The contribution of chromosomal translocations to antigenic variation in Trypanosoma brucei.
Genomic rearrangements influencing gene expression occur throughout nature. Several of these rearrangements disrupt normal gene expression, as exemplified by the genetic alterations caused by the mobile genetic elements of maize or Drosophila (see Shapiro 1983). Other rearrangements are part of the normal developmental programme of an organism. An understanding of the control of genomic rearrangements and their effects on gene expression should contribute to our insight into the mechanism of genetic programming and cellular development. The protozoan parasite Trypanosoma brucei exhibits a variety of genomic rearrangements that influence the expression of genes that code for versions of the variant surface glycoprotein (v.s.g.), which makes up the cell surface coat. V.s.g. genes are expressed in a mutually exclusive manner. Several v.s.g. genes are activated by duplicative transposition of the gene to a telomeric expression site where they are transcribed, while others can be activated without detectable genomic rearrangements. Recently we have been able to fractionate the chromosomes of T. brucei in agarose gels (Van der Ploeg et al. 1984 a). This led to the observations that duplicative transpositions occur inter-chromosomally and that the chromosomes of T. brucei are subject to frequent recombinations that displace hundreds of kilobase pairs. At least two and possibly more telomeric expression sites can be used for v.s.g. gene transcription. How these sites are activated and inactivated is still unsolved, but this does not depend on recombinations in the vicinity of the gene. Gross genomic rearrangements occur sometimes in correlation with antigenic switching and this suggests that such rearrangements have a function in regulating the mutually exclusive transcription of the different expression sites. V.s.g. genes consist of two exons. No physical linkage of the 35 nucleotide (n.t.) mini-exon to the v.s.g. gene main exon occurred within 15 kilobase pairs in variant 118a and possibly 150 kilobase pairs in variant 1.8b. These mapping data give additional support for the hypothesis that both exons might represent separate transcription units. Transcription initiation of v.s.g. genes would thus be from a promoter other than the mini-exon repeat unit. We propose that transcription of the v.s.g. gene in the expression site can be regulated by a position effect on the gene.


Magnetic-induced migration in a sedimenting suspension of magnetic spherical particles.
We study the relative trajectories of two magnetic spheres interacting in a dilute suspension in the presence of particle inertia and Brownian motion effect. The particles settle relative to one another under the action of gravity and when in close contact they exert on each other a magnetic force and torque due to a permanent magnetization. The balance equations of forces and torques for the two particles are considered in the present formulation. The numerical simulations are based on direct computations of the hydrodynamic and the magnetic interactions among the rigid spheres in the regime of no-null Stokes number. The behavior of these suspensions is examined based on the relative trajectories calculated for several initial configurations. The calculations show that fluctuations in particle orientation produced by the continuous magnetic interactions and by the Brownian motion exerts a significant effect on the understanding of particle aggregation and particle migration in magnetic suspensions.


Primary wound closure in chronic osteomyelitis.
The sequelae of chronic osteomyelitis include not only the common clinical and radiographic signs and symptoms unique to it, but also the frequent residual deformity or amputation secondary to surgical intervention. Exacerbations and relapses are common and may occur as a result of trauma or a decrease in the resistance of the patient. Treatment of this condition over the years has been controversial. Some authors (1, 2) advocate treatment with high oral doses of antibiotics over a period of time up to 6 months. Although good results have been obtained with this regimen, other factors must be taken into account before initiation of such therapy such as severity and location of infection, drug allergy, renal and hepatic function, and attainable antibiotic blood levels. However, because of thrombosis of nutrient, marrow, and periosteal blood vessels, along with fibrosis of surrounding soft tissue, there is no guarantee that adequate serum antibiotic levels provide for the minimal inhibitory concentration of the drug in the infected bone. Antibiotic therapy without surgical intervention to improve blood supply cannot cure the disease and may result in an acquired resistance by the organism (3). The most widely accepted treatment today is surgical curetment, sequestrectomy, or resection of the infected osseous tissue with extensive debridement of all sinus tracts and devitalized tissues. Adding to the morbidity of this disease is the excessive scarring produced by inadequate and improper wound closure after surgical intervention. The following is a description of several methods utilized for contaminated wound closure.


[Segmental absence of colonic muscularis propria. Report of a case in an adult].
We report a case of segmental defect of colonic muscularis propria revealed by perendoscopic perforation in a 64-year-old woman. Segmental absence of intestinal musculature is well documented in new-borns and infants and is more frequent in small bowel. It is characterized by localised absence of muscularis propria without fibrous scar. The remaining layers of the bowel wall are intact. The pathogenesis of this lesion is discussed.


Phenyl valerate esterase activity of human butyrylcholinesterase.
Phenyl valerate is used for detecting and measuring neuropathy target esterase (NTE) and has been used for discriminating esterases as potential target in hen model of organophosphorus delayed neuropathy. In previous studies we observed that phenyl valerate esterase (PVase) activity of an enzymatic fraction in chicken brain might be due to a butyrylcholinesterase protein (BuChE), and it was suggested that this enzymatic fraction could be related to the potentiation/promotion phenomenon of the organophosphate-induced delayed neuropathy (OPIDN). In this work, PVase activity of purified human butyrylcholinesterase (hBuChE) is demonstrated and confirms the novel observation that a relationship of BuChE with PVase activities is also relevant for humans, as is, therefore the potential role in toxicity for humans. The KM and catalytic constant (kcat) were estimated as 0.52/0.72 µM and 45,900/49,200 min-1 respectively. Furthermore, this work studies the inhibition by preincubation of PVase and cholinesterase activities of hBuChE with irreversible inhibitors (mipafox, iso-OMPA or PMSF), showing that these inhibitors interact similarly in both activities with similar second-order inhibition constants. Acethylthiocholine and phenyl valerate partly inhibit PVase and cholinesterase activities, respectively. All these observations suggest that both activities occur in the same active center. The interaction with a reversible inhibitor (ethopropazine) showed that the cholinesterase activity was more sensitive than the PVase activity, showing that the sensitivity for this reversible inhibitor is affected by the nature of the substrate. The present work definitively establishes the capacity of BuChE to hydrolyze the carboxylester phenyl valerate using a purified enzyme (hBuChE). Therefore, BuChE should be considered in the research of organophosphorus targets of toxicity related with PVase proteins.


Stress, social support, and the transition to fatherhood.
Over the past ten years, nurses have shown increasing interest in understanding and assisting men in their transition to fatherhood. Inadequate data and lack of a framework for interpreting diverse studies have hindered the development of appropriate intervention strategies. In this article, a paradigm from the field of stress research is adapted to the transition to fatherhood. The new paradigm organizes and integrates the factors that impact on a man's experience of becoming a father. The utility of this paradigm in generating theory and hypotheses for future research is illustrated by fully exploring one of the potential variables impacting on fatherhood, i.e., social support. Through this process a better theoretical understanding of social support as well as a guide to future inquiry concerning fatherhood is acquired.


Lactic acid bacteria - promising vaccine vectors: possibilities, limitations, doubts.
Gram-positive, nonpathogenic lactic acid bacteria (LAB) are considered to be promising candidates for the development of novel, safe production and delivery systems of heterologous proteins. Recombinant LAB strains were shown to elicit specific systemic and mucosal immune responses against selected antigens. For this reason, this group of bacteria is considered as a potential replacement of classical, often pathogenic, attenuated microbial carriers. Mucosal administration of recombinant LAB, especially via the best explored and universal oral route, offers many advantages in comparison to systemic inoculation, and is attractive from the immunological and practical point of view. Research aimed at designing efficient, mucosally applied vaccines in combination with improved immunization efficiency, monitoring of in vivo antigen production, determination of optimal dose for vaccination, strain selection and characterization is a priority in modern vaccinology. This paper summarizes and organizes the available knowledge on the application of LAB as live oral vaccine vectors. It constitutes a valuable source of general information for researchers interested in mucosal vaccine development and constructing LAB strains with vaccine potential.


Prevalence of hs-CRP among Indians with hypertension.
The prevalence of hypertension in the early twentieth century varied in India, ranging from 2-15% in Urban India and 2-8% in Rural India. In the inter heart and inter stroke study, hypertension accounted for 17.9% and 34.6% of population attributable risk for coronary artery disease and stroke respectively. CRP appears in serum in response to a variety of inflammatory stimuli .Raised level of hs-CRP is seen with increasing with age, during an infection, inflammation, coronary artery diseases, obesity, sepsis, smoking and vasculitis. CRP is also a factor in the development of atherosclerotic plaque. Although CRP was believed to be a marker of vascular inflammation, recent research indicates that it plays an active role in atherogenesis. So in this study we measured serum hs- CRP in patients with essential hypertension and correlated with blood pressure. The study consists of 50 patients with essential hypertension with antihypertensive medications. in the age group of 40 to 60 years of both sexes and 25 normotensive subjects with no history of cardiovascular, neoplastic, hepatic, renal, infectious or auto immune disease. IHEC clearance and informed consent were obtained. hs-CRP was measured by ELISA kit. Our study showed significantly elevated serum hs-CRP level in hypertensive subjects in comparison with control subjects. To find out the relationship between physiological and biochemical parameters with CRP Pearson correlation coefficient has been applied. The level of significance has been fixed as 5% (p<0.05). SPSS15 software has been used for calculation. Our study showed significantly elevated serum hs-CRP level in hypertensive subjects in comparison with control subjects. But there is no correlation of hs-CRP level with both systolic and diastolic pressure. Several studies have shown inflammatory markers such as CRP as an independent determinant of endothelium dependent vascular function among patient with coronary heart disease (CHD) in patients with hypertension. There was no significant correlation was observed between levels of hs-CRP and systolic and diastolic blood pressure in this study but there was a significant elevation hs-CRP level was observed in hypertensive patients.


Operative management of penetrating wounds of the chest. Experience with 41 patients on the island of Curaçao.
Of the 157 cases of chest injuries, 41 patients underwent thoracotomy. Thirty-three were male and 7 female with an average age of 27 years. Eighty-three percent had stabwounds and 17 percent gunshotwounds . On admission and on examination only seven thoracotomy patients were in a stable clinical condition. Hypotension and hemo- or pneumothorax were often present. Persisting hemorrhage from chest tubes drainage, cardiac tamponnade , and massive hemothorax were indications for immediate thoracotomy. Only few of the patients with an hemothorax have an hemorrhage from a major systemic vessel. Associated intraabdominal injuries were often found (17%). For exploration of the abdominal lesions a separate explorative laparotomy is indicated. The only patient who died in our series suffered from septicemia after multiple associated intra-abdominal wounds (mortality rate 2.4%). The overall complication rate was 19.7%. The average period of hospitalisation was 15.4 days.


Transverse phase matching of high-order harmonic generation in single-layer graphene.
The efficiency of high-harmonic generation (HHG) from a macroscopic sample is strongly linked to the proper phase matching of the contributions from the microscopic emitters. We develop a combined micro+macroscopic theoretical model that allows us to distinguish the relevance of high-order harmonic phase matching in single-layer graphene. For a Gaussian driving beam, our simulations show that the relevant HHG emission is spatially constrained to a phase-matched ring around the beam axis. This remarkable finding is a direct consequence of the non-perturbative behavior of HHG in graphene-whose harmonic efficiency scaling is similar to that already observed in gases- and bridges the gap between the microscopic and macroscopic HHG in single-layer graphene.


Mechanisms in decorin regulation of vascular endothelial growth factor-induced human trophoblast migration and acquisition of endothelial phenotype.
Extravillous trophoblast (EVT) cells of the human placenta invade the uterine decidua and utero-placental arteries to establish an efficient exchange of key molecules between maternal and fetal blood. Trophoblast invasion is stringently regulated in situ both positively and negatively by a variety of factors at the fetal-maternal interface to maintain a healthy utero-placental homeostasis. One such factor, decorin, a transforming growth factor (TGF)-beta binding, leucine-rich proteoglycan produced by the decidua, negatively regulates EVT proliferation, migration, and invasiveness independent of TGF-beta. We reported that these decorin actions were mediated by its binding to multiple tyrosine kinase receptors, including vascular endothelial growth factor receptor (VEGFR)-2. The present study explores the mechanisms underlying decorin antagonism of VEGF (VEGF-A) stimulation of endovascular differentiation of EVT using our EVT cell line, HTR-8/SVneo. We observe that decorin inhibits VEGF-induced EVT cell migration and endothelial-like tube formation on matrigel. VEGF activates MAPKs (p38 MAPK, MEK3/6, and ERK1/2) in EVT cells, and the activation is blocked in both cases by decorin. Employing selective MAPK inhibitors, we show that both p38 and ERK pathways contribute independently to VEGF-induced EVT migration and capillary-like tube formation. VEGF upregulates the vascular endothelial (VE) markers VE-cadherin and beta-catenin in EVT and endothelial cells, and this upregulation is blocked by decorin and MAPK inhibitors. These results suggest that decorin inhibits VEGF-A stimulation of trophoblast migration and endovascular differentiation by interfering with p38 MAPK and ERK1/2 activation. Thus decorin-mediated dual impediment of endovascular differentiation of the EVT and angiogenesis may have implications for pathogenesis of preeclampsia, a hypoinvasive trophoblast disorder in pregnancy.


Contributions of Body-Composition Characteristics to Critical Power and Anaerobic Work Capacity.
Critical power (CP) and anaerobic work capacity (AWC) from the CP test represent distinct parameters related to metabolic characteristics of the whole body and active muscle tissue, respectively. To examine the contribution of whole-body composition characteristics and local lean mass to further elucidate the differences in metabolic characteristics between CP and AWC as they relate to whole body and local factors. Fifteen anaerobically trained men were assessed for whole-body (% body fat and mineral-free lean mass [LBM]) and local mineral-free thigh lean mass (TLM) composition characteristics. CP and AWC were determined from the 3-min all-out CP test. Statistical analyses included Pearson product-moment correlations and stepwise multiple-regression analyses (P ≤ .05). Only LBM contributed significantly to the prediction of CP (CP = 2.3 [LBM] + 56.7 [r2 = .346, standard error of the estimate (SEE) = 31.4 W, P = .021]), and only TLM to AWC (AWC = 0.8 [TLM] + 3.7 [r2 = .479, SEE = 2.2 kJ, P = .004]). The aerobic component (CP) of the CP test was most closely related to LBM, and the anaerobic component (AWC) was more closely related to the TLM. These findings support the theory that CP and AWC are separate measures of whole-body metabolic capabilities and the energy stores in the activated local muscle groups, respectively. Thus, training programs to improve CP and AWC should be designed to include resistance-training exercises to increase whole-body LBM and local TLM.


Macrophage defences against respiratory tract infections.
Pulmonary macrophages with a key role in defence against respiratory infection are a heterogeneous family of cells with phagocytic, antigen processing and immunomodulatory functions. Macrophages are important in both innate and acquired immunity in the respiratory tract, and have a role in lung defence against viruses, bacteria, mycobacteria and fungi. Interactions of pathogens with lung macrophages is strongly influenced by soluble immune components including complement, collectins and immunoglobulins. Macrophage function can be modulated by cytokines, environmental exposures, recent and chronic infection including HIV infection, drug therapy and gene transfer.


In Silico Discovery and In Vitro Validation of Catechol-Containing Sulfonohydrazide Compounds as Potent Inhibitors of the Diguanylate Cyclase PleD.
Biofilm formation is responsible for increased antibiotic tolerance in pathogenic bacteria. Cyclic di-GMP (c-di-GMP) is a widely used second-messenger signal that plays a key role in bacterial biofilm formation. c-di-GMP is synthesized by diguanylate cyclases (DGCs), a conserved class of enzymes absent in mammals and hence considered attractive molecular targets for the development of antibiofilm agents. Here, the results of a virtual screening approach aimed at identifying small-molecule inhibitors of the DGC PleD from Caulobacter crescentus are described. A three-dimensional (3D) pharmacophore model, derived from the mode of binding of GTP to the active site of PleD, was exploited to screen the ZINC database of compounds. Seven virtual hits were tested in vitro for their ability to inhibit the activity of purified PleD by using circular dichroism spectroscopy. Two drug-like molecules with a catechol moiety and a sulfonohydrazide scaffold were shown to competitively inhibit PleD at the low-micromolar range (50% inhibitory concentration [IC50] of ∼11 μM). Their predicted binding mode highlighted key structural features presumably responsible for the efficient inhibition of PleD by both hits. These molecules represent the most potent in vitro inhibitors of PleD identified so far and could therefore result in useful leads for the development of novel classes of antimicrobials able to hamper biofilm formation. Biofilm-mediated infections are difficult to eradicate, posing a threatening health issue worldwide. The capability of bacteria to form biofilms is almost universally stimulated by the second messenger c-di-GMP. This evidence has boosted research in the last decade for the development of new antibiofilm strategies interfering with c-di-GMP metabolism. Here, two potent inhibitors of c-di-GMP synthesis have been identified in silico and characterized in vitro by using the well-characterized DGC enzyme PleD from C. crescentus as a structural template and molecular target. Given that the protein residues implied as crucial for enzyme inhibition are found to be highly conserved among DGCs, the outcome of this study could pave the way for the future development of broad-spectrum antibiofilm compounds.


A Time-lapse, Label-free, Quantitative Phase Imaging Study of Dormant and Active Human Cancer Cells.
The acquisition of the angiogenic phenotype is an essential component of the escape from tumor dormancy. Although several classic in vitro assays (e.g., proliferation, migration, and others) and in vivo models have been developed to investigate and characterize angiogenic and non-angiogenic cell phenotypes, these methods are time and labor intensive, and often require expensive reagents and instruments, as well as significant expertise. In a recent study, we used a novel quantitative phase imaging (QPI) technique to conduct time-lapse and labeling-free characterizations of angiogenic and non-angiogenic human osteosarcoma KHOS cells. A panel of cellular parameters, including cell morphology, proliferation, and motility, were quantitatively measured and analyzed using QPI. This novel and quantitative approach provides the opportunity to continuously and non-invasively study relevant cellular processes, behaviors, and characteristics of cancer cells and other cell types in a simple and integrated manner. This report describes our experimental protocol, including cell preparation, QPI acquisition, and data analysis.


Sources of parental hope in pediatric oncology.
Hope is a multidimensional concept that is important for all parents of children with cancer. However, most work has focused on advanced cancer and poor prognoses. We examined hopes of all parents of children with cancer longitudinally during the first year of treatment. Prospective, longitudinal, questionnaire-based cohort study of parents and physicians of children with cancer at two academic pediatric hospitals. Parents reported on general sense of hopefulness and specific hopes at time of diagnosis (N = 374); a subset of parents (N = 164) were followed longitudinally at 4 and 12 months. Fifty-five percent of parents (N = 206/374) reported being extremely hopeful in general at baseline. Hopefulness did not significantly change over time, and most parents (51-58%) reported being extremely hopeful regardless of prognosis (P = 0.66). Most parents (N = 327/356) considered hope for cure to be an extremely important source of hope; most also reported hope that the child would feel loved (N = 328/356), that the child would have the best possible quality of life (N = 316/356), and that they would always do all they could for the child (N = 300/356). Hope for cure was slightly lower among parents of children with less than a 50% chance of cure at baseline (N = 53/63) when compared to those with better prognoses (moderately likely cure, N = 76/78; very likely cure, N = 198/215) (P = 0.02). Many hopes contribute to parental hopefulness, not just hope for cure. This hopefulness persists over time, even when the prognosis is poor. Clinicians should focus on supporting the myriad hopes that contribute to overall hopefulness.


Ecdysone Receptor Agonism Leading to Lethal Molting Disruption in Arthropods: Review and Adverse Outcome Pathway Development.
Molting is critical for growth, development, reproduction, and survival in arthropods. Complex neuroendocrine pathways are involved in the regulation of molting and may potentially become targets of environmental endocrine disrupting chemicals (EDCs). Based on several known ED mechanisms, a wide range of pesticides has been developed to combat unwanted organisms in food production activities such as agriculture and aquaculture. Meanwhile, these chemicals may also pose hazards to nontarget species by causing molting defects, and thus potentially affecting the health of the ecosystems. The present review summarizes the available knowledge on molting-related endocrine regulation and chemically mediated disruption in arthropods (with special focus on insects and crustaceans), to identify research gaps and develop a mechanistic model for assessing environmental hazards of these compounds. Based on the review, multiple targets of EDCs in the molting processes were identified and the link between mode of action (MoA) and adverse effects characterized to inform future studies. An adverse outcome pathway (AOP) describing ecdysone receptor agonism leading to incomplete ecdysis associated mortality was developed according to the OECD guideline and subjected to weight of evidence considerations by evolved Bradford Hill Criteria. This review proposes the first invertebrate ED AOP and may serve as a knowledge foundation for future environmental studies and AOP development.


[Dietary calcium and the prevalence of spinal deformities in a sample of the elderly population].
The aim of the study was to determine the role of calcium intake through nutritional consumption of milk and other milk products currently and in three time periods during life (until 25 years, 25-50 years and 50 years and over) and to relate the results to finding of vertebral deformities in an unselected sample of population of Zagreb (Croatia), aged 50 years and above. Each of 425 recruited individuals (269 women and 156 men) completed interviewer administered questionnaire and had lateral thoracolumbar radiography performed according to a standard protocol. The questions related to number of days in which each subject consumed milk and its products in the last week, and milk consumption in three life-periods. The morphometric measurements of vertebral height were used to determine the occurrence of vertebral deformity according to the method described by McCloskey et al. Adding numbers of days in which each subjects in the last week consumed milk and its products the score ranging from 0-28 was obtained. Between two groups of subjects (group I = score 0-10 and group II = score 11 and over), there was no difference by age, but there was by sex, women being those with greater current consumption of milk products. There was an increased risk of finding vertebral deformity in women appertaining to group I (OR = 3.10, 95% CI = 1.20-7.97), but not for men (OR = 0.93, 95% CI = 0.37-2.35), nor for both sexes (OR = 1.89, 95% CI = 0.99-3.63). There was a statistically significant difference in frequency of drinking milk in period 25-50 years of life, women being again more frequent consumers, but not in other periods of life. There was no correlation in frequency of milk consumption and prevalence of vertebral deformity in any of the periods of life, separately for men and women and taken together. To estimate milk consumption throughout the whole life we added the figures for all three periods of life, getting the score ranging from 3-12. The subjects were divided into two groups, and no increased risk of vertebral deformity was found in those who had been drinking less milk (OR = 1.43, 95% CI = 0.77-2.66). In our study women with currently less dietary calcium intake have greater risk for vertebral deformities. No association was found between frequency of milk consumption throughout the life and prevalence of vertebral deformities.


Protamine and mast-cell-mediated angiogenesis in the rat.
Different doses of protamine sulphate (PS) given s.c. (at 12-h intervals) were tested for signs of non-specific toxicity measured as effect on body weight and small-gut proliferation as well as on mast-cell secretion and mast-cell-mediated mitogenesis in the mesenteric windows following i.p. injection of Compound 48/80, a potent mast cell secretagogue, in normal rats. In a non-toxic dose range, the effect of PS on mast-cell-mediated angiogenesis, effected by 48/80, was quantified as the number of vessels per mm of mesenteric window in histological sections at x 400. No intelligible dose-effect relationship was discernible between the dose of PS given and the effect on angiogenesis. Only in a tight interval, at 40 mg PS/kg but not at 20 or 60 mg PS/kg, was the angiogenesis statistically significantly suppressed. Hence, it was concluded that PS can be angiostatic but does not exert a more general angiostatic effect in the autogenous systems used.


Toward Chemically Resolved Computer Simulations of Dynamics and Remodeling of Biological Membranes.
Cellular membranes are fundamental constituents of living organisms. Apart from defining the boundaries of the cells, they are involved in a wide range of biological functions, associated with both their structural and the dynamical properties. Biomembranes can undergo large-scale transformations when subject to specific environmental changes, including gel-liquid phase transitions, change of aggregation structure, formation of microtubules, or rupture into vesicles. All of these processes are dependent on a delicate interplay between intermolecular forces, molecular crowding, and entropy, and their understanding requires approaches that are able to capture and rationalize the details of all of the involved interactions. Molecular dynamics-based computational models at atom-level resolution are, in principle, the best way to perform such investigations. Unfortunately, the relevant spatial and time dimensionalities involved in membrane remodeling phenomena would require computational costs that are today unaffordable on a routinely basis. Such hurdles can be removed by coarse-graining the representations of the individual molecular components of the systems. This procedure anyway reduces the possibility of describing the chemical variations in the lipid mixtures composing biological membranes. New hybrid particle field multiscale approaches offer today a promising alternative to the more traditional particle-based simulations methods. By combining chemically distinguishable molecular representations with mesoscale-based computationally affordable potentials, they appear as one of the most promising ways to keep an accurate description of the chemical complexity of biological membranes and, at the same time, cover the required scales to describe remodeling events.


The Clinical value of brain-gut behavioral therapies for functional esophageal disorders and symptoms.
Functional esophageal disorders (functional chest pain, functional heartburn, reflux hypersensitivity, globus, and functional dysphagia) are the disorders of gut-brain interactions (DGBI) and present with esophageal symptoms not associated with a structural, major motility or underlying inflammatory condition. Notably, many patients with the latter conditions may still experience esophageal symptoms beyond what could be attributed to their underlying disorders. Esophageal visceral hypersensitivity and hypervigilance are the two pathways which drive functional esophageal disorders and symptoms. These functional esophageal symptoms may be severe, leaving patients with impaired quality of life and inadequate treatment outcomes. Neuromodulators are the foundation of the pharmacologic approach of many of the functional esophageal disorders and symptoms, modulating both peripheral and central hyperalgesia. There is also emerging evidence for brain-gut behavioral therapies (BGBT) such as gut-directed hypnotherapy and cognitive behavior therapy for the treatment of a variety of DGBIs. In this issue of Neurogastroenterology and Motility, Hurtte et al. add to the literature on the effectiveness of BGBT in treating functional esophageal symptoms, showing multimodal therapy with pharmacologic and non-pharmacologic approaches led to improvement in health-related quality of life. In this review, we outline the mechanistic underpinnings of BGBT and review the existing evidence for BGBT for functional esophageal disorders and symptoms. We also highlight the future research directions and challenges for scaling these therapies.


The multiple actions of testosterone in men: nature knows best.
In male hormone replacement therapy Finkelstein et al. show that testosterone rather than synthetic "pure" androgens should be prescribed. Testosterone is converted to the superactive androgen dihydrotestosterone and to estradiol, and thus has actions via androgen receptors and both estrogen receptors (ERα, ERβ). Although muscle strength is androgen dependent, estradiol has major physiologic effects in men-on bone, cartilage, and together with androgens, on sexual functioning. Neither dihydrotestosterone nor 'pure' synthetic androgens can be converted to estradiol; those so treated thus risk missing out on the beneficial (and necessary) effects of estrogens in men.


Six Colombian patients with adult T-cell leukemia/lymphoma.
Six Colombian patients with adult T-cell leukemia/lymphoma (ATL) are presented. The clinical and hematological features, the familial clusters of human T lymphotropic virus type 1 (HTLV-I) carriers and the prognoses of the Colombian ATL patients were similar to those previously reported for Japanese ATL patients. The only difference was the mean age of onset, which was more than 20 years younger than in Japanese patients. Three patients with ATL were suffering from strongyloidiasis. In one patient it was suggested that ATL developed after horizontal transmission from his wife. In addition, there was a familial case of ATL and HAM/TSP. It seems that in some areas of Colombia, not only HTLV-I infection and HAM/TSP but also ATL are highly endemic.


Three-Dimensional Printed Pediatric Airway Model Improves Novice Learners' Flexible Bronchoscopy Skills With Minimal Direct Teaching From Faculty.
Training in pediatric flexible bronchoscopy (FB) is predominantly completed on patients. Early trainees are less accurate and slower than experienced bronchoscopists. This report describes the development of a three-dimensional printed airway model and describes how the model was used to teach learners basic FB skills. Postgraduate year two (PGY2) pediatric residents completing a 1-month pediatric pulmonology rotation with minimal previous exposure to FB were randomized into a simulation trainee group (n = 18) or a control resident group (n = 9). The simulation group received four 15-minute practice sessions (3 self-directed, 1 with feedback). Participants completed a bronchoscopy assessment on the model at prestudy, poststudy, and delayed (at least 2 months after the rotation) time points. Outcomes were identification of markers located in the six lung areas and completion time. There was no difference in prestudy scores between groups. In the poststudy assessment, the simulation participants correctly identified more lung area markers (median = 6 vs 1.5, P < 0.001) and were faster (median = 102 vs 600 seconds, P < 0.001). In the delayed assessment, correct marker identification trended toward improvement in the simulation group compared with controls (median = 4 vs 2, P = 0.077). With 1 hour of practice time, requiring 15 minutes of direct teaching, novice resident bronchoscopists are able to more accurately identify and visualize the five lung lobes and lingula via FB and are able to do so in less time than control residents. This anatomically accurate model could be used to train basic FB skills at a low cost compared with other models.


Glutamate and anxiety disorders.
Anxiety disorders are among the most prevalent psychiatric disorders, but they represent a particular challenge for treatment. The standard first-line treatments, including antidepressants, benzodiazepines, and buspirone, result in significant response rates for a majority of patients; however, unfavorable side effect profiles or risk for dependency for particular agents might limit their use by anxious patients, who often have low thresholds for medication discontinuation. Novel pharmacologic agents that modulate particular receptors, ion channels, or transporters relevant to glutamatergic neurotransmission may represent a new approach to the treatment of anxiety disorders, with generally more favorable side effect profiles. Although the role of glutamate in the pathophysiology of anxiety disorders is still being elucidated, the use of these agents in treatment of anxiety disorders and commonly comorbid conditions such as substance abuse and mood disorders will continue to increase.


Online formation of a hierarchical cognitive map for object-place association by theta phase coding.
Object-place associative memory, the storage of object and place conjunctions based on a one-time experience, is hippocampal-dependent in humans. Theta phase precession, a type of neural dynamics observed in the rat hippocampus, has recently been suggested to serve a role in instantaneous memory formation based on a one-time experience, while its functional role in associating distinct types of information (object and place information) is unclear. In this study, we hypothesize that theta phase encoding with theta phase precession contributes to the storage of object-place associations. To examine this hypothesis, we propose a neural network model of the corticohippocampal system, including central-peripheral visual pathways and theta phase coding in the hippocampus. Memory storage computer experiments demonstrate that the hippocampal network successfully stores the object-place associations of a one-time experience. Interestingly, it is also found that a random visual input sequence results in a robust formation of asymmetric connections between objects and scenes instantaneously after a single trial. Furthermore, it is found that scene-object connections and scene-scene connections form a hierarchical network representing the spatial alignment of scenes and objects in the environment. Our findings indicate that the theta phase coding, as observed in the rat hippocampus, can facilitate the online memory storage of complex environments in humans as a hierarchical cognitive map.


Incentives and regulations to reconcile conservation and development: thirty years of governance of the Sami pastoral ecosystem in Finnmark, Norway.
Incentive-based mechanisms are regarded as efficient instruments to reconcile conservation and development. This win-win objective has been difficult to accomplish; cross-compliance has, therefore, been suggested as a mechanism to ensure sustainability. Cross-compliance, which requires producers to conform to production regulations and environmental standards to qualify for direct payments, has been a popular instrument in the Common Agricultural Policy (CAP) reform. Since 1990, cross-compliance has been the main characteristic of policy design in Sami reindeer husbandry in Finnmark, Norway. All direct transfers to the Sami pastoralists have been connected to harvesting demands to decrease the number of reindeer and to conserve pastures. The content of these incentive-based mechanisms are decided through negotiated agreements with the Sami Reindeer Herders' Association of Norway (NRL), and the regulation of reindeer numbers and access to pastures are delegated to co-management boards. Despite the participation of the Sami pastoralists in shaping these policies, win-win objectives have not been achieved. Although the cross-compliance program could have been improved by payment for graded results, the lack of regulations by the administration or co-management boards is more likely to be the cause of failure to reach sustainability. Despite the long-term failures of the cross-compliance program, policies have been slow to change. We might attribute this delay to the NRL's strong position in the negotiated agreements. In general, we argue that the success of the cross-compliance program depends on a well-functioning governance system that can implement regulations and sanctions if incentives do not work as intended.


Amyloid-clearing proteins and their epigenetic regulation as a therapeutic target in Alzheimer's disease.
Abnormal elevation of amyloid β-peptide (Aβ) levels in the brain is the primary trigger for neuronal cell death specific to Alzheimer's disease (AD). It is now evident that Aβ levels in the brain are manipulable due to a dynamic equilibrium between its production from the amyloid precursor protein (APP) and removal by amyloid clearance proteins. Clearance can be either enzymic or non-enzymic (binding/transport proteins). Intriguingly several of the main amyloid-degrading enzymes (ADEs) are members of the M13 peptidase family (neprilysin (NEP), NEP2 and the endothelin converting enzymes (ECE-1 and -2)). A distinct metallopeptidase, insulin-degrading enzyme (IDE), also contributes to Aβ degradation in the brain. The ADE family currently embraces more than 20 members, both membrane-bound and soluble, and of differing cellular locations. NEP plays an important role in brain function terminating neuropeptide signals. Its decrease in specific brain areas with age or after hypoxia, ischaemia or stroke contribute significantly to the development of AD pathology. The recently discovered mechanism of epigenetic regulation of NEP (and other genes) by the APP intracellular domain (AICD) and its dependence on the cell type and APP isoform expression suggest possibilities for selective manipulation of NEP gene expression in neuronal cells. We have also observed that another amyloid-clearing protein, namely transthyretin (TTR), is also regulated in the neuronal cell by a mechanism similar to NEP. Dependence of amyloid clearance proteins on histone deacetylases and the ability of HDAC inhibitors to up-regulate their expression in the brain opens new avenues for developing preventive strategies in AD.


[Dealing with Waiting Times in Health Systems - An International Comparative Overview].
Waiting times in the health system are a form of rationing that exists in many countries. Previous studies on this topic are mainly related to the problem of international comparability of waiting times or on the presentation of national strategies as to how they should be reduced. This review adds to this analysis and examines how the OECD countries deal with waiting times in the health-care system and investigates which information is published about waiting for what purpose. Furthermore, waiting times and the type of health system financing are compared. A systematic internet research on waiting times in the health-care system was conducted on the websites of the competent authorities (Ministry of Health or other authorities and institutions). The identified publications were then examined for the purpose of their deployment. Finally, the OECD Health Data were analysed to determine the relationship between tax and contribution financing of public health care expenditure. The primary form of financing was compared with the results of the waiting time analysis. 16 OECD countries are identified which officially collect and publish administrative data on waiting times on the Internet. The data are processed differently depending on the country. By providing this information, two main objectives are pursued: a public monitoring of waiting times in the health system (14 countries) and information for patients on waiting times (9 countries). Official statistics on waiting times exist mainly in countries with tax-financed health systems, whereas this is not the case in the majority of OECD countries with health systems that are funded through contributions. The publication of administrative waiting times data is primarily intended to inform the patient and as a performance indicator in terms of access to health care. Even if data on waiting times are published, the publication of indicators and the management of waiting lists alone will not solve the problem. Rather, the analysis shows that in tax-funded health systems access to medical care is frequently rationed and the demand side is often regulated by waiting lists.


Not one hormone or another: Aggression differentially affects progesterone and testosterone in a South American ovenbird.
Behaviors such as territorial interactions among individuals can modulate vertebrate physiology and vice versa. Testosterone has been pointed out as a key hormone that can be rapidly affected by aggressive interactions. However, experimental evidence for such a link is mixed. In addition, behaviors can elicit changes in multiple hormones, which in turn have the potential to synergistically feedback to behavior. For example testosterone and progesterone can act interdependently in modulating male behavior. However, if aggression can affect progesterone levels in males remain unknown and - to the best of our knowledge - no one has yet tackled if and how aggressive behavior simultaneously affects testosterone and progesterone in free-living animals. We addressed these questions by performing simulated territorial intrusion experiments measuring both hormones and their ratio in male rufous horneros (Aves, Furnarius rufus) during the mating and parental care periods. Aggression affected testosterone and progesterone differentially depending on the period of testing: challenged birds had higher levels of progesterone during the mating period and lower levels of testosterone during parental care compared to controls. Challenged individuals had similar progesterone to testosterone ratios during both periods and these ratios were higher than those of control birds. In summary, territorial aggression triggered hormonal pathways differentially depending on the stage of the breeding cycle, but equally altered their ratio independent of it. Our results indicate that multiple related hormones could be playing a role rather than each hormone alone in response to social interactions.


Interface geometry and molecular junction conductance: geometric fluctuation and stochastic switching.
Metal/molecule/metal transport junctions can transport charge in the elastic scattering (Landauer) regime if the injection gap is large and the molecule is relatively short. Stochastic switching and broad conduction peak distributions have been observed in such junctions. We examine the effect of altering interface geometry on transport, using density functional calculations. For most structures, variations in conductance of order 0-300% are found, but when an atomic wire of Au binds to the molecule, symmetry changes can modify currents by a factor of 10(3).


Prenatal diagnosis of neural tube defects: predictive value of AF-AFP in a low-risk population.
Amniotic fluid alpha-fetoprotein (AF-AFP) determinations were performed on 1,215 women who were at low risk for fetal neural tube defects and who were undergoing mid-trimester amniocentesis for cytogenetic indications, primarily age-related aneuploidy. Maternal sera obtained before amniocentesis and amniotic fluids were assayed in duplicate for alpha-fetoprotein by radioimmunoassay. Of the 1,215 low-risk women, eight (0.7%) had significant elevations of AF-AFP (greater than or equal to +5 SD). In none of the cases was the elevation associated with a fetal neural tube defect. Two cases with elevated AF-AFP were associated with chromosome aberrations; one with impending fetal demise; one with fetal blood contamination; and one case was due to a laboratory error. In one case, no source for the elevated AFP was found, and a normal infant was delivered at term. In the final two cases, the cause of the elevated AF-AFP was a fetal abdominal wall defect (one gastroschisis and one omphalocele). The predictive value of an elevated AFP varies with the population screened, and is reduced by routine ultrasonography before amniocentesis, which at least identifies anencephaly. In a low-risk population, an elevated AF-AFP is most often not associated with a fetal neural tube defect. Because of the low predictive value and the nonspecificity of AF-AFP, genetic counselors should reconsider the recommendation of routine AF-AFP in low-risk maternal populations.


Advances, interactions, and future developments in the CNS, Phenix, and Rosetta structural biology software systems.
Advances in our understanding of macromolecular structure come from experimental methods, such as X-ray crystallography, and also computational analysis of the growing number of atomic models obtained from such experiments. The later analyses have made it possible to develop powerful tools for structure prediction and optimization in the absence of experimental data. In recent years, a synergy between these computational methods for crystallographic structure determination and structure prediction and optimization has begun to be exploited. We review some of the advances in the algorithms used for crystallographic structure determination in the Phenix and Crystallography & NMR System software packages and describe how methods from ab initio structure prediction and refinement in Rosetta have been applied to challenging crystallographic problems. The prospects for future improvement of these methods are discussed.


Phosphatidylserine binding of class B scavenger receptor type I, a phagocytosis receptor of testicular sertoli cells.
Testicular Sertoli cells phagocytose apoptotic spermatogenic cells in a manner depending on the membrane phospholipid phosphatidylserine (PS) expressed at the surface of the latter cell type. Our previous studies have indicated that class B scavenger receptor type I (SR-BI) is responsible for the PS-mediated phagocytosis by Sertoli cells. We examined here whether SR-BI binds directly to PS. A cell line acquired the ability to bind to PS-exposing apoptotic cells and to incorporate PS-containing liposomes when it was forced to express SR-BI. Furthermore, the extracellular domain of rat SR-BI fused with human Fc (SRBIecd-Fc) bound to PS with a dissociation equilibrium constant of 2.4 x 10(-7) m in a cell-free solid-phase assay, whereas other phospholipids including phosphatidylethanolamine, phosphatidylinositol, and phosphatidylcholine were poor binding targets. The binding activity was enhanced when CaCl(2) was included in the assay or when SRBIecd-Fc was pre-treated with N-glycanase. A portion of the extracellular domain spanning amino acid positions 33 and 191 (numbered with respect to the amino terminus) fused with Fc (SRBI33-191-Fc) showed activity and phospholipid specificity equivalent to those of SRBIecd-Fc. Finally, SRBI33-191-Fc bound to the surface of apoptotic cells with externalized PS, and the injection of SRBI33-191-Fc into the seminiferous tubules of live mice increased the number of apoptotic spermatogenic cells. These results allowed us to conclude that SR-BI is a phagocytosis-inducing PS receptor of Sertoli cells.


Renal cell carcinoma in a duplex kidney in pediatric.
Renal cell carcinoma (RCC) in children is relatively uncommon, especially in the absence of syndromes or hereditary diseases. Duplex kidney - as a common congenital anomalies in children - is usually insignificant with no serious impact or known risk of tumor association. Herein, we report a 5-year-old girl who presented with gross hematuria and a right renal mass in duplex system identified on computed tomography. Radical nephrectomy was performed; the patient was diagnosed with Xp11 translocation RCC and no other modalities of treatments were needed over 3-month follow-up.


Exploring the binding mechanisms of MIF to CXCR2 using theoretical approaches.
Macrophage migration inhibitory factor (MIF) is a multi-functional protein that acts as a cytokine and as an enzyme. Recently, MIF was identified as a non-canonical ligand of G protein-coupled chemokine receptor CXCR2 with low nanomolar affinity in leukocyte arrest and chemotaxis, but the precise knowledge of the molecular determinants of the MIF-CXCR2 interface has remained unknown. Therefore, we employed homology modeling, protein-protein docking, molecular dynamics (MD) simulations, Molecular Mechanics/Generalized Born Surface Area (MM/GBSA) binding free energy calculations and MM/GBSA binding free energy decomposition to obtain insights into the molecular recognition of MIF with CXCR2. The predicted binding pattern of MIF-CXCR2 is in good agreement with the experimental data and sheds light on the functional role of important MIF-CXCR2 interface residues in association with binding and signaling. According to our predictions, the R11A/D44A double mutations of MIF exhibit a pronounced defect in the binding affinity of MIF to CXCR2, resulting in large conformational changes. The potential two-site binding model for the MIF-CXCR2 recognition was proposed: initialized primarily by the non-polar interactions including the van der Waals and hydrophobic interactions, the N-terminal region of CXCR2 contacts the N-like loop and β-sheet of MIF (site 1), and then the ECL2 and ECL3 regions of CXCR2 form strong interactions with the pseudo-(E)LR motif and C-terminus of MIF, which induces the molecular thermodynamic motion of TMs for signal transduction (site 2). This study will extend our understanding to the binding mechanisms of MIF to CXCR2 and provide useful information for the rational design of potent inhibitors selectively targeting the MIF-CXCR2 interactions.


SR-POSE: A Novel Non-Contact Real-Time Rehabilitation Evaluation Method Using Lightweight Technology.
Rehabilitation movement assessment often requires patients to wear expensive and inconvenient sensors or optical markers. To address this issue, we propose a non-contact and real-time approach using a lightweight pose detection algorithm-Sports Rehabilitation-Pose (SR-Pose), and a depth camera for accurate assessment of rehabilitation movement. Our approach utilizes an E-Shufflenet network to extract underlying features of the target, a RLE-Decoder module to directly regress the coordinate values of 16 key points, and a Weight Fusion Unit (WFU) module to output optimal human posture detection results. By combining the detected human pose information with depth information, we accurately calculate the angle between each joint in three-dimensional space. Furthermore, we apply the DTW algorithm to solve the distance measurement and matching problem of video sequences with different lengths in rehabilitation evaluation tasks. Experimental results show that our method can detect human joint nodes with an average detection speed of 14.32ms and an average detection accuracy for pose of 91.2%, demonstrating its computational efficiency and effectiveness for practical application. Our proposed approach provides a low-cost and user-friendly alternative to traditional sensor-based methods, making it a promising solution for rehabilitation movement assessment.


Dipyridamole stress myocardial perfusion by computed tomography in patients with left bundle branch block.
Functional tests have limited accuracy for identifying myocardial ischemia in patients with left bundle branch block (LBBB). To assess the diagnostic accuracy of dipyridamole-stress myocardial computed tomography perfusion (CTP) by 320-detector CT in patients with LBBB using invasive quantitative coronary angiography (QCA) (stenosis ≥ 70%) as reference; to investigate the advantage of adding CTP to coronary computed tomography angiography (CTA) and compare the results with those of single photon emission computed tomography (SPECT) myocardial perfusion scintigraphy. Thirty patients with LBBB who had undergone SPECT for the investigation of coronary artery disease were referred for stress tomography. Independent examiners performed per-patient and per-coronary territory assessments. All patients gave written informed consent to participate in the study that was approved by the institution's ethics committee. The patients' mean age was 62 ± 10 years. The mean dose of radiation for the tomography protocol was 9.3 ± 4.6 mSv. With regard to CTP, the per-patient values for sensitivity, specificity, positive and negative predictive values, and accuracy were 86%, 81%, 80%, 87%, and 83%, respectively (p = 0.001). The per-territory values were 63%, 86%, 65%, 84%, and 79%, respectively (p < 0.001). In both analyses, the addition of CTP to CTA achieved higher diagnostic accuracy for detecting myocardial ischemia than SPECT (p < 0.001). The use of the stress tomography protocol is feasible and has good diagnostic accuracy for assessing myocardial ischemia in patients with LBBB.


Shape differences in the corpus callosum in first-episode schizophrenia and first-episode psychotic affective disorder.
The corpus callosum, the largest white matter tract in the brain, is a midline structure associated with the formation of the hippocampus, septum pellucidum, and cingulate cortex, which have been implicated in the pathogenesis of schizophrenia. Corpus callosum shape deformation, therefore, may reflect a midline neurodevelopmental abnormality. Corpus callosum area and shape were analyzed in 14 first-episode psychotic patients with schizophrenia, 19 first-episode psychotic patients with affective disorder, and 18 normal comparison subjects. No statistically significant corpus callosum area differences between groups were found, but there were differences in the structure's shape between the patients with schizophrenia and the comparison subjects. A correlation between width and angle of the corpus callosum was found in patients with affective disorder. Corpus callosum shape abnormalities in first-episode psychotic patients with schizophrenia may reflect a midline neurodevelopmental abnormality.


Distribution and diversity of twelve Curcuma species in China.
Genus Curcuma a wild species presents an important source of valuable characters for improving the cultivated Curcuma varieties. Based on the collected germplasms, herbariums, field surveys and other literatures, the ecogeographical diversity of Genus Curcuma and its potential distributions under the present and future climate are analysed by DIVA-GIS. The results indicate Genus Curcuma is distributed over 17 provinces in China, and particularly abundant in Guangxi and Guangdong provinces. The simulated current distributions are close to the actual distribution regions. In the future climate, the suitable areas for four Curcuma species will be extended, while for other three species the regions will be significantly decreased, and thus these valuable resources need protecting.


Radiation in orthopaedics (RIO) study: a national survey of UK orthopaedic surgeons.
Orthopaedic surgeons have a responsibility to minimise risks of ionising radiation to patients, themselves and staff. This study aims to establish the understanding of radiation practice, legislation and risk by orthopaedic surgeons. A nationwide online survey of UK-based orthopaedic surgeons was conducted. Participants answered 18 multiple-choice questions assessing level of radiation safety training, basic principles/knowledge of ionising radiation, relevant legislation and operating practice. A total of 406 surgeons completed the survey. 92% reported using intraoperative ionising radiation at least once per week. 38% received no formal training on radiation safety. Knowledge of basic principles of radiation and legislation was limited. There was variable knowledge when labelling an image intensifier machine and choosing its safest orientation. Poor uptake of radiation protection equipment was noted. Only 19% agreed they had adequate training in ionising radiation safety and 27% reported receiving adequate training in equipment emitting ionising radiation in the operating theatre. Many orthopaedic surgeons in the UK do not believe they are adequately trained in radiation safety. There is a deficiency amongst practicing surgeons in basic knowledge, relevant legislation and practicalities of the use of ionising radiation in the operating room. This could potentially put patients and health-care professionals at additional risk. We recommend that a standardised national training programme on the basic principles and safety of ionising radiation is implemented for all practicing orthopaedic surgeons. This paper is the first UK national survey amongst orthopaedic surgeons and is one of the largest reported internationally.


Effect of gonadotrophin releasing hormone upon the pattern of steroidogenesis in isolated preovulatory rat follicles.
The effects of GnRH and a potent GnRH analogue (D-Ala6-des-gly-NH2-GnRH-ethylamide) on steroidogenesis in isolated preovulatory follicles of PMSG-treated immature rats were examined in short-term incubations and compared to the effect of LH. Steroids were analyzed by RIA. GnRH stimulated the accumulation of pregnenolone (2-fold), progesterone (4-fold), 20 alpha-OH-progesterone (38-fold), androstenedione (4-fold), testosterone (3-fold), and oestradiol-17 beta (2-fold) during a 6 h incubation. The time-course of stimulation was the same for each of the steroids analyzed, with a significant effect at 4 and 6 h, but not at 2 h of incubation. Dose-response curves were similar for each steroid, and the GnRH analogue and GnRH gave parallel curves with minimal effective concentrations being 1 and 10 ng/ml, respectively. The stimulatory effect of LH was more pronounced and rapid (2 h) than that of GnRH. During prolonged incubation (6-8 h) with GnRH or LH there was evidence for an inhibition of testosterone production, probably due to suppression of the C21-side chain cleavage enzyme. Thus, the qualitative response to GnRH on follicular steroidogenesis resembled that of LH in some but not all respects. The differences in time-course and maximal steroid secretion between GnRH and LH are compatible with different mechanisms of action in the follicle.


The influence of 'cognitive busyness' on causal attributions of challenging behaviour in dementia: a preliminary experimental study.
This study investigated the influence of 'cognitive busyness' (competing cognitive demands) on residential care staff attributions of challenging behaviour (CB) related to dementia. Following the model of attribution formation proposed by Gilbert, Pelham, and Krull (1988), it was hypothesised that care staff experiencing competing cognitive demands at the time of observing CBs linked with dementia would be more likely to make internal and controllable attributions regarding the causes of such behaviour. This study employed a cross-over experimental design. Thirty formal dementia care-workers viewed two video clips of simulated CB, one under conditions of cognitive 'busyness' and another under control conditions of no extra cognitive demands. These conditions occurred a week apart and were counterbalanced, i.e. one group of participants undertook the control condition first and then the experimental condition whilst another undertook the reverse. Self-report measures of attributions were administered after the viewing of each video clip. Competing cognitive demands significantly influenced staff attributions regarding CB, in relation to internality and controllability, and type of CB emerged as a potential moderating factor. No link was found between cognitive busyness and other attributional dimensions (stability and globality). Concurrent cognitive demands seem capable of impairing the ability to use situational information to form some causal attributions regarding CB in dementia but this might depend on the type of CB being witnessed. The results are discussed in relation to key methodological and conceptual issues.


Immunosuppressive effect of the anti-IL-2-receptor monoclonal antibody, AMT-13, on organ-cultured fetal pancreas allograft survival.
Recently, prolongation of cardiac allograft survival in mice was reported using a rat anti-IL-2R mAb (AMT-13). However, its immunosuppressive action in vivo, alone and in combination with other immunosuppressants, and its effect on other organ transplants has not been extensively studied. We grafted cultured fetal pancreas from CBA (H-2k) donors to Balb/c (H-2d) mice. Recipients were treated with 10 consecutive daily injections each of 20 micrograms AMT-13 only, or with an additional mild immunosuppression of 350 rads irradiation. Control groups received rat immunoglobulin or 350 rads irradiation. Graft survival and the phenotype of infiltrating cells were assessed histologically and immunocytochemically on days 12, 17, and 21, and soluble IL-2R levels were measured in the serum with a quantitative ELISA in all recipients. Two of five grafts in the AMT-13-treated group had islets on day 12 posttransplantation despite lymphocytic infiltration in all grafts, while at this time all grafts of rat Ig treated control mice were completely rejected with only scar tissue and a few lymphocytes remaining. Additional immunosuppression with 350 rads irradiation had a marked additive effect with AMT-13. Soluble IL-2R levels in the serum of untreated recipients were not elevated compared with normal serum levels, but recipients injected with AMT-13 had multifold increased soluble IL-2R levels. The percentage of IL-2R+ cells in the grafts of AMT-13-treated animals was either normal (less than 5%) or increased (20%) in the additionally irradiated mice, providing strong evidence that the immunosuppressive effect of AMT-13 is not due to a depletion of activated IL-2R+ lymphocytes.


Prosthetic energy return during walking increases after 3 weeks of adaptation to a new device.
There are many studies that have investigated biomechanical differences among prosthetic feet, but not changes due to adaptation over time. There is a need for objective measures to quantify the process of adaptation for individuals with a transtibial amputation. Mechanical power and work profiles are a primary focus for modern energy-storage-and-return type prostheses, which strive to increase energy return from the prosthesis. The amount of energy a prosthesis stores and returns (i.e., negative and positive work) during stance is directly influenced by the user's loading strategy, which may be sensitive to alterations during the course of an adaptation period. The purpose of this study was to examine changes in lower limb mechanical work profiles during walking following a three-week adaptation to a new prosthesis. A retrospective analysis was performed on 22 individuals with a unilateral transtibial amputation. Individuals were given a new prosthesis at their current mobility level (K3 or above) and wore it for three weeks. Kinematic and kinetic measures were recorded from overground walking at 0, 1.5, and 3 weeks into the adaptation period at a self-selected pace. Positive and negative work done by the prosthesis and sound ankle-foot were calculated using a unified deformable segment model and a six-degrees-of-freedom model for the knee and hip. Positive work from the prosthesis ankle-foot increased by 6.1% and sound ankle-foot by 5.7% after 3 weeks (p = 0.041, 0.036). No significant changes were seen in negative work from prosthesis or sound ankle-foot (p = 0.115, 0.192). There was also a 4.1% increase in self-selected walking speed after 3 weeks (p = 0.038). Our data exhibited large inter-subject variations, in which some individuals followed group trends in work profiles while others had opposite trends in outcome variables. After a 3-week adaptation, 14 out of 22 individuals with a transtibial amputation increased energy return from the prosthesis. Such findings could indicate that individuals may better utilize the spring-like function of the prosthesis after an adaptation period.


Investigating the effect of processing parameters on pharmaceutical tablet disintegration using a real-time particle imaging approach.
Tablet disintegration is a fundamental parameter that is tested in vitro before a product is released to the market, to give confidence that the tablet will break up in vivo and that active drug will be available for absorption. Variations in tablet properties cause variation in disintegration behaviour. While the standardised pharmacopeial disintegration test can show differences in the speed of disintegration of different tablets, it does not give any mechanistic information about the underlying cause of the difference. With quantifiable disintegration data, and consequently an improved understanding into tablet disintegration, a more knowledge-based approach could be applied to the research and development of future tablet formulations. The aim of the present research was to introduce an alternative method which will enable a better understanding of tablet disintegration using a particle imaging approach. A purpose-built flow cell was employed capable of online observation of tablet disintegration, which can provide information about the changing tablet dimensions and the particles released with time. This additional information can improve the understanding of how different materials and process parameters affect tablet disintegration. Standard USP analysis was also carried out to evaluate and determine whether the flow cell method can suitably differentiate the disintegration behaviour of tablets produced using different processing parameters. Placebo tablets were produced with varying ratios of insoluble and soluble filler (mannitol and MCC, respectively) so that the effect of variation in the formulation can be investigated. To determine the effect of the stress applied during granulation and tableting on tablet disintegration behaviour, analysis was carried out on tablets produced using granular material compressed at 20 or 50bar, where a tableting load of either 15 or 25kN was used. By doing this the tablet disintegration was examined in terms of the tablet porosity by monitoring the tablet area and particle release. It was found that when 20 and 50bar roller compaction pressure was used the USP analysis showed almost identical disintegration times for the consequent tablets. With the flow cell method a greater tablet swelling was observed for the lower pressure followed by steady tablet erosion. Additionally, more particles were released during disintegration due to the smaller granule size distribution within the tablet. When a higher tableting pressure was applied the tablet exhibited a delay in the time taken to reach the maximum swelling area, and slower tablet erosion and particle release were also observed, largely due to the tablet being much denser causing slower water uptake. This was in agreement with the USP analysis data. Overall it was confirmed by using both the standard USP analysis and flow cell method that the tablet porosity affects the tablet disintegration, whereby a more porous tablet disintegrates more slowly. But a more in-depth understanding was obtained using the flow cell method as it was determined that tablets will swell to varying degrees and release particles at different rates depending on the roller compaction and tableting pressure used.


An unusual case of systemic cardiovascular side effects from the application of over-the-counter nasal decongestion drops.
A 78-year-old female with a history of stable angina, phoned for advice with chest pains following the application of 0.5% ephedrine nasal drops for nasal congestion, which she had bought over-the-counter on the recommendation of a pharmacist. On applying the medication, she developed chest pain which she recognised as her angina. The Foundation Year 2 general practitioner on duty consulted the British National Formulary (BNF), issue 56 and thought that nasal decongestant induced angina was unlikely and advised the patient to seek emergency attention should she have any further episodes. After re-applying the medication and suffering the same symptoms, the patient later presented to the Emergency Department. The patient had the relevant tests and was diagnosed with 'ephedrine-induced angina'. This settled on withdrawal of the medication and she had no further episodes of chest pain in the following 6 months.


Synthesis, crystallization, X-ray structural characterization and solid-state assembly of a cyclic hexapeptoid with propargyl and methoxyethyl side chains.
The synthesis and the structural characterization of a cyclic hexapeptoid with four methoxyethyl and two propargyl side chains have disclosed the presence of a hydrate crystal form [form (I)] and an anhydrous crystal form [form (II)]. The relative amounts of form (I) and form (II) in the as-purified product were determined by Rietveld refinement and depend on the purification procedures. In crystal form (I), peptoid molecules assemble in a columnar arrangement by means of side-chain-to-backbone C=CH...OC hydrogen bonds. In the anhydrous crystal form (II), cyclopeptoid molecules form ribbons by means of backbone-to-backbone CH2...OC hydrogen bonds, thus mimicking β-sheet secondary structures in proteins. In both crystal forms side chains act as joints among the columns or the ribbons and contribute to the stability of the whole solid-state assembly. Water molecules in the hydrate crystal form (I) bridge columns of cyclic peptoid molecules, providing a more efficient packing.


Degenerate PCR method for identification of an antiapoptotic gene in BHV-1.
To investigate on the hypothetical presence of an antiapoptotic gene, we utilized the CODEHOP (COnsensus-DEgenerate Hybrid Oligonucleotide Primers) strategy amplifying unknown sequences from a background of genomic (bovine herpesvirus type-1) BHV-1 DNA. An alignment of carboxyl-terminal domains belonging to three proteins encoded by gamma34.5, MyD116 and GADD34 genes, was carried out to design degenerate PCR primers in highly conserved regions. This allowed the amplification of a 110 bp fragment. This fragment was subjected to automatic sequencing and DNA sequence analysis revealed that its position resided between the nt 14363 and the nt 14438 in bovine herpesvirus type-1 (BHV-1) Cooper strain sharing an identity of 86% (UL14). Transient transfections showed that UL14 protein is efficient in protecting MDBK and K562 cells from sorbitol induced apoptosis. The protein's anti-apoptotic function may derive from its heat shock protein-like properties.


Effects of Nanoprobe Morphology on Cellular Binding and Inflammatory Responses: Hyaluronan-Conjugated Magnetic Nanoworms for Magnetic Resonance Imaging of Atherosclerotic Plaques.
Atherosclerosis is an inflammatory disease of arterial walls and the rupturing of atherosclerotic plaques is a major cause of heart attack and stroke. Imaging techniques that can enable the detection of atherosclerotic plaques before clinical manifestation are urgently needed. Magnetic resonance imaging (MRI) is a powerful technique to image the morphology of atherosclerotic plaques. In order to better analyze molecular processes in plaques, contrast agents that can selectively bind to plaque receptors will prove invaluable. CD44 is a cell surface protein overexpressed in plaque tissues, the level of which can be correlated with the risks of plaque rupture. Thus, targeting CD44 is an attractive strategy for detection of atherosclerotic plaques. Herein, we report the synthesis of hyaluronan-conjugated iron oxide nanoworms (HA-NWs). A new purification and gel electrophoresis protocol was developed to ensure the complete removal of free HA from HA-NWs. Compared to the more traditional spherical HA-bearing nanoparticles, HA-NWs had an elongated shape, which interacted much stronger with CD44-expressing cells in CD44- and HA-dependent manners. Furthermore, the HA-NWs did not induce much inflammatory response compared to the spherical HA nanoparticles. When assessed in vivo, HA-NWs enabled successful imaging of atherosclerotic plaques in a clinically relevant model of ApoE knockout transgenic mice for noninvasive plaque detection by MRI. Thus, nanoprobe shape engineering can be a useful strategy to significantly enhance their desired biological properties.


The Effect of Cinnamon on Glycolipid Metabolism: A Dose-Response Meta-Analysis of Randomized Controlled Trials.
(1) Background: The effect of cinnamon on the regulation of glycolipid levels in type 2 diabetic patients is still controversial, and there is a lack of research on the dose-response relationship between cinnamon and glycolipid indicators in type 2 diabetic patients. (2) Methods: This dose-response meta-analysis was performed to explore the effect of the cinnamon intervention on glycolipid metabolism. We conducted a comprehensive database search for literature published before November 2022. Nonlinear models were used for dose-response relationship analysis. (3) Results: We identified that a cinnamon intervention was effective in controlling triglyceride (TG) levels (mean difference = -7.31; 95%CI: -12.37, -2.25, p = 0.005) and low-density lipoprotein cholesterol (LDL-C) levels (mean difference = -6.78; 95%CI: -11.35, -2.22, p = 0.004) in type 2 diabetic patients; however, it also was able to increase high-density lipoprotein cholesterol (HDL-C) levels in patients with type 2 diabetes (mean difference = 1.53; 95%CI: 1.01, 2.05, p < 0.001). However, the cinnamon intervention had no significant effect on the level of fasting blood glucose, glycated hemoglobin (HbA1c), or total cholesterol (TC) levels. We found a significant effect of the cinnamon intervention dose on the TG level (p-nonlinearity = 0.016) and LDL-C (p-nonlinearity = 0.019) in the nonlinear dose-response analysis. In the subgroup analysis, we found a hypoglycemic effect with the cinnamon dose ≤1200 mg (mean difference = -11.1, 95%CI: -14.64, -7.58, p < 0.001). (4) Conclusion: Cinnamon intervention may be beneficial in lowering TG and LDL-C levels while enhancing HDL-C levels, and the dosage of the intervention was an important factor in influencing the TG and LDL-C levels.


Novel insights into the genetic landscape of congenital heart disease with systems genetics.
We recently conducted a large-scale mouse mutagenesis screen and uncovered a central role for cilia in the pathogenesis of congenital heart disease (CHD). Though our screen was phenotype based, most of the genes recovered were cilia-related, including genes encoding proteins important for ciliogenesis, cilia-transduced cell signaling, and vesicular trafficking. Also unexpected, many of the cilia related genes recovered are known direct protein-protein interactors, even though each gene was recovered independently in unrelated mouse lines. These findings suggest a cilia-based protein-protein interactome network may provide the context for congenital heart disease pathogenesis. This could explain the incomplete penetrance and variable expressivity of human CHD, and account for its complex non-Mendelian etiology. Supporting these findings in mice, a preponderance of cilia and cilia related cell signaling genes were observed among de novo pathogenic variants identified in a CHD patient cohort. Further clinical relevance unfolded with the observation of a high prevalence of respiratory cilia dysfunction in CHD patients. This was associated with increased postsurgical respiratory complications. Together these findings highlight the importance of cilia in CHD pathogenesis and suggest possible clinical translation with instituting pulmonary therapy to improve outcome for CHD patients undergoing congenital cardiac surgeries.


Delayed iliacus compartment syndrome following femoral artery puncture: case report and literature review.
Iliacus compartment syndrome is a rare retroperitoneal compartment neuropathy caused by bleeding within the iliacus muscle leading to hematoma formation and compression upon the femoral nerve, causing both sensory and motor deficits. A 75-year-old Caucasian man presented with severe right hip pain associated with motor and sensory deficit in the right lower extremity, 2 weeks post elective balloon aortic valvuloplasty for critical aortic stenosis. A non-contrast computed tomography scan revealed low-attenuation areas in keeping with an iliacus hematoma. An iliacus fasciotomy and hematoma evacuation was performed with retroperitoneal approach. The patient reported marked reduction in his groin pain with clinical improvement of the right hip flexion though the sensory deficit was unchanged. On Day 3, postoperatively the patient died from respiratory and multi-organ failure. Iliac hematomas are rare and can be caused by traumatic and non-traumatic injury, and can be exacerbated by complications of anticoagulant therapy. Delaying surgical evacuation of the hematoma can lead to prolonged or permanent disability. However, there are other reports describing good recovery with non-operative management. Non-surgical intervention is recommended if radiological studies do not explicitly confirm the presence of a discreet hematoma compressing the femoral nerve, unless progression of symptoms increases.


Immunohistochemical profile of canalicular adenoma of the upper lip: a case report.
Canalicular adenoma is an uncommon benign salivary gland neoplasm that has a marked predilection for occurrence in the upper lip. It is composed of columnar cells arranged in branching and interconnecting cords of single or double cell thick rows. This tumor has an excellent prognosis after conservative surgical treatment in all locations. In the present report we describe, using immunohistochemistry, the expression of cytokeratins (CK), S-100 protein and EMA in a canalicular adenoma that arose in the upper lip of a 55-year-old female. Cells of the canalicular adenoma showed an immunohistochemical profile that indicates an excretory duct origin: most of these cells positively expressed AE1/AE3 cytokeratins and S100 protein. A comparison of the immunohistochemical features of canalicular adenoma with other salivary gland neoplasms that share similar histological features is discussed.


Remifentanil/midazolam versus tramadol/midazolam use for colonoscopy.
One of the most commonly performed outpatient procedure is colonoscopy. The pain and anxiety is frequently associated with colonoscopy. The aim of this study was to compare the effectiveness of remifentanil/midazolam, and tramadol/midazolam for iv sedation and analgesia during colonoscopy. Twentysix patients (age range 18-65 years) scheduled for ambulatory colonoscopy were included to study. All patients received midazolam 1 mg intravenous. After two minutes in Group R (remifentanil/midazolam, n=18) remifentanil bolus (10 microg) and infusion 0.03 microg kg(-1) min(-1) were administered until adequate sedation level was achieved. In Group T (tramadol/midazolam, n=18) iv tramadol 50 mg was given concurrently. During procedure 2 L/min oxygen was supplemented via face mask to all patients. Haemodynamic variables, respiratory depression, level of sedation, postoperative recovery, patient and gastroenterologist satisfaction were surveyed. Patients were asked to verbally rate their level of pain, on an 10-point numerical rating scale (1=no pain, 10=severe pain). Chi-square, student t test, and mann whitney U test were used for statistical analysis. Colonoscopy was carried out successfully in all patients. There were no episodes of desaturation or airway compromise. Haemodynamic parameters were similar in both groups. Sistolic arterial and diastolic arterial pressures were increased at 10 and 15 minutes in all patients (P<0.05). There were no significant changes in heart rate in both groups. The level of sedation in group R was higher than group T during colonoscopy. The patients in group T had higher pain scores. Gastroenterologist satisfaction and patient satisfaction were similar in both groups. Our results suggests that, sedoanalgesia with midazolam/remifentanil may be an alternative to sedoanalgesia with midazolam/tramadol for colonoscopy.


Relational database design: evaluation of the recognition, isolation and treatment of hospitalized patients with tuberculosis.
Hospitals have been charged with the the evaluation of their abilities to identify, diagnose, isolate and treat individuals with active tuberculosis. This evaluation can be facilitated by a properly designed relational database. Using Entity Relationship diagrams, a relational data model, and the process of normalization, a database was designed that will contain the information gathered in prospective surveillance of tuberculosis in a community hospital. Although the authors' intent is to implement the design using a personal computer and a commercially available relational database management tool (Microsoft Access), the design is independent of the management tool and can be applied to other systems.


Use of Intracardiac Echocardiography to Evaluate Continuous-Flow Left Ventricular Assist Device Function in a Man With Obesity.
Aortic insufficiency with recirculation can be difficult to diagnose echocardiographically in patients who have continuous-flow left ventricular assist devices. Transthoracic and transesophageal echocardiography can underestimate its severity; moreover, transesophageal echocardiography necessitates general anesthesia. We report the case of a 58-year-old man with obesity and end-stage nonischemic cardiomyopathy who, after 3 months of support with a continuous-flow left ventricular assist device, underwent intracardiac echocardiography to evaluate complications potentially associated with the device. The findings ruled out aortic insufficiency, preventing an unnecessary valvular intervention.


Quality-Related Process Monitoring and Diagnosis of Hot-Rolled Strip Based on Weighted Statistical Feature KPLS.
Rolling is the main process in steel production. There are some problems in the rolling process, such as insufficient ability of abnormal detection and evaluation, low accuracy of process monitoring, and fault diagnosis. To improve the accuracy of quality-related fault diagnosis, this paper proposes a quality-related process monitoring and diagnosis method for hot-rolled strip based on weighted statistical feature KPLS. Firstly, the process-monitoring and diagnosis model of strip thickness and quality based on the KPLS method is introduced. Then, considering that the KPLS diagnosis method ignores the contribution of process variables to quality, it is easy to misjudge the root cause of quality in the diagnosis process. Based on the rolling mechanism model, the influence weight of strip thickness is constructed. By weighing the statistical data features, a quality diagnosis framework of series structure data fusion is constructed. Finally, the method is applied to the 1580 mm hot-rolling process for industrial verification. The verification results show that the proposed method has higher diagnostic accuracy than PLS, KPLS, and other methods. The results show that the diagnostic model based on weighted statistical feature KPLS has a diagnostic accuracy of more than 96% for strip thickness and quality-related faults.


Analysis of GNA13 Protein in Follicular Lymphoma and its Association With Poor Prognosis.
GNA13 is a G protein involved in modulating tumor proliferative capacity, infiltration, metastasis, and migration. Genomic alteration of GNA13 was frequently observed in follicular lymphoma (FL). In this study, we examined 167 cases of FL by immunostaining of GNA13 using tissue microarray to evaluate the clinical significance. There were 26 GNA13-positive cases (15.6%) and 141 GNA13-negative cases (84.4%). GNA13-positive cases had a higher incidence of early progression of disease for which disease progression was recognized within 2 years compared with GNA13-negative cases (P=0.03). There were no significant differences in other clinicopathologic factors including histological grade, BCL2-IGH translocation, immunohistochemical phenotype, and Follicular Lymphoma International Prognostic Index. In addition, overall survival and progression-free survival were poorer in GNA13-positive cases than in GNA13-negative cases (P=0.009 and 0.005, respectively). In multivariate analysis, GNA13 positivity was found to be a poor prognostic factor for overall survival and progression-free survival. Thus, GNA13 protein expression was an independent prognostic factor and may affect disease progression in FL.


Math anxiety and math performance in children: The mediating roles of working memory and math self-concept.
Numerous studies, most of them involving adolescents and adults, have evidenced a moderate negative relationship between math anxiety and math performance. There are, however, a limited number of studies that have addressed the mechanisms underlying this relation. This study aimed to investigate the role of two possible mediational mechanisms between math anxiety and math performance. Specifically, we sought to test the simultaneous mediating role of working memory and math self-concept. A total of 167 children aged 8-12 years participated in this study. Children completed a set of questionnaires used to assess math and trait anxiety, math self-concept as well as measures of math fluency and math problem-solving. Teachers were asked to rate each student's math achievement. As measures of working memory, two backward span tasks were administered to the children. A series of multiple mediation analyses were conducted. Results indicated that both mediators (working memory and math self-concept) contributed to explaining the relationship between math anxiety and math achievement. Results suggest that working memory and self-concept could be worth considering when designing interventions aimed at helping students with math anxiety. Longitudinal designs could also be used to better understand the mediational mechanisms that may explain the relationship between math anxiety and math performance.


Investigation of an acetaldehyde-hemoglobin adduct in alcoholics.
It has been proposed that an ethanol-related adduct is formed with hemoglobin in chronic alcoholics. This proposal is based on the observation that alcoholics were found to have an elevation of minor hemoglobins but normal amounts of glycosylated hemoglobin (HbA1c). Since acetaldehyde is believed to be the primary candidate involved in adduct formation, investigation was focused on this particular compound. This study describes the attempt to isolate and purify an acetaldehyde-hemoglobin adduct in alcoholics by cation-exchange chromatography and m-aminophenylboronic acid affinity chromatography for the purpose of characterization. Using acetaldehyde concentrations of 5 and 10 mM, an acetaldehyde adduct with hemoglobin was formed in vitro, isolated, and characterized. However, a similar adduct could not be isolated in vitro using a pharmacological concentration of 100 microM acetaldehyde nor could this adduct be isolated in human alcoholic subjects.


Paralytic poliomyelitis and nonpolio enteroviruses: studies in Scotland.
Poliomyelitis has been well controlled in Scotland by vaccination. Occasional cases of paralysis still occur in association with enteroviruses, especially coxsackieviruses. Most cases were attributable to coxsackievirus A7, which was identified in 77 cases, 12 of them paralytic (one fatal), from 1956 to 1973 (including outbreaks in 1959 and 1963) but not since then. Serologic findings suggesting poliovirus infection have been obtained in several paralytic illnesses at a late stage, months after acute illnesses in which the possibility of poliomyelitis was not considered by physicians, who no longer expect to encounter cases of poliomyelitis.


Improved cathode for high efficient microbial-catalyzed reduction in microbial electrosynthesis cells.
Microbial electrosynthesis cells (MECs) are devices wherein microorganisms can electrochemically interact with electrodes, directly donating or accepting electrons from electrode surfaces. Here, we developed a novel cathode by using nickel nanowires anchored to graphite for the improvement of microbial-catalyzed reduction in MEC cathode chamber. This porous nickel-nanowire-network-coated graphite electrode increased the interfacial area and interfacial interactions between the cathode surface and the microbial biofilm. A 2.3 fold increase in bio-reduction rate over the untreated graphite was observed. Around 282 mM day(-1) m(-2) of acetate resulting from the bio-reduction of carbon dioxide by Sporomusa was produced with 82 ± 14% of the electrons consumed being recovered in acetate.


Epidemiologic aspects of an outbreak of acquired immunodeficiency in rhesus monkeys (Macaca mulatta).
Since August 25, 1981, an outbreak of simian acquired immunodeficiency syndrome ( SAIDS ) has been recognized in a single outdoor corral housing 77 rhesus monkeys (Macaca mulatta) over a 16-month period. The etiology of this syndrome is unknown but epidemiologic evidence suggests an infectious agent. Thirty-two cases of SAIDS have been identified (31 female, 1 male), and 27 of these animals have died (case fatality rate = 84%). Three of these deaths occurred among 13 infants born in the corral . All 27 deaths were females. For animals in the original cohort, sex was not a statistically significant risk factor. For animals born in the corral females were at greater risk (p = 0.0489; Fisher's Exact Test). SAIDS mortality rates were highest for animals entering the corral at less than 30 months of age (4.4 deaths per 100 monkey months of follow-up) and for animals born into the cage (3.3 deaths per 100 monkey-months of follow-up). The mortality rate was lowest for animals entering the corral at greater than 30 months of age, (0.32 deaths per 100 monkey-months of follow-up). No significant associations were found for the factors weaning history, cage-move history, parentage, generation, and medical history, including history of bite-wound trauma. Nine of the original 64 animals entering the corral on August 25, 1981, were previously associated with a group of 110 rhesus monkeys occupying this same corral from September 1976 to August 1981. Though less dramatic, a similar pattern of morbidity and high mortality was recognized retrospectively in this group.(ABSTRACT TRUNCATED AT 250 WORDS)


Application of artificial intelligence in anterior segment ophthalmic diseases: diversity and standardization.
Artificial intelligence (AI) based on machine learning (ML) and deep learning (DL) techniques has gained tremendous global interest in this era. Recent studies have demonstrated the potential of AI systems to provide improved capability in various tasks, especially in image recognition field. As an image-centric subspecialty, ophthalmology has become one of the frontiers of AI research. Trained on optical coherence tomography, slit-lamp images and even ordinary eye images, AI can achieve robust performance in the detection of glaucoma, corneal arcus and cataracts. Moreover, AI models based on other forms of data also performed satisfactorily. Nevertheless, several challenges with AI application in ophthalmology have also arisen, including standardization of data sets, validation and applicability of AI models, and ethical issues. In this review, we provided a summary of the state-of-the-art AI application in anterior segment ophthalmic diseases, potential challenges in clinical implementation and our prospects.


Feasibility of fluorodeoxyglucose dual-head gamma camera coincidence imaging in the evaluation of lung cancer: comparison with FDG PET.
The purpose of this study was to elucidate the feasibility of fluorodeoxyglucose gamma camera coincidence imaging (FDG GCI) in the evaluation of lung cancer in comparison with FDG PET. Twenty-three patients with recently diagnosed lung cancer were examined with both FDG PET and FDG GCI on the same day. Pulmonary lesions were analyzed visually and semiquantitatively using the ratio of lesion-to-background counts (L/B ratio). The L/B ratio of FDG PET without attenuation correction (AC) was also calculated and compared. Nodal stations were only visually analyzed. FDG GCI and FDG PET could detect 22 and 23, respectively, of 23 pulmonary lesions by visual analysis (95.7% versus 100%). The L/B ratio of FDG GCI was 4.26 +/- 2.55, and significantly lower than that of FDG PET (9.29 +/- 4.95; P < 0.01). The L/B ratio of FDG PET was significantly higher with AC than that without AC (9.29 +/- 4.95 vs. 6.66 +/- 4.65; P < 0.01). When the L/B ratio threshold was set at 5.0 for FDG PET and 2.7 for FDG GCI, their sensitivity was 87.0% and 73.9%, respectively. Of the 3 and 6 patients with false-negative results on semiquantitative analysis, the lesions in 3 patients on FDG PET and 4 patients on FDG GCI were less than or equal to 2.0 cm in greatest diameter, respectively. In the assessment of mediastinal involvement, FDG PET was 77.8% sensitive, 78.6% specific and 78.3% accurate, whereas FDG GCI was 77.8% sensitive, 92.9% specific and 87.0% accurate. In the hilar regions, FDG PET was 100% sensitive, 84.2% specific and 87.0% accurate, whereas FDG GCI was 75.0% sensitive, 89.5% specific and 87.0% accurate. In this study, FDG GCI yielded results comparable to FDG PET on visual analysis to detect pulmonary lesions and lymph node metastases. However, the lesion-to-background contrasts of pulmonary lesions and nodal involvement were lower in FDG GCI than in FDG PET. Comparison between the L/B ratio of FDG PET with and without AC indicated that, with AC, FDG GCI would be closer to FDG PET in the evaluation of lung cancer.


Role of AxyZ Transcriptional Regulator in Overproduction of AxyXY-OprZ Multidrug Efflux System in Achromobacter Species Mutants Selected by Tobramycin.
AxyXY-OprZ is an RND-type efflux system that confers innate aminoglycoside resistance to Achromobacter spp. We investigated here a putative TetR family transcriptional regulator encoded by the axyZ gene located upstream of axyXY-oprZ An in-frame axyZ gene deletion assay led to increased MICs of antibiotic substrates of the efflux system, including aminoglycosides, cefepime, fluoroquinolones, tetracyclines, and erythromycin, indicating that the product of axyZ negatively regulates expression of axyXY-oprZ Moreover, we identified an amino acid substitution at position 29 of AxyZ (V29G) in a clinical Achromobacter strain that occurred during the course of chronic respiratory tract colonization in a cystic fibrosis (CF) patient. This substitution, also detected in three other strains exposed in vitro to tobramycin, led to an increase in the axyY transcription level (5- to 17-fold) together with an increase in antibiotic resistance level. This overproduction of AxyXY-OprZ is the first description of antibiotic resistance acquisition due to modification of a chromosomally encoded mechanism in Achromobacter and might have an impact on the management of infected CF patients. Indeed, tobramycin is widely used for aerosol therapy within this population, and we have demonstrated that it easily selects mutants with increased MICs of not only aminoglycosides but also fluoroquinolones, cefepime, and tetracyclines.