A protocol paper for the MOTION Study-A longitudinal study in a cohort aged 60 years and older to obtain mechanistic knowledge of the role of the gut microbiome during normal healthy ageing in order to develop strategies that will improve lifelong health and wellbeing.
Advances in medicine and public health mean that people are living longer; however, a significant proportion of that increased lifespan is spent in a prolonged state of declining health and wellbeing which places increasing pressure on medical, health and social services. There is a social and economic need to develop strategies to prevent or delay age-related disease and maintain lifelong health. Several studies have suggested links between the gut microbiome and age-related disease, which if confirmed would present a modifiable target for intervention development. The MOTION study aims to determine whether and how changes in the gut microbiome are associated with physical and mental capacity. A comprehensive longitudinal multiparameter study such as this has not been previously undertaken. MOTION is a longitudinal prospective cohort study with a focus on gut health and cognitive function. 360 healthy individuals aged 60 years and older, living in East Anglia, UK will be recruited to the study, stratified into one of three risk groups (cohorts) for developing dementia based on their cognitive function. Participants will attend study appointments every six months over four years, providing stool and blood samples and a health questionnaire. Participants will also undergo physical measurements and cognitive tests at alternating appointments, and undergo Optical Coherence Tomography scans at 3 timepoints. Two subgroups of participants in the study will provide colonic tissue biopsies (n = ≥30 from each cohort), and brain imaging (n = 30) at two timepoints. This study will provide new insights into the gut-(microbiota)-brain axis and the relationship between age-associated changes in gut microbe populations and cognitive health. Such insights could help develop new microbe-based strategies to improve lifelong health and wellbeing. This study is registered in the ClinicalTrials.gov Database with ID: NCT04199195 Registered: May 14, 2019.


Novel polyamine coating providing non-covalent deactivation and reversed electroosmotic flow of fused-silica capillaries for capillary electrophoresis.
A new polycationic coating for use in capillary electrophoresis has been developed that enables chemical modification of fused-silica capillary surfaces for analysis of compounds like basic proteins. The cationic polyamine, containing short aliphatic blocks of combined 2 and 3-carbon length, was physically adsorbed onto the negatively charged fused-silica surface through ionic interaction by flushing the capillary with a polyamine solution, followed by a self-stabilization step. The polyamine coated capillaries generated an anodal electroosmotic flow that was independent of pH in the investigated range of pH 4-8. The capillary performance was demonstrated by fast separations of basic proteins with peak efficiencies in the range of 265,000-584,000 plates.


Reproducing cardiac restitution properties using the Fenton-Karma membrane model.
Modern models of cardiac membranes are often highly complex and computationally expensive, particularly when used in long simulations of spatially extended models of cardiac tissue. Therefore, there is a need for simpler membrane models that preserve the features of the complex models deemed important. This communication describes an empirical procedure that was used to choose the parameters of the three-variable Fenton-Karma (FK3V) model to reproduce the restitution properties of the Courtemanche-Ramirez-Nattel model of atrial tissue. The resulting parameter values for the FK3V model and the sensitivity table for all its parameters are provided. Thus, this study gives insight into the behavior of the FK3V model and the effect of its parameters on restitution properties.


Clinical characteristics of patients with concomitant oral lichen planus and thyroid disease.
To study the prevalence and profile of thyroid disease in a cohort of referred patients with oral lichen planus (OLP) in comparison with a random population sample and to examine the clinical characteristics of OLP patients with and without thyroid disease. Data from 1611 patients with OLP and 1615 patients from the general population were collected by using a standardized registration method. Patients with OLP using levothyroxine (OLP/levothyroxine+) were re-examined to collect information about existing OLP lesions and to confirm the thyroid disease diagnosis. The clinical characteristics of OLP lesions in this group were compared with those in an age- and gender-matched population of patients with OLP without a history of thyroid disease or levothyroxine medication (OLP/levothyroxine-). Nearly 11% (n=170) of the patients with OLP were taking levothyroxine compared with 2.5% (n=40) of the controls (multivariate odds ratio 2.99, 95% confidence interval 2.03-4.44; P<.0001). No difference was found in the thyroid disease profile between the groups. At the time of re-examination, patients with OLP/levothyroxine- displayed more erythematous OLP lesions and complained of more severe symptoms compared with the OLP/levothyroxine+ group (P<.001). The prevalence of thyroid disease in patients with OLP was significantly higher than in the general population. The OLP lesions of patients with concomitant thyroid disease have a different presentation over time, which indicates a specific subgroup of OLP.


Neuronal effects of orexins: relevant to sympathetic and cardiovascular functions.
Orexin A and B, also called hypocretin 1 and 2, were recently discovered in the hypothalamus. This organ, in which a number of neuropeptides have been demonstrated to stimulate or suppress food intake, is considered important for the regulation of appetite and energy homeostasis. Orexins were initially reported as a regulator of food intake. More recent reports suggest their possible important roles in the multiple functions of neuronal systems, such as narcolepsy, a sleep disorder. Orexins and their receptors are distributed in neural tissue and brain regions involved in the autonomic and neuroendocrine control. Functional studies have shown that these peptides evoke changes in cardiovascular and sympathetic responses. The data from our in vivo and in vitro studies suggest that the peptide acting on neurons in the hypothalamic paraventricular nucleus increases the cardiovascular responses. This review will focus on the neural effects of orexins and how these peptides may participate in the regulation of cardiovascular and sympathetic functions.


Lesbian Community and Activism in Britain 1940s-1970s: An Interview with Cynthia Reid.
In this article, I provide a micro(oral)history of Cynthia Reid, one of only five women who founded the Minorities Research group-the first known lesbian organization in Britain, in 1963. Such activism paved the way for further lesbian liberatory action and the group did a great deal to combat the isolation experienced by many queer women across the country. They provided social opportunities as well as advice, and made more public calls for greater social acceptance. The group has been central to the interests of 20th-century queer historians, especially as the Minorities Research Group also produced the first lesbian magazine in Britain Arena Three. As a microhistory Cynthia's story informs many threads within queer history, including conceptualizations of masculinities, community, and change; while also challenging dominant notions that families and medical professionals were consistently unsupportive of queer people in the 1940s-1970s. In doing so, this article amplifies Cynthia's story in a way that means not only does it contribute nuance as a micro(oral)history to the broader field of queer scholarship but it also acts as a resource to stimulate further research.


Heat production and growth kinetics of E. coli K12 from flow calorimetric measurements on chemostat cultures.
The heat production of E. coli K12 growing aerobically in glucose limited chemostat cultures is determined in the range of specific growth rates mu (= dilution rates D) from 0.058 h-1 to 0.852 h-1 for two different glucose concentrations Se in the instream of the chemostat, namely Se1 = 0.3182 g.l-1 and Se2 = 0.6364 g.l-1. Heat production Q and biomass production P per unit of culture volume show well correlated patterns for Se1 and Se2. For Se1 the highest value Q actually measured is 443.10(-3) W.l-1 at D = 0.74 h-1 with P = 0.068 g.l-1.h-1; and for Se2 593.10(-3) W.l-1 at D = 0.497 h-1 with P = 0.108 g.l-1.h-1. Heat production QB per unit of biomass appears to be independent of Se at least up to D = 0.5 h-1. At higher D there is strong indication that QB possesses a real maximum. The highest value of QB actually measured is 4.8 W.g-1 at D = 0.74 h-1. For Se1 and Se2 there were significantly higher specific growth rates verified in chemostat culture than mu Batchmax = 0.717 h-1 which is the maximum specific growth rate in comparable, unlimited batch cultures. The real maximum of QB is estimated to be in the vicinity of mu Batchmax. This suggests the hypothesis of a maximum principle for the growth in batch culture. For Se1 a closed analytical expression is derived for the relationship between mu and the substrate concentration S. mu[S] features a S-shaped characteristic with mu Chemostatmax = 0.905 h-1; 1/2 mu Chemostatmax is reached at S = 2.85.10(-3) g.l-1. Three basic parameters which characterize the overall metabolism of the cells, namely the heat released per unit of substrate consumed, Qs, the effective yield of biomass, Yeff, and mu Chemostatmax are identified to depend on Se.


Quality of life of parents of very preterm infants 4 months after birth: a mixed methods study.
Knowledge about parental quality of life (QoL) is paramount to family-centred and integrated healthcare on prematurity, but evidence is limited. We aimed to explore mothers' and fathers' perspectives about their QoL 4 months after a very preterm childbirth. This is a cross-sectional mixed methods study using a convergent design. Parents of very preterm infants were systematically recruited at all level III neonatal intensive care units in the Northern health region of Portugal for one year. Four months after childbirth, 61 mothers and 56 fathers filled-in the World Health Organization Quality of Life - BREF Inventory, and 26 couples were interviewed. Linear regression models were computed to assess the association between participants' characteristics and the QoL. Qualitative data were thematically analysed. A quantitative analysis revealed that the perception of QoL was not significantly different by gender. QoL scores increased slightly from the environment (Mean (SD): 72.1 (14.2)) to the psychological domains (Mean (SD): 78.7 (14.4)). All scores were influenced by psychological characteristics. Socioeconomic position influenced both parents' perceptions concerning the environment domain, and maternal physical and psychological QoL. Infant-related factors were associated with overall QoL among women and with the physical, psychological, social and environment domains among men. Qualitative findings indicated accommodation mechanisms that intertwine the focus on constraining factors (surveillance, sleep disturbances, non-supportive healthcare policies, hygienization) with facilitating factors (social support, accessibility/quality of healthcare, opportunities for developing parental skills). These processes were anchored in child-centredness and a framework that construct hierarchies of hope and expectations about infant's health and development. To capture parental QoL using mixed methods raises awareness for developing intersectoral family-centred policies, integrated health services and focused-interventions to decrease the disempowering effects of surveillance and hygienization.


[Detecting caries susceptible population in children with gtfB oligonucleotide probe].
To establish a quick, exact and inexpensive method to detect caries susceptibility in children. 125 caries free children, aged 3-4 years, were randomly sampled. A combination of polymerase chain reaction (PCR) and gtfB oligonucleotide probe hybridization method was used to detect Streptococcus mutans in saliva. The participants were followed up for a year and the clinical examination results were compared with the laboratory results. The perspective study was used to evaluate the detecting approach. When the combination of PCR and hybridization method was used to detect caries susceptibility of the sample, the predictive sensitivity, predictive specificity and predictive reliability were all increased to 69.2%, 46.8% and 54.3%, respectively as compared to only PCR, which were 56.4%, 44.2% and 48.3%, respectively. The samples with both the positive and negative results of hybridization detection had caries clinically, but the dmft index and prevalence were higher in the positive (dmft was 2.15 +/- 0.86, and the prevalence was 23.28%) than in the negative(dmft was 1.58 +/- 0.51, and the prevalence was 10.34%) which was statistically significant (P < 0.05). The probe was found to be quite potential in detecting caries susceptibility, but the predictive specificity and predictive reliability values were not significant.


Bleeding risk and safety profile related to the use of eptifibatide: a current review.
Eptifibatide is a glycoprotein IIb/IIIa inhibitor that blocks the final common pathway of platelet aggregation. Its major adverse effect is bleeding. Balancing its safety and efficacy is paramount for its appropriate usage. The development of eptifibatide and its mechanism of action are explored. Clinical trials evaluating its efficacy and safety in a variety of clinical settings, as well as newer dosing regimens, are discussed. Readers will be able to understand the bleeding risks of eptifibatide in specific patient populations. The risk of bleeding with eptifibatide needs to be weighed against the potential benefits. Understanding which patients are at higher risk of bleeding will help the clinician make appropriate decisions.


Bartonellosis.
The role of Bartonella species as pathogens in dogs and cats is being defined. Diagnosis and treatment of Bartonella infections of dogs and cats remain challenging. As new information regarding Bartonella infections of companion animals becomes available, the understanding of the pathogenesis of these infections will improve. Most Bartonella species infecting dogs and cats are zoonotic, with B henselae the most important zoonotic species. B henselae bacteremia is common in domestic cats, and cats transmit B henselae to people. Transmission of Bartonella infections among cats and dogs is believed to occur primarily by way of arthropod vectors. Control of arthropod vectors and avoiding interactions with pets that result in scratches or bites are the most effective means to prevent transmission between animals and people.


SERS Investigation of Cancer Cells Treated with PDT: Quantification of Cell Survival and Follow-up.
In this study Surface Enhanced Raman Spectroscopy (SERS) data recorded from mouse mammary glands cancer cells (4T1 cell line) was used to assess information regarding differences between control, death and viable cells after Photodynamic Therapy (PDT) treatment. The treatment used nanoemulsions (NE/PS) loaded with different chloroaluminumphthalocyanine (ClAlP) photosensitizer (PS) contents (5 and 10 µmol × L-1) and illumination (660 nm wavelength) at 10 J × cm-2 (10 minutes). The SERS data revealed significant molecular alterations in proteins and lipids due to the PDT treatment. Principal Component Analysis (PCA) was applied to analyze the data recorded. Three-dimensional and well reproductive PCA scatter plots were obtained, revealing that two clusters of dead cells were well separated from one another and from control cluster. Overlap between two clusters of viable cells was observed, though well separated from control cluster. Moreover, the data analysis also pointed out necrosis as the main cell death mechanism induced by the PDT, in agreement with the literature. Finally, Raman modes peaking at 608 cm-1 (proteins) and 1231 cm-1 (lipids) can be selected for follow up of survival rate of neoplastic cells after PDT. We envisage that this finding is key to contribute to a quick development of quantitative infrared thermography imaging.


Paper-based multiplex analytical device for simultaneous detection of Clostridioides difficile toxins and glutamate dehydrogenase.
We report a new paper-based multiplex analytical device (mPAD) for simultaneous screening of three analytes (glutamate dehydrogenase, toxin A, and toxin B) known as biomarkers for Clostridioides difficile infection (CDI). To overcome the limitation of common rapid assays (e.g. lateral flow immunochromatographic and enzyme immunoassays) in terms of multiplexing, sensitivity, simplicity, and ease-of-use, the mPAD is constructed with a three dimensional (3D) configuration of paper components with a multi-channel design. Multiple fluidic paths developed with wax-patterned paper allow the simultaneous detection of glutamate dehydrogenase, toxin A, and toxin B without any cross-reactivity. The 3D fluidic network on the mPAD facilitates a self-operating test procedure for the mixing and addition of amplification reagents with a one-step sliding operation. The results of the multiplex CDI assay can be easily interpreted by the naked eye within 10 min, and are visually intensified over time resulting in up to 3-fold signal amplification. Our device exhibited remarkable analytical performances for the simultaneous detection of three CDI biomarkers, providing a sensitivity of 97%, specificity of 88%, accuracy of 95%, and limits of detection for glutamate dehydrogenase, toxin A, and toxin B of 0.16 ng mL-1, 0.09 ng mL-1, and 0.03 ng mL-1, respectively. These results indicate the high applicability and feasibility of mPAD for multiplex testing for CDI with the advantages of being simple, sensitive, inexpensive, user-friendly, and equipment-free.


Isolated tumor cells and micrometastases in regional lymph nodes in stage I to II endometrial cancer.
The aim of this study was to clarify the clinical significance of isolated tumor cells (ITCs) or micrometastasis (MM) in regional lymph nodes in patients with International Federation of Gynecology and Obstetrics (FIGO) stage I to II endometrial cancer. In this study, a series of 63 patients with FIGO stage I to II were included, who had at least one of the following risk factors for recurrence: G3 endometrioid/serous/clear cell adenocarcinomas, deep myometrial invasion, cervical involvement, lympho-vascular space invasion, and positive peritoneal cytology. These cases were classified as intermediate-risk endometrial cancer. Ultrastaging by multiple slicing, staining with hematoxylin and eosin and cytokeratin, and microscopic examination was performed on regional lymph nodes that had been diagnosed as negative for metastases. Among 61 patients in whom paraffin-embedded block was available, ITC/MM was identified in nine patients (14.8%). Deep myometrial invasion was significantly associated with ITC/MM (p=0.028). ITC/MM was an independent risk factor for extrapelvic recurrence (hazard ratio, 17.9; 95% confidence interval [CI], 1.4 to 232.2). The 8-year overall survival (OS) and recurrence-free survival (RFS) rates were more than 20% lower in the ITC/MM group than in the node-negative group (OS, 71.4% vs. 91.9%; RFS, 55.6% vs. 84.0%), which were statistically not significant (OS, p=0.074; RFS, p=0.066). Time to recurrence tended to be longer in the ITC/MM group than in the node-negative group (median, 49 months vs. 16.5 months; p=0.080). It remains unclear whether ITC/MM have an adverse influence on prognosis of intermediate-risk endometrial cancer. A multicenter cooperative study is needed to clarify the clinical significance of ITC/MM.


Conceptional and structural conditions for successful clinical research.
The efficiency of surgical research has again become the subject of debate. Clinical research is required to improve our understanding of surgical disorders and our ability to treat patients. This involves both experimental research (research in the test tube) and clinical research in actual patients. The surgeon must remain the expert because it is he who deals with the patient and is confronted with his problems. On the other hand, care for the patient, must always be the central issue. Here a new orientation is needed, evaluating the effectiveness of surgical research from the patient's point of view. Surgical treatment, particularly surgical research, must be adapted first to the individual patient and only secondly to the surgical disease - the problem must determine the method, not vice versa. While it is clear that a creative atmosphere, supportive structure and efficient organisation are enormously helpful, today's exaggerated attention to matters of structure and organisation are often poor substitutes for creativity and intuition. Surgical research does not refer solely to therapy research but includes methods for carrying out controlled clinical trials, establishing guidelines and scores and designing instruments for measuring outcome. Socioeconomic and analyses and ethical considerations are crucial for facing such conflicts as "quality versus quantity", "profession versus business", "patient care versus economics costs". Proposals for designing more effective concepts, structure and organisation for clinical research are presented here, and three models are introduced: the cooperation model, the integration model and a mixture of the two.


Magnifying visual target information and the role of eye movements in motor sequence learning.
An experiment investigated the influence of eye movements on learning a simple motor sequence task when the visual display was magnified. The task was to reproduce a 1300 ms spatial-temporal pattern of elbow flexions and extensions. The spatial-temporal pattern was displayed in front of the participants. Participants were randomly assigned to four groups differing on eye movements (free to use their eyes/instructed to fixate) and the visual display (small/magnified). All participants had to perform a pre-test, an acquisition phase, a delayed retention test, and a transfer test. The results indicated that participants in each practice condition increased their performance during acquisition. The participants who were permitted to use their eyes in the magnified visual display outperformed those who were instructed to fixate on the magnified visual display. When a small visual display was used, the instruction to fixate induced no performance decrements compared to participants who were permitted to use their eyes during acquisition. The findings demonstrated that a spatial-temporal pattern can be learned without eye movements, but being permitting to use eye movements facilitates the response production when the visual angle is increased.


The type of gum arabic affects interactions with soluble pea protein in complex coacervation.
Complex coacervation is an encapsulation process involving two oppositely charged biopolymers. Since different compositions of gum arabic may affect its interaction with protein, we studied the complex coacervation of two types of gum arabic (GA) (Acacia senegal-GA1 and Acacia seyal-GA2) with soluble pea protein (SPP) through Zeta potential, turbidity, morphology, the secondary structure of SPP, UV/vis absorbance and thermodynamic parameters. The maximum formation of coacervates occurred at SPP:GA 3:1 (w/w) and pH 3.5-4.0 with changes in the secondary structure of SPP. GA1 combination resulted in higher binding constant, implying a stronger affinity between SPP and GA1. Entropy of 0.7 and 0.5 kJ/mol.K, and enthalpy of -151 and -95.5 kJ/mol were obtained for SPP:GA1 and SPP:GA2. The complex coacervation was spontaneous as proved by the negative values of the Gibbs free energy. GA1 resulted in stronger interactions with SPP, offering new alternatives for encapsulation of bioactive compounds.


Metachronous cancer: prognostic factors including prior irradiation.
In this article we evaluate two factors that may be responsible for the reported increased mortality rate in metachronous cancers: prior radiation therapy and stage at presentation. A select group of 358 patients was split into three groups: no prior cancer (group 1), prior cancer treated with radiation therapy (group 2), and prior cancer treated with surgery alone (group 3). We compared survival among the three groups according to stage (T1 or T2 vs. T3 or T4) using the Lifetest procedure. Survival in patients with advanced (T3 or T4) cancers was uniformly poor, and survival in patients with low-staged (T1 or T2) cancers was disproportionately poor only for patients in group 2. Metachronous cancers are not necessarily more lethal, except when the cancer arises within prior irradiated tissue. Initial treatment decisions for patients with primary cancers must always provide for the contingency of a metachronous cancer, and the judicious use of radiation therapy is essential.


Long pedunculated colonic polyp composed of mucosa and submucosa: proposal of a new entity, colonic muco-submucosal elongated polyp.
We encountered 15 patients with colonic polyps showing histologic features that did not belong to any of the known categories. All polyps were elongated and drumstick-shaped, with lengths of 12 to 160 (mean, 29 mm) mm. Histologically, the polyps were covered with normal mucosa and consisted of edematous, loose, fibrous, connective tissues and dense, fibrous submucosal layers, often showing dilation of blood vessels and lymphatics. Although the mechanism of generation of such polyps remains unknown, their elongation may be caused by intestinal motion. Because this kind of polyp has not been described previously outside Japan, we here introduce a new type of polyp, which we have proposed calling the colonic muco-submucosal elongated polyp.


S1PR1-dependent migration of ILC3s from intestinal tissue to the heart in a mouse model of viral myocarditis.
Type 3 innate lymphocytes have recently been reported as key factors in inflammatory diseases, but their role in viral myocarditis is unclear. By flow cytometry, coxsackievirus B3-induced myocarditis mice were detected to increase the number of type 3 innate lymphocytes, and their main type was NKp46+ type 3 innate lymphocytes. In contrast, application of CD90.2 neutralizing antibody in T-cell-deficient mice reduced the number of innate lymphocytes and improved myocarditis. Innate lymphocytes from CD45.1 mouse intestinal lamina propria lymphocytes were adoptively transferred into recipient mice, and a comparable proportion of CD45.1+ cells were observed in the hearts of coxsackievirus B3-infected recipient mice. The upregulation of S1PR1, KLF2, CXCR6, and CXCL16 in the hearts of coxsackievirus B3-infected mice, as well as the greatly reduced numbers of innate lymphocytes infiltrating the hearts after S1PR1 inhibition, suggests that intestinal innate lymphocytes may migrate to the hearts via the CXCL16/CXCR6 axis. Taken together, our results demonstrate that increased type 3 innate lymphocytes in the heart during viral myocarditis may contribute to inflammatory progression and that this increased population of type 3 innate lymphocytes likely originates from the intestine.


Circulating hematopoietic stem cell populations in human fetuses: implications for fetal gene therapy and alterations with in utero red cell transfusion.
Circulating progenitor cell populations in normal human fetuses and fetuses with various hematological problems were evaluated. Thirty blood samples from 21 human fetuses (17-36 weeks of gestation) were assayed for erythroid, myeloid, and mixed-cell progenitor cells. The mean number of progenitor cells/10(4) blood mononuclear cells in the normal fetal population was 103 +/- 47. Granulomonocytic and mixed progenitor cells (capable of giving rise to both erythroid and myeloid progeny) were the predominant progenitor types in these samples, with pure erythroid progenitors barely detectable. The frequency of progenitor cells in the samples from fetuses with hematological disorders was within the range of normal in all but 1 fetus infected with parvovirus in whom very few progenitor cells were detected. The frequency of progenitor cells in the blood did not change after intravascular red cell transfusion for alloimmunization despite the large volumes transfused, indicating that transfusion may have triggered a release of progenitor cells into the circulation. Progenitor cells in human fetal blood are present in distributions similar to those commonly detected in cord blood. Their total number in the circulating blood is in the same order used for pediatric and adult bone marrow transplantation. These results can be used to calculate the number of colony-forming cells which could be obtained from a fetus by in utero apheresis and which could be made available for autologous fetal gene therapy.


The complete mitochondrial genome of Oxyuris equi: Comparison with other closely related species and phylogenetic implications.
The equine pinworm Oxyuris equi (Nematoda: Oxyuridomorpha) is the most common horse nematode, has a worldwide distribution, and causes major economic losses. In the present study, the complete O. equi mitochondrial (mt) genome was sequenced, and the mt genome structure and organization were compared with those of other closely related pinworm species, Enterobius vermicularis and Wellcomia siamensis. The O. equi mt genome is a 13,641-bp circular DNA molecule that encodes 36 genes (12 protein-coding genes, 22 tRNAs, and two rRNAs) and one non-coding region, which is slightly shorter than that of E. vermicularis and W. siamensis. The O. equi mt gene arrangement was consistent with that of GA13-type E. vermicularis but it differs from GA12-type W. siamensis. Phylogenetic analyses using concatenated amino acid sequences of the 12 protein-coding genes with three different computational algorithms (maximum parsimony, maximum likelihood, and Bayesian inference) revealed that there were two distinct clades in Chromadorea nematodes that reflected infraorder. Spiruromorpha formed one clade, whereas Rhabditomorpha, Ascaridomorpha, and Oxyuridomorpha formed another clade. O. equi, E. vermicularis, and W. siamensis represent distinct but closely related species, which indicated that Oxyuridomorpha is paraphyletic. Sequencing the O. equi mt genome provides novel genetic markers for studying the molecular epidemiology and population genetics of pinworms.


The role of EMG awareness in EMG biofeedback learning.
Underlying most research on biofeedback learning is a theoretical model of the processes involved. The current study tested a prediction from the Awareness Model: High initial EMG awareness should facilitate response control during EMG biofeedback training. Seventy-two undergraduates were assessed for forehead EMG awareness by asking them to produce target responses from 1.0 to 5.0 microV every 15 s for 16 trials. Based on this assessment, two groups (high and low awareness) were trained for 64 trials to produce these target levels with either EMG biofeedback, practice (no feedback), or noncontingent EMG feedback. A transfer task was identical to the initial assessment. During training, the biofeedback group deviated less from target than the practice and noncontingent groups. The biofeedback group was the only group to improve from initial EMG awareness activity. During transfer, only the low awareness biofeedback group remained below initial EMG awareness level. These findings can be interpreted in terms of the Two-Process Model.


Variation in the nature of organic acid secretion and mineral phosphate solubilization by Citrobacter sp. DHRSS in the presence of different sugars.
A novel phosphate solubilizing bacterium (PSB) was isolated from the rhizosphere of sugarcane and is capable of utilizing sucrose and rock phosphate as the sole carbon and phosphate source, respectively. This PSB exhibited mineral phosphate solubilizing (MPS) phenotype on sugars such as sucrose and fructose, which are not substrates for enzyme glucose dehydrogenase (GDH), along with GDH substrates, viz., glucose, xylose, and maltose, as carbon sources. PCR amplification of the rRNA gene and sequence analysis identified this bacterium as Citrobacter sp. DHRSS. On sucrose and fructose Citrobacter sp. DHRSS liberated 170 and 100 microM free phosphate from rock phosphate and secreted 49 mM (2.94 g/L) and 35 mM (2.1 g/L) acetic acid, respectively. Growth of Citrobacter sp. DHRSS on sucrose is mediated by an intracellular inducible neutral invertase. Interestingly, in the presence of GDH substrates like glucose and maltose, Citrobacter sp. DHRSS produced approximately 20 mM (4.36 g/L) gluconic acid and phosphate released was 520 and 570 microM, respectively. Citrobacter sp. DHRSS GDH activity was found when grown on GDH and non-GDH substrates, indicating that it is constitutive and could act on a wide range of aldose sugars. This study demonstrates the role of different organic acids in mineral phosphate solubilization by rhizobacteria depending on the nature of the available carbon source.


General Strategies for Glycan Microarray Data Processing and Analysis.
Glycan microarrays provide a high-throughput technology for rapidly profiling interactions between carbohydrates and glycan-binding proteins (GBPs). Use of glycan microarrays involves several general steps, including construction of the microarray, carrying out the assay, detection of binding events, and analysis of the results. While multiple platforms have been developed to construct microarrays, most utilize fluorescence for detection of binding events. This chapter describes methods to acquire and process microarray images, including generating GAL files, imaging of the slide, aligning the grid, detecting problematic spots, and evaluating the quality of the data. The chapter focuses on processing our neoglycoprotein microarrays, but many of the lessons we have learned are applicable to other array formats.


Cell blebbing and membrane area homeostasis in spreading and retracting cells.
Cells remodel their plasma membrane and cytoskeleton during numerous physiological processes, including spreading and motility. Morphological changes require the cell to adjust its membrane tension on different timescales. While it is known that endo- and exocytosis regulate the cell membrane area in a timescale of 1 h, faster processes, such as abrupt cell detachment, require faster regulation of the plasma membrane tension. In this article, we demonstrate that cell blebbing plays a critical role in the global mechanical homeostasis of the cell through regulation of membrane tension. Abrupt cell detachment leads to pronounced blebbing (which slow detachment does not), and blebbing decreases with time in a dynamin-dependent fashion. Cells only start spreading after a lag period whose duration depends on the cell's blebbing activity. Our model quantitatively reproduces the monotonic decay of the blebbing activity and accounts for the lag phase in the spreading of blebbing cells.


Correction to: Assessment of thermally comfortable urban spaces in Amsterdam during hot summer days.
The article was published without special issue designation resulting in regular issue compilation. The author group and publisher regret the error and ask the article be considered for Special Issue: Subjective approaches to thermal perception.


Host and pathogen response to bacteriophage engineered against Mycobacterium abscessus lung infection.
Two mycobacteriophages were administered intravenously to a male with treatment-refractory Mycobacterium abscessus pulmonary infection and severe cystic fibrosis lung disease. The phages were engineered to enhance their capacity to lyse M. abscessus and were selected specifically as the most effective against the subject's bacterial isolate. In the setting of compassionate use, the evidence of phage-induced lysis was observed using molecular and metabolic assays combined with clinical assessments. M. abscessus isolates pre and post-phage treatment demonstrated genetic stability, with a general decline in diversity and no increased resistance to phage or antibiotics. The anti-phage neutralizing antibody titers to one phage increased with time but did not prevent clinical improvement throughout the course of treatment. The subject received lung transplantation on day 379, and systematic culturing of the explanted lung did not detect M. abscessus. This study describes the course and associated markers of a successful phage treatment of M. abscessus in advanced lung disease.


The energy-level crossing behavior and quantum Fisher information in a quantum well with spin-orbit coupling.
We study the energy-level crossing behavior in a two-dimensional quantum well with the Rashba and Dresselhaus spin-orbit couplings (SOCs). By mapping the SOC Hamiltonian onto an anisotropic Rabi model, we obtain the approximate ground state and its quantum Fisher information (QFI) via performing a unitary transformation. We find that the energy-level crossing can occur in the quantum well system within the available parameters rather than in cavity and circuit quantum eletrodynamics systems. Furthermore, the influence of two kinds of SOCs on the QFI is investigated and an intuitive explanation from the viewpoint of the stationary perturbation theory is given.


Specific inhibition of NGF receptor tyrosine kinase activity by K-252a.
An involvement of protein tyrosine kinase in the transduction of the signals initiated by nerve growth factor (NGF) was investigated. A tyrosine kinase inhibitor, herbimycin, inhibited neurite outgrowth of rat pheochromocytoma PC12 cells induced by NGF but not that by dibutyryl-cAMP. Herbimycin and genistein blocked NGF-dependent activation of ras p21 whose essential function in neuronal differentiation has been reported. These observations suggested that tyrosine kinase activity is involved in the signaling pathways. K-252a, by contrast, inhibited NGF-induced but not EGF-dependent activation of ras p21. Tyrosine kinase activity of gp140trk, a constituent of NGF receptor, is activated by NGF for much a longer period compared to the activation of EGF receptor autokinase activity by EGF. We further demonstrated that autophosphorylation of gp140trk is selectively inhibited by K-252a.


Suppression of experimental allergic encephalomyelitis in Lewis rats treated with myelin basic protein-liposome complexes: clinical, histopathological, and cell-mediated immunity correlates.
Guinea pig myelin basic protein (MBP) was inserted into phosphatidylserine liposomes and Lewis rats were injected by the intracardiac (ic) route with 75 microgram doses of MBP-liposomes according to various schedules. After challenge with 75 microgram guinea pig MBP in complete Freund's adjuvant, the rats were followed for clinical signs, were tested for delayed hypersensitivity (DTH) and lymphocyte transformation (LT) to MBP. The animals were sacrificed 30 days after challenge and the central nervous system tissue was examined for histological modifications. Rats treated with two injections of MBP-liposomes, 7 days before and 7 days after challenge, showed the highest degree of protection from clinical manifestations. Histological lesions were not significantly reduced. DTH reactions to MBP were all positive, regardless of treatment. LT assays were positive overall in only 50% of the animals tested. The response to rat MBP was significantly lower than to guinea pig MBP, especially in the groups treated with MBP-liposomes. Adoptive transfer of spleen cells from MBP-liposome-treated donors reduced the clinical scores of actively induced EAE in syngeneic recipients by 40-50%. These results suggest that at least one mechanism responsible for antigen-specific protection in EAE by MBP-liposomes operates through active suppression transferable by spleen cells.


Scalable Synthesis of the Potent HIV Inhibitor BMS-986001 by Non-Enzymatic Dynamic Kinetic Asymmetric Transformation (DYKAT).
Described herein is the synthesis of BMS-986001 by employing two novel organocatalytic transformations: 1) a highly selective pyranose to furanose ring tautomerization to access an advanced intermediate, and 2) an unprecedented small-molecule-mediated dynamic kinetic resolution to access a variety of enantiopure pyranones, one of which served as a versatile building block for the multigram, stereoselective, and chromatography-free synthesis of BMS-986001. The synthesis required five chemical transformations and resulted in a 44% overall yield.


SWI/SNF: the crossroads where extracellular signaling pathways meet chromatin.
The coordinated expression of the genome in response to extracellular cues is ensured by enzymatic cascades signaling to the nucleus. These pathways generate chromatin modifications at specific loci controlling the transcription of signal-dependent and tissue-specific genes. The SWI/SNF chromatin remodeling complex offers the ideal surface for integrating these signals in the execution of diverse or even opposite biological programs.


Heterogeneity of endothelin-sarafotoxin receptors mediating contraction of pig coronary artery.
The contractile effects of endothelin-1, endothelin-3, sarafotoxin 6b and sarafotoxin 6c were studied in endothelium-denuded rings of pig coronary artery. Endothelin-1, sarafotoxin 6b and sarafotoxin 6c produced monophasic concentration-response curves (mean EC50 values 6.7, 14.8 and 1.6 nM), whereas the concentration-response curve to endothelin-3 was biphasic (mean EC50 values 9.6 nM and 0.32 microM). The maximal effect of sarafotoxin 6c was about one third of that reached by the other peptides. The higher sensitivity component of the curve to endothelin-3 was abolished in the presence of sarafotoxin 6c (0.3 microM), while the EC50 value for the other component remained unchanged. Sarafotoxin 6c (0.3 microM) failed to alter the EC50 values of endothelin-1 and sarafotoxin 6b. These data strongly suggest the presence of at least two endothelin-sarafotoxin receptors mediating contraction of pig coronary artery, one with the profile of the endothelin ETA receptor subtype, the other recognizing sarafotoxin 6c and endothelin-3, but not endothelin-1 and sarafotoxin 6b, being thus different from the ETB receptor subtype.


pH-dependent gating of ROMK (Kir1.1) channels involves conformational changes in both N and C termini.
ROMK channels (Kir1.1) are members of the superfamily of inward rectifier potassium channels (Kir) and represent the channels underlying K+ secretion in the kidney. As their native counterparts, Kir1.1 channels are gated by intracellular pH, with acidification leading to channel closure. Although a lysine residue (Lys80) close to the first hydrophobic segment M1 has been identified as the pH sensor, little is known about how opening and closing of the channel is accomplished. Here we investigate the gating process of Kir1.1 channels exploiting their state-dependent modification by water-soluble oxidants and sulfhydryl reagents. Mutagenesis of all intracellular cysteines either alone or in combination revealed two residues targeted by these reagents, one in the N terminus (Cys49) and one in the C terminus (Cys308) of the channel protein. Both sites reacted with the thiol reagents only in the closed state and not in the open state. These results indicate that pH-dependent gating of Kir1.1 channels involves movement of protein domains in both N and C termini of the Kir1.1 protein.


[Persistent non polio enterovirus infections associated with glomerulonephritis. 9 cases (author's transl)].
All patients are excreting the virus in urines and in 4 cases in stools. The virus has also been isolated from the blood. These cases focused on the possible role of enteroviruses as causal agents for the glomerulonephritis.


The annual cycle of zooplankton-associated Vibrio cholerae and related vibrios in Albufera lake and its coastal surrounding waters (Valencia, Spain).
Most probable numbers of zooplankton-associated Vibrio spp. and V. cholerae were determined in Albufera lake, Spain, and in its coastal receiving waters throughout a year. Highest counts of 10(5) bacterial cells/g of plankton were associated to high temperatures and were also related to the kind of water. All isolates were non-01 serovars, and most belonged to Heiberg groups I and II.


Transitions of Care Considerations for Nephrology Patients.
The need for a workforce able to address the health care needs of older adults has been well established. Individuals with kidney disease experience an extensive number of transitions of care across health care settings related to the kidney disease process and the number of health care providers involved in their care. Kidney disease is multifactorial, and the prevention of progression of disease and poor outcomes are key to improving the health of individuals with kidney disease. Nurses and nurse practitioners can improve the outcomes for individuals with complex comorbid conditions and kidney disease especially during the transitions of care.


BI-3406, a Potent and Selective SOS1-KRAS Interaction Inhibitor, Is Effective in KRAS-Driven Cancers through Combined MEK Inhibition.
KRAS is the most frequently mutated driver of pancreatic, colorectal, and non-small cell lung cancers. Direct KRAS blockade has proved challenging, and inhibition of a key downstream effector pathway, the RAF-MEK-ERK cascade, has shown limited success because of activation of feedback networks that keep the pathway in check. We hypothesized that inhibiting SOS1, a KRAS activator and important feedback node, represents an effective approach to treat KRAS-driven cancers. We report the discovery of a highly potent, selective, and orally bioavailable small-molecule SOS1 inhibitor, BI-3406, that binds to the catalytic domain of SOS1, thereby preventing the interaction with KRAS. BI-3406 reduces formation of GTP-loaded RAS and limits cellular proliferation of a broad range of KRAS-driven cancers. Importantly, BI-3406 attenuates feedback reactivation induced by MEK inhibitors and thereby enhances sensitivity of KRAS-dependent cancers to MEK inhibition. Combined SOS1 and MEK inhibition represents a novel and effective therapeutic concept to address KRAS-driven tumors. SIGNIFICANCE: To date, there are no effective targeted pan-KRAS therapies. In-depth characterization of BI-3406 activity and identification of MEK inhibitors as effective combination partners provide an attractive therapeutic concept for the majority of KRAS-mutant cancers, including those fueled by the most prevalent mutant KRAS oncoproteins, G12D, G12V, G12C, and G13D.See related commentary by Zhao et al., p. 17.This article is highlighted in the In This Issue feature, p. 1.


Protocol to construct biomimetic carbon fiber composites with improved interfacial strength.
Weak interfacial strength restricts the mechanical properties of carbon fiber-reinforced composites. Here, inspired by natural hook-groove microstructure system (HGMS) of black kite (Milvus migrans), we detail the steps to construct a biomimetic HGMS based on dopamine-functionalized carbon fibers (CFs) and zinc oxide nanorods (ZnO NRs) using a two-step modification approach. We describe the fabrication of biomimetic carbon fiber composites using vacuum-assisted contact molding (VACM) and subsequent characterization using standard comprehensive mechanical tests techniques. For complete details on the use and execution of this protocol, please refer to Wang et al. (2022).


Influence of noise exposure on antioxidant system and TEOAEs in rabbits.
Noise exposure may cause hearing loss. The precise mechanism leading to cochlear damage in aco trauma is not known. Eight rabbits were used in this study. Transient evoked otoacoustic emissions (TEOAEs) were recorded in all animals and blood malondialdehyde (MDA) and glutathione (GSH) levels were determined. All rabbits were then exposed to 100 dB SPL broadband noise for 1 h. TEOAEs were recorded again and blood MDA and GSH levels determined following noise exposure. The reproducibility scores of the TEOAE measurements were found to be significantly lower (P < 0.01), whereas the amplitudes and signal-to-noise values of emissions decreased (P > 0.01) in rabbits exposed to noise. The TEOAE energies were poor at 4 kHz. During this threshold shift, GSH blood levels decreased and MDA levels increased,indicating that there is a close relationship between noise-induced hearing loss and the antioxidant system. These findings indicate that TEOAE recording is an excellent test for detecting effects of noise on hearing.


Fate of selected pharmaceuticals in hospital and municipal wastewater effluent: occurrence, removal, and environmental risk assessment.
The concentrations and distribution of β-blockers, lipid regulators, and psychiatric and cancer drugs in the influent and effluent of the municipal wastewater treatment plant (WWTP) and the effluent of 16 hospitals that discharge into the wastewater treatment plant mentioned in this study at two sampling dates in summer and winter were examined. The pharmaceutical contribution of hospitals to municipal wastewater was determined. The removal of target pharmaceuticals was evaluated in a WWTP consisting of conventional biological treatment using activated sludge. Additionally, the potential environmental risk for the aquatic receiving environments (salt lake) was assessed. Beta-blockers and psychiatric drugs were detected in high concentrations in the wastewater samples. Atenolol (919 ng/L) from β-blockers and carbamazepine (7008 ng/L) from psychiatric pharmaceuticals were detected at the highest concentrations in hospital wastewater. The total pharmaceutical concentration determined at the WWTP influent and effluent was between 335 and 737 ng/L in summer and between 174 and 226 ng/L in winter. The concentrations detected in hospital effluents are higher than the concentrations detected in WWTP. The total pharmaceutical contributions from hospitals to the WWTP in summer and winter were determined to be 2% and 4%, respectively. Total pharmaceutical removal in the WWTP ranged from 23 to 54%. According to the risk ratios, atenolol could pose a high risk (risk quotient > 10) for fish in summer and winter. There are different reasons for the increase in pharmaceutical consumption in recent years. One of these reasons is the COVID-19 pandemic, which has been going on for 2 years. In particular, hospitals were operated at full capacity during the pandemic, and the occurrence and concentration of pharmaceuticals used for the therapy of COVID-19 patients has increased in hospital effluent. Pandemic conditions have increased the tendency of people to use psychiatric drugs. It is thought that beta-blocker consumption has increased due to cardiovascular diseases caused by COVID-19. Therefore, the environmental risk of pharmaceuticals for aquatic organisms in hospital effluent should be monitored and evaluated.


Behavioral effects of (-)10,11-methylenedioxy-N-n-propylnoraporphine, an orally effective long-acting agent active at central dopamine receptors, and analogous aporphines.
Substituted and unsubstituted 10,11-methylenedioxy derivatives of apomorphine (APO) or its N-propyl congener (NPA) were synthesized and evaluated for their ability to alter motor activity or to induce stereotyped behavior in the rat. Of these, (-)10,11-methylenedioxy-N-n-propylnoraporphine hydrochloride (MDO-NPA) was the most active, and the only compound which was found to be active after oral administration. Also, MDO-NPA was more potent than NPA or APO in producing stereotypy, but large doses of these three aporphines were equipotent in stimulating motor activity. The duration of action of MDO-NPA exceeded that of NPA and APO, and increased with increasing doses. The effects of MDO-NPA on general activity were biphasic: larger doses stimulated activity: smaller doses markedly inhibited it and induced catalepsy. Catalepsy did not occur with NPA or APO and their motor-inhibitory effects were apparent only in aroused rats. The stereotypic effects of MDO-NPA were blocked by small doses of haloperidol, but not by large doses of reserpine. The effects due to large or small doses of MDO-NPA were also blocked by a microsomal enzyme inhibitor which did not interfere with the actions of NPA. These results suggest that MDO-NPA is a long-acting, orally effective prodrug of NPA with depot properties and dose-dependent agonistic and antagonistic interactions with central dopamine-mediated systems.


Strength training integrated in long term collaborative care of patients with schizophrenia.
Skeletal muscle strength is reduced in patients with schizophrenia, contributing to their impaired physical health, functional performance, and potentially mental health challenges. Although short-term training programs have shown promising results, improving muscle strength and functional performance, it is unknown how exercise can be successfully integrated into the long-term clinical care of outpatients with schizophrenia. To investigate effects of strength training with adherence support in a collaborative care model. We randomized 28 men and 20 women (mean ± SD, 35 ± 11 years) to leg press maximal strength training (MST) with 4 sets at 90 % of one repetition maximum (1RM) 2 × week, facilitated by municipal service and professional supervision (TG), or a control group (CG). The TG increased scaled leg press 1RM (0-3 months: 19 %; 0-6 months: 31 %, 0-12 months: 40 %, all p < .001, and 3-12 months: 18 %, p < .05) and power (0-3 months, 11 %; 0-6 months: 22 %, 0-12 months: 26 %, all p < .001, and 3-12 months: 13 %, p < .05) throughout the 1-year period compared to the CG. The increased muscle strength was accompanied by improved sit-to-stand performance (20 %) after 12 months (p < .001). Both groups also exhibited within-group improvements in walking work efficiency after 6 months (TG: 13 %; CG: 23 %) and 1 year (TG: 11 %; CG: 21 %, p < .01-0.05), but with no evident differences between the groups. Stair climbing performance remained unchanged. Our results reveal that strength training can successfully be integrated as a part of long-term clinical care of outpatients with schizophrenia, contributing to improved functional performance.


Climacturia: what treatment options do we offer to those with and without concomitant erectile dysfunction?
Radical prostatectomy for prostate cancer carries many sequelae, including climacturia, which is not commonly discussed and often under-recognized. To better understand treatment options for incontinence and climacturia, as well as those at time of penile implantation surgery, we completed a comprehensive literature review to identify nonoperative and operative treatments for patients with climacturia alone and those with concomitant climacturia and erectile dysfunction. Nonoperative interventions include behavioral modifications, physical therapy, and tension loops. Operative interventions include the artificial urinary sphincter, male urethral slings, Mini-Jupette sling, and a periurethral prosthesis. We also explore options that can be offered to patients who are also in need of penile prosthesis for concomitant erectile dysfunction. Contemporary work suggests that synchronous implantation of certain devices to treat both climacturia and erectile dysfunction can be done with proven safety and efficacy.


Pd(II) and Pt(II) complexes with aromatic diamines: study of their interaction with DNA.
Pd(II) and Pt(II) new complexes with simple aromatic diamines were synthesised and characterised with the aim of studying their possible antitumour activity. The aromatic diamines chosen were 2,3-diaminotoluene (2,3 dat), 3,4-diaminotoluene (3,4 dat), 4,5-diaminoxylene (4,5 dax) and 2,3-diaminophenol (2,3 dap). The complexes, of formulae cis-[MCl(2)(diamine)], were characterised by elemental analysis, conductivity measurements, 1H, 13C(1H) and 195Pt NMR spectroscopy. The X-ray crystal structure was also resolved for the palladium complexes with 2,3-diaminotoluene and 4,5-diaminoxylene. The DNA adduct formation of the eight new complexes synthesised was followed by circular dichroism and electrophoretic mobility. Atomic force microscopy images of the modifications caused by the complexes on plasmid DNA pBR322 were also obtained. Values of IC50 were also calculated for the four platinum complexes against the cisplatin resistant tumour cell line A2780cisR.


Motoneurons of M. semitendinosus in domestic and wild pigs. A horseradish peroxidase and cord-survey study.
In domestic and wild pigs motor nuclei of the M. semitendinosus were labelled by retrograde transport of horseradish peroxidase (HRP) from muscle to spinal cord. Further motoneurons in the lumbosacral cord were stained with Luxol-fast-blue and cresyl violet. Motoneurons innervating M. semitendinosus were present in the ventral horns of the last (6th) lumbal and the first sacral cord segments. They were localized within two motor columns lying parallel to each other in the medial and lateroventral position. Both parts of the semitendinosus motor nuclei showed a spindle-like shape with both cranial and caudal enlargements. Localization, extent, and shape of the semitendinosus motor nuclei were similar in domestic and wild pigs. The average motoneuron diameter was larger in domestic than in wild pigs. The lumbosacral cord of the wild pig was thicker than that of the domestic pig. It is suggested that the size of alpha-motoneurons has increased as a result of selective breeding after domestication. This process might correlate with a higher incidence of myopathies in domestic pigs.


Pulmonary blood volume assessment from a standard cardiac rubidium-82 imaging protocol: impact of adenosine-induced hyperemia.
This study aimed to assess the feasibility of estimating the pulmonary blood volume noninvasively using standard Rubidium-82 myocardial perfusion imaging (MPI) and characterize the changes during adenosine-induced hyperemia. This study comprised 33 healthy volunteers (15 female, median age = 23 years), of which 25 underwent serial rest/adenosine stress Rubidium-82 MPI sessions. Mean bolus transit times (MBTT) were obtained by calculating the time delay from the Rubidium-82 bolus arrival in the pulmonary trunk to the arrival in the left myocardial atrium. Using the MBTT, in combination with stroke volume (SV) and heart rate (HR), we estimated pulmonary blood volume (PBV = (SV × HR) × MBTT). We report the empirically measured MBTT, HR, SV, and PBV, all stratified by sex [male (M) vs female (F)] as mean (SD). In addition, we report grouped repeatability measures using the within-subject repeatability coefficient. Mean bolus transit times was shortened during adenosine stressing with sex-specific differences [(seconds); Rest: Female (F) = 12.4 (1.5), Male (M) = 14.8 (2.8); stress: F = 8.8 (1.7), M = 11.2 (3.0), all P ≤ 0.01]. HR and SV increased during stress MPI, with a concomitant increase in the PBV [mL]; Rest: F = 544 (98), M = 926 (105); Stress: F = 914 (182), M = 1458 (338), all P < 0.001. The following test-retest repeatability measures were observed for MBTT (Rest = 17.2%, Stress = 17.9%), HR (Rest = 9.1%, Stress = 7.5%), SV (Rest = 8.9%, Stress = 5.6%), and for PBV measures (Rest = 20.7%, Stress = 19.5%) CONCLUSION: Pulmonary blood volume can be extracted by cardiac rubidium-82 MPI with excellent test-retest reliability, both at rest and during adenosine-induced hyperemia.


Inhibition of proliferation in colon cancer cell lines and harmful enzyme activity of colon bacteria by Bifidobacterium adolescentis SPM0212.
In this study, we assessed the anticancer activity and bacterial enzyme inhibition of Bifidobacterium adolescentis SPM0212. B. adolescentis SPM0212 inhibited the proliferation of three human colon cancer cell lines: HT-29, SW 480, and Caco-2. SPM0212 also dose-dependently inhibited TNF-á production and changes in cellular morphology. B. adolescentis SPM0212 inhibited harmful fecal enzymes, including â-glucuronidase, â-glucosidase, tryptophanase, and urease. Thus, B. adolescentis SPM0212 exerts an anticancer effect and inhibits harmful fecal enzymes.


Efficacy of the delayed start antagonist protocol for controlled ovarian stimulation in Bologna poor ovarian responders: a systematic review and meta-analysis.
Patients with a poor ovarian response (POR) represent the most difficult group of population to deal with in the clinical fertility practice. Bologna criteria are the first uniform definition of POR. Choosing a suitable controlled ovarian stimulation (COS) protocol which could give adequate oocytes to maximize the chance of obtaining at least one euploid blastocyst is crucial in the management for such patients. The delayed start antagonist protocol is a novel COS protocol designed for POR patients, however, its real efficacy is controversial compared to conventional protocols. The present study aims to summarize all available studies on this topic and perform a meta-analysis to explore the real treatment effect of this novel protocol in terms of reproductive outcomes. PubMed, EMBASE, Google Scholar, and the Cochrane Library from database establishment to June 2019 were searched. Randomized controlled trials (RCTs), which compared delayed start antagonist protocol (Del) to conventional controlled ovarian stimulation (COS) protocols (Con) in terms of reproductive outcomes, were included. The RevMan 5.3 was used to perform statistical analysis. The primary outcomes were the cycle cancellation rate, the clinical pregnancy rate and the miscarriage rate. 5 RCTs yielding 514 patients were eligible, of which 5, 5, 4 studies were included in analyzing the cycle cancellation rate, the clinical pregnancy rate, and the miscarriage rate respectively. Synthesized data of meta-analysis showed: delayed start antagonist protocol introduced a lower risk of cycle cancellation [risk ratio (RR) = 0.63, 95% confidence interval (CI) (0.45, 0.90), P = 0.01; 5 RCTs, 514 women (Del:Con = 256:258); I2 = 0%; with rates of 16.02% (Del) vs. 26.36% (Con)], an increased chance to get clinical pregnancy [RR = 2.30, 95% CI (1.38, 3.82), P = 0.001; 5 RCTs, 514 women (Del:Con = 256:258); I2 = 0%; with rates of 16.80% (Del) vs. 7.36% (Con)], and a comparable miscarriage rate [RR = 0.55, 95% CI (0.24, 1.23), P = 0.15; 4 RCTs, 58 women (Del:Con = 41:17) I2 = 17%; with rates of 19.51% (Del) vs. 35.29% (Con)] compared to conventional COS protocols. Delayed start antagonist protocol was a potentially valuable alternation for poor ovarian responders. However, future RCTs with large sample size and more scientific design are needed to verify its validity and draw a sound conclusion.


The effects of pyrogallol and hydroquinone on the response to NANC nerve stimulation in the rat anococcygeus and the bovine retractor penis muscles.
1. The effects of pyrogallol and hydroquinone on the bovine retractor penis (BRP) and rat anococcygeus muscles to non-adrenergic, non-cholinergic (NANC) nerve stimulation have been examined. Both drugs at a concentration of 10(-4) M significantly reduced the response in the rat anococcygeus muscle but had no effect in the BRP muscle. 2. The inhibition of the NANC response in the rat anococcygeus muscle by pyrogallol was completely reversed by superoxide dismutase suggesting it was due to the generation of superoxide anions. 3. Pyrogallol inhibited the response to nitric oxide (NO) in the rat anococcygeus muscle but not that to 3-isobutyl-1-methyl-xanthine (IBMX) which confirmed a selective action. 4. These results suggest that the NANC neurotransmitter in the rat anococcygeus muscle is susceptible to superoxide anions and may be NO or a substance that can liberate NO.


A copper-sulfur complex in the liver of a patient with Wilson's disease.
An asymptomatic 16-year-old boy was found to have Wilson's disease without Kayser-Fleischer rings. Liver biopsy showed chronic active hepatitis with 1025 micrograms copper/g dry weight. After 19 months of d-penicillamine therapy, the liver histology became almost normal and the copper content decreased to 238 micrograms/g dry weight. The liver specimens obtained before and after treatment were studied by X-ray probe microanalysis. After treatment, both copper and sulfur decreased in hepatocellular lysosomes. The estimated molar ratio of the decreased copper to the decreased sulfur was 32/100. These figures suggest that lysosomal copper exists in the form of metallothionein.


Evolution of the influenza virus neuraminidase gene during drift of the N2 subtype.
The complete genetic information for the neuraminidase (NA) gene of influenza virus A/Bangkok/1/79 has been cloned by in vitro synthesis of dsDNA, insertion into pBR322 plasmid, and transformation of Escherichia coli. The nucleotide sequence of the NA gene has been determined by the Maxam and Gilbert method. It is 1466 nucleotides long and contains a single open reading frame with a coding capacity for 469 amino acids. When compared to the NA genes of the N2 strains A/Victoria/3/75, A/Udorn/72, A/NT/60/68, and A/RI/5-/57, 90% of the nucleotide positions and 87% of the amino acid positions remained invariant. Forty-two nucleotide changes and 14 amino acid changes accumulated in the period 1975-1979, but the general structure of the protein appeared to remain constant.


Determination of serum cholestane-3β,5α,6β-triol by gas chromatography-mass spectrometry for identification of Niemann-Pick type C (NPC) disease.
Niemann-Pick type C (NPC) is a neurological disease caused by an intracellular cholesterol accumulation. Cholesterol oxidation product cholestane-3β,5α,6β-triol (C-triol) serves as diagnostic biomarker for NPC, but its measurement in the routine laboratory remains difficult. We developed an isotope dilution gas chromatography-mass spectrometry (GC-MS) method permitting screening for NPC in plasma. 1440 plasma samples obtained from clinically suspicious patients were subjected to alkaline saponification. C-triol was extracted with carbon tetrachloride, transformed into the trimethylsilylethers, separated on a fused silica capillary column with a nonpolar silicone stationary phase, and analyzed by GC-MS. NPC diagnosis was confirmed by DNA sequencing. The method was linear over a concentration range of 0.03-200ng/mL with a mean recovery rate of 98.6%. The intra- and inter-day variation coefficients assessed at two concentrations were below 15%. Limits of quantification (LOQ) and detection (LOD) were 0.03ng/mL and 0.01ng/mL, respectively. Receiver operating characteristic (ROC) analysis estimated that the area under curve was 0.997 implying a significant discriminatory power to identify subjects with NPC. Nevertheless, 13 NPC patients and 29 control subjects confirmed by sequencing showed false negative or positive results, respectively. Two patients with cerebrotendinous xanthomatosis showed a 5-10-fold increase in C-triol levels. We developed a quick and sensitive GC-MS method for determination of C-triol, which may serve as a simple and inexpensive diagnostic tool aiding NPC diagnosis in a routine hospital laboratory. As C-triol elevation is not limited to NPC, the NPC diagnosis has to be confirmed by DNA sequencing.


Endothelialization of embolized tumor cells during metastasis formation.
The reaction of the endothelial barrier to tumor cell extravasation has been studied using electron microscopy. The model system was pulmonary metastases produced by intravenous injection of B16-F10 melanoma cells. A striking difference was observed in the behavior of the endothelial lining of arterioles versus that of capillaries. In capillaries, partial retraction of endothelial cells took place following the attachment of tumor cells. The tumor cells then immediately attached to the basement membrane and the basolateral surface of the retracted endothelial cells. The endothelial cells extended to cover the tumor cells prior to complete extravasation. In the arterioles, on the other hand, endothelial retraction did not occur following tumor cell attachment. Instead the attached tumor cell emboli became encompassed by endothelial cells, outgrowing from the intact endothelial lining of the arteriole. Owing to the proliferation of the tumor cells, tumor colonies encompassed by endothelial cells expanded within the lumen. When these intravascular growths completely filled the lumen, the tumor cells extravasated from the vessel only after the original endothelial layer became mechanically disrupted and the tumor cells thereby came into contact with the basement membrane.


Prevalence of job burnout in Iranian nurses: A systematic review and meta-analysis.
Nurses experience many job tensions, which lead to job burnout. The consequences of nurses' job burnout include absenteeism, reduced quality of patient care, interpersonal conflicts with colleagues, physical and mental problems, reluctance to provide care with patients, and quitting the job. The present study aimed to investigate the prevalence of job burnout among nurses in Iran using a meta-analysis method. The study was conducted through a meta-analysis method based on the PRISMA checklist. An unlimited search was conducted until 2020 to access the Persian and English papers in national databases, including Medlib, SID, Iranmedex, and Magiran, and databases including Cochrane, Science-Direct, PubMed, Scopus, and Web of Science. The keywords were "job burnout, nurse, and Iran." The data were searched and extracted by two researchers independently. All analyses were performed using version 2.0 of the Comprehensive Meta-Analysis (CMA) software. The prevalence of job burnout was investigated in 14 papers with a sample size of 2271 individuals with an average age of 31.44 years old, and a confidence interval of 55% (44-66%). Fars province, with 89.2%, had the highest, and Zanjan province, with 25.9%, experienced the lowest prevalence of job burnout. The overall prevalence of job burnout was 44% in males and 66% in females so that the highest prevalence was in women. The prevalence of job burnout in nurses was high in some areas of Iran. A special attention by managers is needed in this field because of the several roles played by the nurses in the healthcare system and the improvement of public health. Implementation of plans to reduce the job burnout and to improve the mental health of nurses by reducing work hours, giving more opportunities to them to express their opinion(s) in amount of salary and benefits, and creating better working conditions are recommended.


Motion in the unstable cervical spine when transferring a patient positioned prone to a spine board.
Two methods have been proposed to transfer an individual in the prone position to a spine board. Researchers do not know which method provides the best immobilization. To determine if motion produced in the unstable cervical spine differs between 2 prone logrolling techniques and to evaluate the effect of equipment on the motion produced during prone logrolling. Crossover study. Laboratory. Tests were performed on 5 fresh cadavers (3 men, 2 women; age = 83 ± 8 years, mass = 61.2 ± 14.1 kg). Three-dimensional motions were recorded during 2 prone logroll protocols (pull, push) in cadavers with an unstable cervical spine. Three equipment conditions were evaluated: football shoulder pads and helmet, rigid cervical collar, and no equipment. The mean range of motion was calculated for each test condition. The pull technique produced 16% more motion than the push technique in the lateral-bending angulation direction (F1,4 = 19.922, P = .01, η(2) = 0.833). Whereas the collar-only condition and, to a lesser extent, the football-shoulder-pads-and-helmet condition demonstrated trends toward providing more stability than the no-equipment condition, we found no differences among equipment conditions. We noted an interaction between technique and equipment, with the pull maneuver performed without equipment producing more anteroposterior motion than the push maneuver in any of the equipment conditions. We saw a slight difference in the motion measured during the 2 prone logrolling techniques tested, with less lateral-bending and anteroposterior motion produced with the logroll push than the pull technique. Therefore, we recommend adopting the push technique as the preferred spine-boarding maneuver when a patient is found in the prone position. Researchers should continue to seek improved methods for performing prone spine-board transfers to further decrease the motion produced in the unstable spine.


Effects of chronically administered venlafaxine on 5-HT receptor activity in rat hippocampus and hypothalamus.
The effects of chronic administration of the mixed serotonin [5-hydroxytryptamine (5-HT)]/norepinephrine re-uptake inhibitor venlafaxine (5 mg/kg daily by osmotic minipump for 28 days) on the sensitivity of somatodendritic 5-HT(1A) autoreceptors on serotonergic neurons innervating the hypothalamus, and on 5-HT(1B) autoreceptors in both hypothalamus and hippocampus, were determined using in vivo microdialysis in freely moving rats. Venlafaxine induced a reduction in sensitivity of 5-HT(1B) autoreceptors in hypothalamus, but did not affect the sensitivity of 5-HT(1A) autoreceptors, or of 5-HT(1B) autoreceptors in hippocampus. The corticosterone and oxytocin responses to the 5-HT(1A) receptor agonist 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT, 0.05 or 0.2 mg/kg), a measure of postsynaptic 5-HT(1A) receptor activity in the hypothalamus, were reduced in animals administered 5 or 10 mg/kg venlafaxine daily by intraperitoneal injection for 21 days. This desensitization of post-synaptic 5- HT(1A) receptors in the hypothalamus may be a consequence of increased 5-HT levels induced by desensitization of the presynaptic 5-HT(1B) receptors. These results taken together with those of previous studies suggest that the hypothalamus might be an important site of drug action, and that venlafaxine has an overall mechanism similar to that of selective serotonin re-uptake inhibitors.


Acute hemodynamic and functional effects of surgical ventricular restoration and heart transplantation in patients with ischemic dilated cardiomyopathy.
Peak oxygen uptake (VO(2)) and ventilatory efficiency have prognostic implications in the population with congestive heart failure. This study evaluated quality-of-life functional capacity after the 2 treatment strategies of surgical ventricular restoration and transplantation for severe left ventricular dysfunction of ischemic cause. The 75-patient study population (between 2004 and 2006) with severe heart failure included 35 patients undergoing surgical ventricular restoration (mean age, 62.6 +/- 8.7 years), sometimes together with coronary artery bypass grafting or mitral surgery, and 40 cardiac transplant recipients (mean age, 55.6 +/- 7.7 years). Preoperative and 6-month postoperative function (peak VO(2), the anaerobic threshold, and the slope of minute ventilation/carbon dioxide uptake), cardiac catheterization parameters (left and right), and hospital and early outcomes were evaluated. The 2 groups had comparable baseline functional impairment and experienced similar hospital stay and early outcomes. They also showed similar improvements in left ventricular volume indexes and hemodynamic parameters and sustained significant improvements of median VO(2), anaerobic threshold, and minute ventilation/carbon dioxide uptake values. Both surgical strategies resulted in a significant and comparable improvement of functional capacity at the 6-month evaluation. These early studies must be repeated to determine the long-term benefits of surgical ventricular restoration because maximal VO(2) and ventilatory efficiency lose their prognostic survival role after transplantation.


Antibody detection in matched chicken sera and egg-yolk samples by commercial enzyme-linked immunosorbent assay kits for Newcastle disease virus, infectious bronchitis virus, infectious bursal disease virus, and avian reovirus.
ELISA kits have been used to detect antibody in egg yolk. The major advantage eggs offer over blood samples is the ability to collect samples without compromising flock biosecurity. A disadvantage to using egg yolk over sera concerns the method of preparing yolk for antibody testing. The technique used in this study involved a simple dilution method with no mixing or extraction. To determine the adequacy of yolk samples to replace serum samples, a serum sample and the first six eggs were obtained from each of 50 commercial leghorn hens. Mean titers were consistently larger for serum than for yolk, but the size of the difference varied with the virus. The variation of mean egg titer was comparable to that of the serum titer. Correlations between a hen's serum titer and the mean titer from hen eggs were only moderate, ranging from 0.35 to 0.85 across viruses and systems. The ability to predict the serum titer of a single hen by the mean titer from hen eggs may be inadequate.


Evaluation of chemical castration with calcium chloride versus surgical castration in donkeys: testosterone as an endpoint marker.
For the last few years, researchers have been interested in developing a method for chemical sterilization which may be a better alternative to surgical castration. An ideal chemical sterilant would be one that effectively arrests spermatogenesis and androgenesis as well as libido with absence of toxic or other side effects. Calcium chloride in various solutions and concentrations has been tested in many animal species, but few studies have been evaluated it in equines as a chemical sterilant. So, the objective of this study was to evaluate the clinical efficacy of chemical castration with 20% calcium chloride dissolved in absolute ethanol in comparison with surgical castration in donkeys based on the changes in the serum testosterone level and the histopathological changes in treated testes. Twelve clinically healthy adult male donkeys were used in this study. Donkeys were divided randomly and equally into two groups: a surgical (S) group (n = 6) and a chemical (C) group (n = 6). Animals in the (S) group were subjected to surgical castration while those in the (C) group received a single bilateral intratesticular injection of 20% calcium chloride dissolved in absolute ethanol (20 ml/testis). Animals were kept under clinical observation for 60 days. Changes in animals' behavior and gross changes in external genitalia were monitored daily. Serum concentrations of testosterone were measured prior to treatment and at 15, 30, 45 and 60 days post-treatment. Testicles in the (C) group were examined histopathologically at the end of the experiment. Chemical castration with intratesticular calcium chloride vs. surgical castration failed to reduce serum concentrations of testosterone throughout the whole duration of the study; however it induced orchitis that was evident by focal necrotic areas in seminiferous tubules, cellular infiltration of neutrophils, proliferative intertubular fibrosis with a compensatory proliferation of Leydig cells. Donkeys tolerated the intratesticular injection of calcium chloride. There were no detectable changes in the general health status of the animals with the exception of swelling in external genitalia, scrotal ulcerations and fistulas. Food and water consumption and the gait of animals remained unaffected. Intratesticular calcium chloride can't be considered an effective method for chemical castration in donkeys.


Growth of the pulmonary anulus and pulmonary arteries after the Waterston anastomosis.
Twenty-six patients with tetralogy of Fallot underwent angiocardiography before a Waterston shunt and again several years later, prior to complete repair (mean interval 40 +/- 15.6 [SD] months). The ratio between the diameter of the pulmonary valve anulus (PVA) and that of the descending thoracic aorta (Ao) increased by 0.32 +/- 0.233, significantly more than is reported to occur after a Blalock-Taussig anastomosis (p = 0.0001). This increase had some relation to the interval between the two angiographic studies (r = 0.34, p = 0.08) and to the mean pressure in the main pulmonary artery (MPA) at the time of the second study (r = 0.35, p = 0.08). The ratio of diameter of the right (RPA) and left pulmonary arteries (LPA) and that of the Ao also increased by 0.24 +/- 0.226 and 0.20 +/- 0.201, respectively. These data suggest that an initial large aortopulmonary shunt may result in less need for transannular patching at complete repair.


Characterization of a thermostable phytase from Bacillus licheniformis WHU and further stabilization of the enzyme through disulfide bond engineering.
Phytases are important industrial enzymes widely used as feed additives to hydrolyze phytate and release inorganic phosphate. In this study, a phytase gene PhyBL isolated from Bacillus licheniformis WHU was cloned and expressed in Escherichia coli. PhyBL showed the highest activity at pH 7.0 and retained more than 40 % of its activity at a wide temperature range from 35 to 65 °C. Ca2+ significantly affected the stability and activity of the enzyme. We further improved the stability of PhyBL through extensively disulfide engineering. After constructing and screening a series of variants, an enhanced stable G197C/A358C variant was obtained. The G197C/A358C variant had a half-life at 60℃ roughly 3.8-fold longer than the wild type. In addition, the G197C/A358C variant also showed enhanced proteolytic resistance to pepsin and trypsin. The potential mechanism underlying these improvements was investigated by molecular dynamics analysis. Our results suggest that the G197C/A358C variant may have potential application as an additive enzyme in aquaculture feed.


Methamphetamine induces intestinal injury by altering gut microbiota and promoting inflammation in mice.
Methamphetamine (METH) is a psychostimulant abused worldwide. Its abuse induces intestinal toxicity. Moreover, the gut microbiota is altered by drugs, which induces intestinal injury. Whether gut microbiota mediates METH-induced intestinal toxicity remains to be validated. In the present study, wild-type and TLR4-/- mice were treated with METH. Gut microbiota was determined using 16S rRNA gene sequencing. Transcriptomics of the intestinal mucosa was performed by RNA-Sequencing. Blood levels of pro-inflammatory cytokines and lipopolysaccharide (LPS), the intestinal barrier, and inflammation were also assessed. METH treatment weakened the intestinal barrier and increased pro-inflammatory cytokines and LPS levels in the blood. Moreover, METH treatment significantly decreased the diversity of probiotics but increased the abundance of pathogenic gut microbiota, contributing to the over-production of LPS and disruption of intestinal barrier. Inflammatory pathways were enriched in the intestinal mucosa of METH-treated mice by KEGG analysis. Consistently, activation of the TLR4 pathway was determined in METH-treated mice, which confirmed intestinal inflammation. However, pretreatment with antibiotics or Tlr4 silencing significantly alleviated METH-induced gut microbiota dysbiosis, LPS over-production, intestinal inflammation, and disruption of the intestinal barrier. These findings suggested that the gut microbiota and LPS-mediated inflammation took an important role in METH-induced intestinal injury. Taken together, these findings suggest that METH-induced intestinal injury is mediated by gut microbiota dysbiosis and LPS-associated inflammation.


Multiparametric asymmetry score (MAS)--distinction between normal and ischaemic brains.
A multiparametric asymmetry score (MAS) is presented. It is based on the EEG data of 50 normal subjects and 32 patients with cerebral ischaemia. For the asymmetry measurements, the following parameters appeared to be the most powerful in the given order: the ratio theta/beta power, the peak frequency, absolute delta and theta powers and the ERD in the alpha band. The EEG data were recorded during rest and during voluntary hand movements from the centro-temporal regions. As the MAS can be calculated with or without the peak frequency parameter, it is applicable to all types of EEG data. Using the MAS, 94% of the normal and 92% of the patient data were correctly classified. From the patient group, 6 were without neurological deficits and 9 had 'normal' clinical EEGs.


Investigation of the existence of and a block technique for the inferior lateral genicular nerve: cadaveric study.
Among the four genicular nerves innervating the anterior aspect of the knee, the inferior lateral genicular nerve has been omitted as a target of blocking. Some authors have suggested that the inferior lateral genicular nerve of the knee might pass beneath the lateral collateral ligament of knee. The authors aimed to study the location of the inferior lateral genicular nerve and the spread of injectate during the inferior lateral genicular nerve block. In ten knees from fresh frozen cadavers, the authors performed on each an ultrasound-guided block of the inferior lateral genicular nerve of the knee just below the lateral collateral ligament. The needle was inserted below the lateral collateral ligament, and 2 mL of blue dye was injected. A week later, the cadavers were dissected, and the existence of the inferior lateral genicular nerve and the spread of dye around it was investigated. The proportion of inferior lateral genicular nerves branching from the common peroneal nerve was found in 8 of 10 (80.0%) cadavers. Of these eight cadavers with inferior lateral genicular nerve, five specimens (62.5%) were stained with blue dye. The common peroneal nerve was not infiltrated with dye in any specimens. When 2 mL of dye was inserted inferiorly to the lateral collateral ligament, the inferior lateral genicular nerve could be blocked in 62.5% of specimens. Because the common peroneal nerve was not involved in any specimen, motor weakness would be avoided with this method.


Upregulation of ATM in sclerosing adenosis of the breast.
The gene mutated in ataxia telangiectasia (ATM) has an established tumour suppressor role in breast cancer. ATM appears to be expressed in most normal cells, including breast epithelium, where it has been postulated to have a nuclear role in cell cycle regulation following DNA damage. However, ATM is not upregulated after DNA damage. In this study, we demonstrate an absence of immunohistologically detectable levels of ATM in the normally quiescent myoepithelial cells that line normal breast ducts. This contrasts dramatically with the significant expression of ATM in the proliferative myoepithelium of sclerosing adenosis (n = 7). This upregulation of ATM suggests that ATM expression is coupled to the proliferative status of the myoepithelium. Our results also indicate that there are factors other than ATM gene mutations that can dramatically influence ATM expression in the breast and that these factors should be considered for their possible implications in carcinogenesis.


Genetic variants and expression study of FOXP3 gene in acute coronary syndrome in Iranian patients.
Acute coronary syndrome (ACS) is the most serious form of coronary artery disease. Inflammatory processes participate in different stages of this disorder. FOXP3 gene plays an important role for the development and function of regulatory T cells. Consequently, the expression level and polymorphisms of this gene have been studied in many immune related diseases. In the present study, we analysed the expression of FOXP3 as well as the association between two variants in this gene (rs3761548A/C and rs5902434del/ATT) and occurrence of ACS in Iranian patients. FOXP3 expression analysis showed a significant decrease in patients with ACS compared with controls (P = 0.029). In addition, a significant decrease has been detected in female patients compared with normal female subjects (P = 0.020). No significant change has been observed in FOXP3 expression in male patients compared with normal male subjects. In addition, no difference has been detected between ACS and normal subjects in combined genotype frequencies of both polymorphisms and the allele frequencies of rs5902434. However, rs3761548 C allele was more prevalent in controls compared with patients with ACS (P = 0.024). Consequently, our data demonstrated that FOXP3 expression is markedly decreased in female patients with ACS, which highlight the role of immune responses in plaque destabilization in such patients. Copyright © 2016 John Wiley & Sons, Ltd. Considering the role of immune system in different stages of acute coronary syndrome (ACS), we evaluated the expression of FOXP3 gene as a master regulator of immune response in these patients compared with normal subjects. We detected a significant down-regulation of this gene in patients with ACS. Such decreased expression was more prominent in female patients, which implies the role of immune responses in plaque destabilization in such patients.


Easier Control of Late-Onset Cytomegalovirus Disease Following Universal Prophylaxis Through an Early Antiviral Immune Response in Donor-Positive, Recipient-Negative Kidney Transplants.
Universal prophylaxis for cytomegalovirus (CMV) prevention is viable but, compared with a preemptive strategy, leads to higher incidence of late-onset disease (LOD) associated with poor patient and graft survival. The purpose of this study was to compare LOD with early onset disease (EOD), with a focus on the highest risk kidney transplant recipients (KTRs): CMV seronegative recipients transplanted from seropositive donors (D+R-). Since CMV control depends on both antiviral treatment and specific immune response, we also compared Vδ2-negative (Vδ2(neg) ) γδ T cell expansion involved in CMV infection resolution. EOD was defined as occurring <3 mo and LOD as occurring >3 mo after transplantation. Depending on the period, universal prophylaxis or preemptive treatment was used. Overall, 168 D+R- KTRs were included between 2003 and 2011. LOD was associated with a lower peak DNAemia (p = 0.04), fewer recurrences (odds ratio 0.16; 95% confidence interval 0.05-0.55; p = 0.01) and shorter anti-CMV curative treatment (40 vs. 60 days, p < 0.0001). As a corollary, we found that Vδ2(neg) γδ T cell expansion was faster in LOD than in EOD (31 vs. 168 days after the beginning of CMV disease, p < 0.0001). In D+R- KTRs, universal prophylaxis is associated with more LOD, which had better infection management and a faster immune response. These results support the use of universal prophylaxis over a preemptive strategy and reappraise outcomes of LOD.


Augmented cellular uptake and homologous targeting of exosome-based drug loaded IOL for posterior capsular opacification prevention and biosafety improvement.
Posterior capsular opacification (PCO), the most common complication after cataract surgery, is caused by the proliferation, migration and differentiation of residual lens epithelial cells (LECs) on the surface of the intraocular lens (IOL). Although drug-loaded IOLs have been successfully developed, the PCO prevention efficacy is still limited due to the lack of targeting and low bioavailability. In this investigation, an exosome-functionalized drug-loaded IOL was successfully developed for effective PCO prevention utilizing the homologous targeting and high biocompatibility of exosome. The exosomes derived from LECs were collected to load the anti-proliferative drug doxorubicin (Dox) through electroporation and then immobilized on the aminated IOLs surface through electrostatic interaction. In vitro experiments showed that significantly improved cellular uptake of Dox@Exos by LECs was achieved due to the targeting ability of exosome, compared with free Dox, thus resulting in superior anti-proliferation effect. In vivo animal investigations indicated that Dox@Exos-IOLs effectively inhibited the development of PCO and showed excellent intraocular biocompatibility. We believe that this work will provide a targeting strategy for PCO prevention through exosome-functionalized IOL.


Effect of high hydrostatic pressure on the physiology of Manila mango.
Manila mangoes (Mangifera indica L.) have sensory characteristics that make them attractive for consumption as a fresh fruit. A large portion of the annual yield of this fruit is infested by the Mexican fruit fly (Anastrepha ludens), adversely impacting the quality of the crop. Hence, it is necessary to develop economically viable postharvest treatments to reduce the damage caused by this insect. Currently, high hydrostatic pressures are used to guarantee the safety of many processed foods. The objective of this work was to assess the effects of high hydrostatic pressure on mangoes at their physiological maturity. High hydrostatic pressures were applied to mangoes at three levels: 50, 100 and 200 megapascals applied for four different time periods (0, 5, 10 and 20 min). Physiologically mature mangoes were more resistant to changes in response to the pressure of 50 MPa. Reduction of physiological activity by application of high hydrostatic pressure opens a new avenue for the research on treatments intended to enhance preservation of whole fresh fruit.


Effects of three different combinations of ethinyl estradiol and levonorgestrel on plasma lipids and high density lipoproteins.
Seventy-five menstruating women seeking contraceptive advice were randomly allocated to treatment with combined oral contraceptives containing either ethinyl estradiol 30 micrograms + levonorgestrel 150 micrograms (30/150), ethinyl estradiol 50 micrograms + levonorgestrel 125 micrograms (50/125) or ethinyl estradiol 50 micrograms + levonorgestrel 250 micrograms (50/250). The concentrations of cholesterol, phospholipids, high density lipoprotein (HDL)-cholesterol, HDL-phospholipids and triglycerides were determined prior to treatment and after one, three and six months of medication. Triglycerides increased by 18--42 per cent after one to six months of treatment with 50/125. The HDL-cholesterol and HDL-phospholipids were reduced by 10 per cent during 50/250 medication. No other parameters showed any consistent alteration in any of the treatment groups. Raised triglyceride concentration and/or decreased HDL concentration may increase the risk for cardiovascular disease. It is therefore suggested that in order not to alter the HDL concentration a combined oral contraceptive agent should probably not contain more 19-nortestosterone type of progestogen than corresponding to 125--150 micrograms of levonorgestrel. To avoid a rise of the triglyceride level the weight relation between levonorgestrel and ethinyl estradiol should be about 5:1.


Hepatic Resection for Hepatocellular Carcinoma in Nonalcoholic Fatty Liver Disease: A Systematic Review and Meta-Analysis of 7226 Patients.
To systematically review and compare the overall (OS) and disease-free (DFS) survival after hepatic resections for hepatocellular carcinoma (HCC) of patients with nonalcoholic fatty liver disease (NAFLD) versus other risk factors. Different clinical and tumor characteristics are associated with HCC in the setting of NAFLD in comparison to other risk factors. It is still unclear whether these differences impact patient survival after radical hepatectomies. Randomized controlled trials and observational studies published in the English literature between July 1980 and June 2020 were searched using multiple databases. Patients' baseline characteristics and the hazard ratios (HRs) of the OS and DFS were extracted and meta-analyses were performed. Fifteen retrospective cohort studies with a total of 7226 patients were included. Among them, 1412 patients (19.5%) had NAFLD and 5814 (80.4%) had other risk factors (eg, viral hepatitis B or C, alcoholic cirrhosis, or cryptogenic cirrhosis). Summary statistics showed that patients with NAFLD had better DFS (HR = 0.81; 95% CI: 0.70-0.94; P = 0.006) and OS (HR = 0.78; 95% CI: 0.67-0.90; P = 0.001) than the control group. Subgroups analyses also indicated that the OS favored NAFLD patients versus patients with viral hepatitis B or C (HR = 0.80; 95% CI: 0.67-0.96; P = 0.017) or alcoholic and cryptogenic cirrhosis (HR = 0.68; 95% CI: 0.47-1.0; P = 0.05). After hepatic resections for HCC, NAFLD patients have better DFS and OS than patients with other risk factors. Subgroup analysis and meta-regression suggested that the survival advantage of NAFLD patients was more pronounced in studies published after 2015 and from Asian centers.


Direct interspecies electron transfer enables anaerobic oxidation of sulfide to elemental sulfur coupled with CO2-reducing methanogenesis.
Electric syntrophy between fatty acid oxidizers and methanogens through direct interspecies electron transfer (DIET) is essential for balancing acidogenesis and methanogenesis in anaerobic digestion. Promoting DIET using electrically conductive additives proved effective in enhancing methanogenesis; however, its possibility to affect other microbial redox reactions in methanogenic systems has been little studied. This study provides the first confirmation of the electro-syntrophic coupling of sulfide oxidation to S0 with CO2-reducing methanogenesis in sulfur-rich methanogenic cultures supplemented with conductive magnetite (100-700-nm particle size). The H2S content in biogas, initially exceeding 5000 ppmv, decreased to below 1 ppmv along with an accumulation of extracellular S0 (60-70 mg/L; initially <1 mg/L) at a magnetite dose of 20 mM Fe, while there were no significant changes in methane yield. A comprehensive polyphasic approach demonstrated that the S0 formation occurs through electro-syntrophic oxidation of sulfide coupled with CO2-reducing methanogenesis, involving Methanothrix as the dominant methanogen.