Mitochondrial DNA deletions associated with aging and possibly presbycusis: a human archival temporal bone study.
We attempted to determine if the common mitochondrial DNA aging deletion is also associated with presbycusis. Presbycusis is the most common cause of deafness in adults in the United States, affecting approximately 40% of the population older than 75 years of age. The ability to identify a gene(s) or a specific genetic deficit(s) associated with presbycusis has significant clinical importance. The current study examined mitochondrial DNA (mtDNA) from cochlear sections of 34 human temporal bones: 17 with normal hearing and 17 with presbycusis. DNA was extracted from celloidin-embedded temporal bone sections; and specific oligonucleotide primers were designed to amplify the cytochrome b gene and a 4,977 base pair (bp) deletion of the mtDNA. Polymerase chain reaction (PCR) was used to amplify the base pair products that correspond to targeted gene regions, and sequencing was used to verify the products. Fourteen of the 17 patients with hearing loss showed the 4,977 bp deletion and this deletion was present in only eight of the 17 human specimens with normal audiograms. The cytochrome b gene was amplified from all specimens. The current study demonstrates the presence of a 4,977 bp deletion in human mitochondrial DNA genome that is associated with aging and with some forms of presbycusis. These results, coupled with previous animal studies, suggest that this 4,977 deletion may be associated with presbycusis.


Beneficial non-anticoagulant mechanisms underlying heparin treatment of COVID-19 patients.
Coronavirus disease-2019 (COVID-19) is associated with severe inflammation in mainly the lung, and kidney. Reports suggest a beneficial effect of the use of heparin/low molecular weight heparin (LMWH) on mortality in COVID-19. In part, this beneficial effect could be explained by the anticoagulant properties of heparin/LMWH. Here, we summarise potential beneficial, non-anticoagulant mechanisms underlying treatment of COVID-19 patients with heparin/LMWH, which include: (i) Inhibition of heparanase activity, responsible for endothelial leakage; (ii) Neutralisation of chemokines, and cytokines; (iii) Interference with leukocyte trafficking; (iv) Reducing viral cellular entry, and (v) Neutralisation of extracellular cytotoxic histones. Considering the multiple inflammatory and pathogenic mechanisms targeted by heparin/LMWH, it is warranted to conduct clinical studies that evaluate therapeutic doses of heparin/LMWH in COVID-19 patients. In addition, identification of specific heparin-derived sequences that are functional in targeting non-anticoagulant mechanisms may have even higher therapeutic potential for COVID-19 patients, and patients suffering from other inflammatory diseases.


Glucocerebrosidase genotype of Gaucher patients in The Netherlands: limitations in prognostic value.
Gaucher disease is a recessively inherited lysosomal storage disorder that is caused by a deficiency in glucocerebrosidase activity. The clinical expression is markedly heterogeneous with respect to age of onset, progression, severity, and neurological involvement. The relative incidence of glucocerebrosidase (GC) mutations has been studied extensively for Jewish but not for non-Jewish Caucasian patient populations. The present survey on mutant GC genotypes prevalent in Gaucher disease in The Netherlands was taken of 72 patients from different genetic backgrounds. This number is more than half the total number of affected Gaucher patients to be expected on the basis of the incidence of the disorder in this country. Analysis of nine GC mutations led to the identification of 74% of the mutant GC alleles in patients from 44 unrelated Dutch families (i.e., families that have lived in The Netherlands for at least several generations) and of 44% of the mutant GC alleles in patients from nine unrelated families that recently immigrated from both European and non-European countries. The N370S (cDNA 1226G) GC mutation proved to occur most frequently (41%) in the unrelated Dutch patients and less frequently (6%) in the unrelated immigrant patients and was always associated with the nonneuronopathic (Type 1) form of the disease. Apart from the association of the N370S mutation with Type 1 Gaucher disease, the prognostic value of GC genotyping was limited, since a particular GC genotype did not correlate closely to a specific clinical course, or to a specific relative responsiveness to enzyme-supplementation therapy.


The antiviral effect of phorbol ester and calcium ionophore A23187 is not mediated by interferons.
Phorbol myristate acetate (PMA) and the calcium ionophore, A23187, produce a dose-dependent inhibition of vesicular stomatitis virus (VSV) replication in FL cells, with maximum inhibition when cells are pretreated with 1 ng/ml of PMA or 0.5 microM A23187. No interferon (IFN) activity was detected in culture supernatants from cells treated with these agents, and addition of anti-human IFN antibodies did not prevent the inhibition of VSV replication that they caused. However, their antiviral activities were inhibited by actinomycin D or cyclohexamide treatment. Thus, the antiviral activities of PMA and A23187 involve de novo synthesis of protein but are not mediated through the production of IFN.


Acute tacrolimus overdose and treatment with phenytoin in liver transplant recipients.
As a potent immunosuppressive agent, Tacrolimus is widely used in organ transplantation. Although complications due to chronic Tacrolimus use are rather well recognized, little is known about acute overdose and its treatment. Phenytoin, an anti-convulsant agent, can induce the Cytochrome P450 enzyme in the liver, which metabolizes Tacrolimus. Therefore, it can be considered as a potential treatment option for acute Tacrolimus toxicity. We hereby report two cases of acute Tacrolimus overdose after Orthotopic Liver Transplantation and the treatment with Phenytoin. Probable mechanisms of metabolism and interactions of these two drugs are discussed and the literature is reviewed.


Drug repurposing of anti-infective clinical drugs: Discovery of two potential anti-cytokine storm agents.
Coronavirus Disease 2019 (COVID-19) caused by Severe Acute Respiratory Syndrome Coronavirus -2 (SARS-CoV-2) has been widely spread in the world with a high mortality. Cytokine storm syndrome (CSS) and acute lung injury caused by SARS-CoV-2 infection severely threaten the patients. With the purpose to find effective and low-toxic drugs to mitigate CSS, entecavir and imipenem were identified to reduce TNF-α using a LPS-induced macrophage model from the anti-infective drug library. Entecavir and imipenem efficiently suppressed the release of inflammatory cytokines by partly intervention of NF-κB activity. The acute lung injury was also alleviated and the survival time was prolonged in mice. In addition, entecavir and imipenem inhibited the release of TNF-α and IL-10 in human peripheral blood mononuclear cells (hPBMCs). Collectively, we proposed that entecavir and imipenem might be candidates for the treatment of CSS.


NapF is a cytoplasmic iron-sulfur protein required for Fe-S cluster assembly in the periplasmic nitrate reductase.
The periplasmic nitrate reductase (Nap) is wide-spread in proteobacteria. NapA, the nitrate reductase catalytic subunit, contains a Mo-bisMGD cofactor and one [4Fe-4S] cluster. The nap gene clusters in many bacteria, including Rhodobacter sphaeroides DSM158, contain an napF gene, disruption of which drastically decreases both in vitro and in vivo nitrate reductase activities. In spite its importance in the Nap system, NapF has never been characterized biochemically, and its role remains unknown. The NapF protein has four polycysteine clusters that suggest that it is an iron-sulfur-containing protein. In the present study, a His(6)-tagged NapF protein was overproduced in Escherichia coli and purified anaerobically. The purified NapF protein was used to obtain polyclonal antibodies raised in rabbit, and cellular fractionation of R. sphaeroides followed by immunoprobing with anti-NapF antibodies revealed that the native NapF protein is located in the cytoplasm. This contrasts with the periplasmic location of the mature NapA. However, NapA could not be detected in an isogenic napF(-) strain of R. sphaeroides. The His(6)-tagged NapF protein displayed spectral properties indicative of Fe-S clusters, but these features were rapidly lost, suggesting cluster lability. However, reconstitution of the Fe-S centers into the apo-NapF protein was achieved in the presence of Azotobacter vinelandii cysteine desulfurase (NifS), and this allowed the recovery of nitrate reductase activity in NapA protein that had previously been treated with 2,2'-dipyridyl to remove the [4Fe-4S] cluster. This activity was not recovered in the absence of NapF. Taking into account the cytoplasmic localization of NapF, the presence of labile Fe-S clusters in the protein, the napF(-) strain phenotype, and the NapF-dependent reactivation of the 2,2'-dipyridyl-treated NapA, we propose a role for NapF in assembling the [4Fe-4S] center of the catalytic subunit NapA.


Spatiotemporal classification of environmental monitoring data in the Yeongsan River basin, Korea, using self-organizing maps.
Environmental monitoring data for planning, implementing and evaluating the Total Maximum Daily Loads (TMDL) management system have been measured at about 8-day intervals in a number of rivers in Korea since 2004. In the present study, water quality parameters such as Suspended Solids (SS), Biochemical Oxygen Demand (BOD), Dissolved Oxygen (DO), Total Nitrogen (TN), and Total Phosphorus (TP) and the corresponding runoff were collected from six stations in the Yeongsan River basin for six years and transformed into monthly mean values. With the primary objective to understand spatiotemporal characteristics of the data, a methodologically systematic application of a Self-Organizing Map (SOM) was made. The SOM application classified the environmental monitoring data into nine clusters showing exclusively distinguishable patterns. Data frequency at each station on a monthly basis identified the spatiotemporal distribution for the first time in the study area. Consequently, the SOM application provided useful information that the sub-basin containing a metropolitan city is associated with deteriorating water quality and should be monitored and managed carefully during spring and summer for water quality improvement in the river basin.


Use of cDNA arrays to generate differential expression profiles for inflammatory genes in human gestational membranes delivered at term and preterm.
Inflammatory processes are implicated in preterm labour (PTL). To identify potential novel markers for PTL, we have used commercial cDNA arrays to generate profiles of differential expression of inflammation-associated genes in gestational membranes with term and PTL. RNA for cDNA probe synthesis was isolated from reflected human amnion and choriodecidua membranes delivered following Caesarean section at term before the onset of labour (TNL, n = 4), spontaneous labour at term (TSL, n = 4), and PTL with and without chorioamnionitis (PTL(+INF) and PTL(-INF) respectively, n = 4 each). Profiles were displayed relative to TNL and statistical comparisons of TSL versus TNL and PTL(+INF) versus PTL(-INF) were performed. Elevated expression of chemokines macrophage inflammatory protein 1beta(MIP-1beta) and pulmonary and activation-regulated chemokine (PARC) was observed in PTL(+INF) compared to PTL(-INF) amnion and choriodecidua respectively (P = 0.03). Likewise, the cytokines oncostatin-M and pre-B cell enhancing factor (PBEF) were more highly expressed in PTL(+INF) compared with PTL(-INF) and in TSL compared with TNL respectively (P = 0.03). Conversely, inhibin A, tissue inhibitors of matrix metalloproteinase (TIMP)-3 and TIMP-4 were all significantly elevated in PTL(-INF) compared with PTL(+INF) (P = 0.03). Furthermore, differential expression patterns of classes of genes, grouped according to function (e.g. chemokines), were noted. The cDNA array approach holds promise for identification of new candidate markers or combinations thereof for prediction or diagnosis of PTL, as well as for increasing our understanding of the particular aetiologies involved.


High-risk diabetic patients in Medicare Part D programs: are they getting the recommended ACEI/ARB therapy?
Diabetes patients with hypertension and/or renal disease are at an increased risk of cardiovascular morbidity and mortality. Clinical evidence suggests that the use of ACEI/ARB for these patients improves patient outcomes. To describe ACEI/ARB utilization among high-risk patients with diabetes and to identify patient characteristics that predict suboptimal utilization of ACEI/ARB. A retrospective cohort study. Diabetic patients with coexisting hypertension and/or renal disease with continuous Medicare coverage from October 1, 2005 through June 30, 2006 in six states (Alabama, California, Florida, Mississippi, New York, and Ohio). Any ACEI/ARB use during the first 6 months of 2006. A total of 1,250,466 Medicare Part D enrollees met our inclusion criteria. ACEI/ARB utilization rates were 63%, 58.3%, and 43.1% among diabetic patients with hypertension and renal disease, hypertension without renal disease, and renal involvement without hypertension, respectively. After adjusting for all other characteristics studied, patients in the hypertension only (OR 0.83; 95% CI: 0.82-0.84) and renal disease only (OR: 0.48; 95% CI: 0.46-0.50) risk groups were less likely to use ACEI/ARB compared to diabetes patients with both hypertension and renal disease. Several demographics, including male gender, age older than 65, and white race, were all predictors of suboptimal ACEI/ARB use. Results from state-specific analyses are consistent with those for all six states. In this cohort, less than 60% of high-risk patients with diabetes were receiving the recommended ACEI/ARB therapy. Several patient demographic and clinical characteristics are strongly associated with suboptimal ACEI/ARB use.


Complex Temporal Biology: Towards a Unified Multi-Scale Approach to Predict the Flow of Information.
Two hallmarks of biological processes are complexity and time. While complexity can have many meanings, in this paper we propose an explicit link to the flow of time and how it is experienced by the organism. While the flow of time is rooted in constraints of fundamental physics, understanding the operation of biological systems in terms of processual flow and tempo is more elusive. Fortunately, the convergence of new computational and methodological perspectives will provide a means to transform complicated, nonlinear paths between related phenomena at different time scales into dynamic four-dimensional perspectives. According to the complex temporal biology approach, information flow between time scales of multiple lengths is a transformational process that acts to regulate life's complexity. Interactions between temporal intervals of differing magnitude and otherwise loosely-related mechanisms can be understood as inter-timescale information flow. We further propose that informational flow between time scales is the glue that binds the multiple vertical layers of biocomplexity, as well as yielding surprising outcomes ranging from complex behaviors to the persistence of lineages. Building a foundation of rules based on common interactions between orders of time and common experiential contexts would help to reintegrate biology. Emerging methodologies such as state-of-the-art imaging, visualization techniques, and computational data analysis can help us uncover these interactions. In conclusion, we propose educational and community-level changes that would better enable our vision.


Particle Radiation Side-Effects: Intestinal Microbiota Composition Shapes Interferon-γ-Induced Osteo-Immunogenicity.
Microbiota can both negatively and positively impact radiation-induced bone loss. Our prior research showed that compared to mice with conventional gut microbiota (CM), mice with restricted gut microbiota (RM) reduced inflammatory tumor necrosis factor (TNF) in bone marrow, interleukin (IL)-17 in blood, and chemokine (C-C motif) ligand 20 (CCL20) in bone marrow under anti-IL-17 treatment. We showed that Muribaculum intestinale was more abundant in intestinal epithelial cells (IECs) from the small intestine of female RM mice and positively associated with augmented skeletal bone structure. Female C57BL/6J pun RM mice, which were injected with anti-IL-17 antibody one day before exposure to 1.5 Gy 28Si ions of 850 MeV/u, showed high trabecular numbers in tibiae at 6 weeks postirradiation. Irradiated CM mice were investigated for lower interferon-γ and IL-17 levels in the small intestine than RM mice. IL-17 blockage resulted in bacterial indicator phylotypes being different between both microbiota groups before and after irradiation. Analysis of the fecal bacteria were performed in relation to bone quality and body weight, showing reduced tibia cortical thickness in irradiated CM mice (-15%) vs. irradiated RM mice (-9.2%). Correlation analyses identified relationships among trabecular bone parameters (TRI-BV/TV, Tb.N, Tb.Th, Tb.Sp) and Bacteroides massiliensis, Muribaculum sp. and Prevotella denticola. Turicibacter sp. was found directly correlated with trabecular separation in anti-IL-17 treated mice, whereas an unidentified Bacteroidetes correlated with trabecular thickness in anti-IL-17 neutralized and radiation-exposed mice. We demonstrated radiation-induced osteolytic damage to correlate with bacterial indicator phylotypes of the intestinal microbiota composition, and these relationships were determined from the previously discovered dose-dependent particle radiation effects on cell proliferation in bone tissue. New translational approaches were designed to investigate dynamic changes of gut microbiota in correlation with conditions of treatment and disease as well as mechanisms of systemic side-effects in radiotherapy.


Causing or inciting sexual activity with persons who have a mental disorder.
Richard Griffith, Senior Lecturer in Health Law at Swansea University, discusses the implications of a Court of Appeal decision that considers the scope of the Sexual Offences Act 2003, section 39, in relation to care workers.


Bioethanol production from rice straw residues.
A rice straw - cellulose utilizing mold was isolated from rotted rice straw residues. The efficient rice straw degrading microorganism was identified as Trichoderma reesei. The results showed that different carbon sources in liquid culture such as rice straw, carboxymethyl cellulose, filter paper, sugar cane bagasse, cotton stalk and banana stalk induced T. reesei cellulase production whereas glucose or Potato Dextrose repressed the synthesis of cellulase. T. reesei cellulase was produced by the solid state culture on rice straw medium. The optimal pH and temperature for T. reesei cellulase production were 6 and 25 °C, respectively. Rice straw exhibited different susceptibilities towards cellulase to their conversion to reducing sugars. The present study showed also that, the general trend of rice straw bioconversion with cellulase was more than the general trend by T. reesei. This enzyme effectively led to enzymatic conversion of acid, alkali and ultrasonic pretreated cellulose from rice straw into glucose, followed by fermentation into ethanol. The combined method of acid pretreatment with ultrasound and subsequent enzyme treatment resulted the highest conversion of lignocellulose in rice straw to sugar and consequently, highest ethanol concentration after 7 days fermentation with S. cerevisae yeast. The ethanol yield in this study was about 10 and 11 g.L(-1).


Apoptosis during chick inner ear development: some observations by TEM and TUNEL techniques.
In order to clarify the occurrence, distribution and possible role of apoptosis during inner ear development, the ultrastructural aspects (by TEM) (at 9-19 incubation day and 1 day after hatching) and the distribution of the apoptotic phenomenon (by the TdT-mediated dUTP nick end-labeling technique), were studied in the crista ampullaris of chick embryo at 5-19 days of incubation to hatching and of postnatal 1-day old chick. We found, in the sensorial epithelium, dark supporting cells in chick embryos and mainly dark hair cells in postnatal chicks, both with ultrastructural features consistent with those of apoptosis. The presence of apoptotic phenomena was confirmed by the TUNEL technique. According to our findings, it is hypothesized that apoptosis in the inner ear may be involved: 1) at first, in macroscopic remodelling of the membranous labyrinth in early developmental stages, 2) later, in the correct differentiation of the hair and of the supporting cells, leading to characteristic cellular pattern formation and 3) finally, in physiological cell turnover of the postnatal chicken sensorial epithelium of the crista.


Specific incorporation of L-glutamine into volicitin in the regurgitant of Spodoptera litura.
Volicitin, [N-(17-hydroxylinolenoyl)-L-glutamine], was identified as an elicitor of plant volatiles from a Spodoptera exigua regurgitant. It has been proposed that gut microbes synthesize volicitin from glutamine, a predominant amino acid component in the insect gut. However, we found that glutamine was not a major component in the regurgitant of Spodoptera litura, although L-glutamine was exclusively incorporated into volicitin by S. litura fed on diets enriched with various amino acids. This selectivity of glutamine as a substrate was not due to a dominant occurrence in the insect gut.


Two types of calcium channels are expressed in adult bovine chromaffin cells.
1. Calcium channel activity was recorded in chromaffin cells in the cell-attached condition, using 110 mM-Ba2+ as the permeant ion. 2. One type of calcium channel had a conductance of 16 pS, was completely inactivated at a holding potential of -20 mV and was insensitive to dihydropyridine agonists and antagonists. These characteristics correspond to a calcium channel of the N-type. 3. A second type of calcium channel was active at holding potentials of -30 mV and above, had a channel conductance of 31 pS, and was sensitive to the dihydropyridine agonist, Bay K 8644. The channel opened along two dominant modes with characteristic time constants of 0.5 and 5 ms. The main effect of Bay K 8644 was to increase the probability of both short and long openings with no change in their relative proportions (6 to 1 respectively). These characteristics correspond to a calcium channel of the L-type. 4. omega-Conotoxin affected the activity of both N- and L-type channels. It drastically reduced the number of N-type channel openings and produced complex changes in L-type channel activity. Long openings were less frequent and the conductance during short openings was slightly smaller than that measured in the presence of Bay K 8644. 5. The discussion focuses on modulation of L-type channel activity. Openings of L-type channels are rarely recorded in the cell-attached configuration under control conditions. Addition of Bay K 8644 is needed to reveal the presence of L-type channels. By contrast, L-type currents recorded in the whole-cell configuration are always observed and are insensitive to Bay K 8644. These results indicate that L-type channels are normally inoperable in chromaffin cells.


The DVR-1 (Vg1) transcript of zebrafish is maternally supplied and distributed throughout the embryo.
It is not known how region- or tissue-specific differences are generated in the zebrafish embryo. To look at the potential role of maternal transcripts in generating cell diversity, we have isolated and characterized the zebrafish homologue of Xenopus DVR-1 (Vg1), a maternally supplied RNA that encodes a member of the transforming growth factor-beta superfamily. The zebrafish DVR-1 RNA is maternally supplied and its protein product shares a high degree of sequence identity with Xenopus DVR-1. These conserved features indicate that DVR-1 is likely to have an essential function in early embryogenesis. However, unlike the frog transcript, which is restricted to vegetal cells, DVR-1 RNA is distributed equally among all zebrafish blastomeres. We suggest that the ubiquitous distribution of DVR-1 RNA reflects a significant aspect of the developmental strategy of the zebrafish in which each blastomere retains an equivalent developmental potential throughout the cleavage period.


CP248, a derivative of exisulind, causes growth inhibition, mitotic arrest, and abnormalities in microtubule polymerization in glioma cells.
Exisulind (sulindac sulfone) and two potent derivatives, CP248 and CP461, have been shown previously to cause growth inhibition and apoptosis in several types of human carcinoma cell lines. These and related compounds have not been previously studied with respect to glioma cell lines. In the present study, we found that these three compounds caused marked growth inhibition in four rat glioma and eight human glioma cell lines, with IC50 values of 150, 1, and 0.075 microm, respectively. When studied at these concentrations exisulind and CP461 had no significant effect on the cell cycle profile of glioma cells, but CP248 caused marked arrest in mitosis. Detailed studies of CP248 in the 9L rat gliosarcoma cell line indicated that treatment with 0.075 microM CP248 caused abnormalities in the spindle apparatus and activation of the spindle assembly check point. In interphase glioma cells, CP248 stabilized microtubules (MTs) at low concentrations (0.075 microM) and depolymerized MTs at higher concentrations (0.2-0.4 microM). In NIH 3T3 fibroblasts, 0.1 microM CP248 caused extensive MT depolymerization. CP248 also caused MT depolymerization when added to assembled MTs in vitro, which indicated that it can directly affect MTs, perhaps because it shares certain structural similarities with Colcemid. In glioma cells, the effects of CP248 on MTs were independent of the previously reported effects of this compound on activation of protein kinase G. Therefore, CP248 is a novel MT-active agent that may be useful in the treatment of glioblastoma, and possibly other types of cancer, because of its dual effects on protein kinase G and MTs.


Quantifying origins of cell-to-cell variations in gene expression.
A general dynamic description of protein synthesis was employed to quantify different sources of gene expression noise in cellular systems. To test our approach, we use time-resolved expression data of individual human cells and, from this information, predict the stationary cell-to-cell variation in protein levels in a clonal population. For three of the four human genes investigated, the cellular variations in expression level are not due to fluctuations in promoter activity or transcript copy number, but are almost exclusively a consequence of long-term variations of gene regulatory factors or the global cellular state. Moreover, we show that a dynamic description is much more reliable to discriminate extrinsic and intrinsic sources of noise than it is on grounds of cell-cycle averaged descriptions. The excellent agreement between the theoretical predictions and the experimentally measured noise strengths shows that a quantitative description of gene expression noise is indeed possible on the basis of idealized stochastic processes.


Diurnal and circannual variation in platelet 3H-imipramine binding: comparative data on normal and affectively ill subjects.
Using a cross-sectional design, we examined the diurnal and circannual variation in platelet 3H-imipramine binding in 33 patients with bipolar affective disorder, 34 patients with unipolar affective disorder and 58 normal controls. There was no evidence for statistically significant diurnal or circannual variation in the binding parameters in any of the diagnostic categories.


Rate of 59Fe uptake into brain and cerebrospinal fluid and the influence thereon of antibodies against the transferrin receptor.
Uptake of 59Fe from blood into brains of anaesthetized rats and mice has been studied by intravenous infusion of [59Fe]ferrous ascorbate or of 59Fe-transferrin, the results not being significantly different. Uptakes in the rat were linear with time, but increased at longer times in the mouse. Transfer constants, K(in) (in ml/g/h x 10(3)), for cerebral hemispheres were 5.2 in the adult rat and 5.6 in the mouse. These K(in) values corresponded to 59Fe influxes of 145 and 322 pmol/g/h, respectively. 59Fe uptake into the mouse brain occurred in the following order: cerebellum > brainstem > frontal cerebral cortex > parietal cortex > occipital cortex > hippocampus > caudate nucleus. In genetically hypotransferrinaemic mice, 59Fe uptake into brain was 80-95 times greater than in To strain mice. Pretreatment of young rats and mice with monoclonal antibodies to transferrin receptors, i.e., the anti-rat immunoglobulin G OX 26 and the anti-mouse immunoglobulin M RI7 208, inhibited 59Fe uptake into spleen by 94% and 98%, respectively, indicating saturation of receptors. The antibodies reduced 59Fe uptake into rat brain by 35-60% and that into mouse brain by 65-85%. Although a major portion of iron transport across the blood-brain barrier is normally transferrin-mediated, non-transferrin-bound iron readily crosses it at low serum transferrin levels.


Clinical experience with wound biofilm and management: a case series.
Biofilm is a relatively new concept in the fields of infectious disease, wound infection, and healing. Although scientific research and "noise" regarding wound biofilm is increasing, little is known about the presentation, diagnosis, potential implications, and management strategies regarding wound biofilms. A series of four clinical cases is utilized to demonstrate the existence of wound biofilm. All patients presented with or developed a film on the wound bed that appeared to be distinct from slough; wounds also were failing to progress. Although the slough in some of the wounds was easily removed with traditional debridement methods, removal of the film required physical disruption with a curette or dry gauze. All wounds eventually progressed to healing. Considering the biofilm concept and available preclinical research, it is evident from this small case series that the appearance of biofilm in wounds is quite different from slough and requires different management strategies for its control. The evolving biofilm paradigm could profoundly change approaches to wound management. Additional research is needed in this evolving aspect of wound management.


Optimizing treatment of von Willebrand disease by using phenotypic and molecular data.
The wide clinical spectrum of von Willebrand disease (VWD), its complex pathophysiology and its classification into distinct quantitative (type 1 or type 3) and qualitative (type 2) types with further subtle distinctions have prevented most clinicians from establishing a straightforward approach to diagnosing and treating this inherited bleeding disorder. The results of studies involving large cohorts of patients with a wide range of bleeding manifestations and variable von Willebrand factor (VWF) reduction have recently become available. These data have allowed the proposal of minimal criteria for a clinically useful diagnosis and for differentiating patients with mild VWD from subjects with borderline or only slightly reduced VWF levels who will not benefit from a specific diagnosis. These criteria are based on measurement of VWF ristocetin cofactor (VWF:RCo), VWF antigen (VWF:Ag), factor VIII and a standardized bleeding score (BS). Demonstration of the inheritance of the disorder could help to classify patients for whom insufficient hemostatic challenges may produce a falsely reassuring BS (like in children). Using this approach, mild VWD appears to be mostly composed of type 1 cases. Complemented by the results of desmopressin trial infusion, these parameters form the basis for a clinically oriented classification of all forms of VWD and may be useful for selecting the best treatment according to the severity of the disease. Although few molecular data have revealed practical utility, there is no doubt that the clarification of the molecular pathophysiology of VWD has allowed the unification of this complex disorder into a simple conceptual framework. This framework underlies the proposed utilization of simple phenotypic markers for optimizing treatments in individual patients.


Disability community and mental health among college students with physical disabilities.
College students with physical disabilities are often at a higher risk for mental health problems. In addition, some universities have created disability community spaces, but it is not known whether these spaces are associated with social support or increased mental health and well-being among students who use them. This study investigated differences in feelings of perceived social support, depressive symptomatology, and well-being between students with physical disabilities who live in general student housing and students with physical disabilities who live in a disability community. Research Methods/Design: A mixed-methods online survey was used to collect data from students with physical disabilities who lived in a disability community and from those who did not. Of the participants, 27 college students self-identified as having a physical disability (n = 27), 11 participants lived in the disability community (n = 11), and 16 did not (n = 16). The quantitative results indicated statistically significant differences between the two groups on all three measures. The open-ended responses revealed that those who lived in the disability community setting felt more connected to other students with physical disabilities. However, the results also showed that many students with physical disabilities felt socially disconnected for a myriad of reasons. These findings suggest that living in a disability community may be associated with feeling socially supported and improved mental health outcomes among college students with physical disabilities. Universities and other stakeholders should consider implementing programs to foster disability community among students with physical disabilities. (PsycInfo Database Record (c) 2021 APA, all rights reserved).


Leo1 subunit of the yeast paf1 complex binds RNA and contributes to complex recruitment.
The Paf1 complex (Paf1C) affects RNA polymerase II transcription by coordinating co-transcriptional chromatin modifications and helping recruit mRNA 3' end processing factors. Paf1C cross-links to transcribed genes, but not downstream of the cleavage and polyadenylation site, suggesting that it may interact with the nascent mRNA. Paf1C purified from Saccharomyces cerevisiae binds RNA in vitro, as do the purified Leo1 and Rtf1 subunits of the complex. In vivo cross-linking and immunoprecipitation of RNA associated with Paf1C (RNA-IP) show that Leo1, but not Rtf1, is necessary for the complex to bind RNA. Cells lacking Leo1 have reduced Paf1C recruitment as well as decreased levels of histone H3 and trimethylated H3 Lys(4) within transcribed chromatin. Together, these results suggest that association of Paf1C with RNA stabilizes its localization at actively transcribed regions where it influences chromatin structure.


Effects of Elevated CO(2) Concentrations on Glycolysis in Intact ;Bartlett' Pear Fruit.
Mature intact ;Bartlett' pear fruit (Pyrus communis L.) were stored under a continuous flow of air or air + 10% CO(2) for 4 days at 20 degrees C. Fruit kept under elevated CO(2) concentrations exhibited reduced respiration (O(2) consumption) and ethylene evolution rates, and remained firmer and greener than fruit stored in air. Protein content, fructose 1,6-bisphosphate levels, and ATP:phosphofructokinase and PPi:phosphofructokinase activities declined, while levels of fructose 6-phosphate and fructose 2,6-bisphosphate increased in fruit exposed to air + 10% CO(2). These results are discussed in light of a possible inhibitory effect of CO(2) at the site of action of both phosphofructokinases in the glycolytic pathway, which could account, at least in part, for the observed reduction in respiration.


Blood-Brain Barrier Disruption Increases Amyloid-Related Pathology in TgSwDI Mice.
In Alzheimer's disease (AD), several studies have reported blood-brain barrier (BBB) breakdown with compromised function. P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) are transport proteins localized at the BBB luminal membrane and play an important role in the clearance of amyloid-β (Aβ). The purpose of this study was to investigate the effect of pharmacological inhibition of Aβ efflux transporters on BBB function and Aβ accumulation and related pathology. Recently, we have developed an in vitro high-throughput screening assay to screen for compounds that modulate the integrity of a cell-based BBB model, which identified elacridar as a disruptor of the monolayer integrity. Elacridar, an investigational compound known for its P-gp and BCRP inhibitory effect and widely used in cancer research. Therefore, it was used as a model compound for further evaluation in a mouse model of AD, namely TgSwDI. TgSwDI mouse is also used as a model for cerebral amyloid angiopathy (CAA). Results showed that P-gp and BCRP inhibition by elacridar disrupted the BBB integrity as measured by increased IgG extravasation and reduced expression of tight junction proteins, increased amyloid deposition due to P-gp, and BCRP downregulation and receptor for advanced glycation end products (RAGE) upregulation, increased CAA and astrogliosis. Further studies revealed the effect was mediated by activation of NF-κB pathway. In conclusion, results suggest that BBB disruption by inhibiting P-gp and BCRP exacerbates AD pathology in a mouse model of AD, and indicate that therapeutic drugs that inhibit P-gp and BCRP could increase the risk for AD.


First evidence for truffle production from plants inoculated with mycelial pure cultures.
Truffle (Tuber spp.) cultivation is based on raising mycorrhizal trees in greenhouses that have been inoculated with suspensions of ascospores. The problem with this is that pests, pathogens, and other mycorrhizal fungi can contaminate the trees. Furthermore, because ascospores are produced sexually, each plant potentially has a different genetic mycorrhizal makeup from each other so tailoring the mycorrhizal component of plants to suit a particular set of soil and climatic conditions is out of the question. Here, we report on the production of Tuber borchii-mycorrhized plants using pure cultures, establishing a truffière with these and subsequent production of its fruiting bodies. This study opens up the possibility of producing commercial numbers of Tuber-mycorrhized trees for truffle cultivation using mycelial inoculation techniques. It also poses questions about the mechanism of fertilization between the different strains which were located in different parts of the experimental truffière.


Multiple intracerebral metastases from an islet cell carcinoma of the pancreas: case report.
Computed tomography and magnetic resonance imaging of an 85-year-old woman with bitemporal headaches revealed cystic lesions in the basal ganglia and cerebellum. The patient remained neurologically asymptomatic until just before her death at age 89. Autopsy revealed tumors of the brain, lungs, liver, periaortic lymph nodes, adrenal gland, and the pancreas. Light microscopy demonstrated a malignant small cell tumor with scant cytoplasm. Electron microscopy revealed intracytoplasmic dense core vesicles, characteristic of neuroendocrine tumors, which prompted the diagnosis of islet cell carcinoma. All lesions were found to be microscopically similar. Previous reports of islet cell carcinoma metastatic to the brain could not be found. This case emphasizes the importance of electron microscopy in cases of small cell neoplasms in the brain.


Comparison of Early Efficacy of the Percutaneous Presuture Technique with the Femoral Artery Incision Technique in Endovascular Aortic Repair under Local Anesthesia for Uncomplicated Type B Aortic Dissection.
To compare the efficacy of the percutaneous presuture technique (PPST) and the femoral artery incision technique (FAIT) under local anesthesia in the treatment of endovascular aortic repair (EVAR) for patients with uncomplicated type B aortic dissection (uTBAD). Two hundred and ninety-five patients diagnosed with uTBAD who underwent EVAR under local anesthesia from June 2017 to December 2021 were consecutively and randomly selected for retrospective analysis. The PPST was performed in 178 cases and the FAIT was performed in 117 cases. The clinical characteristics and surgical and postoperative data from the two groups were analyzed. There were no significant differences in clinical characteristics between the two groups (p > 0.05). The operative time of the PPST group was significantly shorter than that of the FAIT group (46 (33, 58) versus 72 (67.5, 78.0) minutes, p < 0.001), as was the operative approach procedure time (6 (4.5, 9.0) versus 38 (36.5, 43.5) minutes, p < 0.001), and length of postoperative hospital stay (5.19 ± 2.26 versus 8.33 ± 3.76 days, p < 0.001). There were fewer postoperative approach-related procedural complications in the PPST group than in the FAIT group (2 versus 12, p < 0.001); similarly, the average frequency of postoperative wound disinfection was significantly lower in the PPST group (1.08 ± 0.39 versus 3.31 ± 0.91 times, p < 0.05). Obesity was identified as an independent risk factor for postoperative approach-related procedural complications (OR, 22.26; 95% CI, 4.74-104.49; p < 0.001). The PPST has comparable safety and efficacy to the FAIT in EVAR under local anesthesia. It can shorten the length of hospital stay, reduce operation time, lower the risk of wound-related complications, reduce the frequency of postoperative wound disinfection, and hasten postoperative recovery. It can therefore be used as a first-line surgical technique in EVAR of uTBAD under local anesthesia, especially in obese patients.


Possible modulation of FAS and PTP-1B signaling in ameliorative potential of Bombax ceiba against high fat diet induced obesity.
Bombax ceiba Linn., commonly called as Semal, is used in various gastro-intestinal disturbances. It contains Lupeol which inhibits PTP-1B, adipogenesis, TG synthesis and accumulation of lipids in adipocytes and adipokines whereas the flavonoids isolated from B. ceiba has FAS inhibitory activity. The present study was aimed to investigate ameliorative potential of Bombax ceiba to experimental obesity in Wistar rats, and its possible mechanism of action. Male Wistar albino rats weighing 180-220 g were employed in present study. Experimental obesity was induced by feeding high fat diet for 10 weeks. Methanolic extract of B. ceiba extract 100, 200 and 400 mg/kg and Gemfibrozil 50 mg/kg as standard drug were given orally from 7th to 10th week. Induction with HFD for 10 weeks caused significant (p < 0.05) increase in % body wt, BMI, LEE indices; serum glucose, triglyceride, LDL, VLDL, cholesterol, free fatty acid, ALT, AST; tissue TBARS, nitrate/nitrite levels; different fat pads and relative liver weight; and significant decrease in food intake (g and kcal), serum HDL and tissue glutathione levels in HFD control rats. Treatment with B. ceiba extract and Gemfibrozil significantly attenuated these HFD induced changes, as compared to HFD control. The effect of B. ceiba 200 and 400 mg/kg was more pronounced in comparison to Gemfibrozil. On the basis of results obtained, it may be concluded that the methanolic extract of stem bark of Bombax ceiba has significant ameliorative potential against HFD induced obesity in rats, possibly through modulation of FAS and PTP-1B signaling due to the presence of flavonoids and lupeol.


[The ultrasonic assessment of the cicatrix after a past cesarean section].
A supersonic study of the lower uterine segment of pregnant women which have had a Caesarean operation in the past has been made. The aim of this study is the confirmation of the supersonic scanning as a part of the struggle for diminution of the second abdominal deliveries. Twenty-six pregnant women with anamnesis of Caesarean operation were observed. The following conditions have been kept: precise probable term of delivery, gestational period--35-37 g.w., one foetus in head position, unspoiled amniotic fluid and full urinary bladder. It is obligatory a longitudinal and cross scanning in the area of the cicatrix to be made. For the assessment of the cicatrix sufficiency the author has applied supersonic criteria known in the literature. They include: shape, thickness, incessancy, outside lines and echo structure of the lower uterine segment. The results show: the scar is sufficient in 24 women--it has a triangular form in the lower uterine segment, even outside lines, the thickness of the cicatrix is above 3-5 mm it is incessant and with homogeneous echo structure. In 2 of th pregnant women there are data for inadequacy-the form is like a balloon, the cicatrix has got thinner under 3 mm, the incessancy of the lower segment is absent-it is with defects and uneven outside lines, the echo structure is heterogeneous with predominance of increased echogenicity. According to the way of delivery the results are confirmed pathohistologically, by microscope or by manual palpation. The effectiveness of the supersonic assessment of the cicatrix has been shown.


Multiview Feature Fusion Representation for Interictal Epileptiform Spikes Detection.
Interictal epileptiform spikes (IES) of scalp electroencephalogram (EEG) signals have a strong relation with the epileptogenic region. Since IES are highly unlikely to be detected in scalp EEG signals, the primary diagnosis depends heavily on the visual evaluation of IES. However, visual inspection of EEG signals, the standard IES detection procedure is time-consuming, highly subjective, and error-prone. Furthermore, the highly complex, nonlinear, and nonstationary characteristics of EEG signals lead to the incomplete representation of EEG signals in existing computer-aided methods and consequently unsatisfactory detection performance. Therefore, a novel multiview feature fusion representation (MVFFR) method was developed and combined with a robustness classifier to detect EEG signals with/without IES. MVFFR comprises two steps: First, temporal, frequency, temporal-frequency, spatial, and nonlinear domain features are transformed by the IES to express the latent information effectively. Second, the unsupervised infinite feature-selection method determines the most distinct feature fusion representations. Experimental results using a balanced dataset of six patients showed that MVFFR achieved the optimal detection performance (accuracy: 89.27%, sensitivity: 89.01%, specificity: 89.54%, and precision: 89.82%) compared with other feature ranking methods, and the MVFFR-related method were complementary and indispensable. Additionally, in an independent test, MVFFR maintained excellent generalization capacity with a false detection rate per minute of 0.15 on the unbalanced dataset of one patient.


Cutaneous nontuberculous mycobacterial infection: a clinicopathological study of 7 cases.
Nontuberculous mycobacteria (NTM) are human opportunistic pathogens with an environmental source of infection. The reports of cutaneous NTM infections has increased, and NTM have been regarded as important pathogens in recent years. This study aimed to identify characteristic clinical and histological features of cutaneous NTM infections. We evaluated the medical records and histopathologic slides of 7 cases of NTM infections that were confirmed by polymerase chain reaction between 2003 and 2007. The results showed that cutaneous NTM infections occurred in various aged people independent of their immune states and were associated with fish-related jobs or intramuscular medicinal injection. The main clinical feature was a painful erythematous nodule. Histopathologically, the most common findings were diffuse infiltration of mixed inflammatory cells and small vessel proliferation in the dermis (100%). Epidermal proliferation (71%) and dermal granuloma (71%) were also very common. Suppurative granuloma was found in 43% of the cases, and eosinophil infiltration was uncommon (14%). The lesions disappeared after a mean of 7 months (range, 1.5-12 months) with treatment by oral clarithromycin alone or in combination with other antimycobacterial agents. These clinical and histopathological data should assist clinicians in the diagnosis of NTM.


Electrophysiological responses of hypertrophied rat myocardium to combined hypoxia, hyperkalemia, and acidosis.
We studied whether electrophysiological response to ischemia could be different in hypertrophied left ventricle of spontaneously hypertensive rats (SHRs) and in normal left ventricle of normotensive Wistar-Kyoto (WKY) rats. For that purpose, we used a two-compartment tissue bath in which one-half of a left ventricular strip was exposed to normal conditions and the other part to ischemic conditions (low pH, hypoxia, and hyperkalemia). Electrical activity was recorded using standard microelectrodes in normal and hypertrophied preparations. Under basal conditions, the action potential duration (APD) and effective refractory period (ERP) were longer in SHRs than in WKY rats (118 +/- 9 ms vs 81 +/- 3 ms, p less than 0.05 and 90 +/- 9 ms vs. 74 +/- 4 ms, p less than 0.05, respectively). During ischemia, the APD and ERP changed in opposite ways in both groups and we observed the development of postrepolarization refractoriness that was greater in hypertrophied than in normal hearts. Maximum upstroke velocity (Vmax) values were 229 +/- 12 and 227 +/- 10 V/s in the SHR and the WKY preparations, respectively. Three minutes after the induction of ischemia, Vmax values decreased to 46 +/- 7 V/s in SHRs and to 106 +/- 12 V/s in WKY rats. A significant increase in subendocardial collagen density was measured in SHR left ventricle compared to WKY rats (4.39 +/- 0.34% vs. 1.66 +/- 0.15%, p less than 0.05), which might partly explain the impaired conduction observed in hypertrophied preparations during ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)


Molecular and Clinical Characterization of a Novel Prognostic and Immunologic Biomarker GPSM3 in Low-Grade Gliomas.
Background: as the most common malignancy of the central nervous system, low-grade glioma (LGG) patients suffered a poor prognosis. Tumor microenvironment, especially immune components, plays an important role in the progression of tumors. Thus, it is critical to explore the key immune-related genes, a comprehensive understanding of the TME in LGG helps us find novel cancer biomarkers and therapeutic targets. Methods: the GPSM3 expression level and the correlations between clinical characteristics and GPSM3 levels were analyzed with the data from CGGA and TCGA dataset. Univariate and multivariate cox regression model were built to predict the prognosis of LGG patients with multiple factors. Then the correlation between GPSM3 with immune cell infiltration was explored by ESTIMATE, CIBERSORT and TIMER2.0. At last, the correlation analyzed between GPSM3 expression and immune checkpoint related genes were also analyzed. Results: GPSM3 expression was overexpressed in LGG and negatively correlated to the GPSM3 DNA methylation. Univariate and multivariate Cox analysis demonstrated that GPSM3 expression was an independent prognostic factor in LGG patients. Functional characterization of GPSM3 revealed that it was associated with many immune processes to tumor cells. GPSM3 expression was positive related to the immune score, Stromal scores and ESTIMATE scores, but negative related to the Tumor purity. Immune features in the TME of GPSM3-high LGG group is characterized by a higher infiltrating of regulatory T cells, neutrophils, macrophages M2, and a lower proportion of monocytes than to the GPSM3-low group. Furthermore, GPSM3 expression exhibited significant correlations with the immune checkpoint-related genes, especially PD-1, PD-L1, PD-L2, CTLA4 and TIM3. Conclusions: these findings proved that GPSM3 could serve as a prognostic biomarker and potential immunotherapy target for LGG.


Computational identification of rare codons of Escherichia coli based on codon pairs preference.
Codon bias is believed to play an important role in the control of gene expression. In Escherichia coli, some rare codons, which can limit the expression level of exogenous protein, have been defined by gene engineering operations. Previous studies have confirmed the existence of codon pair's preference in many genomes, but the underlying cause of this bias has not been well established. Here we focus on the patterns of rarely-used synonymous codons. A novel method was introduced to identify the rare codons merely by codon pair bias in Escherichia coli. In Escherichia coli, we defined the "rare codon pairs" by calculating the frequency of occurrence of all codon pairs in coding sequences. Rare codons which are disliked in genes could make great contributions to forming rare codon pairs. Meanwhile our investigation showed that many of these rare codon pairs contain termination codons and the recognized sites of restriction enzymes. Furthermore, a new index (F(rare)) was developed. Through comparison with the classical indices we found a significant negative correlation between F(rare) and the indices which depend on reference datasets. Our approach suggests that we can identify rare codons by studying the context in which a codon lies. Also, the frequency of rare codons (F(rare)) could be a useful index of codon bias regardless of the lack of expression abundance information.


Epidermolysis bullosa letalis with pyloric atresia in an infant.
Epidermolysis bullosa (EB) is a group of inherited diseases, that are characterized by vesiculobullous lesions that arise in response to minimal trauma or friction. The three major groups of EB differ according to the ultrastructural level of cleavage namely: simplex (epidermolytic), junctional and dystrophic (dermolytic). The combination of EB and pyloric atresia in rare and there is a definite association between them. We report a baby boy who died epidermolysis bullosa complications despite successful surgical correction of this pyloric atresia.


An experimental model for side-to-side microvascular anastomosis.
Side-to-side microvascular anastomosis may be required in certain clinical situations, although the technique is difficult and the incidence of usage remains low. A new experimental model using rat femoral vessels for side-to-side microvascular anastomosis is presented, in which 100 percent patency was accomplished immediately and was maintained for 7 days after anastomosis. This model can provide a training tool for acquisition of advanced microsurgical technique for side-to-side anastomosis of small vessels.


Control of erythropoietin secretion by doxycycline or mifepristone in mice bearing polymer-encapsulated engineered cells.
Cell encapsulation offers a safe and manufacturable method for the systemic delivery of therapeutic proteins from genetically engineered cells. However, control of dose delivery remains a major issue with regard to clinical application. We generated populations of immortalized murine NIH 3T3 fibroblasts that secrete mouse erythropoietin (Epo) in response to stimulation by doxycycline or mifepristone. Engineered cells were introduced into AN69 hollow fibers, which were implanted in the peritoneal cavity or recipient mice. Animals receiving doxycycline or mifepristone showed stable polyhemia and increased serum Epo concentrations over a 6-month observation period, whereas animals not receiving the inducer drug had normal hematocrits. Epo secretion could be switched on and off, depending on the presence of doxycycline in the drinking water. In contrast, polyhemia was hardly reversible after subcutaneous injections of mifepristone. These data show that a permanent and regulated systemic delivery of a therapeutic protein can be obtained by the in vivo implantation of engineered allogeneic cells immunoprotected in membrane polymers.


[Crigler-Najjar syndrome type II in a 17-year-old girl].
The Crigler-Najjar-Syndrome type II is characterised by the decreased activity of the bilirubin-UDP-glucuronyltransferase. This fact leads to an increase of the indirect bilirubin to 6-10 mg/dl. The mode of hereditary transmission is autosomal dominant with variable penetrance. The age of manifestation varies from the first year to the second decade of life. The Crigler-Najjar-Syndrome type II of a 17-year-old girl is reported. The diagnosis was made on the basis of the pattern of laboratory parameters in combination with an uneventful morphology of the liver. Under treatment with Chlofibrat the decrease of the serum total bilirubin from 10.4 mg/dl to 2 mg/dl was achieved.


Nutritional and toxicological evaluations of kochia hay (Kochia scoparia) fed to lambs.
Kochia foliage that had tested positive to Dragendorff's reagent (presumptive alkaloids) and had elicited chronic toxicosis when fed to rats was fed to sheep to characterize early stages of kochia toxicosis and evaluate treatments that might improve tolerance. Twelve fine-wool lambs (46 +/- 9 kg BW) were fed chopped kochia hay (35%) mixed with chopped alfalfa hay (65%) for 4 wk. The kochia diet had 14.3% CP and 39.9% ADF. Dry matter intake averaged 3.4% of BW/d. Body weight did not change during 4 wk and blood serum components were not changed from values at the onset. Thereafter, kochia was increased to 50% of diet for five more weeks, during which four treatments were imposed randomly (three lambs/treatment): 1) none; 2) N-acetyl-L-cysteine plus trans-stilbene oxide, 21 and 52 mg/kg of BW, respectively, given i.p. twice weekly; 3) retinyl palmitate, 275 mg, plus alpha-tocopherol, 300 mg/lamb dosed i.m. twice weekly; and 4) zinc sulfate mixed in the feed to provide 500 mg daily. Kochia contained 4.8% oxalate. The diet with 50% kochia had 16% CP and 36% ADF, and digestibility coefficients were 59% for DM, 72% for CP, and 59% for ADF. After 5 wk, blood glucose was elevated slightly, total bilirubin was increased about 1.5-fold (P less than .05), alanine aminotransferase was elevated slightly (P less than .05), and inorganic phosphorus and urea (blood urea N) were diminished (P less than .05); other serum components, including calcium, were unchanged from initial levels (P greater than .10). Treatments had negligible effects for modifying serum signs of mild chronic toxicosis associated with kochia hay fed as 50% of diet.


Solid-phase synthesis of the 2-aminobenzoxazole library using thioether linkage as the safety-catch linker.
An efficient solid-phase methodology has been developed for the synthesis of 2-aminobenzoxazole derivatives. The key step in this procedure involves preparation of polymer-bound 2-mercaptobenzoxazole resins 3 by reaction of the Merrifield resin with 2-aminophenols and CS(2) in the presence of DIC in MeCN. Oxidation of the resulting resins followed by treatment with amines gives the desired 2-aminobenzoxazole products 5. Further diversification can be introduced to the key resin 11, derived from the nitro group containing resin 3c. This process produces the corresponding amine, which upon reaction with acid chlorides and isocyanates can be used to generate various 6-functionalized 2-aminobenzoxazole analogues 13 and 15.


Ground state spectroscopy of hydroxyquinolines: evidence for the formation of protonated species in water-rich dioxane-water mixtures.
We have recently used 6-, 7-, and 8-hydroxyquinolines (HQs) as fluorescent probes to study the binding mechanism in one of the drug binding sites of human serum albumin. In the present work we study the absorption spectra of the HQ molecules in neat and binary mixtures of dioxane and water in order to identify the different tautomeric species in the ground state. This study should help in identifying the environment in nanocavities of macromolecules when HQs are used as local reporters. The enol form is shown to be the only tautomer for the three HQs in dioxane and water, with the exception of 7HQ in which both the enol and the zwitterion tautomers exist in equilibrium in water. The results are confirmed by the density functional theory (DFT) calculations using the B3LYP method with a 6-311++G(2d,p) basis set. In water-rich dioxane mixtures, all HQs are protonated. The results were confirmed by comparing the absorption spectra in binary solvents with those in acidic and basic aqueous solutions, and by DFT calculations of the Franck-Condon S1 ← S0 transitions. The number of water molecules solvating the polar sites in each HQ molecule was estimated from the spectral change in the binary solvent mixtures, and structures were calculated by DFT. Mapping the water density around the polar sites in each HQ using molecular dynamics (MD) simulations shows well-defined hydrogen bonds around the N-heteroatom in each HQ molecule. Water density is only well-defined around the hydroxyl group in 8HQ. The MD simulations indicate free rotation of the OH group in 6HQ and 7HQ, and the stability of the cis-isomer in 8HQ. The results point to the unique spectral signatures of 7HQ in water which make this molecule a potential probe to detect the presence of water in nanocavities of macromolecules, and to the ability of the three HQs to detect acidic media in binding sites.


Non-local means filter denoising for DEXA images.
Dual high and low energy images of Dual Energy X-ray Absorptiometry (DEXA) suffer from noises due to the use of weak amount of X-rays. Denoising these DEXA images could be a key process to enhance and improve a Bone Mineral Density (BMD) map which is derived from a pair of high and low energy images. This could further improve the accuracy of diagnosis of bone fractures, osteoporosis, and etc. In this paper, we present a denoising technique for dual high and low energy images of DEXA via non-local means filter (NLMF). The noise of dual DEXA images is modeled based on both source and detector noises of a DEXA system. Then, the parameters of the proposed NLMF are optimized for denoising utilizing the experimental data from uniform phantoms. The optimized NLMF is tested and verified with the DEXA images of the uniform phantoms and real human spine. The quantitative evaluation shows the improvement of Signal-to-Noise Ratio (SNR) for the high and low phantom images on the order of 30.36% and 27.02% and for the high and low real spine images on the order of 22.28% and 33.43%, respectively. Our work suggests that denoising via NLMF could be a key preprocessing process for clinical DEXA imaging.


N-nitrosodiethylamine-induced hepatocarcinogenesis in estuarine sheepshead minnow (Cyprinodon variegatus): neoplasms and related lesions compared with mammalian lesions.
Groups of estuarine sheepshead minnows (Cyprinodon variegatus) were exposed to approximately 57 mg N-nitrosodiethylamine [(DENA) CAS: 55-18-5]/liter for 5-6 weeks. Exposure was stopped and the fish were then transferred to clean, flowing seawater. Induced liver lesions were studied in periodic samples of fish taken during the next 140 weeks of holding. Lesions found following exposure were early altered basophilic and eosinophilic foci, oval cell hyperplasia, clear cell foci, neoplastic nodules, hepatocellular carcinomas, cholangiolar carcinomas, possible pericytomas originating in liver, hemangiopericytomas, spongiosis hepatis, and cholangiofibrosis. The relative prevalence of these lesions was given. Most of these lesions morphologically were compared to their counterpart lesions in the rat. Certain lesions in our fish such as hepatocellular carcinomas, cholangiolar carcinomas, pericytomas, hemangiopericytomas, spongiosis hepatis, and cholangiofibrosis have apparent similar cellular origins and morphogenesis to those lesions in rats and perhaps in other mammals. Spongiosis hepatis in the sheepshead minnow apparently arises from perisinusoidal cells and may be a neoplasm of this cell type. The general similarity of response to DENA in sheepshead minnows and rats suggests that this fish has promise as a model subject for studying some hepatocarcinogens and as a sentinel organism for detecting hepatocarcinogens in contaminated coastal waters.


Literature review and implications for social work practice with Hispanic dialysis patients.
Many renal social workers are uncertain about what to expect when providing services to Hispanic patients. The Hispanic dialysis population is a growing minority with a diverse culture. The Hispanic patient's family members are a source of natural support and strength. This article profiles a review of the literature available regarding working with Hispanic patients and their families in a medical setting and provides implications for renal social work practice.


Gift of life or cultural taboo: effects of an educational pamphlet on young adults' knowledge and attitudes regarding organ donation.
As a result of a shortage of organs that can be used for transplantation in South Africa, as well as a lack of awareness and cultural taboos around organ donation, many individuals do not receive the organs they need and are sent home to die, raising questions about distributive justice and the right to life. The study therefore investigated whether an educational pamphlet might change perceptions of young adults regarding organ donation. A questionnaire comprising a knowledge scale, an attitudinal scale, and open-ended questions was administered to 18 young adults from Johannesburg via individual interviews before and after providing them with an educational brochure on organ donation. Findings suggested that the brochure changed participants' knowledge and attitudes regarding organ donation. The study enhances understanding of factors influencing organ donation and highlights the role of social workers in this regard.


Notes from the field: Strongyloidiasis in a rural setting--Southeastern Kentucky, 2013.
Strongyloidiasis is caused by Strongyloides stercoralis, a parasitic nematode (worm). Initial symptoms can include abdominal pain, diarrhea, or rash. Infection is often asymptomatic in the chronic phase but can be life-threatening in immunosuppressed persons. Transmission typically occurs when larvae from stool-contaminated soil penetrate skin; intraintestinal autoinfection is also possible, sometimes allowing infection to persist for decades. Serologic studies are often used in prevalence estimates because intermittent shedding can make stool-based testing insensitive. Strongyloidiasis is most common in tropical and subtropical environments with poor sanitation. In the United States, it is commonly reported among refugees and immigrants; in the 1980s, studies in the rural southeastern United States also reported prevalence estimates ranging from 1.2%-6.1%. Prevalence might have since decreased because of investments in sanitation; however, no recent studies have been done, and strongyloidiasis is not a reportable disease in any state.


Fast and accurate hashing via iterative nearest neighbors expansion.
Recently, the hashing techniques have been widely applied to approximate the nearest neighbor search problem in many real applications. The basic idea of these approaches is to generate binary codes for data points which can preserve the similarity between any two of them. Given a query, instead of performing a linear scan of the entire data base, the hashing method can perform a linear scan of the points whose hamming distance to the query is not greater than rh , where rh is a constant. However, in order to find the true nearest neighbors, both the locating time and the linear scan time are proportional to O(∑i=0(rh)(c || i)) ( c is the code length), which increase exponentially as rh increases. To address this limitation, we propose a novel algorithm named iterative expanding hashing in this paper, which builds an auxiliary index based on an offline constructed nearest neighbor table to avoid large rh . This auxiliary index can be easily combined with all the traditional hashing methods. Extensive experimental results over various real large-scale datasets demonstrate the superiority of the proposed approach.


Hemispheric asymmetry of primary auditory cortex and Heschl's gyrus in schizophrenia and nonpsychiatric brains.
Heschl's gyrus (HG) is reported to have a normal left>right hemispheric volume asymmetry, and reduced asymmetry in schizophrenia. Primary auditory cortex (A1) occupies the caudal-medial surface of HG, but it is unclear if A1 has normal asymmetry, or whether its asymmetry is altered in schizophrenia. To address these issues, we compared bilateral gray matter volumes of HG and A1, and neuron density and number in A1, in autopsy brains from male subjects with or without schizophrenia. Comparison of diagnostic groups did not reveal altered gray matter volumes, neuron density, neuron number or hemispheric asymmetries in schizophrenia. With respect to hemispheric differences, HG displayed a clear left>right asymmetry of gray matter volume. Area A1 occupied nearly half of HG, but had less consistent volume asymmetry, that was clearly present only in a subgroup of archival brains from elderly subjects. Neuron counts, in layers IIIb-c and V-VI, showed that the A1 volume asymmetry reflected differences in neuron number, and was not caused simply by changes in neuron density. Our findings confirm previous reports of striking hemispheric asymmetry of HG, and additionally show evidence that A1 has a corresponding asymmetry, although less consistent than that of HG.


Impact of SARS-CoV-2 variants on inpatient clinical outcome.
Prior observation has shown differences in COVID-19 hospitalization rates between SARS-CoV-2 variants, but limited information describes differences in hospitalization outcomes. Patients admitted to 5 hospitals with COVID-19 were included if they had hypoxia, tachypnea, tachycardia, or fever, and data to describe SARS-CoV-2 variant, either from whole genome sequencing, or inference when local surveillance showed ≥95% dominance of a single variant. The average effect of SARS-CoV-2 variant on 14-day risk of severe disease, defined by need for advanced respiratory support, or death was evaluated using models weighted on propensity scores derived from baseline clinical features. Severe disease or death within 14 days occurred for 950 of 3,365 (28%) unvaccinated patients and 178 of 808 (22%) patients with history of vaccination or prior COVID-19. Among unvaccinated patients, the relative risk of 14-day severe disease or death for Delta variant compared to ancestral lineages was 1.34 (95% confidence interval [CI] 1.13-1.55). Compared to Delta variant, this risk for Omicron patients was 0.78 (95% CI 0.62-0.97) and compared to ancestral lineages was 1.04 (95% CI 0.84-1.24). Among Omicron and Delta infections, patients with history of vaccination or prior COVID-19 had one-half the 14-day risk of severe disease or death (adjusted hazard ratio 0.46, IQR 0.34-0.62) but no significant outcome difference between Delta and Omicron infections. Although the risk of severe disease or death for unvaccinated patients with Omicron was lower than Delta, it was similar to ancestral lineages. Severe outcomes were less common in vaccinated patients, but there was no difference between Delta and Omicron infections.


Quantification of radiological damage in inflammatory arthritis: rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis.
Quantification of radiological damage in inflammatory arthritis is important. It has proven its value in clinical trials, but its use in clinical practice is becoming more important as well. Scoring methods for rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis are available. These differ in the joints and features assessed. This results in differences in the scoring range, but also in the method of performance. The various methods for the three diseases are detailed in this chapter. Most information is available for rheumatoid and for this disease the relationship between radiological damage and long-term outcome is summarised.


Consumption of low-fat dairy foods for 6 months improves insulin resistance without adversely affecting lipids or bodyweight in healthy adults: a randomized free-living cross-over study.
Given the highly debated role of dairy food consumption in modulating biomarkers of metabolic syndrome, this study was conducted to examine the influence of long-term (6 month) dairy consumption on metabolic parameters in healthy volunteers under free-living conditions without energy restriction. Twenty-three healthy subjects completed a randomized, crossover trial of 12 months. Participants consumed their habitual diets and were randomly assigned to one of two treatment groups: a high dairy supplemented group instructed to consume 4 servings of dairy per day (HD); or a low dairy supplemented group limited to no more than 2 servings of dairy per day (LD). Baseline, midpoint, and endpoint metabolic responses were examined. Endpoint measurements of body weight and composition, energy expenditure, blood pressure, blood glucose, and blood lipid and lipoprotein responses did not differ (p > 0.05) between the LD and HD groups. HD consumption improved (p < 0.05) plasma insulin (-9%) and insulin resistance (-11%, p = 0.03) as estimated by HOMA-IR compared with the LD group. Study results suggest that high dairy consumption (4 servings/d) may improve insulin resistance without negatively impacting bodyweight or lipid status under free-living conditions. Clinical Trials.gov: NCT01761955.


The response of the dietary anti-oxidants vitamin E and vitamin C to oxidative stress in pre-eclampsia.
The relationship of oxidants and anti-oxidants in preeclampsia with reference to the dietary anti-oxidants vitamin C and vitamin E was investigated. Three groups of patients were studied in the third trimester of pregnancy: normotensives ( n = 32), mild pre-eclamptics ( n = 15) and severe pre-eclamptics ( n = 31) with a group of healthy non-pregnant women ( n = 18) serving as a control. Total anti-oxidant concentration, the concentrations of vitamin C, vitamin E, superoxide dismutase, uric acid and the concentration of total oxidant activity, as reflected by lipid peroxides, were measured in plasma or red blood cells. Total anti-oxidants and vitamin C concentrations were significantly lower in pre-eclamptic patients than in pregnant controls (P < 0.05), with the concentrations in the pregnant controls being significantly lower than in the non-pregnant controls (P < 0.05). There was no significant difference in vitamin E concentration for all four groups. Superoxide dismutase activity was significantly lower in the normal pregnancy group. Lipid peroxides were significantly increased in the three pregnant groups (P < 0.05) with no differences noted between these groups. The relationship of oxidants to anti-oxidants in pregnancy and pre-eclampsia is dependent on many factors but balance appears to be upset in pre-eclampsia. The reduction in anti-oxidant concentrations in pre-eclampsia suggests either a primary deficit or consumption of the anti-oxidants measured. Of the dietary anti-oxidants studied, vitamin C was most affected in pre-eclampsia.


Phenotype-genotype relationships of SULT1A1 in human liver and variations in the IC50 of the SULT1A1 inhibitor quercetin.
Human sulfotransferases catalyze sulfate conjugation and 2 polymorphic genes, SULT1A1 and SULT1A2 in this family of transferases have been identified, encoding for 2 isoenzymes with very similar properties and substrate specificities. In order to test the hypothesis that variability in sulfation is due to genetic polymorphism in SULT1A1, the sulfation rate of 4-nitrophenol, a diagnostic substrate, was measured in 50 human liver samples and the genotype at the SULT1A1 locus was analyzed. The rate of 4-nitrophenol sulfation varied from 473 - 1,405 pmol/min/mg between the 5th and 95th percentiles, with a median and a mean +/- SD of 757 and 807 +/- 292 pmol/min/mg, respectively. The activities detected among the SULT1A1*2/*2 homozygotes (5 cases) were significantly lower than those of the other 2 genotypes, SULTA1*11/*1 and SULT1A1*1/*2 (5 and 40 cases, respectively), whereas there was no significant difference found between the SULT1A1*1/*1 and SULT1A1*1/*2 genotypes. To evaluate the possible influence of SULT1A2 polymorphism, genotype assays were also performed for this locus. No SULT1A2*2/*2 carrier, 26 SULT1A2*1/*1 and 24 SULT1A2*1/*2 were detected in the population sample under study. However, no correlation between the rate of 4-nitrophenol sulfation and the SULT1A2 genotype was detected. These results confirm that the variation in the rate of 4-nitrophenol sulfation in human liver is mainly due to SULT1A. Since SULT1A1*1/*2 polymorphism accounts for no more than 10% of the phenotypic variation seen in this cohort, other factors must also contribute to the variability in the rate of 4-nitrophenol sulfation in human liver. However, on the basis of the data obtained, variations in age, gender and liver function as possible causative factors can be excluded. The IC50 of quercetin, a potent inhibitor of 4-nitrophenol sulfation, was measured in the liver samples and ranged from 4.6 to 17.3 nM between the 5th and 95th percentiles. The median and the mean +/- SD were 7.7 nM and 8.3 +/- 2.5 nM, respectively. There was a weak but significant correlation between the IC50 value and age of the liver donors (r = 0.283, p = 0.046). The observed variation did not correlate with the genotypes at the SULT1A1 and SULT1A2 loci.


Influence of body mass index on median nerve function, carpal canal pressure, and cross-sectional area of the median nerve.
Obese individuals have slowed conduction in the median nerve across the wrist, but the mechanism for this is not established. This case-control study of 27 obese subjects and 16 thin subjects was designed to test the hypothesis that obese individuals have higher carpal canal pressures and more median nerve swelling than thin individuals. All subjects were asymptomatic for hand symptoms, and had measurements of median and ulnar sensory nerve conduction in the nondominant hand, ultrasound measurement of the median nerve cross-sectional area proximal to the carpal canal, and carpal canal pressure measurement. There was no difference in age or gender ratio between the obese and thin groups. The median nerve cross-sectional area was equal in the obese and thin groups (9.3 mm2 vs. 9.4 mm2), as was the carpal canal pressure (16.2 mmHg vs. 15.5 mmHg, respectively). There was a strong correlation between median nerve conduction slowing across the wrist and median nerve cross-sectional area at the wrist (r = 0.55, P = 0.002). Obesity does not influence carpal canal pressure or the size of the median nerve at the wrist. However, there is a strong association between slowed median nerve conduction and increased nerve size which suggests endoneurial edema as a metabolic mechanism; the conduction slowing does not appear to be related to mechanical stress.


Benchmarking Bacterial Promoter Prediction Tools: Potentialities and Limitations.
The promoter region is a key element required for the production of RNA in bacteria. While new high-throughput technology allows massively parallel mapping of promoter elements, we still mainly rely on bioinformatics tools to predict such elements in bacterial genomes. Additionally, despite many different prediction tools having become popular to identify bacterial promoters, no systematic comparison of such tools has been performed. Here, we performed a systematic comparison between several widely used promoter prediction tools (BPROM, bTSSfinder, BacPP, CNNProm, IBBP, Virtual Footprint, iPro70-FMWin, 70ProPred, iPromoter-2L, and MULTiPly) using well-defined sequence data sets and standardized metrics to determine how well those tools performed related to each other. For this, we used data sets of experimentally validated promoters from Escherichia coli and a control data set composed of randomly generated sequences with similar nucleotide distributions. We compared the performance of the tools using metrics such as specificity, sensitivity, accuracy, and Matthews correlation coefficient (MCC). We show that the widely used BPROM presented the worse performance among the compared tools, while four tools (CNNProm, iPro70-FMWin, 70ProPred, and iPromoter-2L) offered high predictive power. Of these tools, iPro70-FMWin exhibited the best results for most of the metrics used. We present here some potentials and limitations of available tools, and we hope that future work can build upon our effort to systematically characterize this useful class of bioinformatics tools.IMPORTANCE The correct mapping of promoter elements is a crucial step in microbial genomics. Also, when combining new DNA elements into synthetic sequences, predicting the potential generation of new promoter sequences is critical. Over the last years, many bioinformatics tools have been created to allow users to predict promoter elements in a sequence or genome of interest. Here, we assess the predictive power of some of the main prediction tools available using well-defined promoter data sets. Using Escherichia coli as a model organism, we demonstrated that while some tools are biased toward AT-rich sequences, others are very efficient in identifying real promoters with low false-negative rates. We hope the potentials and limitations presented here will help the microbiology community to choose promoter prediction tools among many available alternatives.


Beyond diversity: toward a cultural community psychology.
We are increasingly considering culture as the context of diversity and, in the process, becoming a cultural community psychology. Our recent progress is discussed and a suggestion to accelerate our progress through greater collaboration with cultural psychology(4) is offered. The development of a cultural community psychology has implications for the traditional distinction between basic and applied psychology, our understanding of context, partnerships between academicians and practitioners, and the place of community psychology within the discipline of psychology. These implications are presented and discussed.


Introduction to the Novel Techniques in Microscopy feature issue.
The editors introduce the feature issue on "Novel Techniques in Microscopy", which was the topic of a symposium held on April 14-18, 2013, in Waikoloa Beach, HI. This symposium was part of the Optics in the Life Sciences Congress.


In vitro fertilization-induced pregnancies predispose to gastroesophageal reflux disease.
Women conceiving following in vitro fertilization (IVF) likely have a variety of risk factors that predispose them to gastroesophageal reflux disease (GERD) in the future. We aimed to investigate whether pregnancy through IVF may predispose to subsequent GERD compared with pregnancies without IVF. We also evaluate whether twin IVF pregnancies lead to additional risk for having GERD compared with singleton IVF pregnancies. A validated reflux questionnaire was administered to 156 women with singleton (n = 102) or twin (n = 54) IVF birth (IVF group) and 111 women with a naturally conceived singleton birth (control group). All women included in the study were primiparas who had given birth at least 1 year prior to data collection. The diagnosis of GERD was based on the occurrence of typical symptoms (heartburn, regurgitation, or both) at least once a week. The prevalence of GERD was 13.5% and 4.5% in IVF and control groups (p = 0.015); in the IVF group, this was slightly higher, but not statistically significant, in women with twin compared with singleton pregnancies (14.8% vs. 12.7%, p = 0.749). Logistic regression analysis showed that IVF was strongly associated with subsequent GERD (OR, 3.30; 95% CI 1.20-9.04; p = 0.02). The risk of developing GERD at least 1 year after delivery increased following IVF. Long-term follow-up studies are required to determine whether therapy during pregnancy can prevent this risk.


Localized severe scleroderma: a retrospective study of 26 pediatric patients.
Juvenile localized scleroderma includes different conditions characterized by skin hardening with increased collagen deposition. Although juvenile localized scleroderma is considered a relatively benign disease, lesions may extend through the dermis, subcutaneous tissue, muscles, and the underlying bone, leading to significant functional and cosmetic deformities. Furthermore, extracutaneous manifestations are described. We retrospectively analyzed a cohort of 26 patients with severe Juvenile localized scleroderma with particular attention to clinical features, therapy, and long-term outcome. A subgroup of three patients has been further evaluated with infrared thermography. Our findings were consistent with the current literature for demographic, laboratory, and clinical characteristics at disease onset, but, with our patients, the prevalence of extracutaneous manifestations was higher, thus confirming the potential for severe juvenile localized scleroderma to affect organs other than the skin, without increased risk of development toward systemic sclerosis. Correlation between various treatments and clinical endpoint showed that systemic therapy lead to a better outcome: in particular, methotrexate appeared the most effective drug, capable in halting the progression of the disease and sometimes inducing its regression.


Amyloid-beta: acute-phase apolipoprotein with metal-binding activity.
In monomeric form, amyloid-beta (Abeta), an amphipatic 4 kDa peptide which plays a key role in the pathogenesis of Alzheimer's disease (AD), is associated with lipoproteins in biological fluids and possesses high affinity to transition metal ions; in addition, synthesis of Abeta is upregulated under acute phase conditions. These data suggest that Abeta can be regarded as a normal physiological component of lipoproteins and may represent an acute-phase apolipoprotein with metal-binding activity. Interaction with transition metal ions may cause aggregation of Abeta, leading to formation of oligomers. Such oligomerised Abeta may lose its normal biological functions and acquire deleterious activities. To be efficient, novel anti-AD therapies should target oligomeric forms of Abeta while preserving the monomeric form of the peptide.


Isolation and Characterization of Factors in Sweet Potato Root Which Agglutinate Germinated Spores of Ceratocystis fimbriata, Black Rot Fungus.
A factor which agglutinates the germinated spores of Ceratocystis fimbriata was isolated from the sweet potato root. The factor is a glycoprotein with a molecular weight of 1.6 x 10(6) daltons and required divalent cations such as Ca(2+), Mn(2+), Ni(2+), and Mg(2+) for activity. The activity of the factor was pH-dependent. The factor also agglutinated rabbit erythrocytes and is classified as a phytohemagglutinin or lectin. The factor agglutinated germinated spores of seven strains of C. fimbriata to almost the same degree. The factor showed differential agglutinating activity toward the strains in the presence of unidentified low molecular weight factor(s) in the sweet potato root. These results support our earlier suggestion that the spore-agglutinating factors in host plants function as the determinants of specificity in some host-parasite interactions.


Low interleukin-8 level predicts the occurrence of the postpericardiotomy syndrome.
The objective of this study was to investigate inflammatory markers of the postpericardiotomy syndrome (PPS) and to determine individuals prone to develop the PPS. The study included 75 patients with a stable coronary disease that had underwent coronary artery bypass surgery. Serum samples were collected prior to the surgery and on the 5th day after the operation, to measure the concentration of IL-8, IL-6, IL-1β, IL-10, TNF, IL-12p70. All included patients were screened for the PPS before discharge from the hospital and 6 months after the surgery. The 49 patients developed the PPS (65.4%), among them 42 (56%) patients had pleural effusion, and 23 (31%) had pericardial effusion. The cytokine analysis has shown an inverse correlation between IL-8 concentration before the surgery, and the occurrence of the PPS (p = 0.026). There were also positive correlations between the magnitude of increase of IL-8 and IL-1β concentrations on the 5th day after the surgery and the occurrence of the PPS (p = 0.006 and p = 0.049 respectively). Multivariate analysis revealed IL-8 concentration before surgery as an independent risk factor of the PPS development (HR = 0.976; 95%CI: 0.956-0.996, p = 0.02). Cut-off point was established to assess the predictive value of IL-8 concentration (21.1 pg/ml). The test parameters were: sensitivity: 62.5%, specificity: 75%, positive predictive value: 83% and negative predictive value: 50%. Clinical evaluation showed the relationship between the hemoglobin concentration before the surgery and the PPS occurrence (p = 0.01). The IL-8 and IL-1β may participate in the postpericardiotomy syndrome pathogenesis, and the IL-8 concentration measurement may select patients with the risk of the PPS development.


Results of a phase II concurrent chemoradiotherapy study using three-dimensional conformal radiotherapy with cisplatin and oral etoposide in stage III nonsmall-cell lung cancer.
This phase II study was designed to utilize conformal radiation therapy with cisplatin and oral etoposide in patients with stage III or locally recurrent non-small-cell lung cancer to determine tolerance and toxicity of therapy. From April 1992-February 1996, 18 patients with pathologically confirmed stage IIIA, IIIB, or locally recurrent non-small-cell lung cancer (NSCLC) were entered on study. Metastatic workup included a CT scan of the thorax and upper abdomen as well as a bone scan. Chemotherapy consisted of IV cisplatin (100 mg/m2) with IV etoposide (25 mg/m2) on day 1; oral etoposide was given (50 mg/m2) days 2-14. Using three-dimensional planning, 40-45 Gy were delivered to the clinical target volume, followed by a boost to the gross tumor volume for a total of 70 Gy. Patients with recurrent disease received 40-50 Gy in total. Eighteen patients were enrolled: 16 patients were treated with curative intent and were evaluable for outcome. Two patients were treated for locally recurrent NSCLC and were not included in the outcome analysis. Stages included IIIA (44%) and stage IIIB (54%). Forty-four percent had T3/4 tumors, and 69% had N2/3 disease. Overall survival at 1 year was 64%, while 2-year overall survival was 50%. Distant metastasis-free survival at 1 year was 67%, and at 2 years 60%. The 1-year chest progression-free survival was 57%, and at 2 years 50%. Sixty-three percent required hospitalization for dehydration or neutropenia. Fifty-six percent developed leukopenia (<1,000 cells/microl) sometime during the therapy. We conclude that concurrent cisplatin and oral etoposide with conformal radiation therapy provide encouraging results in stage III lung cancer. The major toxicities of this therapy included leukopenia, thrombocytopenia, and mucosal esophagitis. Local progression of disease continues to be a problem with the current doses given. Future studies should evaluate dose escalation of radiation therapy with limited volumes, utilizing conformal radiation and chemotherapy to improve local control and potentially impact upon distant metastases.


Individualized Music Interventions for Dementia-Related Behavior Management.
Dementia presents many challenges for the person diagnosed, as well as for caregivers. The use of psychotropic medications for dementia-related behaviors has been linked to adverse reactions and increased mortality. Alternative approaches such as the use of personalized music playlists and musically-related spiritual care have had promising results including improved quality of life for persons with dementia and reduced stress for caregivers. Implementing an individualized music program is relatively simple and avoids deleterious side effects that may accompany medication use.


Structural determinants for transcriptional activation by cAMP-responsive DNA elements.
A transcriptional cAMP-responsive enhancer element (CRE) consisting of the 8-base pair (bp) palindrome, 5' TGACGTCA 3', is found in several eukaryotic genes. We analyzed the effects on gene transcription of point mutations within the CRE, the influence of the bases surrounding the CRE, and the requirements for transcriptional synergism of tandemly repeated CREs. When inserted as an oligonucleotide with restriction enzyme linker sites, the 8-bp CRE itself is as active in conferring cAMP responsivity on an enhancerless chloramphenicol acetyltransferase reporter plasmid as is a single copy of the choriogonadotropin alpha (CG alpha), twice repeated 18-bp sequence containing the CRE. Point mutations in the first (T to A), fourth (C to G), or eighth (A to T) positions of the CRE, when contained within the CG alpha 18-bp sequence, each inhibited transcriptional activity greater than 90%. However, the identical eighth position A to T mutation occurs in the cAMP-responsive sequence of the vasoactive intestinal peptide (VIP) gene, and that mutant sequence in the context of the adjacent bases of the native VIP sequence is maximally cAMP responsive when inserted in the reporter plasmid. The substantially reduced activity of the core 8-bp CRE when synthesized as a cassette including the adjacent bases of the rat glucagon or bovine parathyroid hormone gene further emphasizes the restrictive influence of particular surrounding sequences. Active oligonucleotides containing the 8-bp palindrome and different but equally permissive contexts have comparable properties in transfected reporter genes and gel mobility-shift assays. The pair of tandemly repeated 18-bp elements containing the CRE in the CG alpha gene synergistically stimulate transcription either with paired native CREs or when one native CRE is paired with one mutant CRE, suggesting the presence of cooperative interactions. Tandem insertion of more than two 18-bp sequences, or insertion of additional sequences between the two CREs, inhibits transcription. These observations indicate that the contexts of the bases adjacent to CREs exert profound influences on the transcriptional activities mediated by the cAMP-responsive elements.


Caregiver burden and unmet patient needs.
Four-hundred eighty-three patients with cancer and their informal caregivers were studied. Patients reported on met and unmet needs in personal care activities (bathing and dressing), instrumental activities (heavy and light housekeeping, cooking, shopping), transportation (medical and general), and home health care (health/treatment assistance). A minority (18.9%) experienced an unmet need. Hierarchical logistic regression was used to identify significant predictors of any unmet need. Patients were more likely to report any unmet needs when their illness/treatment resulted in restricted activity days, when their financial resources were reduced enough for them to apply for Medicaid or Public Assistance, or when their caregivers were not their spouses. Although in general, the likelihood of an unmet need decreased as the number of domains of assistance provided by the caregiver increased, if that care was associated with a high level of burden, the odds of a patient reporting an unmet need actually increased.


Cigarette smoke reduces short chain fatty acid production by a Porphyromonas gingivalis clinical isolate.
We hypothesized that short chain fatty acid (SCFA) production by oral pathogens is suppressed by exposure to cigarette smoke extract (CSE). Tobacco smoking is a major risk factor for plaque-induced periodontal diseases. Despite increased disease susceptibility, overt oral inflammation is suppressed in smokers, presenting a diagnostic conundrum. Bacterial-derived SCFAs can penetrate into oral tissues where they influence multiple components of immune and healing responses. Indeed, the SCFA burden has been correlated with the inflammatory condition of the gingiva. However, the influence of cigarette consumption on SCFA production is unknown. GC/MS was employed to monitor the production of several SCFAs (propionic acid, isobutyric acid, butyric acid, and isovaleric acid) by representative anaerobic oral pathogens (Filifactor alocis 35896, Fusobacterium nucleatum 25586, Porphyromonas gingivalis 33277) that were exposed, or not, to a physiologically relevant dose of CSE (2000 ng/ml nicotine equivalents) generated from 3R4F reference cigarettes. The growth of all three bacterial species was unaffected by CSE. The capacity to produce SCFAs by these bacteria was highly varied. F alocis produced the highest concentration of a specific SCFA (butyrate); P gingivalis provided the most robust overall SCFA signal, while F alocis and F nucleatum did not release detectable levels of isobutyrate or isovalerate. As P gingivalis 33277 was the broadest SCFA producer, three low-passage clinical isolates (10208C, 5607, and 10512) were also examined. Compared to unconditioned microbes, reduced SCFA release was apparent in CSE-exposed low-passage clinical isolates of P gingivalis which reached significance for one of the three isolates (propionic, isobutyric, butyric, and isovaleric acids, all P < 0.05). There is high disparity in the SCFA profiles of variant chronic periodontitis-associated bacteria, while CSE exposure reduces SCFA production by a specific clinical strain of P gingivalis. If the latter phenomenon occurs in vivo, a reduced SCFA burden may help explain the reduced vascular response to dental plaque in tobacco smokers.