Arf proteins. However, understanding the role of both the myristoyl group and the N-terminal helix based on the details of their molecular structures is of great interest. In the solution structure of myristoylated N-terminal peptide of Arf6 described here, the myristoyl group folds toward the N-terminus to interact with the hydrophobic residues in particular, the phenyl ring. Also, the structure of the dodecylphosphocholine (DPC) micelle-bound of the peptide together with paramagnetic studies showed that the myristoyl group is inserted into the micelle while residues V4-G10 interact with the surface of the micelle. The structural differences between the unbound and micelle-bound myristoylated N-terminal peptide of Arf6 involves the myristoyl group and the side chains of the hydrophobic residues.


Depressive symptoms in a sample of Afro-Caribbean and Latino immigrant cancer patients: a comparative analysis.
This study aims to describe the depressive symptoms in a sample of African-Caribbean and Latino cancer patients and examine differences in specific symptoms between the two groups. The sample included immigrant Afro-Caribbean (n = 44) and Latino (n = 145) underserved cancer patients recruited from five hospitals in New York City. Participants completed a questionnaire comprised of measures of depression (Patient Health Questionnaire-9), health-related quality of life (EuroQol 5D), sociodemographic, and health-related questions. Results of the comparison of mean scores and percentage of patients meeting the cutoff scores showed that Afro-Caribbean patients reported comparable depressive symptoms to the Latino patients. But, upon closer inspection of specific symptoms and other self-report variables, Latino patients reported more frequently depressed mood, having a history of a depressive disorder, and overall higher psychological distress than Afro-Caribbean patients. Different presentation of symptoms associated with depression is expressed by Afro-Caribbean and Latino cancer patients. Studies analyzing in detail the presentation of psychological responses of different cultural groups with chronic medical conditions are greatly needed.


Long-term physical therapy for neuropathic pain after cervical spinal cord injury and resting state electroencephalography: a case report.
Neuropathic pain after spinal cord injury is difficult to treat, and it is associated with abnormalities in the function of the thalamus-to-cortex neural circuitry. Aerobic exercise provides immediate improvement in neuropathic pain and is associated with abnormal resting electroencephalography (EEG) findings in patients with spinal cord injury. This study aimed to investigate whether physical therapy, including walking, can improve neuropathic pain and EEG peak alpha frequency (PAF) in the long term in a patient with cervical spinal cord injury. A 50-year-old man was admitted with a cervical spinal cord insufficiency injury sustained one week prior. The residual height was C5. Neuropathic pain was observed in the fingers bilaterally. A numerical rating scale (NRS) was evaluated to measure the weekly mean and maximum intensities of pain. Resting EEG was measured, and the PAF was calculated. Each time point was evaluated in 2-week intervals from the time of admission, and the rate of change (Δ) of PAF was calculated based on the initial evaluation. Interventions included 18 weeks of standard physical therapy focusing on gait, with additional intensive gait training (4-10 weeks). The NRS scores for the mean and maximum intensities of pain decreased significantly after 6 weeks, and ΔPAF increased significantly after 4 weeks. Improvement in PAF coincided with the start of intensive gait training. PAF shifts to a high frequency during intensive gait training, suggesting the effectiveness of aerobic exercise. Furthermore, there is a close relationship between PAF, pain, and the quantification of pain changes.


Transfer of peanut allergy from the donor to a lung transplant recipient.
Among solid organs, transfer of peanut allergy from donor to recipient has been implicated after liver transplantation. We report the first case in which such transfer occurred after a lung transplant. A 42-year-old woman with history of sarcoidosis underwent a successful bilateral lung transplant from a donor who died from anaphylactic shock after eating peanut-related food. Seven months later, she ate a peanut butter cookie at a transplant support group meeting. Immediately thereafter, she developed an anaphylactic reaction, but survived with prompt treatment. During subsequent follow-up, she could recall three prior episodes of wheezing and difficulty breathing after eating peanut-related foods. The first episode occurred 4 days after the transplant. Prior to her transplant, she never had problems eating peanuts. Skin-prick testing confirmed peanut sensitization. She avoided peanuts and, although her skin-prick test became negative, she still manifested peanut allergy when formally challenged orally with the food. She was advised to continue abstaining from all peanut-related foods. This case emphasizes the importance of considering donor allergy transfer when caring for all solid-organ transplant recipients in order to avoid a life-threatening event.


Effect of an ultrasound-first clinical decision tool in emergency department patients with suspected nephrolithiasis: A randomized trial.
Previously, we found that the use of ultrasonography for patients with suspected nephrolithiasis resulted in similar outcomes and less radiation exposure vs. CT scan. In this study, we evaluated the implementation of an ultrasound-first clinical decision support (CDS) tool in patients with suspected nephrolithiasis. This randomized trial was conducted at an academic emergency department (ED). We implemented the ultrasound-first CDS tool, deployed when an ED provider placed a CT order for suspected nephrolithiasis. Providers were randomized to receiving the CDS tool vs. usual care. The primary outcome was receipt of CT during the index ED visit. Secondary outcomes included radiation dose and ED revisit. 64 ED Providers and 254 patients with suspected nephrolithiasis were enrolled from January 2019 through Dec 2020. The US-First CDS tool was deployed for 128 patients and was not deployed for 126 patients. 86.7% of patients in the CDS arm received a CT vs. 94.4% in the usual care arm, resulting in an absolute risk difference of -7.7% (-14.8 to -0.6%). Mean radiation dose in the CDS arm was 6.8 mSv (95% CI 5.7-7.9 mSv) vs. 6.1 mSv (95% CI 5.1-7.1 mSv) in the usual care arm. The CDS arm did not result in increased ED revisits, CT scans, or hospitalizations at 7 or 30 days. Implementation of the US-first CDS tool resulted in lower CT use for ED patients with suspected nephrolithiasis. The use of this decision support may improve the evaluation of a common problem in the ED. ClinicalTrials.gov#NCT03461536.


Imaging findings and referral outcomes of rapid assessment stroke clinics.
A rapid assessment stroke clinic (RASC) was established to provide a rapid diagnostic service to individuals with suspected transient cerebral or ocular ischaemia or recovered non-hospitalized strokes. In this report we review imaging findings and clinical outcomes of patients proceeding to the carotid surgery programme. Between October 2000 and December 2002, 1339 people attended the RASC. The findings of head CT and carotid Doppler ultrasound of the 1320 patients who underwent brain and carotid imaging were reviewed, and the number subsequently proceeding to carotid angiography and intervention was reported. CT head scans were normal in 57% of cases; 38% demonstrated ischaemia or infarction; and 3% yielded incidental or other significant findings not related to ischaemia. On screening with carotid Doppler ultrasound, 7.5% showed greater than 50% stenosis on the symptomatic side. A total of 83 patients (6.2%) proceeded to cerebral angiography and 65 (4.8%) underwent carotid endarterectomy or endovascular repair. Rapid-access neurovascular clinics are efficient in selecting patients for carotid intervention, but this is at a cost and the number of potential strokes prevented is small. Alternative management pathways based on immediate medical treatment need to be evaluated.


Shear Wave Elastography in Head and Neck Lymph Node Assessment: Image Quality and Diagnostic Impact Compared with B-Mode and Doppler Ultrasonography.
The aim of this study was to assess the diagnostic performance of shear wave elastography (SWE) in comparison to B-mode and Doppler ultrasonography in differentiating benign from malignant head and neck lymph nodes (HNLNs). Sixty-two HNLNs from 56 patients were prospectively examined using B-mode, Doppler and SWE. The standard of reference was histopathology or cytology and follow-up. Qualitative malignant criteria (hilum infiltration, cortical hypo-echogenicity, irregular margins, abnormal vessels) were assessed on a five-point scale. Four quantitative parameters were obtained: long axis length, short axis length, short axis/long axis ratio, resistive index and maximum shear elasticity modulus (μmax). Diagnostic performance was analyzed with special emphasis on the sub-centimeter HNLN subgroup. Thirty HNLNs were malignant (48%). μmax intra-observer reproducibility was 0.899 (0.728 in sub-centimeter subgroup). Malignant HNLNs were stiffer (μmax = 72.4 ± 59.0 kPa) compared with benign nodes (μmax = 23.3 ± 25.3 kPa) (p < 0.001). Among the quantitative criteria, μmax had the highest diagnostic accuracy (area under the curve = 0.903 ± 0.042), especially in the sub-centimeter subgroup (area under the curve = 0.929 ± 0.045; p < 0.001) in which the area under the curve was significantly higher compared with the other quantitative criteria (p < 0.05). The additional use of SWE combined with B-mode tended to improve diagnostic accuracy (p > 0.05). SWE is a promising reproducible quantitative tool with which to predict malignant HNLNs, especially sub-centimeter nodes.


Location of colorectal adenomas and serrated polyps in patients under age 50.
The incidence of colorectal cancer, especially located in distal colorectum, is rising markedly in young patients. Conventional adenomas and serrated polyps have been widely recognized as precursors of colorectal cancer. To investigate the correlation of polyp feature with polyp location in patients under age 50. Patients under age 50 who had received colonoscopy were included from 2010 to 2018. Clinical data including number, location, size, and histopathology of polyps were collected. Odd ratios and 95% confidence interval of adenomas with their location were calculated. In total, 25,636 patients aged 18-49 were enrolled, among which 4485 patients had polyps, with polyp detection rate of 17.5%. A total of 2484 and 2387 patients had conventional adenomas and serrated polyps, respectively. 76.0% advanced adenomas and 69.5% ≥ 10-mm serrated polyps were located in the distal colorectum. The detection rate of advanced adenomas was higher in patients aged 45-49. Patients with adenomas especially advanced adenomas in the distal colorectum were more likely to have advanced adenoma in the proximal colon. Among patients under age 50, advanced adenomas and ≥ 10-mm serrated polyps were predominantly in the distal colorectum. Advanced adenomas tended to be found in patients aged 45-49. Our results might explain the rising trend of distal colorectal cancer and emphasize the necessity for colonoscopy screening among these populations.


Social capital and use of assisted reproductive technology in young couples: Ecological study using application information for government subsidies in Japan.
Assisted reproductive technology (ART) is a globally established treatment; however, large disparities exist in ART use among young couples. We investigated regional-level factors associated with ART use in Japan. We calculated the use rate of ART using the number of women aged <35 years who applied for government subsidies in 2017; we divided that figure by the number of women aged 20-35 years in each prefecture. Prefectural-level average household income; social capital indicators including voting rate, volunteer rate, and move-in rate; and Gini coefficients as indicators of income inequality were linked to ART use, adjusting for prefectural size, the mean age of women at first marriage, number of ART facilities, and additional prefectural subsidies. The rate of ART use (per 10,000 women) varied significantly from 22.0 to 58.8 across Japan's 47 prefectures. Multivariate analysis demonstrated that the use rate increased by 0.048 (95% confidence interval [CI], 0.007 to 0.088) for each 10,000-yen increase in average household income and 1.5 (95% CI, 0.65 to 2.3) for each 1% increase in volunteer rate. Conversely, the use rate decreased by 18.4 (95% CI, -28.6 to -8.1) for each 1% increase in the move-in rate. There was no significant association between ART use and income inequality. Although we cannot infer causal relationships, the findings suggest that improving financial access and enhancing social capital may increase access to ART. Further research, particularly multilevel analysis using individual data, is required to confirm these findings.


Adoptive transfer of double negative T regulatory cells induces B-cell death in vivo and alters rejection pattern of rat-to-mouse heart transplantation.
Antibody-mediated hyperacute and acute graft rejection are major obstacles in achieving long-term graft survival in xenotransplantation. It is well documented that regulatory T (Treg) cells play a very important role in regulating immune responses to self and non-self antigens. Our previous studies have shown that TCRalphabeta+CD3+CD4-CD8- (double negative, DN)-Treg cells can suppress anti-donor T-cell responses and prolong graft survival in allo- and xenotransplantation models. We have demonstrated that DN-Treg cells can induce B-cell apoptosis in vitro through a perforin-dependent pathway. B6 mice received rat heart grafts, followed by 14 days of LF15-0195 treatment. Some mice received Lewis rat cell activated DN-Treg cells after LF treatment. DN-Treg cells, purified from perforin-/- mice and from B6 mice pre-immunized with third party rat cells, were used as controls. In this study, we investigated the possibility that adoptive transfer of xenoreactive DN-Treg cells could suppress B cells in vivo, thus prolonging xenograft survival. We found that apoptotic death of B cells significantly increased after adoptive transfer of DN-Treg cells. In addition, anti-donor IgG subtypes were significantly inhibited in the DN-Treg cell-treated group, in which the rejection pattern was altered towards cellular-mediated rejection rather than antibody-mediated acute vascular rejection. However, perforin-deficient DN-Treg cells failed to induce B-cell death and to prolong heart graft survival, indicating a perforin-dependent mechanism contributes to B-cell death in vivo. This study suggests that adoptive transfer of xenoreactive DN-Treg cells can inhibit B-cell responses in vivo. DN-Treg cells may be valuable in controlling B-cell responses in xenotransplantation.


Neural correlates underlying preference changes induced by food Go/No-Go training.
Consistently not responding to appetitive foods during food go/no-go training could change individuals' food choices and sometimes even body weight, however, fewer studies have explored the neural pathways underlying the effects of food go/no-go training. In this study, we scanned eighty-six female participants using functional magnetic resonance imaging and investigated the neural bases of preference changes in a binary food choice task following action (e.g., go) or inaction (e.g., no-go) toward distinct foods within a food go/no-go training paradigm. In line with prior behavioral work, we found that participants' food preferences changed as a function of food go/no-go training, with participants choosing more "go" over "no-go" foods for consumption following training. At a neural level, preference changes were inversely associated with frontoparietal and salience network activity when choosing go (vs. no-go) foods. Additionally, task-related functional connectivities from the inferior parietal lobule to the pre-supplementary motor cortex, dorsolateral prefrontal cortex, and dorsal anterior cingulate cortex were related to these preference changes. Together, current work supports that food go/no-go training reliably changes people's preferences. More importantly, our findings suggest that a neural pathway centered on areas traditionally associated with selective attention may interface with prefrontal regions to guide preference changes induced by food go/no-go training, though future studies using other tasks (e.g., passive viewing tasks) are still needed to test this potential neural mechanism.


Counteracting antibiotic resistance enzymes and efflux pumps.
Bacterial pathogens are constantly evolving new resistance mechanisms against antibiotics; hence, strategies to potentiate existing antibiotics or combat mechanisms of resistance using adjuvants are always in demand. Recently, inhibitors have been identified that counteract enzymatic modification of the drugs isoniazid and rifampin, which have implications in the study of multi-drug-resistant mycobacteria. A wealth of structural studies on efflux pumps from diverse bacteria has also fueled the design of new small-molecule and peptide-based agents to prevent the active transport of antibiotics. We envision that these findings will inspire microbiologists to apply existing adjuvants to clinically relevant resistant strains, or to use described platforms to discover novel antibiotic adjuvant scaffolds.


Perfusion abnormalities in pulmonary embolism studied with perfusion MRI and ventilation-perfusion scintigraphy: an intra-modality and inter-modality agreement study.
To compare perfusion magnetic resonance imaging (MRI) and ventilation-perfusion scintigraphy (V-P scan) in the study of perfusion abnormalities in pulmonary embolism (PE) and to compare the PE results to the findings previously reported for pneumonia and chronic obstructive pulmonary disease (COPD), in terms of perfusion abnormalities. Dynamic contrast-enhanced MR images and V-P scans of 20 patients with PE, 11 patients with acute pneumonia, and 13 patients with exacerbation of COPD were studied. Five categories of perfusion abnormalities within each imaging modality were defined. Intra- and inter-modality agreement (kappa values) in the evaluation of perfusion abnormalities were calculated, based on the two observers of each imaging modality (all blinded to each other and true diagnosis). Finally, three categories of perfusion MRI diagnosis (PE, pneumonia, and COPD) were also defined and the inter-observer agreement (kappa value) was calculated. For PE, the intra-modality agreement (kappa value) in the evaluation of perfusion abnormalities was 0.77 for MRI and 0.65 for V-P scan. The inter-modality agreement varied from 0.52 to 0.57, respectively, and was observer-dependent. For the pooled group of PE, pneumonia, and COPD, the intra-modality agreement of perfusion abnormalities was 0.76 for MRI and 0.65 for V-P scan, and the inter-modality agreement varied from 0.51 to 0.56. The kappa value for inter-observer agreement for MRI diagnosis was 0.92. Evaluation of perfusion abnormalities in PE, pneumonia, and COPD using perfusion MRI and V-P scan showed a high intra-modality agreement that was higher than the inter-modality agreement. Further studies are now needed in patients presenting with possible PE to evaluate the sensitivity and specificity of the method.


Effect of acute limb ischaemia on neuromuscular function in rats.
To locate the exact site of the primary lesion in the neuromuscular system in acutely ischaemic extremities. Experimental study. University hospital, Greece. 22 adult rats. Isometric tensions of extensor digitorum longus muscles were recorded before ischaemia and every 5 minutes after the arterial occlusions by indirect stimulation. When no contractile activity was elicited, the muscle was stimulated directly and recordings made every 5 minutes. The sciatic nerve function was checked by recordings of nerve conduction velocity. Specimens from the muscles were examined under electron microscopy. Muscle contractile properties, conduction velocity, and electron microscopic appearance. After a period of about 50 minutes neuromuscular function under indirect stimulation in the ischaemic limbs was lost, whilst under direct stimulation the extensor digitorum longus muscles and the sciatic nerves still functioned. Electron microscopic study showed distinct alterations at the neuromuscular junctions. The response of the neuromuscular system to acute ischaemia indicated that the neuromuscular junction is probably the site most susceptible to acute ischaemia.


An Archetype Query Language interpreter into MongoDB: Managing NoSQL standardized Electronic Health Record extracts systems.
The fast development of today's healthcare and the need to extract new medical knowledge from exponentially-growing volumes of standardized Electronic Health Records data, as required by studies in Precision Medicine, brings up a challenge that may probably only be addressed using NoSQL DBMSs, due to the non-optimal performance of traditional relational DBMSs on standardized data; and these database systems operated by semantic archetype-based query languages, because of the expected generalized extension of standardized EHR systems. An AQL into MongoDB interpreter has been developed to its first version. It translates system-independent AQL queries posed on ISO/EN 13606 standardized EHR extracts into the NoSQL MongoDB query language. The new interpreter has the advantages of both the archetype-based system-independent AQL queries and the dual-model-based standardized EHR extracts stored on document-centric NoSQL DBMSs, such as MongoDB. AQL queries are independent of applications, programming languages and system environments due to the use of the dual model, but EHR extracts featuring this model are best persisted on document-based NoSQL databases. Consequently, the interpreter allows us to query standardized EHR extracts semantically, and also affording optimal performance.


Telomere attrition and inflammatory load in severe psychiatric disorders and in response to psychotropic medications.
Individuals with severe psychiatric disorders have a reduced life expectancy compared to the general population. At the biological level, patients with these disorders present features that suggest the involvement of accelerated aging, such as increased circulating inflammatory markers and shorter telomere length (TL). To date, the role of the interplay between inflammation and telomere dynamics in the pathophysiology of severe psychiatric disorders has been scarcely investigated. In this study we measured T-lymphocytes TL with quantitative fluorescent in situ hybridization (Q-FISH) and plasma levels of inflammatory markers in a cohort comprised of 40 patients with bipolar disorder (BD), 41 with schizophrenia (SZ), 37 with major depressive disorder (MDD), and 36 non-psychiatric controls (NPC). TL was shorter in SZ and in MDD compared to NPC, while it was longer in BD (model F6, 137 = 20.128, p = 8.73 × 10-17, effect of diagnosis, F3 = 31.870; p = 1.08 × 10-15). There was no effect of the different classes of psychotropic medications, while duration of treatment with mood stabilizers was associated with longer TL (Partial correlation controlled for age and BMI: correlation coefficient = 0.451; p = 0.001). Levels of high-sensitivity C-Reactive Protein (hsCRP) were higher in SZ compared to NPC (adjusted p = 0.027), and inversely correlated with TL in the whole sample (r = -0.180; p = 0.042). Compared to NPC, patients with treatment resistant (TR) SZ had shorter TL (p = 0.001), while patients with TR MDD had higher levels of tumor necrosis factor-α (TNFα) compared to NPC (p = 0.028) and to non-TR (p = 0.039). Comorbidity with cardio-metabolic disorders did not influence the observed differences in TL, hsCRP, and TNFα among the diagnostic groups. Our study suggests that patients with severe psychiatric disorders present reduced TL and increased inflammation.


Metal nanoparticle-embedded bacterial cellulose aerogels via swelling-induced adsorption for nitrophenol reduction.
Bacterial cellulose aerogels were chosen as the substrate for supporting and dispersing metal nanoparticles (Cu and Ni). During the catalyst preparation, we found that the swelling-induced adsorption process could control the metal size and dispersion simultaneously. Cu and Ni nanoparticles were confined into the bacterial cellulose network and SEM results demonstrated that Cu particles had a smaller size compared to Ni particles. The metal-loaded catalysts exhibited good catalytic performance in the 4-nitrophenol reduction reaction. The optimal sample (BC-Cu-0.5) prepared with 0.5 wt% CuSO4 solution could complete the reduction process within 8 min. Besides, the BC-Cu-0.5 catalyst showed excellent stability and reusability. This study sheds light on the deposition of metal particles and provides a wider application for bacterial cellulose.


Isolated left upper extremity myositis and severe rhabdomyolysis in an adult with H1N1 Influenza, a case report with literature review.
Acute viral myositis is a fairly rare condition and usually seen in recovery phase of illness, especially in pediatric or geriatric population. Influenza type A, specifically H1N1 may present with generalized myositis and mild elevation of creatinine kinase in addition to usual manifestations. We would like to discuss an atypical presentation of Type A Influenza (H1N1) in a middle aged male who was never immunized for influenza, presenting with fever, vomiting, anuria and acute severe left upper extremity pain. The most interesting presentation in our patient was that, it was limited to a single extremity, unlike generalized presentation, which was previously reported, acute renal failure warranting renal replacement therapy. This case serves as a reminder for clinicians about atypical manifestations of H1N1 and its threatening metabolic complications. Hence the practitioners should be aware of this rare but possible presentation of certain strains of influenza virus. It also accentuates the importance of being immunized, reminding us of the Old but Golden Adage "Prevention is better than Cure."


Genomic Features of Muscle-invasive Bladder Cancer Arising After Prostate Radiotherapy.
Muscle-invasive bladder cancer (MIBC) is a rare but serious event following definitive radiation for prostate cancer. Radiation-associated MIBC (RA-MIBC) can be difficult to manage given the challenges of delivering definitive therapy to a previously irradiated pelvis. The genomic landscape of RA-MIBC and whether it is distinct from non-RA-MIBC are unknown. To define mutational features of RA-MIBC and compare the genomic landscape of RA-MIBC with that of non-RA-MIBC. We identified patients from our institution who received radiotherapy for prostate cancer and subsequently developed MIBC. We performed whole exome sequencing of bladder tumors from RA-MIBC patients. Tumor genetic alterations including mutations, copy number alterations, and mutational signatures were identified and were compared with genetic features of non-RA-MIBC. We used the Kaplan-Meier method to estimate recurrence-free (RFS) and overall (OS) survival. We identified 19 RA-MIBC patients with available tumor tissue (n = 22 tumors) and clinical data. The median age was 76 yr, and the median time from prostate cancer radiation to RA-MIBC was 12 yr. The median RFS was 14.5 mo and the median OS was 22.0 mo. Compared with a cohort of non-RA-MIBC analyzed in parallel, there was no difference in tumor mutational burden, but RA-MIBCs had a significantly increased number of short insertions and deletions (indels) consistent with previous radiation exposure. We identified mutation signatures characteristic of APOBEC-mediated mutagenesis, aging, and homologous recombination deficiency. The frequency of mutations in many known bladder cancer genes, including TP53, KDM6A, and RB1, as well as copy number alterations such as CDKN2A loss was similar in RA-MIBC and non-RA-MIBC. We identified unique mutational properties that likely contribute to the distinct biological and clinical features of RA-MIBC. Bladder cancer is a rare but serious diagnosis following radiation for prostate cancer. We characterized genetic features of bladder tumors arising after prostate radiotherapy, and identify similarities with and differences from bladder tumors from patients without previous radiation.


Bendamustine combined with rituximab for patients with relapsed or refractory diffuse large B cell lymphoma.
Patients with relapsed or refractory diffuse large B cell lymphoma (DLBCL) are treated with salvage regimens and may be considered for high-dose chemotherapy and autologous stem cell transplantation if disease is chemosensitive. Bendamustine is active in indolent B cell lymphomas and chronic lymphocytic leukemia but has not been extensively studied in aggressive lymphomas. This trial examines the combination of bendamustine and rituximab in patients with relapsed and refractory DLBCL. Patients received bendamustine at 90 mg/m² (n = 2) or 120 mg/m² (n = 57) on days 1 and 2 and rituximab at 375 mg/m² on day 1 every 28 days for up to 6 cycles. The study evaluated objective response rate (ORR), duration of response (DOR), progression-free survival (PFS), and treatment safety. Fifty-nine patients were treated, and 48 were evaluable for response. Median age was 74; 89 % had stage III or IV disease, and 63 % had high revised International Prognostic Index scores; the median number of prior therapies was 1. Based on analysis using the intent-to-treat population, the ORR was 45.8 % (complete response, 15.3 %; partial response, 30.5 %). The median DOR was 17.3 months, and the median PFS was 3.6 months. Grade 3 or 4 hematological toxicities included neutropenia (36 %), leukopenia (29 %), thrombocytopenia (22 %), and anemia (12 %). The combination of bendamustine and rituximab showed modest activity in patients with relapsed and refractory DLBCL and has an acceptable toxicity profile.


Chronic stress and age-related pattern of blood pressure: A cross-sectional study in rural China.
Chronic stress is a risk factor for hypertension in adults. However, there is conflicting evidence for older adults. We hypothesized that age-related arterial stiffening, which leads to a lower blood pressure (especially diastolic blood pressure [DBP]), is more pronounced among older adults with high vs low stress. The objectives of this study were (a) to investigate age-related trends in systolic and DBPs among adults in rural Fujian, China, and (b) to examine differences in age-related blood pressure trends according to levels of stress by using Epstein-Barr virus (EBV) antibody titer as a marker of chronic stress status. We collected cross-sectional data from 764 rural community-dwelling adults in rural Fujian, China (mean age = 59.4). Participants were categorized into high and low stress groups by median split of EBV antibody titer. A least-squares regression analysis was used to investigate the association between age and blood pressures. We observed an inverted U-shaped association between age and DBP, while there was a linear association between age and systolic blood pressure in the overall sample. When stratified by stress, the inverted U-shaped associations with age (both systolic and DBPs) were seen only among those with high stress; DBP peaked at the age of ~68 years, and the declining trend later in life was more clearly observed among those with high chronic stress. Decrease of DBP was more pronounced among older adults with high vs low chronic stress in rural China.


Increased cytomegalovirus infection of human fibroblast and endothelial cells by electroporation.
Electroporation of fibroblasts and endothelial cells in the presence of HCMV caused an increase in the infection of these cells by the virus. This method could be applied to cells that are difficult to infect by ordinary laboratory methods and also in cases when synchronized infection of the cells by the virus is needed.


Using fractals to understand the opening and closing of ion channels.
Looking at an old problem from a new perspective can sometimes lead to new ways of analyzing experimental data which may help in understanding the mechanisms that underlie the phenomena. We show how the application of fractals to analyze the patch clamp recordings of the sequence of open and closed times of cell membrane ion channels has led to a new description of ion channel kinetics. This new information has led to new models that imply: (a) ion channel proteins have many conformational states of nearly equal energy minima and many pathways connecting one conformational state to another, and (b) that these many states are not independent but are linked by physical mechanisms that result in the observed fractal scaling. The first result is consistent with many experiments, simulations, and theories of globular proteins developed over the last decade. The second result has stimulated the suggestion of several different physical mechanisms that could cause the fractal scalings observed.


A finite element-based machine learning approach for modeling the mechanical behavior of the breast tissues under compression in real-time.
This work presents a data-driven method to simulate, in real-time, the biomechanical behavior of the breast tissues in some image-guided interventions such as biopsies or radiotherapy dose delivery as well as to speed up multimodal registration algorithms. Ten real breasts were used for this work. Their deformation due to the displacement of two compression plates was simulated off-line using the finite element (FE) method. Three machine learning models were trained with the data from those simulations. Then, they were used to predict in real-time the deformation of the breast tissues during the compression. The models were a decision tree and two tree-based ensemble methods (extremely randomized trees and random forest). Two different experimental setups were designed to validate and study the performance of these models under different conditions. The mean 3D Euclidean distance between nodes predicted by the models and those extracted from the FE simulations was calculated to assess the performance of the models in the validation set. The experiments proved that extremely randomized trees performed better than the other two models. The mean error committed by the three models in the prediction of the nodal displacements was under 2 mm, a threshold usually set for clinical applications. The time needed for breast compression prediction is sufficiently short to allow its use in real-time (<0.2 s).


Crystal structure of an intact type II DNA topoisomerase: insights into DNA transfer mechanisms.
DNA topoisomerases resolve DNA topological problems created during transcription, replication, and recombination. These ubiquitous enzymes are essential for cell viability and are highly potent targets for the development of antibacterial and antitumoral drugs. Type II enzymes catalyze the transfer of a DNA duplex through another one in an ATP-dependent mechanism. Because of its small size and sensitivity to antitumoral drugs, the archaeal DNA topoisomerase VI, a type II enzyme, is an excellent model for gaining further understanding of the organization and mechanism of these enzymes. We present the crystal structure of intact DNA topoisomerase VI bound to radicicol, an inhibitor of human topo II, and compare it to the conformation of the apo-protein as determined by small-angle X-ray scattering in solution. This structure, combined with a wealth of experimental data gathered on these enzymes, allows us to propose a structural model for the two-gate DNA transfer mechanism.


Geographic Variation in Anticoagulant Use and Resident, Nursing Home, and County Characteristics Associated With Treatment Among US Nursing Home Residents.
To quantify geographic variation in anticoagulant use and explore what resident, nursing home, and county characteristics were associated with anticoagulant use in a clinically complex population. A repeated cross-sectional design was used to estimate current oral anticoagulant use on December 31, 2014, 2015, and 2016. Secondary data for United States nursing home residents during the period 2014-2016 were drawn from the Minimum Data Set 3.0 and Medicare Parts A and D. Nursing home residents (≥65 years) with a diagnosis of atrial fibrillation and ≥6 months of Medicare fee-for-service enrollment were eligible for inclusion. Residents in a coma or on hospice were excluded. Multilevel logistic models evaluated the extent to which variation in anticoagulant use between counties could be explained by resident, nursing home, and county characteristics and state of residence. Proportional changes in cluster variation (PCVs), intraclass correlation coefficients (ICCs), and adjusted odds ratios (aORs) were estimated. Among 86,736 nursing home residents from 11,860 nursing homes and 1694 counties, 45% used oral anticoagulants. The odds of oral anticoagulant use were 18% higher in 2016 than 2014 (aOR: 1.18; 95% confidence interval: 1.14-1.22). Most states had counties in the highest (51.3-58.9%) and lowest (31.1%-41.4%) deciles of anticoagulant use. Compared with the null model, adjustment for resident characteristics explained one-third of the variation between counties (PCV: 34.8%). The full model explained 65.5% of between-county variation. Within-county correlation was a small proportion (ICC < 2.2%) of total variation. In this older adult population at high risk for ischemic stroke, less than half of the residents received treatment with anticoagulants. Variation in treatment across counties was partially attributable to the characteristics of residents, nursing homes, and counties. Comparative evidence and refinement of predictive algorithms specific to the nursing home setting may be warranted.


Hepatitis, HIV, and the dermatologist: a risk review.
The practice of dermatology has always carried with it the risk of patient-acquired infection. This review covers health risks associated with the care of HIV-infected patients and patients who are chronic carriers of hepatitis B or C virus, protection options to reduce exposure, and protocols should exposure occur. Hepatitis B continues to be a major risk to health care workers, killing approximately 200 per year. In contrast, as of 1990, only 327 total health care personnel had acquired HIV, with no deaths reported. Data are lacking regarding hepatitis C, but it appears to be an increasing concern. Needlesticks are the most common form of occupational transmission, with an infectivity rate of 30% for hepatitis B, 3% for hepatitis C, and 0.3% for HIV. Universal precautions are the cornerstones of safety. Hepatitis B vaccination, zidovudine prophylaxis, and hepatitis C therapy are discussed as postexposure recommendations are reviewed.


Cost-Effectiveness of Sacubitril/Valsartan Compared with Enalapril in Patients with Heart Failure with Reduced Ejection Fraction: A Systematic Review.
To assess the cost-effectiveness of sacubitril/valsartan compared with enalapril in patients with heart failure with reduced ejection (HFrEF). A systematic literature search was conducted searching in major electronic databases from inception to January 1, 2021. All relevant full economic evaluation studies of sacubitril/valsartan versus enalapril for the treatment of patients with HFrEF were identified using ad hoc search strategies. Mortality, hospital admissions, quality-adjusted life years (QALYs), life-years (LYQs), annual drug costs, total lifetime costs, and incremental cost-effectiveness ratio (ICER) were considered as the outcomes. The quality of the included studies was assessed using the CHEERS checklist. This study was conducted and reported in accordance with the "Preferred Reporting Items for Systematic Reviews and Meta-Analyses" (PRISMA) guidelines. The initial search yielded a pool of 1026 articles, of which 703 unique articles were screened, 65 full-text articles were assessed for eligibility and 15 studies finally included in the qualitative synthesis. Studies show that sacubitril/valsartan reduces mortality and hospitalization rate. The mean of death risk ratio and hospitalization were computed at 0.843 and 0.844, respectively. Sacubitril/valsartan produced higher annual and total lifetime costs. The lowest and highest lifetime costs for sacubitril/valsartan were found in Thailand ($4,756) and Germany ($118,815), respectively. The lowest ICER was reported in Thailand ($4857/QALY) and the highest in the USA ($143,891/QALY). Sacubitril/valsartan is associated with better outcomes and may be cost-effective compared to enalapril for the management of HFrEF. However, in developing countries such as Thailand, sacubitril-valsartan costs must be reduced to yield an ICER below the threshold.


A novel tool to standardize rheology testing of molten polymers for pharmaceutical applications.
Melt rheology provides information about material properties that are of great importance for equipment design and simulations, especially for novel pharmaceutical manufacturing operations, including extrusion, injection molding or 3d printing. To that end, homogeneous samples must be prepared, most commonly via compression or injection molding, both of which require costly equipment and might not be applicable for shear- and heat-sensitive pharmaceutical materials. Our study introduces a novel vacuum compression molding (VCM) tool for simple preparation of thermoplastic specimens using standard laboratory equipment: a hot plate and a vacuum source. Sticking is eliminated by applying polytetrafluoroethylene (PTFE) coated separation foils. The evacuation of the tool leads to compression of the sample chamber, which is cost-efficient compared to conventional methods, such as compression molding or injection molding that require special equipment. In addition, this compact design reduces the preparation time and the heat load. The VCM tool was used to prepare samples for a rheological study of three pharmaceutical polymers (Soluplus(®), Eudragit(®)E, EVA Rowalit(®) 300-1/28). The prepared samples were without any air inclusions or voids, and the measurements had a high reproducibility. All relative standard deviations were below 3%. The obtained data were fitted to the Carreau-Yasuda model and time-temperature superposition was applied.


Lipopolysaccharide directly inhibits bicarbonate absorption by the renal outer medullary collecting duct.
Acidosis is associated with E. coli induced pyelonephritis but whether bacterial cell wall constituents inhibit HCO3 transport in the outer medullary collecting duct from the inner stripe (OMCDi) is not known. We examined the effect of lipopolysaccharide (LPS), on HCO3 absorption in isolated perfused rabbit OMCDi. LPS caused a ~ 40% decrease in HCO3 absorption, providing a mechanism for E. coli pyelonephritis-induced acidosis. Monophosphoryl lipid A (MPLA), a detoxified TLR4 agonist, and Wortmannin, a phosphoinositide 3-kinase inhibitor, prevented the LPS-mediated decrease, demonstrating the role of TLR4-PI3-kinase signaling and providing proof-of-concept for therapeutic interventions aimed at ameliorating OMCDi dysfunction and pyelonephritis-induced acidosis.


A randomized trial of dalteparin compared with ibuprofen for the treatment of superficial thrombophlebitis.
Superficial thrombophlebitis can produce pain and result in a deep vein thrombosis (DVT) if not treated. Conservative therapies including prescription of non-steroidal anti-inflammatory drugs (NSAID) and heat have been standard care. Recently, studies have been published reporting efficacy and safety of low-molecular-weight heparin for the treatment of superficial thrombophlebitis. However, there are few comparative trials to conservative therapy. We studied the effectiveness and safety of treatment with dalteparin compared with ibuprofen in patients with confirmed superficial thrombophlebitis. Consecutive patients were randomized to receive daily dalteparin vs. ibuprofen three times daily for up to 14 days. The primary outcome measure was the incidence of extension of thrombus or new symptomatic venous thromboembolism during the 14-day and 3-month follow-up period. The secondary outcome was a reduction in pain. The outcome measure of safety was the incidence of major and minor bleeding. Of 302 consecutive patients screened, 72 were enrolled. Four patients receiving ibuprofen compared with no patients receiving dalteparin had thrombus extension at 14 days (P = 0.05), however, there was no difference in thrombus extension at 3 months. Both treatments significantly reduced pain. There were no episodes of major or minor bleeding during the treatment period. Dalteparin is superior to the NSAID ibuprofen in preventing extension of superficial thrombophlebitis during the 14-day treatment period with similar relief of pain and no increase in bleeding. However, questions concerning the optimal treatment duration should be explored in future trials.


[Off-label use of intravenous immunoglobulin therapy in the treatment of lupus myocarditis: Two case reports and literature review].
Several case reports have reported the benefit of intravenous immunoglobulin therapy in many autoimmune diseases, including systemic lupus erythematosus. Here, we report on two cases of lupus myocarditis treated with high dose of intravenous immunoglobulin. The first patient was a 42-year-old woman who presented with lupus myocarditis that was resistant to corticosteroids and cyclophosphamide, and who was finally successfully treated with a single dose of 2 g/kg of intravenous immunoglobulin. The patient displayed clinical improvement a few days later. The second case - a 43-year-old woman was diagnosed with lupus myocarditis and immunosuppressive drugs were contraindicated because of the context of a recent infective endocarditis. She was treated with repeated dose of 2 g/kg of intravenous immunoglobulin. Clinical improvement was observed and the left ventricular ejection fraction increased from 20 % to 60 % within a few days. We also report 9 similar observations identified from a literature review. The use of intravenous immunoglobulin in lupus myocarditis is not officially recognized but could be considered as an alternative when conventional therapies have failed or are contraindicated.


McrBC: a multisubunit GTP-dependent restriction endonuclease.
McrBC-mediated restriction of modified DNA has been studied extensively by genetic methods, but little is known of its molecular action. We have used overproducing plasmid constructs to facilitate purification of the McrBL and McrC proteins, and report preliminary characterization of the activity of the complex. Both proteins are required for cleavage of appropriately modified DNA in vitro, in a reaction absolutely dependent on GTP. ATP inhibits the reaction. The sequence and modification requirements for cleavage of the substrate reflect those seen in vivo. The position of cleavage was examined at the nucleotide level, revealing that cleavage occurs at multiple positions in a small region. Based upon these observations, and upon cleavage of model oligonucleotide substrates, it is proposed that the recognition site for this enzyme consists of the motif RmC(N40-80)RmC, with cleavage occurring at multiple positions on both strands, between the modified C residues. In subunit composition, cofactor requirement, and relation between cleavage and recognition site, McrBC does not fit into any of the classes (types I to IV) of restriction enzyme so far described.


Reverse gateways? Frequent cannabis use as a predictor of tobacco initiation and nicotine dependence.
To examine the risk posed by cannabis use in young people for tobacco use disorders. Specifically we examined whether cannabis use in non-smokers predicted later initiation of tobacco use and whether cannabis use predicted later nicotine dependence in tobacco users. A 10-year eight-wave cohort study. State of Victoria, Australia. A community sample of 1943 participants initially aged 14-15 years. Self-report of tobacco and cannabis use was assessed in the teens using a computerized interview assessment and in young adulthood with a CATI assessment. The Fagerström Test for Nicotine Dependence was used to define nicotine dependence. For teen non-smokers, at least one report of weekly cannabis use in the teens predicted a more than eightfold increase in the odds of later initiation of tobacco use (OR 8.3; 95% CI 1.9-36). For 21-year-old smokers, not yet nicotine-dependent, daily cannabis use raised the odds of nicotine dependence at the age of 24 years more than threefold (OR 3.6, 1.2, 10) after controlling for possible confounders, including level of tobacco use and subsyndromal signs of nicotine dependence. Weekly or more cannabis use during the teens and young adulthood is associated with an increased risk of late initiation of tobacco use and progression to nicotine dependence. If this effect is causal, it may be that a heightened risk of nicotine dependence is the most important health consequence of early frequent cannabis use.


Inhibition of anandamide breakdown reduces pain and restores LTP and monoamine levels in the rat hippocampus via the CB1 receptor following osteoarthritis.
Chronic pain is a persistent, complex condition that contributes to impaired mood, anxiety and emotional problems. Osteoarthritis (OA) is one of the major causes of chronic pain in adults and elderly people. A substantial body of evidence demonstrate that hippocampal neural circuits, especially monoamine dopamine and serotonin levels, contributes to negative affect and avoidance motivation experienced during pain. Current pharmacological strategies for OA patients are unsatisfying and the endocannabinoid system modulation might represent an alternative for the treatment of OA-related pain. In the present study, we used a rat model of osteoarthritis induced by intra-articular injection of sodium monoiodoacetate to assess, 28 days post-induction, the contribution of endocannabinoid system on the possible alteration in pain perception and affective behavior, in LTP and monoamine levels in the lateral entorhinal cortex-dentate gyrus pathway. The results show that OA-related chronic pain induces working memory impairment and depressive-like behavior appearance, diminishes LTP, decreases dopamine levels and increases serotonin levels in the rat dentate gyrus. URB597 administration (i.p., 1 mg/kg) reduces hyperalgesia and mechanical allodynia, improves recognition memory and depressive-live behavior, restores LTP and normalizes monoamine levels in the hippocampus. The effect was observed 60-120 min post-treatment and was blocked by AM251, which proves the action of URB597 via the CB1 receptor. Therefore, our study confirms the role of anandamide in OA-related chronic pain management at the behavioral and hippocampal levels. This article is part of the Special Issue on 'Advances in mechanisms and therapeutic targets relevant to pain'.


Interfacial tension measured at high expansion rates and within milliseconds using microfluidics.
To understand droplet formation and stabilisation, technologies are needed to measure interfacial tension at micrometer range and millisecond scale. In this paper, microtechnology is used, and that allows us to access these ranges and derive a model for surfactant free systems. The predicting power of the model was tested, and we found that it can be used to accurately (validated with >60 experiments) describe droplet size for a wide range of flow rates, interfacial tensions, and continuous phase viscosities. The model was used next to determine interfacial tensions in a system with hexadecane and sodium dodecylsulfate (SDS) solutions, and it was found that the model can be used for droplet formation times ranging from 0.4 to 9.4ms while using a wide range of process conditions. The method described here differs greatly from standard dynamic interfacial tension methods that use quiescent, mostly diffusion-limited situations. The effects that we measured are much faster due to enhanced mass transfer; this allows us to assess the typical time scales used in industrial emulsification devices.


Left ventricular diastolic function and right atrial size are important rhythm outcome predictors after intraoperative ablation for atrial fibrillation.
Left ventricular (LV) diastolic function and right atrial (RA) size are not routinely included in preoperative echocardiographic examination in patients undergoing cardiac surgery with concomitant ablation for atrial fibrillation (AF). To investigate the role of echocardiographic variables including LV diastolic function and RA area in long-term rhythm outcome prediction, in patients with documented AF undergoing intraoperative ablation concomitant to coronary artery bypass grafting (CABG). Thirty-five consecutive patients, scheduled for CABG, and with a history of paroxysmal or permanent AF for 8.5 ± 11.3 years (mean ± SD) (median 5.8 years), were included in this prospective study. Echocardiography was performed prior to and 2.3 ± 0.4 years after the surgical procedure. Both LA and RA areas, LV diastolic function, paroxysmal AF, and sinus rhythm (SR) preoperatively were associated with SR at long-term follow-up. In the multivariate analysis, RA area (P = 0.004), and decreased LV diastolic function preoperatively, measured as the maximal LV long-axis relaxation velocity (P = 0.02), predicted SR at follow-up. RA size and LV diastolic function may be important variables in prediction of long-term rhythm outcome after intraoperative ablation for AF.


Impact of parental substance use disorder and child neglect severity on substance use involvement in male offspring.
Two child self-report scales were developed to measure parental neglect (emotional distance and parental involvement) in a sample of 344 boys between 10 and 12 years of age. Psychometric analyses of the parental emotional distance and involvement scales demonstrated their unidimensionality; construct, concurrent, and predictive validity; and reliability. Cross-sectional analyses indicated that neglect was more severe among boys who had a parent with a DSM-III-R lifetime substance use disorder (SUD) compared to youth whose parents had no Axis I psychiatric disorder. In addition, children reported more severe neglect by the mother than the father. Longitudinal analyses of a subsample (n = 99) revealed that child neglect at ages 10-12 predicted significant variance on a composite measure of substance use involvement and severity of substance use as well as increased the risk for SUD at age 19.


Quaternary ammonium salts targeted regulate the surface charge distribution of activated carbon: A study of their binding modes and modification effects.
Activated carbon (AC) is negatively charged in aqueous solution, which seriously restricts its application range. Quaternary ammonium salt as a common cationic surfactant was utilized to modify the surface charge distribution of materials. The evolution of the surface charge distribution of AC modified by benzalkonium chloride (BAC), diallyl dimethyl ammonium chloride (DDA) and 3-chloro-2-hydroxypropyl tri-methyl ammonium chloride (CTA) was investigated. Results showed that the surface charge of AC modified by CTA does not change significantly. BAC has a high molecular weight, low surface electrostatic potential and large steric hindrance due to its hydrophobic long-chain alkyl. The diffusion of BAC molecules from solution to AC changed its charge distribution. But these molecules were difficult to combine with AC surface, and most of them were adsorbed into the pores of AC to form aggregates, resulting in a significant reduction in the surface area. BAC modified AC could enhance the adsorption capacity of F- in aqueous solution through electrostatic attraction, but the improvement effect was limited due to the reduction of surface area, and the maximum adsorption capacity was only increased from 1.18 to 3.31 mg/g. DDA has a small molecular weight and high surface electrostatic potential and easily binds to the surface of AC. Some CC bonds in DDA combined with the ionized hydrogen ions derived from phenolic hydroxyl groups in AC to form carbonium-ions. Then, they could react with AC to form ether bonds, causing DDA to be closely bonded with the surface of AC. DDA realizes the targeted regulation of the surface charge distribution of AC, it has little effect on the porous structure of AC. The modified AC still maintained strong adsorption capacity, and the maximum adsorption capacity for F- was 54.98 mg/g. Meanwhile, a large number of zeolites were loaded on the modified AC and formed coating structures.


Updates and comments on: Influence of transcutaneous electrical nerve stimulation on spasticity, balance, and walking speed in stroke patients: A systematic review and meta-analysis.


Infant event-related potentials to speech are associated with prelinguistic development.
Neural auditory processing and prelinguistic communication build the foundation for later language development, but how these two are associated is not well known. The current study investigated how neural speech processing is associated with the level and development of prelinguistic skills in 102 infants. We recorded event-related potentials (ERPs) in 6-months-olds to assess the neural detection of a pseudoword (obligatory responses), as well as the neural discrimination of changes in the pseudoword (mismatch responses, MMRs). Prelinguistic skills were assessed at 6 and 12 months of age with a parental questionnaire (Infant-Toddler Checklist). The association between the ERPs and prelinguistic skills was examined using latent change score models, a method specifically constructed for longitudinal analyses and explicitly modeling intra-individual change. The results show that a large obligatory P1 at 6 months of age predicted strong improvement in prelinguistic skills between 6 and 12 months of age. The MMR to a frequency change was associated with the concurrent level of prelinguistic skills, but not with the improvement of the skills. Overall, our results highlight the strong association between ERPs and prelinguistic skills, possibly offering opportunities for early detection of atypical linguistic and communicative development.


Construction of a promoter-probe vector for Bacillus thuringiensis: the identification of cis-acting elements of the chiA locus.
The expression and application of Bacillus thuringiensis (Bt) chitinase genes have been extensively investigated. However, little information is available regarding the regulation of chitinase gene expression in Bt. In this study, a shuttle promoter-probe vector was constructed incorporating the thermostable β-galactosidase gene bgaB of B. stearothermophilus as the reporter for the study of Bt promoters. Using this plasmid, the activity of the chiA gene promoter in Bt was investigated. Deletion analysis of the putative chiA promoter region revealed that the sequence located ~75 bp DNA from positions -116 to -42, with respect to the translation start site, is the core promoter of chiA gene. Furthermore, a site for chitin induction was identified near position -36. This site for negative regulation was indicated downstream of the RNA polymerase binding sites of the promoter of chiA. The expression of chiA started in cell grown for about 6 h and reached the maximum after 60 h of incubation. Induction of chiA expression by chitin was demonstrated by an increase in β-galactosidase activity of ~2.5-fold.


Membrane abnormalities of pyruvate kinase deficient red cells.
Two experimental systems have been applied to the study of PK-deficient red cells in an attempt to reveal possible membrane abnormalities of these erythrocytes: (1) the glycoprotein self-digestion of intact erythrocytes during in vitro incubation at 37 degrees C; (2) the red cell sensitivity to the lytic action of mouse macrophages. PK-deficient erythrocytes display a more precocious than normal membrane glycoprotein self-digestion and are much more susceptible than normal to the cytotoxic activity of mouse macrophages. This latter effect is more pronounced in young than in old PK-deficient red cells. These observations indicate the existence of membrane abnormality in PK-deficient red cells other than those so far suspected.


Major royal jelly protein 3 modulates immune responses in vitro and in vivo.
We have recently shown that royal jelly has potent antiallergic properties in a mouse model of immediate hypersensitivity. However, it is still unclear which components of royal jelly exhibit antiallergic activity. In this study, we have screened for antiallergic factors in royal jelly based on inhibition of IL-4 production by anti-CD3 stimulated spleen cells derived from OVA/alum-immunized mice. Using a series of column chromatographies, we purified a 70 kDa glycoprotein, major royal jelly protein 3 (MRJP3), that suppresses IL-4 production. In in vitro experiments, MRJP3 suppressed the production of not only IL-4 but also that of IL-2 and IFN-gamma by T cells concomitant with inhibition of proliferation. The MRJP3-mediated suppression of IL-4 production was also evident when lymph node cells from OVA/alum-immunized mice were stimulated with OVA plus antigen presenting cells. We next examined the purified suppressive factor on OVA/alum-induced allergic responses in mice. Interestingly, in spite of the antigenicity of MRJP3 itself as an extraneous foreign protein, intraperitoneal administration of MRJP3 inhibited serum anti-OVA IgE and IgG1 levels in immunized mice. In addition, heat-treated soluble MRJP3 treatment reduced its antigenicity while maintaining its inhibitory effects on antibody responses to OVA. These results indicate that MRJP3 can exhibit potent immunoregulatory effects in vitro and in vivo. Furthermore, considering the intriguing immunomodulatory effects of MRJP3, it may be of clinical significance to design MRJP3-derived antiallergic peptides by identifying the associated polypeptide regions.


Cells participating in immunologic memory induced with RNA from the spleens of immunized mice.
Ribonucleic acid (immune RNA, iRNA) extracted from the spleens of mice immunized with heterologous red blood cells induced antigen-specific immunologic memory. The type of cells (T cells, B cells) which participate in immunologic memory induced with iRNA was investigated. Immune RNA-primed T cells cooperated with normal, iRNA-primed or antigen-primed B cells and induced a high IgM response. Immune RNA-primed B cells did not cooperate with normal T cells, but did with iRNA- or antigen-primed T cells. The activities of iRNA-primed T and B cells were antigen-specific.


Accurate measurement of flash-evoked alpha attenuation.
An accurate method for measuring flash evoked alpha attenuation has been derived, based on a model of the alpha generator. The method has been applied to 10 healthy volunteers in order to determine their alpha attenuation latencies (AALs). For the 9 subjects which showed at least some alpha rhythm, the AAL group mean is 95 msec. The AAL inaccuracy (S.D. 5 msec) is smaller than interindividual differences (S.D. 13 msec). There exists no relationship between the AAL and the frequency of the alpha rhythm.


The effect of norbinaltorphimine, beta-funaltrexamine and naltrindole on NPY-induced feeding.
The non-selective opioid receptor antagonist naloxone decreases the robust feeding observed after i.c.v. injection of neuropeptide Y (NPY). In the present study we evaluated the effects of three selective opioid receptor antagonists on NPY-induced feeding. Graded doses of norbinaltorphimine (norBNI), beta-funaltrexamine (beta-FNA) and naltrindole (NTI), antagonists of the kappa, mu and delta receptors respectively, were preinjected (i.c.v.) in male rats prior to injection of 5 micrograms NPY (i.c.v.). Food intake was measured 1, 2 and 4 h post-NPY injection. Injection of beta-FNA and norBNI were most effective in reducing NPY-induced feeding, whereas NTI had little effect on NPY-induced feeding.


Individual variation and specific cognitive deficits in the fra(X) syndrome.
Mental retardation has been associated with fra(X) but comprehensive psychological evaluation has rarely been applied to 2 major behavioral questions 1) the extent of individual variation in IQ among fra(X) males and the possibility of some fra(X) males being of normal IQ; and 2) whether there is a depression in general IQ or whether specific abilities are impaired. The problems of developing an effective battery of tests for assessing fra(X) are discussed. These questions were examined in 54 individuals, comprising fra(X) males, their obligate carrier mothers and those sisters shown to have the fra(X). Among noninstitutionalised males nonverbal IQ as measured on a Block Design test ranged from 100 to 0, and vocabulary scores while generally higher, ranged from 79-33. The males scored low on a digit span memory task, while performance on a memory of objects task was adequate. Despite lower overall scores, a similar pattern and variability emerged in institutionalised males. Daughters were extremely variable in performance and the mothers performed much better, supporting the view that women who have children are a selected subset of fra(X) syndrome individuals. The performance of one male is discussed in detail. His vocabulary and nonverbal IQ scores were normal, despite his having other specific cognitive deficits. The pattern of abilities and behavior seen in fra(X) may result in an overestimation of intelligence and underestimation of penetrance when based on clinical impressions rather than formal psychological assessment. The implications of this for molecular and for population genetic approaches to fra(X) are discussed.