AraC-like transcriptional activator CuxR binds c-di-GMP by a PilZ-like mechanism to regulate extracellular polysaccharide production.
Cyclic dimeric GMP (c-di-GMP) has emerged as a key regulatory player in the transition between planktonic and sedentary biofilm-associated bacterial lifestyles. It controls a multitude of processes including production of extracellular polysaccharides (EPSs). The PilZ domain, consisting of an N-terminal "RxxxR" motif and a β-barrel domain, represents a prototype c-di-GMP receptor. We identified a class of c-di-GMP-responsive proteins, represented by the AraC-like transcription factor CuxR in plant symbiotic α-proteobacteria. In Sinorhizobium meliloti, CuxR stimulates transcription of an EPS biosynthesis gene cluster at elevated c-di-GMP levels. CuxR consists of a Cupin domain, a helical hairpin, and bipartite helix-turn-helix motif. Although unrelated in sequence, the mode of c-di-GMP binding to CuxR is highly reminiscent to that of PilZ domains. c-di-GMP interacts with a conserved N-terminal RxxxR motif and the Cupin domain, thereby promoting CuxR dimerization and DNA binding. We unravel structure and mechanism of a previously unrecognized c-di-GMP-responsive transcription factor and provide insights into the molecular evolution of c-di-GMP binding to proteins.


Conceptual framework for the insect metamorphosis from larvae to pupae by transcriptomic profiling, a case study of Helicoverpa armigera (Lepidoptera: Noctuidae).
Insect metamorphosis from larvae to pupae is one of the most important stages of insect life history. Relatively comprehensive information related to gene transcription profiles during lepidopteran metamorphosis is required to understand the molecular mechanism underlying this important stage. We conducted transcriptional profiling of the brain and fat body of the cotton bollworm Helicoverpa armigera (Lepidoptera: Noctuidae) during its transition from last instar larva into pupa to explore the physiological processes associated with different phases of metamorphosis. During metamorphosis, the differences in gene expression patterns and the number of differentially expressed genes in the fat body were found to be greater than those in the brain. Each stage had a specific gene expression pattern, which contributed to different physiological changes. A decrease in juvenile hormone levels at the feeding stage is associated with increased expression levels of two genes (juvenile hormone esterase, juvenile hormone epoxide hydrolase). The expression levels of neuropeptides were highly expressed at the feeding stage and the initiation of the wandering stage and less expressed at the prepupal stage and the initiation of the pupal stage. The transcription levels of many hormone (or neuropeptide) receptors were specifically increased at the initiation of the wandering stage in comparison with other stages. The expression levels of many autophagy-related genes in the fat body were found to be gradually upregulated during metamorphosis. The activation of apoptosis was probably related to enhanced expression of many key genes (Apaf1, IAP-binding motif 1 like, cathepsins, caspases). Active proliferation might be associated with enhanced expression levels in several factors (JNK pathway: jun-D; TGF-β pathway: decapentaplegic, glass bottom boat; insulin pathway: insulin-like peptides from the fat body; Wnt pathway: wntless, TCF/Pangolin). This study revealed several vital physiological processes and molecular events of metamorphosis and provided valuable information for illustrating the process of insect metamorphosis from larvae to pupae.


Surface characteristics of orthodontic adhesives and effects on streptococcal adhesion.
In this study, we analyzed the surface roughness (SR) and surface free energy (SFE) characteristics of various orthodontic adhesives and their effects on the adhesion of mutans streptococci (MS). Three nonfluoride-releasing composites, 1 fluoride-releasing composite, 1 polyacid-modified composite (compomer), and 2 resin-modified glass ionomers (RMGIs) were analyzed with confocal laser scanning microscopy and the sessile drop method. Each material was incubated with whole saliva or phosphate-buffered saline solution. Adhesion assays were then performed by incubating each material with tritium-labeled cariogenic streptococci. We found that SFE and its components were significantly different among the adhesives, despite relatively uniform SR. RMGIs showed significantly higher SFE-particularly, dispersive, polar, and acidic characteristics-than did the composites. The compomer had intermediate characteristics between the composites and RMGIs. MS adhered to RMGIs significantly more than to the composites and the compomer, but there was no significant difference among the composites. The longer incubation time increased MS adhesion, whereas saliva coating did not significantly influence MS adhesion. There was a correlation between SFE and MS adhesion. SFE and its dispersive, polar, and acid components significantly influenced MS adhesion irrespective of saliva coating. This study suggests that initial MS adhesion is significantly influenced by SFE characteristics of adhesives rather than SR or saliva coating.


Topical application of Jatyadi Ghrita and Jatyadi Taila accelerates wound healing in Sprague-Dawley rats: a study in gamma-radiation-induced skin wound model.
Radiation-induced skin wounds/dermatitis can occur due to therapeutic, occupational, or accidental exposure to ionizing radiation. This study investigated the therapeutic efficacy of standardized Ayurvedic formulations [Jatyadi ghrita (JG) and Jatyadi taila (JT)] against 60Co-γ-radiation-induced acute skin wounds in rats. Animal's [Sprague-Dawley rats (200 ± 20 g)] flanked skin was locally exposed to 45 Gy radiation (R45Gy) in Cobalt-60-teletherapy unit (Bhabhatron) to generate radiation wounds. JG and JT were applied topically twice daily on wounds from day 14 onwards after appearance of moist desquamation and wound healing efficacy was observed for a period of 42 days. R45Gy induced significant time dependent changes in rat's skin with erythema on day 7 followed by dry and moist desquamation. JG and JT application significantly (p < .001) reduced skin damage score, wound area (92% and 97% respectively on day 42), and bacterial load, when compared with R45Gy and showed better efficacy than sucralfate and betamethasone (positive controls). Formulations significantly reduced lipid peroxidation and enhanced antioxidant defenses, reduced inflammatory infiltrates and collagen fibers deposition as evident by decreased myeloperoxidase and hydroxyproline levels, and also reduced transforming growth factor-beta 1 (TGF-β1) expression. Further, histology revealed reduced epidermal hyperplasia and dermal thinning with improved densities of hair follicles. Formulations were found to be nontoxic on 28 days application. The results demonstrated that JG and JT accelerated wound healing in irradiated skin tissue by faster re-epithelialization; reducing inflammation, collagen fibers deposition, and TGF-β1 expression, indicated their potential human application in countering radiation wounds.


Meniscus tear developed by pulling of the anomalous insertion of medial meniscus on anterior cruciate ligament.
There is no report regarding a medial meniscus tear arising from an anomalous insertion of medial meniscus on the ACL, which seemed to be developed by the same mechanism as ACL tear. A case of a combined medial meniscus tear with ACL tear in the presence of an anomalous insertion of the medial meniscus on the ACL is reported.


Wolff-Parkinson-White syndrome: long follow-up and an Anglo-American historical note.
A patient who developed palpitation in 1917 was later found to have the Wolff-Parkinson-White syndrome and survived to the age of 86, when he died of emphysema. Shortly before he first presented, a report of another patient had been published that can now retrospectively be recognized as containing the first tracings from a case of the Wolff-Parkinson-White syndrome; its coauthors were a distinguished American cardiologist, Alfred E. Cohn, who had worked with Sir Thomas Lewis, and his British research fellow, Francis R. Fraser.


[Factors affecting osteointegration and the use of early functional load to reduce the duration of treatment in dental implantation].
The article presents literature data on the impact of the surface and shape of dental implants and early functional load with aesthetic and functional rehabilitation on osteointegration and stability of implants at various implantation terms.


[Biology of lectins and their application in clinical biochemistry (author's transl)].
Lectins are proteins or glycoproteins, originally isolated from plant seeds. Characteristics are their ability to bind glycoproteins or glycolipids depending on the carbohydrate residues. The present review describes the structure of the lectins, their binding specificity and their functions with respect to precipitation of glycoproteins, agglutination of cells, transformation of lymphocytes and toxic action. Recently, lectin-analogs have been described in rabbit liver, which are responsible for hepatic uptake of circulating glycoproteins. The regulation of this process is intimately linked to the terminal N-Acetylneuraminic acid (NA-NA). Moreover, its significance is shown during fetal development, oncogenic transformation, immunologic recognition as well as homostasis. Due to the different terminal carbohydrate residues, glycoproteins of adult, fetal or transformed cells can be separated using affinity chromatography. Besides the purification of glycoproteins, lectins are also used for the separation of intact cells. Therefore the use of lectins is recommended for preparative and analytical methods, for the measurements of glycoprotein-turnover and for clinical diagnostics.


COVID-19 Pandemic and Upcoming Influenza Season-Does an Expert's Computed Tomography Assessment Differentially Identify COVID-19, Influenza and Pneumonias of Other Origin?
(1) Background: Time-consuming SARS-CoV-2 RT-PCR suffers from limited sensitivity in early infection stages whereas fast available chest CT can already raise COVID-19 suspicion. Nevertheless, radiologists' performance to differentiate COVID-19, especially from influenza pneumonia, is not sufficiently characterized. (2) Methods: A total of 201 pneumonia CTs were identified and divided into subgroups based on RT-PCR: 78 COVID-19 CTs, 65 influenza CTs and 62 Non-COVID-19-Non-influenza (NCNI) CTs. Three radiology experts (blinded from RT-PCR results) raised pathogen-specific suspicion (separately for COVID-19, influenza, bacterial pneumonia and fungal pneumonia) according to the following reading scores: 0-not typical/1-possible/2-highly suspected. Diagnostic performances were calculated with RT-PCR as a reference standard. Dependencies of radiologists' pathogen suspicion scores were characterized by Pearson's Chi2 Test for Independence. (3) Results: Depending on whether the intermediate reading score 1 was considered as positive or negative, radiologists correctly classified 83-85% (vs. NCNI)/79-82% (vs. influenza) of COVID-19 cases (sensitivity up to 94%). Contrarily, radiologists correctly classified only 52-56% (vs. NCNI)/50-60% (vs. COVID-19) of influenza cases. The COVID-19 scoring was more specific than the influenza scoring compared with suspected bacterial or fungal infection. (4) Conclusions: High-accuracy COVID-19 detection by CT might expedite patient management even during the upcoming influenza season.


GTP regulation of platelet-activating factor binding to human neutrophil membranes.
Radiolabeled ligand binding studies showed that specific receptors for platelet-activating factor are present in human neutrophil membranes. GTP at 10(-7) to 10(-3) M decreased the specific binding of platelet-activating factor to neutrophil membranes in a dose-dependent manner. Inhibition of platelet-activating factor binding was also induced by other guanine nucleotides but not by adenine nucleotides. Our results suggest that platelet-activating factor receptor in human neutrophil membranes may be coupled to a guanine nucleotide binding protein.


The Glaesserella parasuis phosphoglucomutase is partially required for lipooligosaccharide synthesis.
Lipooligosaccharides (LOSs) are virulence determinants of Glaesserella parasuis, a pathogen of the respiratory tract of pigs. We previously reported that disruption of the galU or galE gene in G. parasuis results in increased sensitivity to porcine serum, indicating that the galactose catabolism pathway is required for polysaccharide formation in G. parasuis. Here, we evaluated the role of the HAPS_0849 gene in LOS synthesis. The G. parasuis SC096 HAPS_0849 mutant produced a highly truncated LOS molecule, although a small fraction of intact LOS was still observed, and this mutant was found to be more sensitive to serum than the parental strain. HAPS_0849 was overexpressed and purified for biochemical assays, and this protein exhibited phosphoglucomutase (PGM) activity. Heterologous expression of a pgm gene from Escherichia coli in the HAPS_0849 mutant led to restoration of the wild-type LOS glycoform, further demonstrating the PGM function of HAPS_0849 in G. parasuis. The autoagglutination and biofilm formation ability of this strain were also investigated. Disruption of HAPS_0849 led to an increased tendency to autoagglutinate and form more biofilms, and these enhanced phenotypes were observed in the absence of glucose. In addition, LOSs from HAPS_0849, galU and lgtB mutants had similar truncated glycoforms, while LOSs from the galE and lex-1 mutants exhibited another type of defective LOS pattern. These findings imply that HAPS_0849 may function upstream of GalU in the generation of glucose 1-phosphate. In conclusion, our results preliminarily described the functions of HAPS_0849 in G. parasuis, and this gene was partially required for LOS synthesis.


Proliferation of fetal brown adipocyte primary cultures: relationship with the genetic expression of glucose 6 phosphate dehydrogenase.
Fetal brown adipocyte primary cultures increase DNA synthesis; cell number; and DNA, RNA, and protein contents in response to 10% fetal calf serum, IGF-I, and EGF plus vasopressin plus bombesin when added for 64 h to quiescent cells. IGF-I is a complete growth factor in this system while EGF needs the presence of vasopressin plus bombesin for its maximal proliferative effects. These mitogens induce the genetic expression of G6P dehydrogenase, increasing its mRNA content as well as its specific activity and amount of immunoreactive protein. The presence of cAMP elevating agents prevents the stimulatory effect of EGF plus vasopressin plus bombesin on DNA synthesis, cell number, and DNA content as well as on the induction of G6P dehydrogenase expression. Thus, changes on the proliferative state of these cells are associated with the level of expression of G6P dehydrogenase.


Spontaneous supra-modal encoding of number in the infant brain.
The core knowledge hypothesis postulates that infants automatically analyze their environment along abstract dimensions, including numbers. According to this view, approximate numbers should be encoded quickly, pre-attentively, and in a supra-modal manner by the infant brain. Here, we directly tested this idea by submitting the neural responses of sleeping 3-month-old infants, measured with high-density electroencephalography (EEG), to decoders designed to disentangle numerical and non-numerical information. The results show the emergence, in approximately 400 ms, of a decodable number representation, independent of physical parameters, that separates auditory sequences of 4 vs. 12 tones and generalizes to visual arrays of 4 vs. 12 objects. Thus, the infant brain contains a number code that transcends sensory modality, sequential or simultaneous presentation, and arousal state.


Lipofuscin accumulation in cultured retinal pigment epithelial cells causes enhanced sensitivity to blue light irradiation.
Lipofuscin accumulates with age within secondary lysosomes of retinal pigment epithelial (RPE) cells of humans and many animals. The autofluorescent lipofuscin pigment has an excitation maximum within the range of visible blue light, while it is emitting in the yellow-orange area. This physico-chemical property of the pigment indicates that it may have a photo-oxidative capacity and, consequently, then should destabilize lysosomal membranes of blue-light exposed RPE. To test this hypothesis, being of relevance to the understanding of age-related macular degeneration, cultures of heavily lipofuscin-loaded RPE cells were blue-light-irradiated and compared with respect to lysosomal stability and cell viability to relevant controls. To rapidly convert primary cultures of RPE, obtained from neonatal rabbits, into aged, lipofuscin-loaded cells, they were allowed to phagocytize artificial lipofuscin that was prepared from outer segments of bovine rods and cones. Following blue-light irradiation, lysosomal membrane stability was measured by vital staining with the lysosomotropic weak base, and metachromatic fluorochrome, acridine orange (AO). Quantifying red (high AO concentration within intact lysosomes with preserved proton gradient over their membranes) and green fluorescence (low AO concentration in nuclei, damaged lysosomes with decreased or lost proton gradients, and in the cytosol) allowed an estimation of the lysosomal membrane stability after blue-light irradiation. Cellular viability was estimated with the delayed trypan blue dye exclusion test. Lipofuscin-loaded blue-light-exposed RPE cells showed a considerably enhanced loss of both lysosomal stability and viability when compared to control cells. It is concluded that the accumulation of lipofuscin within secondary lysosomes of RPE sensitizes these cells to blue light by inducing photo-oxidative alterations of their lysosomal membranes resulting in a presumed leakage of lysosomal contents to the cytosol with ensuing cellular degeneration of apoptotic type. The suggested mechanism may have bearings on the development of age-related macular degeneration.


Clinical and histopathological analysis of cystic meningiomas.
Between 1993 and 2003, we treated 21 patients with cystic meningioma (of 365 with meningioma, 5.5%). We grouped these patients according to classifications by Nauta and Rengachary and analyzed them by gender, age, tumor location, clinical manifestations, MRI features and histopathology. The mean duration of symptoms was relatively short at 1.6 months. There were five atypical and 16 benign meningiomas on histopathology. In type I and II cystic meningiomas, with intratumoral cysts, all cyst walls enhanced on MRI and had tumor cells in the cyst wall on histopathology. In type III and IV cystic meningiomas, with peritumoral cysts, the cyst wall did not enhance on MRI and only one case (type III) had tumor cells in the cyst wall on histopathology. We suggest that when the cyst wall shows contrast enhancement on imaging, the cyst wall should be completely removed at surgery. If there is no contrast enhancement, multiple biopsies of the cyst wall should be taken to assess the presence of tumor cells in the cyst wall.


alpha7 nicotinic acetylcholine receptor agonist properties of tilorone and related tricyclic analogues.
The alpha7 nicotinic acetylcholine receptor (nAChR) has attracted considerable interest as a target for cognitive enhancement in schizophrenia and Alzheimer's Disease. However, most recently described alpha7 agonists are derived from the quinuclidine structural class. Alternatively, the present study identifies tilorone as a novel alpha7-selective agonist and characterizes analogues developed from this lead. Activity and selectivity were determined from rat brain alpha7 and alpha4beta2 nAChR binding, recombinant nAChR activation, and native alpha7 nAChR mediated stimulation of ERK1/2 phosphorylation in PC12 cells. Tilorone bound alpha7 nAChR (IC(50) 110 nM) with high selectivity relative to alpha4beta2 (IC(50) 70 000 nM), activated human alpha7 nAChR with an EC(50) value of 2.5 microM and maximal response of 67% relative to acetylcholine, and showed little agonist effect at human alpha3beta4 or alpha4beta2 nAChRs. However, the rat alpha7 nAChR maximal response was only 34%. Lead optimization led to 2-(5-methyl-hexahydro-pyrrolo[3,4-c]pyrrol-2-yl)-xanthen-9-one (A-844606) with improved binding (alpha7 IC(50) 11 nM, alpha4beta2 IC(50)>30 000 nM) and activity at both human and rat alpha7 nAChR (EC(50)s 1.4 and 2.2 microM and apparent efficacies 61 and 63%, respectively). These compounds also activated native alpha7 nAChR, stimulating ERK1/2 phosphorylation in PC12 cells. Tilorone, known as an interferon inducer, is a selective alpha7 nAChR agonist, suggesting utility of the fluorenone pharmacophore for the development of alpha7 nAChR selective agonists. Whether alpha7 stimulation mediates interferon induction, or whether interferon induction may influence the potential anti-inflammatory properties of alpha7 nAChR agonists remains to be elucidated.


The effect of an internet-based intervention for depression on cortisol and alpha-amylase.
Psychotherapeutic interventions for major depressive disorder (MDD) have been suggested to be associated with a normalization of biological stress system (i.e., the hypothalamic-pituitary-adrenal axis and the autonomic nervous system) dysregulation. Furthermore, pre-intervention cortisol parameters have been identified as prescriptive biological markers of treatment success. However, evidence of treatment effects on the biological stress systems is still sparse, and results are heterogeneous. The current study examined the effect of an internet-based intervention for MDD on salivary cortisol and alpha-amylase as well as hair cortisol concentrations. Moreover, the prescriptive capacity of pre-intervention cortisol and alpha-amylase concentrations on treatment response was explored. Thirty-eight participants suffering from mild to moderate MDD collected saliva and hair samples throughout the intervention. Biological outcome parameters were salivary cortisol and alpha-amylase (awakening response, total diurnal output, diurnal slope) and hair cortisol concentrations. Treatment response was indicated by change in depression severity and perceived chronic stress. Treatment response on depression scores or chronic stress was not associated with changes in any of the cortisol or alpha-amylase parameters. Exploratory analysis indicated that non-responders showed a steeper alpha-amylase slope pre-intervention. The results indicate that changes in depressive symptoms did not correspond to changes of the biological stress systems, contradicting the suggested normalization of dysregulated hypothalamic-pituitary-adrenal axis or autonomic nervous system activity through a psychotherapeutic intervention. However, the results point to a potential role of pre-intervention alpha-amylase slope as a prescriptive marker of treatment response for depression.


Effect of increasing cardiac preload, sympathetic antagonism, or vasodilation on visceral blood flow during pneumoperitoneum.
An impaired visceral perfusion caused by pneumoperitoneum may contribute to morbidity after laparoscopic surgery. The following three therapeutic concepts: increasing cardiac preload, controlled vasodilation, or selective sympathetic antagonism, were evaluated regarding a possible increase of visceral blood flow during pneumoperitoneum with carbon dioxide. Forty three pigs were assigned to treatment with an increase of preload and vasodilation (group A) or selective sympathetic antagonism with esmolol (group B). In both groups, pigs were assigned to head-up, head-down, or supine position. Perfusion of the vena porta and renal artery was measured by transonic volume flow meters and documented before capnoperitoneum, after induction of a 14-mmHg capnoperitoneum in each body position, after controlled vasodilation with sodium nitroprusside, and after controlled increase of intravascular volume by colloidal infusion. Increasing intravascular volume improved portal blood flow in all body positions (p<0.05), but not renal blood flow. Medication of esmolol did not alter the measured parameters in any body position compared to control. Vasodilation with sodium nitroprusside reduced renal blood flow in supine and in head-up position. An optimal intravascular volume was most effective in improving portal blood flow during capnoperitoneum in this trial. Esmolol had no negative effects on portal and renal blood flow. Patients with renal dysfunction might be treated carefully with sodium nitroprusside during capnoperitoneum.


Intention to stay and intention to leave: are they two sides of the same coin? A cross-sectional structural equation modelling study among health and social care workers.
"Intention to leave" (ITL) has been used interchangeably with the more positive construct "intention to stay" (ITS). The implicit assumption appears to be that both constructs represent different sides of the same coin. This study challenges this assumption. The objectives were (i) to test whether these constructs were similar measures of the same construct, and (ii) to assess the strength of the relationships between ITL and ITS with work-related outcomes. The Workforce Dynamics Questionnaire (WDQ) was administered to 298 staff. The WDQ included two items on ITL and was supplemented with three items on ITS. Structural equation modelling (SEM) was used. The response rate was 43%. The correlation between the two constructs was negative and quite high (r=-0.84), indicating potential issues with discriminant validity. However, the constructs behaved differently in relation to job satisfaction and job integration. ITS was a strong predictor (0.95, p<0.001), whereas ITL was not significantly related (0.34, p=0.195) to JS. The direct effects of JI on ITS was 0.30 and on ITL was -0.42. The indirect effects of JI were more contrasting, being 0.56 for ITS and -0.30 for ITL, via job satisfaction. This is the first study amongst British health and social care workers that has demonstrated that ITS and ITL are not measuring the same construct. While there is overlap, care should be taken when using these constructs interchangeably, particularly when measuring these concepts in organizations and when developing retention programs, policies, or activities to modify ITS and ITL.


Effects of the biliopancreatic diversion on energy balance in the rat.
This study was carried out to determine the effects of the biliopancreatic diversion (BPD), a bariatric surgery applied to the treatment of morbidly obese humans, on energy balance in rats. BPD was performed on a group of male Wistar rats. Body weight and food intake were measured daily throughout the study. Feces were also collected to assess energy losses and the determination of digestible energy. Energy expenditure and body composition were also determined for the 50-day length of the protocol. On the day of killing, the brain, the entire intestinal tract and white and brown adipose tissues were collected and weighed. Expression of neuropeptide Y (NPY) and agouti-related protein (AgRP) in the ARC nucleus were assessed by in situ hybridization. Marked changes in the regulation of energy balance were observed in the BPD-operated rats. A decrease in digestible energy and food intake coupled with an increase in the fecal energy density and protein fecal energy led to an important weight loss in the BPD-operated rats. This weight loss was observed in the loss of fat mass (specifically the white epididymal, inguinal, retroperitoneal and brown adipose tissues). The rats modified their food intake pattern to be able to potentially eat more during the entire day. An increase in the surfaces of all intestinal structures (muscular and mucosal layers) was observed in the BPD-operated rats. The NPY and AgRP expression in the brain were both shown to be greater in the BPD-operated rats than in the control animals. At the beginning of the study, the surgery led to an energy expenditure decrease, which, however, did not persist throughout the study despite the fact that BPD-operated rats exhibited persistent lower fat free masses. BPD led to a noticeable reduction in weight and fat gains in rats, which was in large part owing to a decrease in digestible energy intake led to by the gastrectomy, the intestinal malabsorption inherent to the surgery and to potentially a thermogenesis stimulation that occurred in the second end of the study. The reduction in energy gain occurs despite adaptations to thwart the intestinal malabsorption and the hunger signals from the central nervous system.


MaREA4Galaxy: Metabolic reaction enrichment analysis and visualization of RNA-seq data within Galaxy.
We present MaREA4Galaxy, a user-friendly tool that allows a user to characterize and to graphically compare groups of samples with different transcriptional regulation of metabolism, as estimated from cross-sectional RNA-seq data. The tool is available as plug-in for the widely-used Galaxy platform for comparative genomics and bioinformatics analyses. MaREA4Galaxy combines three modules. The Expression2RAS module, which, for each reaction of a specified set, computes a Reaction Activity Score (RAS) as a function of the expression level of genes encoding for the associated enzyme. The MaREA (Metabolic Reaction Enrichment Analysis) module that allows to highlight significant differences in reaction activities between specified groups of samples. The Clustering module which employs the RAS computed before as a metric for unsupervised clustering of samples into distinct metabolic subgroups; the Clustering tool provides different clustering techniques and implements standard methods to evaluate the goodness of the results.


Fed-batch fermentation of GM-CSF-producing glycoengineered Pichia pastoris under controlled specific growth rate.
Yeast expression systems with altered N-glycosylation are now available to produce glycoproteins with homogenous, defined N-glycans. However, data on the behaviour of these strains in high cell density cultivation are scarce. Here, we report on cultivations under controlled specific growth rate of a GlycoSwitch-Man5 Pichia pastoris strain producing Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) at high levels (hundreds of milligrams per liter). We demonstrate that homogenous Man5GlcNAc2 N-glycosylation of the secreted proteins is achieved at all specific growth rates tested. Together, these data illustrate that the GlycoSwitch-Man5 P. pastoris is a robust production strain for homogenously N-glycosylated proteins.


Molecular characterization of a cucumber nitrate reductase (CsNR) gene under NO(3) (-) stress.
Nitrate reductase is a key enzyme in the overall process of nitrate assimilation by plants. A full-length cDNA clone encoding nitrate reductase (NR; EC 18.104.22.168) was isolated from cucumber (Cucumis sativus L.) by RT-PCR and RACE techniques. The NR of cucumber (CsNR), a full-length cDNA sequence of 3032 bp contains an open reading frame of 2748 bp encoding 915 amino acids. The deduced 915 amino acid sequence showed high identities with NR from other plants. Quantitative real-time PCR analysis indicated that CsNR expression was different in root, stem, leaf, flower and mature fruit tissues. CsNR transcript level and nitrate reductase activity (NRA) was down-regulated and the change in NO(3) (-) concentration showed a negative trend with NRA in leaves when subjected to the 182 mM NO(3) (-) treatment. However, the CsNR transcript level was up-regulated in roots by 182 mM NO(3) (-) treatment. Furthermore, NRA in roots lagged behind CsNR expression and there was no obvious lag of NRA in leaves. This study found that in roots, there was no obvious relationship between NRA and NO(3) (-) content. These results indicated that NRA was not only controlled by the level of CsNR mRNA and there was an obvious negative relationship between NO(3) (-) content and NRA in leaves but not in roots.


There's a Problem With the Problem List: Incongruence of Patient Problem Information Across the Home Care Admission.
Illustrate patterns of patient problem information received and documented across the home health care (HHC) admission process and offer practice, policy, and health information technology recommendations to improve information transfer. Observational field study. Three diverse HHC agencies using different commercial point-of-care electronic health records (EHRs). Six nurses per agency each admitted 2 patients (36 total). Researchers observed the admission process and photographed documents and EHR screens across 3 phases: referral, assessment, and plan of care (POC). To create a standardized data set, we mapped terms within medical diagnoses, signs, symptoms, and Problems to 5 of the 42 Omaha System Problem Classification Scheme problem terms. This created 180 problem pattern cases (5 problem patterns per patient). Each pattern of problem information being present or absent was observed. In 52 cases (28.9%), a problem did not appear. In 36 cases (20%), the problem appeared in all 3 phases. In 46 cases (25.6%), the problem appeared in referral and/or assessment phases and not on the POC. Conversely, in 37 cases (20.5%), the problem appeared in referral or assessment phases and on the POC. In 9 cases (5%), the problem only appeared on the POC. Within the EHRs, there were no rationale fields to clarify including Problems or not and no problem status fields to identify active, resolved, or potential ones. Diagnosis or problem information transferred from the referral source or gathered during an in-home assessment did not appear in the POC. Because of the EHR structure, clinicians could not identify inactive problem or problem priority. Documentation or mapping of a structured problem list using a standardized interprofessional terminology such as the Omaha System coupled with identification of rationale could support the documentation of problem status and priority and reduce information loss.


Racial/ethnic differences in treatment efficacy and safety for moderate-to-severe plaque psoriasis: a systematic review.
Biologic medications have revolutionized treatment of psoriasis; however, there remains uncertainty in which medications should be used to maximize efficacy based on race/ethnicity. The purpose was to determine if efficacy of biological medications differs based on race/ethnicity. A systematic review identified all clinical trials focused on biologic treatment outcomes from inception of database until March 5th, 2021. Included studies provided data on racial/ethnic differences in biologic skin clearance efficacy using the Psoriasis Area and Severity Index (PASI) and "clear/almost clear" scores. There were 1220 studies identified, and 24 included in the review. The races/ethnicities included were Asian (n = 2740), White (n = 9745), Black (n = 138), and Latino (n = 728). Ixekizumab provided the highest "clear/almost clear" score (90.7%, 89.4%) and PASI 75 (98.8%, 96.6%) for Asian and Latino patients, respectively. Guselkumab had the highest "clear/almost clear" score for White (86.8%) patients, while Black patients had highest "clear/almost clear" (75.0%) and PASI 75 (91.7%) scores to brodalumab. Limitations included lack of studies reporting outcome data based on race/ethnicity and lack of patients of color within psoriasis clinical trials. For treatment of plaque psoriasis, there is evidence of differences in efficacy of biologics improving clinical disease severity between different races or ethnicities.


Effects of Glycon and Temperature on Self-Assembly Behaviors of α-Galactosyl Ceramide in Water.
α-Galactosyl ceramide (GalCer) is an anticancer glycolipid consisting of d-galactose and phytosphingosine-based ceramide. Although the amphiphilic structure of GalCer is expected to form self-associates in water, the self-assembly behaviors of GalCer and its derivatives have not been systematically investigated at this moment in spite of its great importance. The evaluation of morphologies and properties of the associates should open new insights into glycolipid chemistry such as the application of GalCer derivatives to a nanocarrier and the elucidation of the detailed pharmacological mechanism of GalCer. Herein, we show the synthesis of the aglycon fragment (Aglycon) of GalCer and the self-assembly behaviors of both GalCer and Aglycon in water. The critical aggregation concentrations of Aglycon and GalCer were determined using UV-vis spectral measurements at various concentrations. The transmission electron microscopy observations of the aqueous sample solutions indicated that the solution of GalCer includes vesicles, while that of Aglycon comprises giant micelles in the absence of vesicles. The vesicle formation in the solution of GalCer was also confirmed by Triton X-100-triggered dye-release experiments. To reveal the effects of glycon on the self-assembly behaviors in detail, we performed the measurements of dynamic light scattering, temperature-dependence of turbidity, differential scanning calorimetry, and wide-angle X-ray diffraction. The results clarify that the glycon moiety of GalCer has a significant role in the formation inhibition of second associates and the plasticization of the hydrophobe. This work will shed light on the other natural glycosides to evaluate the self-assembly behaviors for supramolecular and pharmacological applications in the near future.


Bloodstream infection due to β-hemolytic streptococci: a population-based comparative analysis.
Although the burden of illness due to Streptococcus pyogenes is widely recognized, other β-hemolytic streptococci are also important causes of invasive infections. The objective of this study was to compare the population-based epidemiology of groups A, B, and C/G β-hemolytic streptococcal bloodstream infection (BSI). Population-based surveillance was conducted in the western interior of British Columbia, Canada, 2011-2018. A total of 210 episodes were identified for an incidence of 14.4 per 100,000; the incidences of groups A, B and C/G streptococcal BSI were 4.2, 4.7, and 5.5 per 100,000, respectively. There was an increasing annual incidence of β-hemolytic streptococcal BSI from 2011 through to a peak incidence in 2016 that decreased thereafter. Fifty-two percent (110) of BSIs were community associated, 43% (91) were healthcare associated, and 4% (9) were hospital onset. Patients with group A were younger, more likely to be female, and have fewer co-morbidities than patients with groups B and C/G streptococcal BSI. The most common focus of infection was soft tissue (109/52%), followed by primary (33; 16%), and bone and joint (20; 10%) and these varied by streptococcal species (p < 0.001). The 30-day all-cause case fatality rate was 11% (24/210) and did not significantly vary by group (p = 0.7). Although the determinants vary, the overall burden of disease related to BSI is similar amongst groups A, B and C/G β-hemolytic streptococci.


Transcriptome-based identification and characterization of genes responding to imidacloprid in Myzus persicae.
Myzus persicae is a serious and widespread agricultural pest, against which, imidacloprid remains an effective control measure. However, recent reports indicate that this aphid has evolved and developed resistance to imidacloprid. This study aimed to elucidate the underlying mechanisms and genetic basis of this resistance by conducting comparative transcriptomics studies on both imidacloprid-resistant (IR) and imidacloprid-susceptible (IS) M. persicae. The comparative analysis identified 252 differentially expressed genes (DEGs) among the IR and IS M. persicae transcriptomes. These candidate genes included 160 and 92 genes that were down- and up-regulated, respectively, in the imidacloprid-resistant strain. Using functional classification in the GO and KEGG databases, 187 DEGs were assigned to 303 functional subcategories and 100 DEGs were classified into 45 pathway groups. Moreover, several genes were associated with known insecticide targets, cuticle, metabolic processes, and oxidative phosphorylation. Quantitative real-time PCR of 10 DEGs confirmed the trends observed in the RNA sequencing expression profiles. These findings provide a valuable basis for further investigation into the complicated mechanisms of imidacloprid resistance in M. persicae.


Neuromodulation of neuronal circuits: back to the future.
All nervous systems are subject to neuromodulation. Neuromodulators can be delivered as local hormones, as cotransmitters in projection neurons, and through the general circulation. Because neuromodulators can transform the intrinsic firing properties of circuit neurons and alter effective synaptic strength, neuromodulatory substances reconfigure neuronal circuits, often massively altering their output. Thus, the anatomical connectome provides a minimal structure and the neuromodulatory environment constructs and specifies the functional circuits that give rise to behavior.


Reproductive and developmental toxicity of potassium perfluorohexanesulfonate in CD-1 mice.
Potassium perfluorohexanesulfonate (K+PFHxS) was evaluated for reproductive/developmental toxicity in CD-1 mice. Up to 3 mg/kg-d K+PFHxS was administered (n = 30/sex/group) before mating, for at least 42 days in F0 males, and for F0 females, through gestation and lactation. F1 pups were directly dosed with K+PFHxS for 14 days after weaning. There was an equivocal decrease in live litter size at 1 and 3 mg/kg-d, but the pup-born-to-implant ratio was unaffected. Adaptive hepatocellular hypertrophy was observed, and in 3 mg/kg-d F0 males, it was accompanied by concomitant decreased serum cholesterol and increased alkaline phosphatase. There were no other toxicologically significant findings on reproductive parameters, hematology/clinical pathology/TSH, neurobehavioral effects, or histopathology. There were no treatment-related effects on postnatal survival, development, or onset of preputial separation or vaginal opening in F1 mice. Consistent with previous studies, our data suggest that the potency of PFHxS is much lower than PFOS in rodents.


Regeneration of ethyl parathion antibodies for repeated use in immunosensor: a study on dissociation of antigens from antibodies.
Reliable analysis using an immunosensor strongly depends on the specificity, activity, and sensitivity of the antibody. Immobilization of antibody on the solid matrix enables its repeated use, for which it is required to dissociate the antigens and antigen-enzyme conjugate from the immobilized antibody matrix after each use and while doing so, a maximum retention of activity and specificity are crucial requirements. In the present investigation, on the development of an immunosensor for the organophosphorus pesticide ethyl parathion (EP) using EP antibodies, different dissociating agents such as organic solvents, detergents and acidic buffers, that is, dimethyl sulphoxide (DMSO), Tween-20, cetyl trimethylammonium bromide (CTAB), methanol, chloroform, guanidium chloride (GdmCl), glycine-HCl (Gly-HCl) buffer in the pH range of 1.5-3.0, pierce buffer and combination of DMSO and methanol in phosphate buffer and Gly-HCl buffer and salts like NaCl and MgCl2 were used. Generally about 50-60% dissociation was obtained with some degree of denaturation of the antibody immobilized on the sepharose matrix. However, 1% DMSO in combination with 0.2 M Gly-HCl buffer at a pH of 2.3 showed 97% dissociation and the immobilized antibody retained sufficient activity to carry out 14 reproducible assays for EP.


Unusual localization and presentation of non-visceral hydatid cysts: review article.
Echinococcosis is a major parasitic zoonosis of public health importance worldwide. This is particularly true in sheep-raising countries including Egypt. Therefore, it is very important to identify the significant risk factors of the diseases by reviewing studies done in the region in the past decade to help policy makers design appropriate control strategies.


A phase II study of low-dose megestrol acetate using twice-daily dosing for anorexia in nonhormonally dependent cancer.
Anorexia is a common problem in advanced cancer. Low-dose megestrol acetate, a semi-synthetic progesterone, given twice daily, is an effective appetite stimulant in advanced cancer patients. There was an excellent correlation between patient satisfaction and the primary response criteria (appetite improvement). Given cost, side-effect profile, ease of administration, and efficacy, 80 mg twice daily after meals is an appropriate starting dose of megestrol acetate for anorexia in advanced cancer. If this is not effective, considerable dose escalation is possible.


Melatonin Ameliorates Neuropharmacological and Neurobiochemical Alterations Induced by Subchronic Exposure to Arsenic in Wistar Rats.
An experimental study was conducted in Wistar rats to characterize the arsenic ("As")-induced alterations in neurobiochemistry in brain and its impact on neuropharmacological activities with or without the melatonin (MLT) as an antioxidant given exogenously. Male Wistar rats were randomly divided in to four groups of six each. Group I served as untreated control, while group II received As [sodium (meta) arsenite; NaAsO2] at 10 mg/kg bw (p.o.) for a period of 56 days. Experimental rats in group III received treatment similar to group II but in addition received MLT at 10 mg/kg bw (p.o.) from day 32 onwards. Rats in group IV received MLT alone from day 32 onwards similar to group III. Sub-chronic exposure to As (group II) significantly reduced both voluntary locomotor and forced motor activities and melatonin supplementation (group III) showed a significant improvement in motor activities, when subjected to test on day 42 or 56. Rats exposed to As showed a significant increase in anxiety level and a marginal nonsignificant reduction in pain latency. Sub-chronic administration of As induced (group II) significant increase in the levels of thiobarbituric acid reactive substance (TBARS) called malondialdehyde (MDA) in the brain tissue (5.55 ± 0.57 nmol g-1), and their levels were significantly reduced by MLT supplementation (group III 3.96 ± 0.15 nmol g-1). The increase in 3-nitrotyrosine (3-NT) levels in As-exposed rats indicated nitrosative stress due to the formation of peroxynitrite (ONOO-). However, exogenously given MLT significantly reduced the 3-NT formation as well as prostaglandin (PGE2) levels in the brain. Similarly, MLT administration have suppressed the release of pro-inflammatory cytokines (viz., IL-1β, IL-6, and TNF-α) and amyloid-β1-40 (Aβ) deposition in the brain tissues of experimental rats. To conclude, exogenous administration of melatonin can overcome the sub-chronic As-induced oxidative and nitrosative stress in the CNS, suppressed pro-inflammatory cytokines, and restored certain disturbed neuropharmacological activities in Wistar rats.


Impact of ivermectin on the ultrastructure of the testis of Argas (Persicargas) persicus (Ixodoidea: Argasidae).
Mated male Argas persicus were dissected 1 and 2 weeks after feeding on untreated and ivermectin (IVM)-treated pigeons. One week after feeding, testes of untreated ticks were filled with rounded spermatids with subplasmalemmal vesicles and cytoplasmic organelles, but lacking in treated ticks. Two weeks after feeding, testes were crowded with elongated spermatozoa supported by double-walled cisternal tubes. The tubes consisted of two opposite walls, each with outer-fringed processes and inner elongated cisternae. Both were supported with electron dense striated plates in the middle of the spermatozoon. Internally, the cisternal tubes contained mitochondria and vacuoles. The nuclei were elongated dense masses between the tubes and the cell membranes. Subcutaneous inoculation of IVM at the dose 400 microg/kg pigeon resulted in extensive alterations in the testis of A. persicus. IVM prevented the development of new spermatids. There was a break down of cell membranes and cytoplasmic organelles of spermatozoa. Multivesicular bodies and numerous vacuoles were noticed in their cytoplasm. Double membranes of elongated cisternae and striation of electron dense plates became indistinct. IVM caused granulation and vacuolization of the nucleus as well as injury of mitochondrial cristae. The results suggest that IVM may bind to the neurotransmitter or the hormone involved in the process of sperm development or may be toxic to the germinal cells of A. persicus testis.


Inferior shoulder dislocation after shortening osteotomy of the humerus. A case report.
We present a case of a post-surgical complete dislocation after excessive proximal humeral shortening osteotomy performed in a patient operated on for atrophic non-union of a proximal humeral fracture. This complication has not been previously reported. The dislocation occurred due to extensive laxity of the soft tissue envelope, predominantly the deltoid muscle, as well as rotator cuff tear. The reconstructive procedurę consisted of vertical duplication of the capsule, reinforcement of the repair with coracoacromial ligament, tenodesis of the long head of the biceps tendon to the conjoined tendon and distal transfer of the deltoid muscle. The repair was reinforced with transarticular Steinmann pins. 15 months after surgery, there is an inferior subdislocation present, with full reduction in active abduction. Patient is pain-free at rest, and pain grade 4 in VAS scale in activity with loading.


Trends in urolithiasis in various ethnic groups and by age, in Israel.
A survey of upper urinary tract stone composition was carried out over 8 years (1974-1982) in 1147 patients, following a previous survey (1966-1974). Trends in the development of stone formation were found. The most obvious differences were fewer pure calcium oxalate (0.75 versus 5.50%) and uric acid stones (6.11 versus 13.30%) and more mixed stones than in our previous study. In most ethnic groups urinary stones were composed of calcium oxalate/calcium phosphate. A higher prevalence of stones in Israeli-born Jews was noted, in comparison with our previous survey. Age group analysis showed this increase to be limited to the 21-50-year-old group, in contradistinction to a clear decrease in stone formation in Israeli-born Arabs and Jews under the age of 20 years.


Should Medicaid include adult coverage for preventive dental procedures? What evidence is needed?
Medicaid programs may have a salient financial incentive to provide adult coverage for cost-effective preventive dental procedures because they face responsibility for catastrophic costs of dental disease. Whether there is sufficient evidence to support adult Medicaid coverage of preventive dental services is unclear. Using an optimal insurance model, the author examines what evidence there is to support coverage of cost-effective preventive dental services in Medicaid and what evidence gaps remain. There is insufficient evidence to support adult Medicaid coverage for preventive dental procedures. More research is needed to identify preventive dental procedures that are cost-effective from a Medicaid perspective, quantify the impact dental prevention has on dental-related health care costs and overall health care costs, and quantify the impact patient-side and provider-side financial incentives have on take-up of specific preventive dental treatments. Although Medicaid programs may have an interest in preventing catastrophic costs of dental disease (that is, dental-related emergency department visits), there is insufficient evidence for Medicaid programs to provide coverage for preventive dental procedures.


Determination of Caspase Activation by Western Blot.
Apoptosis is a type of programmed cell death induced by a cascade of biochemical events, which leads to distinct morphological changes characterized by cell shrinkage, membrane blebbing, chromatin condensation, and DNA fragmentation. Apoptosis is executed by a class of cysteine proteases called caspases. Caspases are synthesized as inactive pro-caspases and activated by a series of cleavage reactions. Active caspases cleave cellular substrates and are thus the main effectors of the apoptotic cell death pathway. Detection of caspase cleavage by western blot analysis is a conventional method to demonstrate the induction of apoptosis. In the context of apoptosis, the proper analysis of western blot results depends on the understanding of the mechanisms and outcomes of caspase processing during the course of its activation. In this chapter, we describe the step-by-step methodology in the western blot analysis of caspase cleavage during apoptosis. We detail protocols for protein extraction, quantitation, casting, and running gel electrophoresis and western blot analysis of caspase -8 and caspase -9 activation. The described methods can be applied to any particular protein of interest.


Dual-Functional Electrolyte Additives toward Long-Cycling Lithium-Ion Batteries: Ecofriendly Designed Carbonate Derivatives.
Long-term stability of the solid electrolyte interphase (SEI) and cathode-electrolyte interface (CEI) layers formed on anodes and cathodes is imperative to mitigate the interfacial degradation of electrodes and enhance the cycle life of lithium-ion batteries (LIBs). However, the SEI on the anode and CEI on the cathode are vulnerable to the reactive species of PF5 and HF produced by the decomposition and hydrolysis of the conventional LiPF6 electrolyte in a battery inevitably containing a trace amount of water. Here, we report a new class of cyclic carbonate-based electrolyte additives to preserve the integrity of SEI and CEI in LIBs. This new class of additives is designed and synthesized by an ecofriendly approach that involves fixing CO2 with functional epoxides bearing various reactive side chains. It was found that the cyclic carbonates of 3-(1-ethoxyethoxy)-1,2-propylene carbonate and 3-trimethoxysilylpropyloxy-1,2-propylene carbonate, possessing high capability for the stabilization of Lewis-acidic PF5, exhibit a capacity retention of 79.0% after 1000 cycles, which is superior to that of the pristine electrolyte of 54.7%. Moreover, TMSPC has HF-scavenging capability, which, along with PF5 stabilization, results in enhanced rate capability of commercial LiNi0.6Mn0.2Co0.2O2 (NCM622)/graphite full cells, posing a significant potential for high-energy-density LIBs with long cycle stability.


Comparison of fluconazole with amphotericin B in treatment of histoplasmosis in normal and immunosuppressed mice.
The activities of fluconazole and amphotericin B against Histoplasma capsulatum were investigated. The minimum inhibitory concentrations ranged from 0.12 to 0.47 microgram/mL for amphotericin B and from 16 to 250 micrograms/mL for fluconazole. Fluconazole given orally twice a day for 6 consecutive days compared favorably with amphotericin B given intraperitoneally once every other day for a total of six doses in the treatment of histoplasmosis in normal and leukopenic mice.


Hospital-physician alignment: the 1990s versus now.
Although the employment model was a bust in the 1990s, it can be successful today if hospitals: Allow physicians to shape health system strategy. Engage physicians and offer opportunities for leadership. Develop best practices to share across physician practices. Use management services organizations to add efficiency and profitability. Use technology wisely.


Laparoscopic complete mesocolic excision with D3 lymph node dissection for right colon cancer in elderly patients.
Complete mesocolic excision (CME) with D3 lymph node dissection is considered an oncological surgery for right colon cancer. However, there is still controversy for extensive oncological surgery in elderly patients. The aim of this study is to evaluate the safety and oncological outcomes of laparoscopic CME with D3 lymph node dissection for right colon cancer in elderly patients. Patients who underwent laparoscopic right colectomy, from 2004 to 2014, were divided into Groups A (age ≥ 70 years, n = 80) or B (age < 70 years, n = 127). Short and long-term outcomes were analysed. Basic demographics and short-term surgical outcomes were similar between groups. Among pathological outcomes, the mean number of harvested lymph nodes was significantly less in Group A. Adjuvant chemotherapy refusal rate was significantly higher in Group A. Overall and recurrence-free survival were similar between groups. We found laparoscopic CME with D3 lymph node dissection is a safe and feasible surgical option for right colon cancer in elderly patients.


Effects of chronic treatment with diazepam, phenobarbital, or amphetamine on naloxone-precipitated morphine withdrawal.
The present study examines the severity of naloxone-precipitated opiate withdrawal in morphine-pelleted rats and mice. Animals were chronically pretreated with either saline, diazepam, phenobarbital or amphetamine for 8 days prior to withdrawal precipitation. Indicators of withdrawal were changes in plasma corticosterone in rats and jumping behavior in mice. The use of chronic intravenous catheters in rats and one-way vision boxes allowed for serial blood sampling and sequential hormone determinations. Opiate dependence was established by the subcutaneous implantation of a 75-mg morphine pellet 72 h prior to withdrawal precipitation. All pretreated groups of rats with morphine pellets showed a substantial elevation of plasma corticosterone following the injection of naloxone (0.4 mg/kg, i.v.). Those with lactose pellets showed little change. The group pretreated with phenobarbital showed a lower, more attenuated withdrawal response as compared to saline or the other pretreated groups. The responsiveness of the hypothalamo-pituitary-adrenal axis to ether stress was evaluated. This was found to be unaffected by chronic phenobarbital suggesting that the drug may have a more specific effect on opiate dependence/withdrawal mechanisms. Similar studies in mice showed no differences in ED50 for naloxone-induced jumping behavior in any of the pretreatment groups.


Lessons Learned From the Implementation of Seek, Test, Treat, Retain Interventions Using Mobile Phones and Text Messaging to Improve Engagement in HIV Care for Vulnerable Populations in the United States.
In the United States, little is known about interventions that rely on mobile phones and/or text messaging to improve engagement in HIV care for vulnerable populations. Domestic studies using these technologies as part of the National Institute on Drug Abuse "Seek, Test, Treat, Retain" research initiative were queried regarding intervention components, implementation issues, participant characteristics, and descriptive statistics of mobile phone service delivery. Across five studies with 1,135 predominantly male, minority participants, implementation challenges occurred in three categories: (1) service interruptions; (2) billing/overage issues, and; (3) the participant user experience. Response rules for automated text messages frequently frustrated participants. The inability to reload minutes/texting capacity remotely was a significant barrier to intervention delivery. No study encountered confidentiality breaches. Service interruption was common, even if studies provided mobile phones and plans. Future studies should attend to the type of mobile phone and service, the participant user experience, and human subjects concerns.


Expression of estrogen receptors α and β in paratesticular tissues in boys operated on for unilateral cryptorchidism between the 1st and 4th years of life.
The aim of this study was to assess the expression of estrogen receptors alpha and beta in paratesticular tissues in a group of boys with and without cryptorchidism, and evaluation of karyotypes, localization, morphology and the major length of the undescended testes. Fifty boys (1-4 years old) with unilateral cryptorchidism were evaluated. Fifty healthy boys within the same age range, with inguinal hernia, served as a control group. Measurements concerning expression of ERalpha ERbeta receptors were preformed using monoclonal mouse antibodies against human receptor alpha and beta. In the mesothelial layer, the expression of ERalpha was higher in the patients group with undescended testes and it was statistically significant (p=0.04). There was no difference in the expression of ERbeta in this layer between groups. In the stromal cell layer there was statistically significant higher expression of ERbeta (p<0.05) in the group of patients with undescended testes. There was no difference between expressions of ERalpha in stromal cell layer. In the endothelial layer there was no difference in expression of ERalpha and ERbeta. In the smooth muscle layer there was no expression of ERalpha in either group. The expression of ERbeta in the smooth muscle layer was nearly identical in both groups. Undescended testes were generally found in the superficial inguinal pouch (n=46). The major lengths of the undescended testes were smaller in comparison to the testes positioned normally. In 9 of the cases the testes had different shape, and turgor deficit, and epididymides were smaller, dysplastic and separated from the testis.


The effect of type 2 diabetes mellitus on multiple obstructive coronary artery disease.
Although type 2 diabetes mellitus (T2DM) individuals easily develop three-vessel disease (3VD) coronary artery disease (CAD), there is very little information available about their left ventricle (LV) functions. The purpose of this study is to evaluate the LV function using two-dimensional speckle tracking echocardiography (2-D STE) in T2DM patients with 3VD. One hundred and three consecutive patients with confirmed 3VD CAD were enrolled and divided into two groups, while 53 patients with DM and 50 patients without. The control group was composed of 30 age- and sex-matched healthy individuals. All patients underwent 2-D STE and standard echocardiograms. The durations of DM and the level of HbA1c were also recorded. Between the 3VD-DM and 3VD-non-DM groups, normal echocardiography did not reveal any appreciable differences. However, patients with 3VD-DM had significantly lower global longitudinal strain (GLS) than those with 3VD-non-DM (15.87 ± 2.51 vs.17.56 ± 2.72, p < .05) by 2-D STE strain measurement. Besides, patients whose duration of DM excess 5 years showed significant lower GLS than those with less than 5 years duration (14.25 ± 2.31 vs. 16.65 ± 1.96, p = .007). However, there was no difference in GLS between the 3VD-DM patients with HbA1c ≥ 7% and HbA1c < 7%. Compared to patients with 3VD alone, those with 3VD-DM have a lower cardiac function. In 3VD-DM patients, the duration of DM is a significant factor that contributes to cardiac function deterioration, whereas, the glucose control state has limited influence.


A quantitative comparison of the influence of individual versus population-derived vascular input functions on dynamic contrast enhanced-MRI in small animals.
For quantitative analysis of dynamic contrast enhanced magnetic resonance imaging data, the time course of the concentration of the contrast agent in the blood plasma, or vascular input function (VIF), is required. We compared pharmacokinetic parameters derived using individual and population-based VIFs in mice for two different contrast agents, gadopentetate dimeglumine and P846. Eleven mice with subcutaneous 4T(1) breast cancer xenografts were imaged at 7 T. A precontrast T(1) map was acquired along with dynamic T(1) -weighted gradient echo images before, during, and after a bolus injection of contrast agent delivered via a syringe pump. Each animal's individual VIF and derived population-averaged VIF were used to extract parameters from the signal-time curves of tumor tissue at both the region of interest and voxel level. The results indicate that for both contrast agents, K(trans) values estimated using population-averaged VIF have a high correlation (concordance correlation coefficient > 0.85) with K(trans) values estimated using individual VIF on both a region of interest and voxel level. This work supports the validity of using of a population-based VIF with a stringent injection protocol in preclinical dynamic contrast enhanced magnetic resonance imaging studies.


HCMV-encoded miR-UL112-3p promotes glioblastoma progression via tumour suppressor candidate 3.
Glioblastoma (GBM) is the most prevalent and lethal type of primary malignant brain tumour. Recent studies suggest that the discovery of human cytomegalovirus (HCMV)-encoded microRNAs (miRNAs) might play a role in the pathogenesis of diseases, including GBM. In this study, we aimed to analyse the expression and function of HCMV-encoded miRNAs in GBM. We found that miR-UL112-3p expression was significantly elevated in GBM, and its expression levels were highly associated with glioma size, differentiation, WHO stage and the overall and disease-free survival of patients. The overexpression of miR-UL112-3p in the GBM cells promoted cell proliferation, clone formation, migration and invasion. In contrast, the down-regulation of miR-UL112-3p exerted an inverse effects. Tumour suppressor candidate 3 (TUSC3), a potential target gene of miR-UL112-3p, was inversely correlated with miR-UL112-3p expression in GBM tissues and cell lines. Furthermore, we demonstrated that TUSC3 was directly regulated by miR-UL112-3p, and the ectopic expression of TUSC3 reversed the effects of miR-UL112-3p on GBM progression via the AKT signalling pathway. Taken together, these findings collectively demonstrate that miR-UL112-3p exerts its oncogene function by directly targeting TUSC3 in GBM, indicating a potential novel therapeutic target for GBM.


Seroprevalence and risk factors of Toxoplasma gondii infection in invasive raccoons (Procyon lotor) in Central Europe.
Toxoplasma gondii is an obligate intracellular protozoan that causes toxoplasmosis in warm-blooded animals. Most mammals, including humans, can become intermediate host, resulting in subclinical infection or even death. Generally, there is limited information on the epidemiology of T. gondii of game species in Germany. As omnivores, raccoons, which are particularly widespread and abundant in Germany, are particularly exposed to infection the parasite. Here, we report the seroprevalence of T. gondii antibodies from 15 study sites located in Luxembourg and Germany. Using the indirect modified agglutination test (MAT), 170 (37.4%; 95% CI: 33.0-41.9) out of 454 raccoons were surveyed to be T. gondii seropositive. While values ranged from 19.0% to 53.3%, there was no significant difference in seroprevalence between study areas. Animal weight had a strong influence on the presence of T. gondii antibodies in raccoon sera, with heavier animals more likely to be seropositive. Our results show that T. gondii infection is widespread in central European raccoons, suggesting a high degree of ecosystem circulation of the parasite.


Synovial fluid glycosaminoglycan (acid mucopolysaccharide) analysis in assessment of temporomandibular joint dysfunction. A pilot study.
Temporomandibular joint (TMJ) synovial fluid was aspirated from normal control subjects and patients undergoing surgery for TMJ dysfunction. The glycosaminoglycan (GAG) composition of this fluid was analysed and compared with the clinical diagnosis and histological appearance of the condylar tissues. Changes in GAG composition were observed where a histologically hyperplastic response was seen in joint tissues, but these findings did not necessarily correlate with the initial clinical diagnosis. It is suggested that the fluid composition reflects the current metabolic activities of the tissues and may provide a useful marker of such processes.


The role of protein phosphorylation in renal amino acid transport.
Changes in tubular reabsorption of amino acids and other solutes are characteristic of the immature renal tubule and of various hereditary nephropathies. The cellular mechanisms governing these aberrations in renal amino acid transport have not been established. Calcium (Ca2+)-dependent protein kinases are known to phosphorylate membrane-bound carrier proteins, thereby modulating transport of various solutes by the proximal tubule. The role of these enzymes in regulating renal tubular amino acid transport, particularly during kidney development, is unknown. We investigated: (1) the effect of Ca(2+)- and phospholipid-dependent protein kinase [protein kinase C (PKC)] and Ca2+/calmodulin-dependent protein kinase II (CaMKII) on sodium chloride (NaCl)-linked proline transport by renal brush border membrane vesicles (BBMV) from adult rats using the "hypoosmotic shock" technique (lysis of vesicles); (2) the activity, expression and subcellular distribution (cytosol, particulate, BBM) of Ca(2+)-dependent protein kinases in kidneys from 7-day-old and adult rats using MBP 4-14 and autocamtide II phosphorylation assays for PKC and CaMKII, respectively, endogenous protein phosphorylation (using gel electrophoresis and autoradiography) and Western immunoblot analysis to detect PKC and CaMKII. The studies showed: (1) endogenous (membrane-bound) CaMKII and PKC as well as exogenous, highly purified PKC inhibit proline uptake by phosphorylated, lyzed/resealed BBMV when compared with control vesicles; the voltage-clamped, nonelectrogenic component of proline transport was inhibited by PKC- but not CaMKII-mediated phosphorylation; (2) a Ca(2+)-dependent activity of both kinases was evident in all subcellular fractions tested in immature and adult kidneys.(ABSTRACT TRUNCATED AT 250 WORDS)


The rate of horizontal transmission of antibiotic resistance plasmids is increased in food preservation-stressed bacteria.
The aim of this study was to investigate the possibility that sublethal food preservation stresses (high/low temperature, osmotic and pH stress) can alter the rate of horizontal transmission of antibiotic resistance (ABR) plasmids between Escherichia coli strains and between E. coli and Salmonella serotype Typhimurium. Escherichia coli donor cultures, carrying F1 plasmid R386 and Inc I1 plasmid TP307 and E. coli and Salm. Typhimurium recipient cultures were prestressed under a range of sublethal environmental conditions (high/low temperature, osmotic and pH stress). The prestressed donor and recipient cultures were then mated and the transmission rate calculated. The study found that the horizontal transmission rate of plasmids R386 and TP307 was significantly increased (P < 0.05) when prestressed donor and recipient cells are mated under conditions of environmental stress. The results from this study indicate that, the sublethal stresses that food pathogens encounter in modern food preservation systems increase the inter- and intra-specific horizontal transmission of selected ABR plasmids. Increased use of bacteriostatic (sublethal), rather than bacteriocidal (lethal) food preservation systems, may be contributing to the dissemination of ABR among important food borne pathogens.


Lateral Ovarian Transposition before Radiation Treatment of Hodgkin Disease
Preservation of ovarian function by repositioning the ovaries out of the irradiation field is suggested in women of reproductive age before pelvic radiotherapy for cervical cancer or Hodgkin disease. In women with Hodgkin disease this is usually done at the time of staging laparotomy. A 21-year-old woman with stage IIIa Hodgkin disease underwent repositioning of the ovaries during staging laparotomy, but before planned irradiation therapy it was noted that the ovaries were back in their normal anatomic position. Outpatient laparoscopic lateral transposition of the ovaries was performed without complication. Five years after pelvic irradiation she still has normal ovarian function. In selected women with malignancy and planned irradiation therapy, laparoscopy is an alternative to laparotomy to preserve ovarian function by lateral ovarian transposition.


Factors related to prognosis of acquired aphasia in children.
In a follow up study of 15 children with acquired aphasia, it was found that the persistent presence of concomitant neurological disorders was important for the final outcome. Prognosis seemed to be related to etiology, EEG disturbances and the severity of comprehension deficit at the onset of aphasia.


Experimental models of complete heart block.
Methods of creating experimental complete heart block developed since 1883 are reviewed in detail. The three most commonly used techniques at present are: (I) Thoracotomy, atriotomy and ligation of the A-V bundle. (II) Thoracotomy and injection of a chemical into the A-V node or bundle. (III) Injection of a chemical through a transvenous catheter into the node or bundle. The results in different species, complications, and variations in procedure are discussed. The bibliography provides a comprehensive index of work performed in animals with experimental complete heart block. We produced complete heart block in sixteen pigs but subsequently eleven died during Stokes-Adams attacks. Pigs have not been used previously as models of heart block for experimental purposes and prophylactic pacing appears mandatory in this species.


A cytometric exercise in plant DNA histograms, with 2C values for 70 species.
An introduction is given to the literature concerning methods and objectives for cytometric DNA analysis of plant nuclei. This area has gained relevance with applications in plant breeding and seed production industries, where laboratories unfamiliar with cytometry are adopting the method. An extensive graphical guide to interpreting DNA histograms and their problems is given. Conversely, cytometry laboratories unfamiliar with plant sciences will find herein a guide, and references, to adapt their methods to plant material. A table of 2C values reassessed by flow cytometry for 70 plant species, plus the genome composition (GC%) in many instances, is also included.


Total rhinoplasty with a free osteocutaneous flap.
A new approach to total rhinoplasty, using a free dorsalis pedis flap containing part of the second metatarsal bone, is reported.


Screening of diabetic children for coeliac disease with antigliadin antibodies and HLA typing.
IgA and IgG antigliadin antibodies were measured in 498 patients with insulin dependent diabetes mellitus and no history of intestinal malabsorption. Thirty patients had abnormal concentrations of antigliadin antibodies; 22 of these had an intestinal biopsy carried out and 16 of the 22 had subtotal villous atrophy suggestive of coeliac disease (prevalence 3.2%). There were no significant differences between patients with coeliac disease and diabetes and diabetic patients with normal IgA antigliadin antibodies in any of the nutritional variables measured, duration of diabetes, and mean insulin requirement. The mean age of onset of diabetes and attainment of expected height for age were both significantly lower in the patients with both diseases. Typing HLA classes I and II was done in 242 patients. The incidence of HLA-B8, DR3, and DQW2, which are commonly associated with both the diseases, is increased when both are present.


4-Phenyl-1,2,3,6-tetrahydropyridine, an excellent fragment to improve the potency of PARP-1 inhibitors.
We have shown that a 4-phenyl-1,2,3,6-tetrahydropyridine fragment plays an important role in improving inhibitory potency against poly(ADP-ribose) polymerase-1 (PARP-1). Various benzamide analogues linked with this fragment via alkyl spacers have been prepared and evaluated. As a result, some of them have been found to be highly potent PARP-1 inhibitors.


Back related outcome assessment instruments.
A literature review of the most widely used condition specific, self administered assessment questionnaires for low back pain had been undertaken. General and historic aspects, reliability, responsiveness and minimum clinically important difference, external validity, floor and ceiling effects, and available languages were analysed. These criteria, however, are only part of the consideration. Of similar importance are the content, wording of questions and answers in each of the six questionnaires and an analysis of the different score results. The issue of score bias is discussed and suggestions are given in order to increase the construct validity in the practical use of the individual questionnaires.


Disorder and dissolution enhancement: deposition of ibuprofen on to insoluble polymers.
Microcrystalline cellulose (MCC) and cross-linked polyvinylpyrrolidone (PVP-CL) were examined as polymeric carriers to support amorphous ibuprofen (IB). Drug/carrier systems were prepared as physical mixes, and drug was loaded onto the polymers by hot mix and solvent deposition methods. The systems were examined using differential scanning calorimetry (DSC), X-ray powder diffractometry (XRD) and by dissolution testing. PVP-CL reduced drug crystallinity more than MCC and, surprisingly, even very simple mixing of ibuprofen with PVP-CL induced disordering of the drug. Increased ibuprofen dissolution rates were achieved with both polymers, in the order of solvent deposition>hot mixes>physical mixes. The increased dissolution rates could be attributed to a combination of faster dissolution from amorphous ibuprofen, microcrystalline drug deposition on carrier surfaces and polymer swelling. However, no clear relationship was observed between ibuprofen dissolution rates (using first order, Higuchi or Hixson-Crowell relationships) and drug crystallinity.


Labeling, stability and biodistribution studies of 99mTc-cyclized Tyr3-octreotate derivatives.
To probe the interplay between radiotracer stability and somatostatin receptor affinity, Tyr(3)-octreotate and six variations of its peptide sequence, for which the Re-cyclized products were previously reported, were radiolabeled with (99m)Tc and investigated for their in vitro stability. Radiolabeling of the peptides was effected by ligand exchange from (99m)Tc-glucoheptonate, and the desired products were purified by radio-RP-HPLC. The in vitro stability in phosphate buffered saline, mouse serum and cysteine solutions at physiological temperature and pH for all seven (99m)Tc-cyclized peptides was determined by radio-RP-HPLC and radio-TLC. Normal CF-1 mouse biodistribution studies were performed for three of the (99m)Tc-cyclized peptides. Based on the fully characterized Re-cyclized peptide analogues, four (99m)Tc-coordination motifs were proposed for the (99m)Tc-cyclized peptides. Technetium-99m-cyclized Tyr(3)-octreotate derivatives with N(2)S(2) metal coordination modes and large metal ring sizes were susceptible to oxidation and loss of (99m)Tc in the form of (99m)TcO(4)(-), as evidenced by their instability in the various solutions under physiological conditions (15-58% intact at 24 h). As anticipated, the addition of a third cysteine to the sequence stabilized the (99m)Tc metal coordination, and peptides with NS(3) coordination modes remained >85% intact out to 24 h. No significant differences were observed in the biodistribution studies performed with three peptides of varying stabilities. Improvements in stability were not sufficient to outweigh the low somatostatin receptor affinity for the peptides in this study. Further improvements in the peptide sequence and/or metal coordination are needed to result in a radiodiagnostic/radiotherapeutic pair for targeting the somatostatin receptor.


Deep Learning Hybrid Method to Automatically Diagnose Periodontal Bone Loss and Stage Periodontitis.
We developed an automatic method for staging periodontitis on dental panoramic radiographs using the deep learning hybrid method. A novel hybrid framework was proposed to automatically detect and classify the periodontal bone loss of each individual tooth. The framework is a hybrid of deep learning architecture for detection and conventional CAD processing for classification. Deep learning was used to detect the radiographic bone level (or the CEJ level) as a simple structure for the whole jaw on panoramic radiographs. Next, the percentage rate analysis of the radiographic bone loss combined the tooth long-axis with the periodontal bone and CEJ levels. Using the percentage rate, we could automatically classify the periodontal bone loss. This classification was used for periodontitis staging according to the new criteria proposed at the 2017 World Workshop on the Classification of Periodontal and Peri-Implant Diseases and Conditions. The Pearson correlation coefficient of the automatic method with the diagnoses by radiologists was 0.73 overall for the whole jaw (p < 0.01), and the intraclass correlation value 0.91 overall for the whole jaw (p < 0.01). The novel hybrid framework that combined deep learning architecture and the conventional CAD approach demonstrated high accuracy and excellent reliability in the automatic diagnosis of periodontal bone loss and staging of periodontitis.


Binding of colchiceine to tubulin. Mechanisms of ligand association with tubulin.
Colchiceine, a closely related structural analog of colchicine possessing a C-ring tropolone, has been shown to be a potent inhibitor of microtubule assembly in vitro (I50 = 20 microM). The mechanism of inhibition is mediated through binding to tubulin (KA = 1.2 +/- 0.7 x 10(4) M-1), although potentially not through the colchicine receptor site. Supporting the hypothesis of an alternate receptor are the observation of colchiceine binding to the isolated colchicine-tubulin complex (KA = 2.2 +/- 1.0 x 10(4) M-1), the poor correlation between the competitive inhibition of colchicine binding (KI = 125 microM) and the inhibition of microtubule assembly, and different structure-activity relationships for colchiceine analogs as compared to the colchicine series.


Oral bisphosphonate-related osteonecrosis of the jaws in rheumatoid arthritis patients: a critical discussion and two case reports.
Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a clinical condition characterized by the presence of exposed bone in the maxillofacial region. Its pathogenesis is still undetermined, but may be associated with risk factors such as rheumatoid arthritis (RA). The aim of this paper is to report two unpublished cases of BRONJ in patients with RA and to conduct a literature review of similar clinical cases with a view to describe the main issues concerning these patients, including demographic characteristics and therapeutic approaches applied. Two case reports of BRONJ involving RA patients were discussed Both patients were aging female taking alendronate for more than 3 years. Lesions were detected in stage II in posterior mandible with no clear trigger agent. The treatment applied consisted of antibiotics, oral rinses with chlorhexidine, drug discontinuation and surgical procedures. Complete healing of the lesions was achieved. This paper brings to light the necessity for rheumatologists to be aware of the potential risk to their patients of developing BRONJ and to work together with dentists for the prevention and early detection of the lesions. Although some features seem to link RA with oral BRONJ and act as synergistic effects, more studies should be developed to support the scientific bases for this hypothesis.


Efficacy of Cartoon Viewing Devices During Phlebotomy in Children: A Randomized Controlled Trial.
The purpose of this study was to examine the efficacy of different cartoon viewing devices during phlebotomy in children. This study was a prospective, randomized controlled trial. The study included inpatients from the Biochemical Laboratory of a private university hospital in Turkey and was conducted between September 2017 and April 2018. A computer-based random number generator was used to randomly assign the patients into three groups (virtual reality [VR], tablet, and control) with 40 children each. Data were collected using the Wong-Baker FACES Pain Rating Scale and the Children's Fear Scale. Pain and anxiety scores were reported by children, parents, and observers in tablet and control groups. In the VR group, pain and anxiety were determined only by children's reports. According to the children reports, the VR group reported significantly less pain and anxiety than those in the tablet and control groups (P < .05). The cartoon distraction performed using a VR device reduced the perception of pain and anxiety during phlebotomy in school-age children.


The scaphoid shift test.
The scaphoid test described by Watson has generally been accepted as the definitive test for scaphoid instability and uses pressure against the scaphoid tubercle as the wrist moves from ulnar to radial deviation for the evaluation. This article describes a stress test done with the wrist in neutral position, which actively provokes scaphoid instability. Variations in stability can be used to grade scaphoid laxity.


The 17beta-hydroxysteroid dehydrogenase 4: Gender-specific and seasonal gene expression in the liver of brown trout (Salmo trutta f. fario).
Previously, it was documented that liver peroxisomes display seasonal size changes in the adult Salmo trutta fario, especially in females (and negatively correlated with ovary maturation). It was then hypothesized that decreases in peroxisome size could be paralleled by changes in peroxisomal beta-oxidation and estradiol catabolism actions. The 17beta-hydroxysteroid dehydrogenase 4 has been portrayed as playing an important role in both processes. To elucidate its function in the described peroxisomal pattern, we isolated the cDNA and predicted the protein sequence of the enzyme in that species. The seasonal gene expression pattern in both genders was addressed through quantitative PCR. Fish sampling was in post-spawning period, early and advanced gonad maturation, and pre-spawning. Males did not vary seasonally. As to females, a seasonal pattern was evidenced according to our previous hypothesis. We suggest that the decreased levels observed during vitellogenesis are related to lipid needs for ovary maturation, and, additionally, with the need of modulating estradiol titers.


The endoscopic and surgical management of portal hypertension in children: analysis of 123 cases.
Since 1973, 178 children with portal hypertension (PH) have been seen at Instituto da Criança of the University of São Paulo Medical School. Fifty-five of these children were excluded from this analysis for various reasons, including no treatment required, death before treatment, or incomplete data. From the remaining 123 children with esophageal varices, only 96 (76.1%) of them had at least one episode of upper gastrointestinal hemorrhage. Eighty-eight children were submitted to injection sclerotherapy; 26 treated prophylactically, and 62 for treatment of previous bleeding. Eleven (42.3%) children from the prophylactic group bled from esophageal varices during the treatment. They were all successfully managed thereafter. Satisfactory results were achieved in 53 (85.4%) children in the therapeutic group. Twenty-eight (45.1%) children had at least one episode of bleeding after beginning of sclerotherapy, 19 of whom eventually had successful control of the variceal bleeding. From 1973 to 1984, distal splenorenal shunt (DSS) was the procedure of choice for the treatment of bleeding esophageal varices. Forty-two children have undergone DSS during this period. Only one child was shunted prophylactically. Since 1985, injection sclerotherapy has been the first choice for the treatment and only seven children with sclerotherapy failure have since been treated by DSS. Characteristically these children had very similar splenoportographic pattern with huge esophageal and gastric varices and deviation of portal vein blood flow toward the left gastric vein.(ABSTRACT TRUNCATED AT 250 WORDS)


Oral Antibiotics in Clinical Development for Community-Acquired Urinary Tract Infections.
The treatment of urinary tract infections (UTIs) has been complicated by the emergence of multidrug-resistant, β-lactamase-expressing pathogens. As a result of the limited treatment options, patients often require hospitalization and intravenous therapy. In essence, a strong unmet need for oral antibiotics, active against extended-spectrum β-lactamase (ESBL) uropathogens has emerged. Oral carbapenems (tebipenem and sulopenem) and oral cephalosporin/β-lactamase inhibitor combinations are in various stages of clinical development for the treatment of uncomplicated and complicated UTI. Tebipenem, if approved, will be the first oral treatment for complicated UTI while sulopenem will be for uncomplicated UTI. The β-lactamase inhibitors ETX0282, VNRX7145, ARX1796, and QPX7728 are combined with cefpodoxime proxetil or ceftibuten that achieve favorable exposures in urine compared to other uropathogen-active oral cephalosporins. The combination ceftibuten-QPX7728 has potential broad-spectrum coverage against carbapenemase producers including metallo β-lactamase producers. Other novel combinations, namely cefpodoxime/ETX0282, ceftibuten/VNRX-7145, and ceftibuten/ARX1796, have also demonstrated excellent activity against Klebsiella pneumoniae carbapanemase (KPC) and OXA-48-like producers. All these agents, upon their arrival for commercial use, would strengthen the outpatient therapy.


Colonic mechanism of serum NAD+ depletion induced by DEHP during pregnancy.
Di (2-ethylhexyl) phthalate (DEHP) is a widely used plasticizer in polyvinyl chloride products such as feed piping, packing bag, and medical consumable. Our previous studies have demonstrated that DEHP exposure reduced the concentration of nicotinamide adenine dinucleotide (NAD+) in pregnant mice serum, which cuts off the source of NAD+ to placenta and results fetal growth restriction. However, the mechanism of serum NAD+ depletion by DEHP remains elusive. This study investigated the intestinal mechanism of NAD+ shortage-induced by DEHP in pregnant mice. The transcriptome results implicated that the mRNA level of oxidative response genes Cyp1a1, Gsto2, Trpv1 and Trpv3 were upregulated in colon. These changes induced intestinal inflammation. Transmission Electron Microscopy results displayed that DEHP destroyed the tight junctions and cell polarity of colonic epithelial cells. These dysfunctions diminished the expression of NAD+ precursor transporters SLC12A8, SLC5A8, SLC7A5, and the NAD+ biosynthetic key enzymes NAMPT, NMNAT1-3, and TDO2 in colonic epithelial cells. Analysis of the gut microbiota showed that DEHP led to the dysbiosis of gut microbiota, reducing the relative abundance of Prevotella copri which possesses the VB3 biosynthetic pathway. Therefore, maternal DEHP exposure during pregnancy decreased the transportation of NAD+ precursors from enteric cavity to colonic epithelial cells, and inhibited the synthesis of NAD+ in colonic epithelial cells. Meanwhile, DEHP reduced the NAD+ precursors provided by gut microbiota. Eventually, serum NAD+ content was lowered. Taken together, our findings provide a new insight for understanding the intestinal mechanisms by which DEHP affects serum NAD+ levels.


Pentobarbital-like effects of N-methyl-D-aspartate antagonists in mice.
The effects of the competitive N-methyl-D-aspartate (NMDA) antagonist, 3-[(+/-)-2-carboxypiperazin-4-yl]propyl-1-phosphonic acid (CPP), and of the noncompetitive NMDA antagonist, dizocilpine (MK-801), were determined in mice trained to discriminate pentobarbital (20 mg/kg i.p.) from saline under a standard two-lever fixed-ratio 20 schedule of sweetened milk reinforcement. CPP substituted for pentobarbital; however, pentobarbital-lever responding was usually associated with decreases in response rates. Dizocilpine produced a maximum average of only 62% pentobarbital-lever responding, accompanied by a 50% decrease in response rates. These results suggest that pentobarbital-like discriminative stimulus effects are more likely to be produced by competitive than by noncompetitive NMDA antagonists. This extends previous observation in rats and provides further evidence for differences in the behavioral effects of competitive and noncompetitive NMDA antagonists and for an overlap in the behavioral pharmacology of NMDA antagonists and classical CNS depressants.


Genome Sequence of Sulfide-Dependent Denitrification Bacterium Thermomonas sp. Strain XSG, Isolated from Marine Sediment.
We report the draft genome sequence of Thermomonas sp. strain XSG, isolated from a marine sediment. The genome is 3,047,478 bp long with a GC content of 68.5%. Strain XSG was found to be closely related to strain NBRC 101115 of Thermomonas koreensis.


Color disparities in cognitive aging among Puerto Ricans on the archipelago.
This research seeks to contribute new understanding of color disparities and gender in cognitive aging among older adults residing in Puerto Rico. We use the island-representative Puerto Rican Elderly Health Conditions (PREHCO) longitudinal study that measures cognitive health at baseline and cognitive decline between waves. In pooled models, we discern little or no color disparities in cognition at baseline. Sex-stratified models of baseline cognition indicate that Trigueño men slightly outperform white men. In contrast, color disparities in cognitive decline are apparent. In just four years between the two waves of PREHCO, on a 20-point cognitive test scale, Black men experienced 0.78 more points of cognitive decline, while Trigueño men experienced 0.44 more points of cognitive decline than white men in Puerto Rico. Mestiza women experience 0.80 less points of cognitive decline relative to white women. Nearly all of the color/race association with cognitive decline appears to be independent from health behaviors and conditions, individual human capital attainment, and family background. While lower-status color groups more frequently report discrimination, discrimination does not mediate the impact of color/skin tone and cognitive performance, suggesting the importance of further research on the role of broader dimensions of life course structural racism.


Impact of the combined use of opioids and surgical procedures on workers' compensation cost among a cohort of injured workers in the state of Louisiana.
To determine the impact of surgical procedures and opioids on workers' compensation claim cost. A cohort of 11,394 lost time claims filed with the Louisiana Workers' Compensation Corporation from 1999 to 2002 was followed for 7 years. Controlling for gender, attorney involvement, and claim duration, multivariate logistic regression analysis indicated that odds ratios (ORs) for a catastrophic claim (final cost ≥ $100,000) associated with short-acting and long-acting opioids (vs no opioids) were 4.28 and 12.19. The ORs for catastrophic claims associated with a spinal surgical procedure or spinal fusion (vs no procedure) were 4.27 and 11.40. Spinal surgical procedures plus opioid use significantly increased the OR for catastrophic claims; for example, spinal fusion plus long-acting opioids had an OR of 138.96. Spinal surgery and opioid utilization are associated with catastrophic claim costs.


Hypnosis as a Valuable Tool for Surgical Procedures in the Oral and Maxillofacial Area.
Hypnosis is a valuable tool in the management of patients who undergo surgical procedures in the maxillofacial complex, particularly in reducing and eliminating pain during surgery and aiding patients who have dental fear and are allergic to anesthesia. This case report demonstrates the efficacy of hypnosis in mitigating anxiety, bleeding, and pain during dental surgery without anesthesia during implant placement of tooth 14, the upper left first molar.


Secular trends in Swedish hip fractures 1987-2002: birth cohort and period effects.
Recently, a leveling off in hip-fracture incidence has been reported in several settings, but the annual number is nonetheless predicted to increase due to the growing elderly population. Using Swedish national data for 1987-2002 for all inpatients 50 years or older, we examined the annual number and incidence of hip fractures and explored age, period, and cohort effects. Age adjustment was done by direct standardization, time-trend analysis by linear regression, changes in linear trends by joinpoint regression, and age-period-cohort effects by log-likelihood estimates in Poisson regression models. Before 1996, the age-standardized hip fracture incidence was stable (0.1% per year [95% confidence interval = -0.2% to 0.5%]), and the annual number of hip fractures increased (2.1% per year [1.8% to 2.4%]). After 1996, both the age-standardized hip fracture incidence (-2.2% per year [-2.8% to -1.6%]) and the number of hip fractures (-0.9% per year [-1.5% to -0.4%]) decreased. The period + cohort effects were more marked among women than men, with a major reduction in hip fracture incidence in subsequent birth cohorts (estimated incidence rate ratio = 2.2 comparing women born 1889-1896 with 1945-1952) or periods (estimated incidence rate ratio = 1.1 comparing women living 1987-1990 with 1999-2002). The age-standardized hip fracture incidence has decreased since 1996, more than counteracting the effects of the aging population and resulting in a decline in the annual number of hip fractures through 2002. The magnitude of the combined period and cohort effects in women seems to be of biologic importance. If this persists into older age, the annual number of hip fractures will be lower than has been projected.