[Antitumor drugs and potentiators aiming circumvention of drug resistance].
We have been studying the resistance mechanisms of various antitumor drugs and screening substances from natural and synthetic products which overcome resistance. In this paper, we described compounds mainly obtained from our screening systems. I. Circumvention of multidrug resistance (MDR). Lactoquinomycin was discovered from the culture broth of a strain of Streptomyces sp. and it showed preferential growth inhibition against multidrug-resistant L5178 Y cells. The mechanism of action of lactoquinomycin was studied. Another novel antibiotic, resorthiomycin, exhibited not only preferential inhibition against MDR tumor cells but also augmentation of cytotoxicity of several antitumor drugs. As synthetic potentiators, dipyridamole, cepharanthine, AHC-52 and analogs of dihydropyridines were described; all of them were thought to interact with a P-glycoprotein and inhibit active efflux of drugs from tumor cells. SDB-ethylenediamine was unique because it overcame MDR and also potentiates a wide range of antitumor drugs including 5-FU and bleomycin. II. E-64 was found to inhibit the activity of a bleomycin-inactivating enzyme. It potentiated the activity of peplomycin in vitro and in vivo. III. Cadeguomycin was discovered from the culture filtrate of a Streptomyces sp. and it potentiated Ara-C by inhibition of the activity of dCMP deaminase, an Ara-C-inactivating enzyme.


Polycystic ovary syndrome with hyperandrogenism as a risk factor for non-obese non-alcoholic fatty liver disease.
Non-alcoholic fatty liver disease (NAFLD) is known to be associated with polycystic ovary syndrome (PCOS). However, most studies investigated the prevalence of NAFLD in obese PCOS patients. To compare the prevalence of non-obese NAFLD in women with or without PCOS, and to assess an independent association between PCOS and NAFLD in a non-obese Asian cohort. This was a case-control study using a prospective PCOS cohort. After subjects with other potential causes of chronic liver disease were excluded, 275 non-obese women with PCOS and 892 non-obese controls were enrolled. NAFLD was determined by hepatic ultrasonography. Main outcomes were the prevalence of NAFLD on hepatic ultrasonography between non-obese women with or without PCOS, and an independent association between non-obese NAFLD and PCOS. Non-obese women with PCOS had a significantly higher prevalence of NAFLD than those without PCOS (5.5% vs. 2.8%, P = 0.027). PCOS was associated with non-obese NAFLD (odds ratio: 2.62, 95% confidence intervals: 1.25-5.48) after adjustment for age and body mass index (BMI). In women with PCOS, the level of androgenicity represented by free testosterone or free androgen index was associated with NAFLD after adjustment for age, BMI, lipid profile, insulin resistance or glycaemic status. Non-obese NAFLD is more prevalent in women with polycystic ovary syndrome than in those without. In non-obese patients with polycystic ovary syndrome, hyperandrogenemia may be an independent risk factor for non-obese NAFLD.


Do 18F-FDG PET/CT findings have a relationship with histopathological and immunohistochemical factors of breast cancer in men?
We aimed to investigate the relationship between histopathological and immunohistochemical features of male breast cancer (MBC) and comprehensive fluorine-18-fluorodeoxyglucose (F-FDG) PET/computed tomography (CT) parameters. Fifteen male patients with newly diagnosed breast cancer who underwent F-FDG PET/CT were included in the study. Maximum and average standardized uptake value (SUVmax and SUVavg), metabolic total volume, and total lesion glycolysis (TLG) were compared with the histopathological and immunohistochemical findings of patients. In addition, metabolic tumor-node-metastases (TNM) staging was performed following the determination of metastatic axillary lymph nodes and tumor size by F-FDG PET/CT and verified by histopathological evaluation. There were no significant differences between all groups classified on the basis of histopathological and immunohistochemical parameters for SUVmax, SUVavg, TLG, and metabolic total volume. The only difference was found in patients with distant metastases and stage IV. SUVmax, SUVavg, and TLG were higher in patients with distant metastases compared with patients without distant metastases (P: 0.005, 0.011, and 0.042, respectively). Strong correlations were found between metabolic TNM staging and histopathological TNM staging (for T stage; r: 0.590, P: 0.021, N stage; r: 0.694, P: 0.002, TNM stage; r: 0.835, P: 0.002). In addition, no differences were found with any metabolic F-FDG PET/CT parameters in survival. Although no correlation was found between metabolic parameters and groups categorized on the basis of histopathological or immunohistochemical features, F-FDG PET/CT is a reliable imaging modality to determine tumor size, axillary lymph node involvement, and metabolic TNM staging of MBC. In addition, none of those metabolic F-FDG PET/CT parameters predicted survival in MBC.


Nurses' attitutudes about the ESAS scale in oncology: cross sectional observational study.
The evaluation of signs and symptoms in cancer patients has to be realized by validated screening tools, such as the ESAS scale that is considerend by scientistists an appropriate instrument. I conducted an observational study. The primary objective of my study was to describe the nurses' attitude towards the ESAS questionnaire. The secondary objective was to assess the level of agreement between the compilation of the ESAS by the nurse and by the patient. I prepared a questionaire with eleven items for the nurses in order to understand their attitude forward the ESAS scale. Secondly, I administered the ESAS scale to the cancer patients and the nurses also completed the scale; they answered using their knowledges about the patients. 12 nurses took part to my project. For each question at least one nurse answered "completely in agreement" and no one answered "disagreement" or "completely disagreement". Furthermore, a significant difference between the answers gave by the nurses and the answers gave by the patients is present for 5 symptoms of the ESAS scale: pain, tiredness, drowsiness, nausea, shortness of breath. For the other symptoms (depression, anxiety, appetite and wellbeing) I didn't find significant differences. The evaluation of signs and symptoms in cancer patients is an activity of primary importance as it is able to significatly improve the quality of life and the therapeutic results. nurses must take responsibility in order to promote and protect the health of cancer patients.


Entropy generation optimization of cilia regulated MHD ternary hybrid Jeffery nanofluid with Arrhenius activation energy and induced magnetic field.
This study deals with the entropy generation analysis of synthetic cilia using a ternary hybrid nanofluid (Al-Cu-Fe2O3/Blood) flow through an inclined channel. The objective of the current study is to investigate the effects of entropy generation optimization, heat, and mass transfer on ternary hybrid nanofluid passing through an inclined channel in the proximity of the induced magnetic field. The novelty of the current study is present in studying the combined effect of viscous dissipation, thermophoresis, Brownian motion, exponential heat sink/source, porous medium, endothermic-exothermic chemical reactions, and activation energy in the proximity of induced magnetic field is examined. The governing partial differential equations (PDEs) are transformed into the ordinary differential equations (ODEs) using appropriate transformations. Applying the low Reynolds number and the long-wavelength approximation, resultant ODEs are numerically solved using shooting technique via BVP5C in MATLAB. The velocity, temperature, concentration, and induced magnetism profiles are visually discussed and graphically analyzed for various fluid flow parameters. Graphical analysis of physical interest quantities like mass transfer rate, heat transfer rate, entropy generation optimization, and skin friction coefficient are also graphically discussed. The entropy generation improves for enhancing values of Reynolds number, solutal Grashof number, heat sink/source parameter, Brinkman number, magnetic Prandtl number, and endothermic-exothermic reaction parameter while the reverse effect is noticed for chemical reaction and induced magnetic field parameter. The findings of this study can be applied to enhance heat transfer efficiency in biomedical devices, optimizing cooling systems, designing efficient energy conversion processes, and spanning from renewable energy technologies to aerospace propulsion systems.


Bits and pieces: the ethics of uterine morcellation.
Intensive media and policy attention has been focused on the ongoing controversy surrounding uterine morcellation in gynecologic surgery. What has been missing from this impassioned discourse is an objective analysis of the ethical implications of uterine power morcellation in gynecologic surgery. This article discusses competing ethical duties of physicians, industry, the U.S. Food and Drug Administration, and the media to develop a more robust and nuanced understanding of informed consent for the use of morcellation in benign gynecologic surgery. Ultimately, as physicians, we must remain steadfast in our dedication to the use of evolving technologies to better patient health in a safe and ethical manner that is well-studied, informed, and implemented with appropriate training and precautions.


Caspase-3 gene expression in human luteinized granulosa cells is inversely correlated with the number of oocytes retrieved after controlled ovarian stimulation.
Granulosa cells control oocyte maturation through paracrine signalling and changes to the microenvironment around the oocyte. Apoptosis occurs as a physiological mechanism of granulosa cell renewal, but how it relates with the ovarian response to induced ovulation is still unclear. Therefore, this study evaluated apoptosis-related gene expression levels in granulosa cells of patients undergoing controlled ovarian stimulation. We enrolled prospectively 59 consecutive IVF patients referred to a tertiary academic hospital for couple infertility treatment. Luteinized granulosa cells were isolated from follicular fluid and the RNA was extracted, reverse-transcribed and the gene expression of apoptosis inducers (caspase-3, caspase-8 and bax) and inhibitor (Bcl-2) was quantified by real-time polymerase chain reaction. Caspase-3 gene expression correlated negatively with the number of pre-ovulatory follicles (Spearman's r = -0.308), the number of collected oocytes (r = -0.451), the number of mature oocytes (r = -0.526), the number of fertilized oocytes (r = -0.439) and the number of viable embryos (r = -0.443, all statistically significant at p < 0.02 level). No such associations were found with caspase-8, bax or bcl-2. These preliminary findings suggest that increased caspase-3 gene expression in granulosa cells is associated with a worse ovulatory response in humans.


Evolution of a primary lymphoma of the orbit.
A patient with a histologically benign lymphoid pseudotumour of the orbit developed a recurrent mass which proved to be a well differentiated lymphocytic lymphoma. Immunohistological studies showed that a majority of cells in the pseudotumour bore the same immunological markers as the subsequent lymphoma. There were no clinical or radiographic features of the initial lesion which indicated its eventual malignant course.


Autolysosomes in Alzheimer's disease and their possible role in its pathogenesis. An ultrastructural study.
In 10 cases of senile dementia of Alzheimer's type (AD) a systematic post-mortem ultrastructural analysis was performed. Attention was paid mainly to the presence of autolysosomes in the neuropil of the brain cortex. Autolysosomes appeared as osmiophilic dense bodies (DB) which originated in synaptic terminals and peripheral nerve-cell processes. DBs contained sequestrated cellular material wrapped by pinched off, invaginated cell membrane. DB were very frequent also in fields where no senile plaques (SP) and/or nerve-cell processes with paired helical filaments (PHF) were present. Abnormal fermentative degradation of DBs and their possible negative influence on the plasmatic flow in nerve-cell processes is discussed.


Structural and electronic properties of hetero-transition-metal Keggin anions: a DFT Study of alpha/beta-[XW12O40]n- (X = CrVI, VV, TiIV, FeIII, CoIII, NiIII, CoII, and ZnII) relative stability.
Density functional theory calculations have been carried out to investigate the electronic structures and the alpha/beta relative stability of Keggin-typed [XW(12)O(40)]n- anions with transition metal as heteroatom X (X = Cr(VI), V(V), Ti(IV), Fe(III), Co(III), Ni(III), Co(II) and Zn(II)). Nice agreement in geometries between computation and experiment has been obtained, and the higher stability of the alpha isomer over the beta one has been confirmed. Structural parameter analysis reveals that the {M(3)O(13)} triads in both alpha and beta isomers contract considerably with the increase of the negative anionic charge, while the overall size of both isomers shrinks only slightly. Fragment molecular orbital analysis shows that except alpha/beta-[TiW(12)O(40)]4-, the electronic structures of Keggin anions can be described by the insertion of the e and/or t2 orbital of XO4n- into the frontier orbitals of W(12)O(36) cage, and this leads to the specific redox property, which is different from that of the Keggin anions with main-group elements as heteroatoms. Energy decomposition analysis shows that the enhanced intrinsic stability of the alpha isomer in Td arrangement of W(12)O(36) shell and the larger deformation of the alpha over the beta isomer are two dominating factors and contribute oppositely to the alpha/beta relative stability.


Influence of fermentation level and geographical origin on cocoa bean oligopeptide pattern.
Peptides and amino acids generated during cocoa bean fermentation are the most important precursors for the development of cocoa aroma, however cocoa oligopeptide fraction is under-investigated. In this study, we perform a deep investigation of the presence of oligopeptides in unfermented, under fermented, and well-fermented cocoa beans from all of the main producing countries, with the aim to obtain a better definition of cocoa quality and a deeper comprehension of biochemical changes occurring during fermentation. Oligopeptides were determined by UPLC/ESI-MS and 35 low-molecular weight peptides were identified and subjected to semi-quantitative analysis. Results showed that fermented cocoas can be differentiated from unfermented cocoas by their possession of a higher total amount of oligopeptides and a lower ratio of vicilin to 21kDa cocoa seed albumin peptides. A variability in the peptide pattern was observed also among well-fermented cocoa samples of different geographical origin, suggesting diversified proteolytic activities.


Biochemical Recurrence in Prostate Cancer Is Associated with the Composition of Lactobacillus: Microbiome Analysis of Prostatic Tissue.
Many human pathologies, such as malignancy, are linked with specific bacteria and changes in the constituents of the microbiome. In order to examine the association between an imbalance of bacteria and prostate carcinoma, a comparison of the microbiomes present in patients with biochemical recurrence (BCR) or NO BCR (NBCR) was performed. Additionally, 16S rRNA-based next-generation sequencing was applied to identify the bacterial profiles within these tumors in terms of the bacteria and operational genes present. The percentage average taxonomic composition between the taxa indicated no difference between BCR and NBCR. In addition, alpha and beta diversity indices presented no distinction between the cohorts in any statistical method. However, taxonomic biomarker discovery indicated a relatively higher population of Lactobacillus in the NBCR group, and this finding was supported by PCR data. Along with that, differences in the operational activity of the bacterial genes were also determined. It is proposed that the biochemical recurrence was linked to the quantity of Lactobacillus present. The aim of this study was to investigate the microbiome involved in prostate carcinoma and the potential association between them.


Treating acute migraine with ubrogepant.
Acute migraine affects millions of people and is one of the most common primary care complaints in the United States. Available first-line abortive treatments are limited and vary in efficacy. Newer medications such as calcitonin gene-related peptide (CGRP) receptor antagonists may be a useful alternative. This article describes the use of ubrogepant, a new CGRP receptor antagonist, in a patient with contraindications to traditional medications used for acute migraine.


Role of Unit Physicians and Challenges Encountered in the Follow-up of Military Personnel with Cancer.
General practitioners (GPs) play a central role in the management and coordination of care of patients with malignant tumors and blood diseases. Civilian GPs encounter certain difficulties during the care of such patients. The practice of unit medicine in a military environment differs from that in a civilian context through expertise in fitness to serve and to deployment and the target population. We identified the difficulties encountered by "unit" physicians during and after cancer treatment. We conducted a multicenter cross-sectional descriptive study from July 2, 2021, to September 30, 2022, targeting all military GPs belonging to the French Armed Forces Health Service. We sent a questionnaire consisting of 1 open- and 16 closed multiple-choice questions describing the population of unit physicians and their patients (questions 1-5), the difficulties encountered by physicians in the follow-up of military personnel with cancer (Questions 6, 7, 11, 12, and 13), and the potential information networks accessible to physicians (questions 8-10, 14, and 17). Three hundred and ninety physicians completed the questionnaires. Among the 700 military GPs, 390 physicians responded to the questionnaire and 327 completed it exhaustively. The questionnaire response rate was 55%. Of the responding physicians, 49% and 70% reported following patients with an "active" malignant tumor and a malignant tumor pathology in remission, respectively. Thirty-one percent of the physicians encountered difficulties with these patients as follows: 26% concerning fitness for duty, 17% in medical follow-up, 14% in addressing the psychological aspect, 11% concerning specialist accessibility for advice, 10% in managing deconditioning to effort, 9% in addressing the social aspect, 7% in medical management, and 6% concerning other issues. Difficulties in the follow-up of patients with cancer affect military doctors. They mainly concern fitness for duty and medical follow-up.


Oxidant-induced restriction polymorphism maps to kinase region of c-abl oncogene.
Reactive oxygen species generated by activated human phagocytes can cause a variety of genetic injuries and produce malignant transformation in target cells. We previously reported that DNA extracted from phagocyte-transformed 10T1/2 mouse fibroblasts contained Msp I-dependent restriction fragment length polymorphisms in the c-abl oncogene. The data suggested that the oxidant-induced RFLP resulted from an alteration in the methylation pattern in c-abl. We have now mapped one of these RFLP to a specific 'CCGG' tetramer found within the tyrosine kinase region of the gene. The polymorphic 'CCGG' site has been localized to the intron between exon 2 and 3a. Restriction analysis indicates that a repetitive sequence exists within this intron and that the RFLP is associated with this repeat.


Reactivation of DNA replication in nuclei from terminally differentiated cells: nuclear membrane permeabilization is required for initiation in Xenopus egg extract.
We have used Xenopus egg extract to investigate the requirements for reactivation of DNA replication in nuclei isolated from terminally differentiated chicken erythrocytes. Previous work has shown that reactivation of erythrocyte nuclei in egg extract is accompanied by chromatin decondensation, nuclear envelope reformation, and the accumulation of egg lamin, LIII. However, in those studies, erythrocyte nuclei were prepared by methods that were not designed to maintain the selective permeability of the nuclear membrane, and as such, it is not clear if loss of nuclear membrane integrity played a role in the reactivation process. Therefore, the purpose of this study was to determine if changes in nuclear membrane permeability are required for reactivation of erythrocyte nuclei in egg extract. Nuclei with intact nuclear membranes were prepared from erythrocytes with streptolysin O and permeable nuclei by treatment of intact nuclei with the detergent Nonidet-P40. Like permeable nuclei, most intact nuclei decondensed, imported nuclear protein, and accumulated lamin LIII from the extract. However, unlike permeable nuclei, which replicated extensively in the extract, few intact nuclei initiated replication under the same conditions. These data demonstrate that permeabilization of the nuclear membrane is required for reactivation of DNA replication in terminally differentiated erythrocyte nuclei by egg extract and suggest that loss of nuclear membrane integrity may be a general requirement for replication of quiescent cell nuclei by this system.


Identification of surgically-induced longitudinal lesions of the equine deep digital flexor tendon in the digital flexor tendon sheath using contrast-enhanced ultrasonography: an ex-vivo pilot study.
Longitudinal tears in the lateral aspect of the deep digital flexor tendon are the most common causes of pain localised to the equine digital flexor tendon sheath. However conventional ultrasonographic techniques provide limited information about acute lesions. Ultrasonographic contrast agents are newly developed materials that have contributed to advancement in human diagnostic imaging. They are currently approved for intravenous use in human and animal models. In this study we described intrathecal use in the horse. This study was undertaken to evaluate the reliability of standard and angle contrast-enhanced ultrasonography to detect and characterize surgically-induced longitudinal lesions in the deep digital flexor tendons.In this pilot study surgically-induced lesions were created in the lateral aspect of the deep digital flexor tendon within the digital flexor tendon sheath in 10 isolated equine limbs to generate a replicable model for naturally occurring lesions. Another 10 specimens were sham operated. All the limbs were examined ultrasonographically before and shortly after the intrasynovial injection of an ultrasound contrast agent containing stabilised microbubbles. The images were blindly evaluated to detect the ability to identify surgically-created lesions. The deep digital flexor tendons were dissected and a series of slices were obtained. The depth of longitudinal defects identified with contrast-enhanced ultrasound scans was compared to the real extent of the lesions measured in the corresponding gross tendon sections. Contrast-enhanced ultrasonography with both angle and standard approach provided a significant higher proportion of correct diagnoses compared to standard and angle contrast ultrasonography (p < 0.01). Contrast-enhanced ultrasonography reliably estimated the depth of surgically-induced longitudinal lesions in the deep digital flexor tendons. Contrast-enhanced ultrasound of the digital flexor tendon sheath could be an effective tool to detect intrasynovial longitudinal tears of the deep digital flexor tendon, although an in vivo study is required to confirm these results for naturally occurring lesions.


A Cu2+(S = 1/2) kagomé antiferromagnet: Mg(x)Cu(4-x)(OH)6Cl2.
Spin-frustrated systems are one avenue for inducing macroscopic quantum states in materials. However, experimental realization of this goal has been difficult because of the lack of simple materials and, if available, the separation of the unusual magnetic properties arising from exotic magnetic states from behavior associated with chemical disorder, such as site mixing. Here we report the synthesis and magnetic properties of a new series of magnetically frustrated materials, Mg(x)Cu(4-x)(OH)(6)Cl(2). Because of the substantially different ligand-field chemistry of Mg(2+) and Cu(2+), site disorder within the kagomé layers is minimized, as directly measured by X-ray diffraction. Our results reveal that many of the properties of these materials and related systems are not due to disorder of the magnetic lattice but rather reflect an unusual ground state.


Reimagining Ambulatory Care in Urology: Conversion of the Urology Clinic into a Procedure Center Improves Patient's Experience.
Introduction: The coronavirus disease 2019 (COVID-19) pandemic made it necessary to practice social distancing and limited in-person encounters in health care. These restrictions created alternative opportunities to enhance patient access to care in the ambulatory setting. We hypothesized that by transforming clinics into centers that prioritize procedures and transitioning ambulatory appointments to telehealth, we could establish a secure, streamlined, and productive method for providing patient care. Methods: Clinic templates were restructured to allow the use of the physical space to perform procedure-based clinics exclusively, while switching to virtual telemedicine for all nonprocedural encounters. Staff members were given specific roles to support one of the patient care modalities for a given day (Procedures vs. Telehealth). Performance and patient satisfaction metrics were collected between two periods of time defined as P1 (February-June 2019) and P2 Post-COVID (February-June 2020) and compared. These served as proxies of periods when the clinic workflow and templates were structured in the traditional versus the emerging way. Statistical analysis was performed using bivariate analyses. Results: The percentage of procedures performed among all in-person visits were higher in P2 compared to P1 (45% vs. 29%, p < 0.001). Although total charges and relative value units were lower in P2, the overall revenue generated was higher compared to P1 ($4,597,846 vs. $4,517,427$, respectively). This increase in revenue was mainly driven by the higher relative income generated by procedures. Patient experience, reflected through patient-reported outcomes, was more favorable in P2 where patients seemed more likely to "Recommend this provider office" (90% vs. 85.7%, p = 0.01), report improved "Access overall" (56% vs. 49%, p = 0.02), and felt they were "Moving through your visit overall" (59% vs. 51%, p = 0.007). Conclusions: Our data suggest that reorganizing urology clinics into a space that is centered around outpatient procedures can represent a model that improves the patient's access to care and clinical experience, while simultaneously improving operational financial strength. This efficient care model could be considered for many practice settings and drive high-value outpatient care.


Cytogenetic studies in dogs after total body irradiation and allogeneic transfusion with cryopreserved blood mononuclear cells: observations in long-term chimeras.
Cytogenetic studies were performed on two dog groups after total body irradiation and allogeneic transfusion with cryopreserved blood mononuclear cells. The first group of dogs was transfused with unseparated leukocytes and suffered from graft-versus-host disease (GvHD). Cytogenetic studies demonstrated only cells of donor origin in all dogs of this group. The second group of animals was transfused with fraction 2 of a discontinuous albumin gradient. The dogs of this group did not develop GvHD, and the cytogenetic studies showed the presence of a mosaic of cells from donor and recipient origin in all of them. These results suggest that the GvHD may suppress autochthonous regeneration.


Asymmetric synthesis of cyclo-archaeol and β-glucosyl cyclo-archaeol.
An efficient asymmetric synthesis of cyclo-archaeol and β-glucosyl cyclo-archaeol is presented employing catalytic asymmetric conjugate addition and catalytic epoxide ring opening as the key steps. Their occurrence in deep sea hydrothermal vents has been confirmed by chromatographic comparison with natural samples.


Endothelial HIF-1α Enables Hypothalamic Glucose Uptake to Drive POMC Neurons.
Glucose is the primary driver of hypothalamic proopiomelanocortin (POMC) neurons. We show that endothelial hypoxia-inducible factor 1α (HIF-1α) controls glucose uptake in the hypothalamus and that it is upregulated in conditions of undernourishment, during which POMC neuronal activity is decreased. Endothelium-specific knockdown of HIF-1α impairs the ability of POMC neurons to adapt to the changing metabolic environment in vivo, resulting in overeating after food deprivation in mice. The impaired functioning of POMC neurons was reversed ex vivo or by parenchymal glucose administration. These observations indicate an active role for endothelial cells in the central control of metabolism and suggest that central vascular impairments may cause metabolic disorders.


CNS expression of anti-inflammatory cytokine interleukin-4 attenuates Alzheimer's disease-like pathogenesis in APP+PS1 bigenic mice.
Cytokines play an emerging role as neurotransmitters, neuromodulators, and neurohormones in the brain. This paradigm shift in cytokine function offers a new framework to understand their roles in ameliorating neurodegenerative disorders, such as Alzheimer's disease (AD). Molecular adjuvant therapy of AD animal models with glatiramer acetate induces anti-inflammatory responses and therapeutic effects. Although these effects are potentially mediated through anti-inflammatory cytokine signaling, the exact molecular identities and pathways are poorly understood. Here, we show that virus-mediated expression of the mouse interleukin (IL)-4 gene in beta-amyloid precursor protein + presenilin-1 (APP+PS1) bigenic mice attenuates AD pathogenesis. Introduction of an adeno-associated viral (AAV) vector encoding IL-4 into the hippocampus resulted in sustained expression of IL-4, reduced astro/microgliosis, amyloid-beta peptide (Abeta) oligomerization and deposition, and enhanced neurogenesis. Moreover, increased levels of IL-4 improved spatial learning, promoted phosphorylation of N-methyl-D-aspartate receptor subunit 2B at Tyr 1472, and enhanced its cell surface retention both in vivo and in vitro. Our data suggest that neuronal anti-inflammatory cytokine signaling may be a potential alternative target for non-Abeta-mediated treatment of AD.


Mode of neuromuscular blocking action of toxic phospholipases A2 from Vipera ammodytes venom.
The effects of toxic phospholipases A2 ( fraxtions "j", "k1" and "k2") isolated from the venom of Vipera ammodytes were studied on the chick biventer cervicis muscle and the mouse phrenic nerve-diaphragm preparations. In the chick muscle, all of these PLA2s caused neuromuscular (N-M) blockade without producing contracture or affecting the response of the muscle to acetylcholine. In the mouse diaphragm, these PLA2s inhibited completely the indirectly elicited contraction without affecting that evoked directly. The order of their N-M blocking potency is "k2" greater than "k1" greater than or equal to "j". In a low Ca2+ (0.5 mM) medium, they produced a triphasic change in the indirectly elicited contractions: an initial inhibition followed by an enhancement and then a progressive depression leading to complete N-M blockade. The frequency of miniature endplate potentials (m.e.p.p.s) in the mouse diaphragm first increased 2-3 fold and then gradually decreased after "k2" treatment, while the amplitude of m.e.p.p.s did not decrease even after the evoked release of transmitter failed. Giant potentials and bursts of m.e.p.p.s were frequently observed. The quantal content of e.p.p.s was first increased and then decreased gradually. The resting membrane potential was only slightly reduced at 30 micrograms per ml. The ultrastructure of motor nerve terminals in the "k2"-intoxicated mouse diaphragm showed an increase in omega-shaped indentation in the axolemma. The mitochondria in the nerve terminal were swollen and vacuolized. No structural changes were found in the muscle fibers, fibrocytes and myelinated axons in the diaphragm. It is concluded that the toxic PLA2s from Vipera ammodytes venom produce a N-M blockade by acting selectively on the presynaptic site.


Combat-related disorders: a persistent chimera.
Whilst there may be some individuals who genuinely enjoy combat, for most troops it represents many emotional challenges, such as, overcoming fear and being witness to death, suffering and mutilation, as well as having to tolerate extremes of physical discomfort. At present we lack sufficiently valid and reliable methods of screening out those personnel particularly vulnerable to adverse reactions to these challenges. The authorities should aim to provide good training, an appreciative milieu, and a working climate in which those with genuine psychopathology feel confident to admit this, without censure and stigma, and to have access to evidence-based treatments. We should also remember that military life offers much to many men and women, and that surviving physically and psychologically the unavoidable brutalities of combat can often leave a legacy of positive outcomes. We must avoid becoming preoccupied with risk and psychopathology.


Y chromosome microdeletion screening using a new molecular diagnostic method in 1030 Japanese males with infertility.
The azoospermia factor (AZF) region is important for spermatogenesis, and deletions within these regions are a common cause of oligozoospermia and azoospermia. Although several studies have reported this cause, the present research, to the best of our knowledge, is the first large-scale study assessing this factor in Japan. In this study, 1030 male patients with infertility who were examined for Y chromosome microdeletion using the polymerase chain reaction-reverse sequence-specific oligonucleotide (PCR-rSSO) method, a newly developed method for Y chromosome microdeletion screening, were included. The study enrolled 250 patients with severe oligospermia and 717 patients with azoospermia. Among the 1030 patients, 4, 4, 10, and 52 had AZFa, AZFb, AZFb+c, and AZFc deletions, respectively. The sperm recovery rate (SRR) of microdissection testicular sperm extraction in patients with AZFc deletions was significantly higher than that in those without AZF deletions (60.0% vs 28.7%, P = 0.04). In patients with gr/gr deletion, SRR was 18.7%, which was lower than that in those without gr/gr deletion, but was not statistically significant. In conclusion, our study showed that the frequency of Y chromosome microdeletion in male patients in Japan was similar to that reported in patients from other countries, and SRR was higher in patients with AZFc deletion.


Applying a Foucauldian lens to the Canadian code of ethics for registered nurses as a discursive mechanism for nurses professional identity.
This study examines the Canadian Code of Ethics for Registered Nurses as a discursive mechanism for shaping nurses' professional identity using a Foucauldian lens. Nurses are considered essential in healthcare, yet the nursing profession has struggled to be recognized for its discipline-specific knowledge and expertise and, as such, has remained the subject of and subject to the dominant discourses within healthcare and society generally. Developing a professional identity in nursing begins after the necessary education and training are achieved and embodies the profession's history, values, code of ethics, and expectations of the profession that distinguish it from other professions. Since nurses' professional identity is shaped through discourse, it raises the question of whether there are spaces to reconceptualize nurses' subject position within health care. Since professional identity is considered the embodiment of knowledge and practice, the code of ethics bears examination both for its effect on nurses' professional identity and as a potential site from which to challenge hegemonic assumptions. This article discusses the concept of professional identity in nursing and its development through the discursive formations in the code of ethics. The sources of power/knowledge are examined as both mechanisms of control and as spaces for change.


Comparison of the biodegradability of the grey fraction of municipal solid waste of Barcelona in mesophilic and thermophilic conditions.
The results of the start-up of two digesters in mesophilic and thermophilic conditions, together with its steady results at several organic loading rates are described. A kinetic study is also carried out which allows one to estimate the ultimate methane production, together with the first-order kinetic constant. Operation at thermophilic temperature yields better results as it allows a more loaded reactor and the methane production is slightly higher.


Circumscription of the genus Lepra, a recently resurrected genus to accommodate the "Variolaria"-group of Pertusaria sensu lato (Pertusariales, Ascomycota).
Pertusarialean lichens include more than 300 species belonging to several independent phylogenetic lineages. Only some of these phylogenetic clades have been comprehensively sampled for molecular data, and formally described as genera. Here we present a taxonomic treatment of a group of pertusarialean lichens formerly known as "Pertusaria amara-group", "Monomurata-group", or "Variolaria-group", which includes widespread and well-known taxa such as P. amara, P. albescens, or P. ophthalmiza. We generated a 6-locus data set with 79 OTUs representing 75 species. The distinction of the Variolaria clade is supported and consequently, the resurrection of the genus Lepra is followed. Thirty-five new combinations into Lepra are proposed and the new species Lepra austropacifica is described from mangroves in the South Pacific. Lepra is circumscribed to include species with disciform ascomata, a weakly to non-amyloid hymenial gel, strongly amyloid asci without clear apical amyloid structures, containing 1 or 2, single-layered, thin-walled ascospores. Chlorinated xanthones are not present, but thamnolic and picrolichenic acids occur frequently, as well as orcinol depsides. Seventy-one species are accepted in the genus. Although the distinction of the genus from Pertusaria is strongly supported, the relationships of Lepra remain unresolved and the genus is tentatively placed in Pertusariales incertae sedis.


The demand for preventive and restorative dental services among older adults.
Many older Americans have poor access to dental care, resulting in a high prevalence of oral health problems. Because traditional Medicare does not include dental care benefits, only older Americans who are employed, have post-retirement dental benefits or spousal coverage, or enroll in certain Medicare Advantage plans are able to obtain dental care coverage. We seek to determine the extent to which poor access to dental insurance and high out-of-pocket costs affect dental service use by the elderly. Using the 2007-2015 Medical Expenditure Panel Survey and supplemental data on dental care prices, we estimate a demand system for preventive dental services and basic and major restorative services. Selection into dental and medical insurance is addressed using a correlated random effects panel data specification. Consistent with prior studies of the nonelderly population, dental service use was not sensitive to out-of-pocket prices. However, private dental insurance increased preventive service use by 25%, and dental coverage through Medicaid increased basic and major service use by 23% and 36%, respectively. The use of services was more responsive to dental insurance for women than men. These estimates suggest that a Medicare dental benefit could significantly increase dental service use by older Americans.


Investigation on the Trace Elemental Profile of Sewage Workers in Kolkata, an Indian Megacity.
Environmental pollution has become a global health risk. Exposure to pollutants at the work place, i.e. occupational exposure, is one of the areas that need immediate attention. The civic drainage workers are exposed to pollutants present in the wastewater they handle and most of them are toxic heavy metals. Exposure to such pollutants may be a health hazard, since it can lead to the imbalance in nutrient elements status. In the present study, profiling of trace elements in the blood of drainage worker population from an Indian megacity, Kolkata, was carried out by energy dispersive x-ray fluorescence (EDXRF) and compared with the control group population of the same area. The elements detected by EDXRF spectrometry include P, S, Cl, K, Fe, Cu, Zn, Se, Br, and Rb. By using ANOVA with 5% significance level, we observed significant alterations in the trace elements status, iron over loading, selenium deficiency, and in Cu-Zn ratio. Gender specific variations within the same population were also observed. The results indicate that the drainage workers have altered elemental profile in comparison to that of control population. Significance for public healthEnvironmental pollution is a global health risk and awareness among sewage workers is growing very slowly in many developing countries. Due to this fact, workers are often exposed to different pollutants which are responsible for several health complications. Imbalances in the presence of trace elements in blood are a symptom of different health status and could also indicate new health perspectives for the future. In the present scenario, this paper is essential since this kind of analysis has not been done yet, especially regarding the health status of sewage workers. We hope this initial study will be a starting point for future investigations.


Patient resistance as a resource: candidate obstacles in diabetes consultations.
This study uses conversation analysis to explore 'candidate obstacles', a practice observed in sequences of patient resistance to lifestyle advice within health professional consultations. This article presents illustrative analyses of selected data excerpts drawn from audio-visual recordings of 116 tracked consultations between health professionals and 34 patients newly diagnosed with type 2 diabetes mellitus in New Zealand. The analysis shows that in consultations where health promotion activities are central, patient resistance can provide space for patients to identify obstacles to their compliance with lifestyle advice. Identifying candidate obstacles provides opportunities for health professionals to align advice with concerns of patients and potentially improve patient outcomes.


3D finite element analysis of the gamma nail and dhs plate in trochanteric hip fractures.
The finite element method (FEM) was used to evaluate the short-term mechanical stability of trochanteric fractures treated by two types of implants: the Gamma" nail (Howmedica) and the Dynamic Hip Screw, DHS" (Synthes). The displacement and stress distributions of bone and implants were computed using a complete 3D FE model. The main conclusion is that proximal stable femoral fractures can be treated correctly with the Gamma Nail and DHS. For unstable fractures, the Gamma Nail achieves good stabilization but DHS is insufficient and requires a static screw due to the lack of torsional stiffness. Both extramedullary and intramedullary systems were found to distort the load transmission with respect to the anatomic pattern, so they both have biomechanical limitations in the long-term. (Hip International 2004; 14: 18-23)NO PDF AVAILABLE!


Role of endothelin in cardiovascular disease.
Endothelins are a family of peptides, which comprises endothelin-1 (ET-1), endothelin-2 (ET-2) and endothelin-3 (ET-3), each containing 21 amino-acids. ET-1 is a peptide secreted mostly by vascular endothelial cells, the predominant isoform expressed in vasculature and the most potent vasoconstrictor currently known. ET-1 also has inotropic, chemotactic and mitogenic properties. In addition, it influences salt and water homeostasis through its effects on the renin-angiotensin-aldosterone system (RAAS), vasopressin and atrial natriuretic peptide and stimulates the sympathetic nervous system. The overall action of endothelin is to increase blood pressure and vascular tone. Therefore, endothelin antagonists may play an important role in the treatment of cardiac, vascular and renal diseases associated with regional or systemic vasoconstriction and cell proliferation, such as essential hypertension, pulmonary hypertension, chronic heart failure and chronic renal failure. Long-term anti-endothelin therapy may improve symptoms and favourably alter the progression of heart failure. Endothelin appears to participate in induction and progression of sclerotic renal changes, leading to progression to end-stage renal disease. Anti-endothelin therapy might offer additional benefits in the prevention of progression of chronic renal failure in addition to the known benefits of RAAS inhibition. Clinical trials have demonstrated potentially important benefits of endothelin antagonists for patients with essential hypertension, pulmonary hypertension and heart failure. Further studies are necessary to determine the role of anti-endothelin therapy in the treatment of cardiovascular diseases and determine the different roles of selective receptor antagonism vs. mixed ET(A/B)-receptor antagonism in human diseases.


Cell death mechanisms and potentially cytotoxic natural immune cells in human pregnancies complicated by preeclampsia.
Preeclampsia, which occurs in about 2% to 3% of all pregnancies, is a severe multisystem disorder showing symptoms in the second half of human pregnancy. Its prevention, early diagnosis, and treatment are insufficient, since etiology and pathogenesis of the disease are still not totally understood. Recent studies confirm that preeclampsia is the extreme end of a normal inflammatory reaction, which also occurs in healthy pregnancies. This review focuses on maternal immune changes during preeclampsia leading to altered cytotoxic responses. The potential role of perforin/granzyme-, Fas/Fas-ligand-, tumor necrosis factor α (TNF-α)- or TNF-related apoptosis-inducing ligand-mediated apoptotic mechanisms in the pathomechanism is analyzed. The frequency and function of effector cytotoxic cells of natural immunity itself such as natural killer (NK) cells, NKT cells, and γδT cells are also changed both in the periphery and locally in the uterus influencing the outcome of pregnancy. Here, authors conclude that beside exaggerated inflammatory responses, apoptotic and killing mechanisms also seem to be implicated in the pathogenesis of preeclampsia.


Microbial metabolism of mandelate: a microcosm of diversity.
This review highlights the diversity of prokaryotic and eukaryotic microorganisms that can metabolise mandelate and it describes how a wide range of compounds related to mandelate is formed in many environments. The chief aspects that are summarised include the various pathways whereby mandelate and its structural analogues are converted into catechol or protocatechuate, the properties of the enzymes that are involved in the pathways, and the regulation and genetics of the pathways. The review incorporates the idea that the study of peripheral metabolic pathways is particularly useful for illuminating evolutionary speculations and it concludes with a list of questions that need to be answered.


Detection of adenovirus DNA in peripheral blood mononuclear cells by polymerase chain reaction assay.
Adenovirus can establish persistent infections which may reactivate and cause disease in immunocompromised hosts. Lymphocytes have been postulated to serve as a site of adenoviral persistence based upon the ability to isolate adenovirus from tonsils and to detect adenovirus DNA by Southern blot hybridization in peripheral blood mononuclear cells (PBMC). To test this hypothesis, a more sensitive and specific polymerase chain reaction (PCR) assay was developed to detect adenovirus DNA. Two sets of nested primers were designed to conserved sequences in the adenovirus E1A and hexon genes. The E1A and hexon primers amplified DNA from representative adenoviral serotypes in all six adenoviral groups (A-F). Both primers detected a single copy of the adenovirus type 2 genome but were less sensitive for the group B type 35. None of 33 PBMC specimens from healthy adults and only one of 40 pediatric samples was positive (at a low level) for adenovirus DNA by nested PCR assay. In comparison, PBMC from two children with fatal adenoviral infection were both strongly positive for adenovirus DNA. It is concluded that, in contrast to a previous study, PBMC are not a common site of persistent group C adenoviral infection. In addition, assay of PBMC by the adenovirus-specific PCR may help detect early invasive disease and warrants further evaluation.


Paraxial focal length calculation using Strehl definition measurement.
This work describes a method for determination of a paraxial focal length of optical systems using measurements of the Strehl definition. The influence of spherical aberration on the value of the measured effective focal length of an optical system is analyzed, and a method is proposed for an elimination of this influence and determination of the paraxial focus position and the paraxial focal length of a lens from the measurement of the effective focal length and the Strehl definition.


Species-specific posttranscriptional regulation of interferon synthesis.
Human fibroblast and Syrian hamster embryo cells were induced to synthesize interferon (IF) with rIn . rCn and rIn . rCn + DEAE-dextran, respectively. Following induction, these cells synthesized IF for only a short time before entering into a repressed state and shutting off the synthesis of IF. Homologous and heterologous whole cell translational systems were developed to investigate the molecular basis for the shut-off of IF synthesis. These systems allowedd for the introduction of exogenous hamster and human IF-mRNAs into intact normal and repressed hamster and human cells via an improved CaCl2 precipitation technique. Human IF-mRNA was translated in normal human and hamster cells and in repressed hamster cells but not in repressed human cells. In contrast, the hamster IF-mRNA was translated in normal human, normal hamster, and repressed human cells but not in repressed hamster cells. These results indicate that a species-specific mechanism inhibiting translation of IF-mRNA is directly responsible for the shut-off of IF synthesis in human fibroblasts and Syrian hamster embryo cells.


Characterization of transcriptional initiation from promoters P1 and P2 of the pyrBI operon of Escherichia coli K12.
Expression of the pyrBI operon of Escherichia coli K12, which encodes the pyrimidine biosynthetic enzyme aspartate transcarbamylase, is negatively regulated by pyrimidine availability, primarily through an attenuation control mechanism, and also appears to be subject to stringent control. Previous in vitro transcription studies indicated that the pyrBI operon is transcribed from tandem promoters designated P1 and P2, which appeared to be of similar strength. In this study, we characterized these promoters in detail and examined their role in pyrBI expression. Our results show that although transcription is initiated at both promoters in vivo, greater than 99% of the pyrBI transcripts are initiated at promoter P2, indicating that this is the only physiologically significant promoter. The level of transcripts initiated at promoter P2 was found to be higher in cells grown under pyrimidine-limiting conditions compared to that in cells grown under conditions of pyrimidine excess, indicating pyrimidine-mediated regulation at the level of transcriptional initiation. In vitro characterization of transcription from the pyrBI promoter region showed that non-physiological reaction conditions used in the original identification of the two promoters greatly overestimated the strength of promoter P1. Further in vitro characterization of the two promoters showed that transcription from promoter P2, but not from promoter P1, is inhibited by guanosine tetraphosphate and exhibits salt and heparin sensitivity typical of a stringently controlled promoter. In addition, heparin-challenge experiments revealed a UTP-induced instability of transcriptional initiation complexes at promoter P2 which may be of regulatory significance.


Meaningful objects avoid attribute amnesia due to incidental long-term memories.
Attribute amnesia describes the failure to unexpectedly report the attribute of an attended stimulus, likely reflecting a lack of working memory consolidation. Previous studies have shown that unique meaningful objects are immune to attribute amnesia. However, these studies used highly dissimilar foils to test memory, raising the possibility that good performance at the surprise test was based on an imprecise (gist-like) form of long-term memory. In Experiment 1, we explored whether a more sensitive memory test would reveal attribute amnesia in meaningful objects. We used a four-alternative-forced-choice test with foils having mis-matched exemplar (e.g., apple pie/pumpkin pie) and/or state (e.g., cut/full) information. Errors indicated intact exemplar, but not state information. Thus, meaningful objects are vulnerable to attribute amnesia under the right conditions. In Experiments 2A-2D, we manipulated the familiarity signals of test items by introducing a critical object as a pre-surprise target. In the surprise trial, this critical item matched one of the foil choices. Participants selected the critical object more often than other items. By demonstrating that familiarity influences responses in this paradigm, we suggest that meaningful objects are not immune to attribute amnesia but instead side-step the effects of attribute amnesia.


Anatomical associations and radiological characteristics of Scimitar syndrome on CT and MR.
To report the anatomical associations and radiological characteristics of Scimitar syndrome on CT and MR. Retrospective review of the medical records between February 2001 and February 2016 was performed. To identify patients, radiological reports were queried for "Scimitar" or "partial anomalous pulmonary venous return." Patients with radiological findings of Scimitar syndrome were included. Patients without cross-sectional imaging were excluded. Patients' demographics, radiologic images, and medical notes were reviewed. Two radiologists re-read the available imaging studies. Images were reviewed for Scimitar syndrome confirmation, number and location of Scimitar vein drainage, number of lobes drained by the Scimitar vein, and right pulmonary artery and lung hypoplasia. In addition, the number of pulmonary veins draining into the left atrium, left sided anomalous pulmonary veins, congenital heart disease, aortic arch anomalies, cardiac dextroposition, right ventricular enlargement, pulmonary artery enlargement, and elevated QP:QS ratios were identified. Other associated anomalies including the presence of an anomalous feeding artery and pulmonary sequestration, abnormal lobar pattern, localized bronchiectasis, horseshoe lung, accessory diaphragm, diaphragmatic hernia, vertebral anomalies, and genitourinary tract anomalies were reviewed. Sixteen patients (3 males, 13 females; mean age 39.5 years, range 14 days-72 years) with confirmed Scimitar syndrome on CT and MR imaging were identified. The Scimitar vein drained to the infra-diaphragmatic inferior vena cava (IVC) in ten patients and to the supra-diaphragmatic IVC in six patients. The most common associated anomalies were right ventricle enlargement (93.3%), variant lobar pattern of the right lung (92.9%), enlarged pulmonary arteries (60%), and cardiac dextroposition (50%). Recognizing the radiologic characteristics and anatomical associations of Scimitar syndrome is important as features of the primary condition and associated anomalies may have implications in surgical management.


Scaling and universality of self-organized patterns on unstable vicinal surfaces.
We propose a unified treatment of the step bunching instability during epitaxial growth. The scaling properties of the self-organized surface pattern are shown to depend on a single parameter, the leading power in the expansion of the biased diffusion current in powers of the local surface slope. We demonstrate the existence of universality classes for the self-organized patterning appearing in models and experiments.


Cleaning validation of ofloxacin on pharmaceutical manufacturing equipment and validation of desired HPLC method.
Inadequate cleaning of a pharmaceutical manufacturing plant or inadequate purging of the individual pieces of equipment used in multi-product manufacturing or equipment not dedicated to individual products may lead to contamination of the next batch of pharmaceutics manufactured using the same equipment. Challenges for cleaning validation are encountered especially when developing sensitive analytical methods capable of detecting traces of active pharmaceutical ingredients that are likely to remain on the surface of the pharmaceutical equipment after cleaning. A method's inability to detect some residuals could mean that either the method is not sensitive enough to the residue in question or the sampling procedure is inadequate. A sensitive and reproducible reversed-phase, high-performance liquid chromatographic method was developed for the determination of ofloxacin in swab samples. The method for determining ofloxacin residues on manufacturing equipment surfaces was validated in regard to precision, linearity, accuracy, specificity, limit of quantification, and percent recovery from the equipment surface, as well as the stability of a potential contaminant in a cleaning validation process. The active compound was selectively quantified in a sample matrix and swab material in amounts as low as 0.55 ng/mL. The swabbing procedure using cotton swabs was validated. A mean recovery from stainless steel plate of close to 85% was obtained. Chromatography was carried out on a pre-packed Merck (Dermstadt, Germany) Lichrospher model 100 Rp-18 (5.0 microm, 250 mm X 4.0 mm) column using a mixture of sodium lauryl sulfate (0.024% aqueous solution), acetonitrile, and glacial acetic acid (500:480:20,v/v) as the mobile phase at a flow rate of 1.5 mL/min with a column temperature of 35 degrees C and 294 nm detection. The assay was linear over the concentration range of 2 ng/mL to 2000 ng/mL (R approximately 0.99998). The method was validated for accuracy and precision. The stability of ofloxacin in the swab samples was also assessed. In regard to the 10-ppm acceptance criteria in the succeeding batch, the calculated limit was 437 microg/cm2 while according to the 0.1% dosing approach the calculated value was 116 microg/cm2. The calculated recovery values from swab samples were below these acceptable limits during three consecutive cleaning trials. This confirms that the desired level of cleanliness is achieved using the current cleaning procedures, which were consequently validated.


Evaluating combined effect of noise and heat on blood pressure changes among males in climatic chamber.
Exposure to noise and heat causes individuals to experience some changes in the function of cardiovascular system in workplaces. This study aimed to find the combined effect of heat and noise on systolic and diastolic types of blood pressure in experimentally controlled conditions. This quasi-experimental study was performed with 12 male students in a climatic chamber in 2014. Blood pressure including systolic and diastolic was measured in the following conditions: 15 min after rest in exposure to heat (40°C, relative humidity [RH]: 30%), exposure to noise with 75, 85, and 95 dB rates in thermal comfort condition (22.1 ± 0.9 wet-bulb globe temperature), and combined exposure to heat (40°C, RH: 30%) and noise with 75, 85, and 95 dB. Friedman test was used to analyze the data. The mean change of systolic blood pressure was different significantly before and after exposure to heat and noise levels including 75, 85, and 95 dB (P = 0.015, P = 0.001, P > 0.001, P = 0.027, respectively). Although systolic and diastolic blood pressures changed drastically, it was not significantly different in simultaneous exposure to heat and noise. Both systolic and diastolic blood pressures decreased in exposure to heat, while exposure to different levels of noise elevates systolic and diastolic blood pressures. However, when exposed to a combination of heat and noise, subtle changes of blood pressure were traced, which can be characterized as average, considering heat-only and noise-only tension situations.


Social representations of media reception during the COVID-19 lockdown in Colombia: from messages to meanings.
Recent studies on COVID-19 have focused on the pandemic's effects on public health and the biosafety controls and their socioeconomic implications. The current mixed-methods study takes a new look at the topic, combining qualitative and quantitative strategies to identify the social representations of media reception in a sector of the Colombian population during social isolation in the COVID-19 pandemic. The results indicate that these representations vary and are associated with the media channel and the effect the reception produces on mood and mental health. A total of 80 interviews and 1,068 online survey forms were applied in different regions of Colombia. The qualitative phase showed that the programs or messages received were represented positively when they came from audiovisual entertainment and contributed to the family unit and reduced stress during the lockdown. Meanwhile, media reception was represented negatively when the messages or news came from journalism or social networks and increased the misinformation, anxiety, and fear of contagion. The quantitative phase found that media reception decreased as the lockdown continued, due to information saturation and the proliferation of news emphasizing the risks of COVID-19. The results reveal the need to focus health communication on the development of information skills that allow people to learn and assess the veracity and relevance of information received during the pandemic.


MATE CHOICE BASED UPON NATURALLY OCCURRING COLOR-PATTERN VARIATION IN A GUPPY POPULATION.
This study tested the effect of differences in the extent of orange pigment in the color pattern of male guppies on the sexual responsiveness of females. Fish used in this study were descendants of a single natural population from the Paria River of Trinidad. Males from this population have unusually large, brilliant orange spots. I used three experimental approaches to test for discrimination by females among males based on the relative area of orange in color patterns: 1) the time to mating when a male was presented to a virgin female; 2) the frequency of sexual responses of females to passing, nondisplaying males; and 3) the proportion of a male's courtship displays that elicited a female sexual response. In all three experiments, females appeared to discriminate against males with less-than-average amounts of orange in their color patterns. In at least one experiment, however, the increase in female responsiveness with increasing amounts of orange leveled off and possibly decreased at high levels of orangeness. This suggests that there may be no advantage of increased amounts of orange above a certain level. These results suggest that female choice is a mechanism for the evolution of color patterns in guppies and may have contributed to the distinctive color pattern of the Paria population.


Work productivity loss due to flares in patients with chronic gout refractory to conventional therapy.
Joint pain and swelling during gout flares may lead to considerable morbidity and disability, having an impact on patient work productivity and social participation. The objective of this study was to assess how gout flares affect these activities in patients with chronic gout refractory to conventional therapy. A 1-year prospective observational study was conducted among patients with symptomatic disease in the United States in 2001. Inclusion criteria required patients (1) to be age 18 years or older, (2) to have documented, crystal-proven gout, (3) to have symptomatic gout, and (4) to be intolerant or unresponsive to conventional therapy, reflected by SUA ≥ 6.0 mg/dL. Patients were evaluated every 2 months. At each visit, patients completed a gout diary, which included number of flares experienced, duration and severity of each flare, and whether the flare caused: (1) work loss, (2) missed appointments or social events, or (3) impairment of self-care activities. The Short-Form Health Survey (SF-36) was also completed each visit. Analyses were restricted to those who completed the first 6 months of the study (n = 81). Mean number of flares per patient per year was 8.8. Of the patients who were <65 years, 78% reported at least 1 work day lost due to a gout attack during the year. Mean annual work day loss for those <65 years was 25.1 days. A total of 545 of patients reported at least one flare per year that impaired social activities, with a mean of 17.1 social days lost and 52% reported at least one flare per year that compromised normal self-care activities, with a mean of 16.9 days impairment. Correlations between the diary reports and activity-related questions from the SF-36 were significantly positive. The study is limited by small sample size, lack of reference group, and inability to explicitly collect employment information. Age under 65 years was used as a proxy for employment eligibility. Flares in patients with chronic gout refractory to conventional therapy significantly affect patient work productivity and social activities.


Use of porous aluminosilicate pellets for drug delivery.
Three pelletized porous aluminosilicate ceramics were obtained commercially and their potential to act as extended release drug delivery systems was assessed. The pellets were drug loaded using a vacuum impregnation technique. Factors such as the concentration of the loading solution and the porosity and bulk density of the ceramic influenced the drug loading. The release of drug from the pellets was extended as the drug was entrapped within their porous interior. The rate of release was influenced by the porous microstructure of the pellets and the physicochemical properties of the drug. Extrusion-spheronization was used to prepare pellets similar to the porous ceramics. The pellet formulations contained an aluminosilicate clay mineral (kaolin or halloysite), ethylcellulose 100 cps, ethanol and varying quantities of sucrose. The latter two components acted as pore forming agents. Diltiazem HCl was loaded into the pellets and its release was extended. The release rate could be modified by changing the quantity of sucrose included in the initial formulation, as this influenced the porous microstructure of the pellets. In halloysite-based products the release was further extended due to entrapment of the drug within the halloysite microtubules. Porous kaolin-based pellets were also prepared by cryopelletization. This involved freezing droplets of an aqueous suspension containing kaolin, sodium silicate solution and sodium lauryl sulphate. The resulting pellets were freeze-dried, which removed ice from them to leave pores behind. The pellets gave extended drug release with the release rate being influenced by the porous microstructure of the pellets and their microclimate pH.


Immunoglobulin heavy chain variable region family usage is independent of tumor cell phenotype in human B lineage leukemias.
During B cell development, immunoglobulin heavy chain (IgH) variable region (VH) genes are rearranged and expressed in a programmed manner and accumulating evidence suggests recurrent utilization of developmentally restricted VH genes in malignant B lymphoid populations. We have used polymerase chain reaction gene amplification in conjunction with a panel of VH family-specific amplimers to directly compare the repertoire of VH region rearrangement in mature, CD5+ B cell chronic lymphocytic leukemia with that in immature, CD5 B lineage acute lymphoblastic leukemia. The results revealed a diverse pattern of VH family utilization common to both disease groups in which VH regions most proximal to the IgH joining locus were preferentially rearranged relative to their family sizes with recurrent utilization of several known developmentally restricted VH genes in close to germ-line configuration. These results indicate that biased VH family usage is independent of tumor cell phenotype in B lineage leukemias. This bias may reflect similar stages or compartments in normal B lymphopoiesis from which diverse types of B cell malignancy may arise. Moreover, since blast cells in acute lymphoblastic leukaemia do not express functional immunoglobulin, we infer that the tumor cell-associated VH family repertoire is determined through antigen-independent mechanisms.


Legionella pneumophila inhibits type I interferon signaling to avoid cell-intrinsic host cell defense.
The host type I interferon (IFN) response protects against Legionella pneumophila infections. Other bacterial pathogens inhibit type I IFN-mediated cell signaling; however, the interaction between this signaling pathway and L. pneumophila has not been well described. Here, we demonstrate that L. pneumophila inhibits the IFN-β signaling pathway but does not inhibit IFN-γ-mediated cell signaling. The addition of IFN-β to L. pneumophila-infected macrophages limited bacterial growth independently of NOS2 and reactive nitrogen species. The type IV secretion system of L. pneumophila is required to inhibit IFN-β-mediated cell signaling. Finally, we show that the inhibition of the IFN-β signaling pathway occurs downstream of STAT1 and STAT2 phosphorylation. In conclusion, our findings describe a novel host cell signaling pathway inhibited by L. pneumophila via its type IV secretion system.


Control of gene conversion and somatic hypermutation by immunoglobulin promoter and enhancer sequences.
It is thought that gene conversion (GCV) and somatic hypermutation (SHM) of immunoglobulin (Ig) genes occur in two steps: the generation of uracils in DNA by activation-induced cytidine deaminase, followed by their subsequent repair by various DNA repair pathways to generate sequence-diversified products. It is not known how either of the two steps is targeted specifically to Ig loci. Because of the tight link between transcription and SHM, we have investigated the role of endogenous Ig light chain (IgL) transcriptional control elements in GCV/SHM in the chicken B cell line DT40. Promoter substitution experiments led to identification of a strong RNA polymerase II promoter incapable of supporting efficient GCV/SHM. This surprising finding indicates that high levels of transcription are not sufficient for robust GCV/SHM in Ig loci. Deletion of the IgL enhancer in a context in which high-level transcription was not compromised showed that the enhancer is not necessary for GCV/SHM. Our results indicate that cis-acting elements are important for Ig gene diversification, and we propose that targeting specificity is achieved through the combined action of several Ig locus elements that include the promoter.


Awareness of pediatric hypertension. Measuring blood pressure.
Surveys of patients at three pediatric teaching hospitals showed a low percentage of blood pressure recordings by the examining physician in the walk-in or emergency clinics. The frequency of blood pressure measurement was higher among inpatients, especially on medical services. A recommendation for obtaining blood pressure measurements is made on three bases: 1. many patients use these ambulatory services as their major source of care, 2. many conditions for which care is sought and many therapeutic agents are associated with hypertension, and 3. unless measurements of blood pressure become customary during training, it is likely that blood pressure recording may not be included as part of routine physical examinations.


Simulation of impact test for determining "health" of percutaneous bone anchored implants.
There is an ongoing requirement for a clinically relevant, noninvasive technique to monitor the integrity of percutaneous implants used for dental restorations, bone-anchored hearing aids, and to retain extra-oral prostheses (ear, eye, nose, etc). Because of the limitations of conventional diagnostic techniques (CT, MRI), mechanical techniques that measure the dynamic response of the implant-abutment system are being developed. This paper documents a finite element analysis that simulates a transient response to mechanical impact testing using contact elements. The detailed model allows for a specific interface between the implant and bone and characterizes potential clinical situations including loss of bone margin height, loss of osseointegration, and development of a soft connective tissue layer at the bone-implant interface. The results also show that the expected difference in interface stiffness between soft connective tissue and osseointegrated bone will cause easily measurable changes in the response of the implant/abutment system. With respect to the loss of bone margin height, changes in the order of 0.2 mm should be detectable, suggesting that this technique is at least as sensitive as radiography. A partial loss of osseointegration, while not being as readily evident as a bone margin loss, would still be detectable for losses as small as 0.5 mm.


Heparin-binding, highly basic regions within the thyroglobulin type-1 repeat of insulin-like growth factor (IGF)-binding proteins (IGFBPs) -3, -5, and -6 inhibit IGFBP-4 degradation.
MC3T3-E1 murine osteoblasts produce insulin-like growth factor (IGF)-binding protein-4 (IGFBP-4)-degrading proteinase activity, which is inhibited by IGFBP-3 and a highly basic, C-terminal domain of IGFBP-3. Of all the other five IGFBPs, IGFBP-5 and -6 share the highest degree of homology with this domain of IGFBP-3; therefore, we investigated whether these two IGFBPs inhibit IGFBP-4 degradation. Both IGFBP-5 and IGFBP-6 inhibit the degradation of 125I-IGFBP-4 by MC3T3-E1-conditioned media, and their inhibitory effects are variably reversed by IGFs. Synthetic peptides containing highly basic, C-terminal regions of IGFBP-5 and IGFBP-6 inhibit 125I-IGFBP-4 degradation, as does an homologous IGFBP-3 peptide, yet each peptide displays a different IC50, with the IGFBP-5 peptide being the most potent and the IGFBP-6 peptide being the least potent. In contrast, a homologous, yet neutral, IGFBP-4 peptide does not inhibit 125I-IGFBP-4 proteolysis, confirming the role of basic residues in the inhibitory process. The IGFBP-3, -5, and -6 peptides, each of which contains the heparin-binding consensus sequence XBBBXXBX, bind heparin, yet the IGFBP-3 and -5 peptides bind heparin with the highest affinities, whereas the IGFBP-6 peptide binds heparin with approximately 10-fold less affinity. Consistent with these regions being involved in proteinase inhibition, heparin completely reverses their inhibitory effects on 125I-IGFBP-4 proteolysis. Together, these data demonstrate that IGFBP-3, -5, and -6 can function as IGF-reversible inhibitors of IGFBP-4 proteolysis, likely through homologous, highly basic, heparin-binding domains contained within the conserved thyroglobulin type-1 motif present in the C-termini of these IGFBPs.


Tyrosine phosphorylation is a signal for the trafficking of pp85, an 85-kDa phosphorylated polypeptide associated with phosphatidylinositol kinase activity.
A family of 85/86-kDa (85K/86K) polypeptides closely linked to phosphatidylinositol kinase activity is found in polyoma middle-sized tumor antigen (MTAg)/pp60c-src complexes. MTAg and the 85-kDa phosphoprotein (pp85) could be reassociated in solution, or on blots, after denaturation with SDS. Results from such experiments focus attention on phosphorylation in controlling intracellular sorting and activation of pp85. Tyrosine phosphorylation seems important for recruitment of pp85 from cytosol to membrane. By blotting, pp85 is substantially cytosolic, whereas that recognized by anti-phosphotyrosine antibody is almost exclusively in membranes. Tyrosine phosphorylation also determined association of pp85 with MTAg. Manipulation of MTAg tyrosine phosphorylation, for example, by expressing MTAg using baculovirus vectors in the absence or presence of pp60c-src, dramatically affects reassociation. Finally, tyrosine phosphorylation appears to be involved in release of pp85 from MTAg, since vanadate increased its rate of dissociation.


Antibiofilm activity of Vetiveria zizanioides root extract against methicillin-resistant Staphylococcus aureus.
Methicillin-resistant Staphylococcus aureus (MRSA) is a leading human pathogen responsible for causing chronic clinical manifestation worldwide. In addition to antibiotic resistance genes viz. mecA and vanA, biofilm formation plays a prominent role in the pathogenicity of S. aureus by enhancing its resistance to existing antibiotics. Considering the role of folk medicinal plants in the betterment of human health from the waves of multidrug resistant bacterial infections, the present study was intended to explore the effect of Vetiveria zizanioides root on the biofilm formation of MRSA and its clinical counterparts. V. zizanioides root extract (VREX) showed a concentration-dependent reduction in biofilm formation without hampering the cellular viability of the tested strains. Micrographs of scanning electron microscopy (SEM) and confocal laser scanning microscopy (CLSM) portrayed the devastating impact of VREX on biofilm formation. In addition to antibiofilm activity, VREX suppresses the production of biofilm related phenotypes such as exopolysaccharide, slime and α-hemolysin toxin. Furthermore, variation in FT-IR spectra evidenced the difference in cellular factors of untreated and VREX treated samples. Result of mature biofilm disruption assay and down regulation of genes like fnbA, fnbB, clfA suggested that VREX targets these adhesin genes responsible for initial adherence. GC-MS analysis revealed the presence of sesquiterpenes as a major constituent in VREX. Thus, the data of present study strengthen the ethnobotanical value of V. zizanioides and concludes that VREX contain bioactive molecules that have beneficial effect over the biofilm formation of MRSA and its clinical isolates.


[The prevalence of sleep related disorders among the drivers and it's relation with traffic accidents].
Studies consistently show that patients with sleep related diseases (SRD) have higher accident rates. Polysomnography (PSG) is the gold standard for the diagnosis of SRD. Sleep habits questionnaires are also useful tool for research of the prevalence of SRD on large populations. The aim of this study is to investigate the prevalence of SRD and SRD related traffic accidents on the whole population of professional drivers in Sivas city. A questionnaire that includes questions about drivers' background such as how long they have been driving, if they had any accidents, and if they drive just in Sivas city or inter state. This questionnaire composed of 50 questions about SRD and was asked to drivers answer them face to face. Three hundred forty male drivers participated for this study. Their mean age was 39.5+/-9.3 (21-68) years. The mean driving duration was 13.3+/-7.9 years. The percentage of drivers who drove in Sivas was 52.1% and 47.9% of the drivers drove inter state. The percentage of drivers who had at least one accident was 36.3%. The prevalence of habitual snoring, insomnia, sleep apnea, nocturnal myoklonus were 41.2%, 39.1%, 32.9%, and 33.6% respectively. The traffic accident Odds ratio was 1.619 for drivers with habitual snoring (95% CI, 1.034 to 2.536, p=0.02). In conclusion, this study found out that drivers with habituel snoring seems to have tendency (approximately 2-folds) of involving in traffic accidents than drivers who do not have habituel snoring. Polysomnography of candidate drivers with sleep disordered symptoms has to be logical before giving to driving license.


BRCA1 and BRCA2 heterozygosity and repair of X-ray-induced DNA damage.
Up to 90% of hereditary breast cancer cases are linked to germ-line mutations in one of the two copies of the BRCA1 or BRCA2 genes. Brca1 and Brca2 proteins are both involved in the cellular defence against DNA damage, although the precise function of the proteins is still not known. Some studies on a small number of samples as well as the present pilot study also suggested that BRCA1 heterozygosity may lead to impaired repair of ionizing-radiation-induced DNA double-strand breaks. The purpose of the study was to test in a larger family-matched study whether carriers of BRCA1 or BRCA2 mutations have an increased sensitivity to ionizing radiation. In a blind study, the effect of different germ-line mutations in one allele of the BRCA1 or BRCA2 gene on the ability to repair X-ray-induced DNA breaks was investigated. Fibroblasts and lymphocytes were taken from heterozygotic individuals (BRCA1+ /- and BRCA2+ /-) with different mutations and from relatives proven to be non-carriers of the BRCA mutations. Rejoining of DNA breaks was analysed by pulsed-field gel electrophoresis (for fibroblasts) or the comet assay (for lymphocytes). Significant interindividual differences were found in the capacities of the fibroblasts and lymphocytes to rejoin DNA breaks induced by X-radiation. However, these differences were not related to heterozygosity in BRCA1 or BRCA2. Cells from carriers of mutations in one allele of the BRCA1 or BRCA2 genes have no gross defects in their ability to rejoin radiation-induced DNA breaks. Hence, these carriers may not be at risk of developing excess normal tissue reactions after radiotherapy consistent with data from recent clinical studies.


Topological charge-density method of identifying phase singularities in cardiac fibrillation.
Spiral waves represent the key motifs of typical self-sustained dynamical patterns in excitable systems such as cardiac tissue. The motion of phase singularities (PSs) that lies at the center of spiral waves captures many qualitative and, in some cases, quantitative features of their complex dynamics. Recent clinical studies suggested that ablating the tissue at PS locations may cure atrial fibrillation. Here, we propose a different method to determine the location of PSs. Starting from the definition of the topological charge of spiral waves, we obtain the expression of the topological charge density in a discrete case. With this expression, we can calculate the topological charge at each grid in the space directly, so as to accurately identify the position of PSs.


The frequency of celiac disease in children with autoimmune thyroiditis.
Although the presence of autoimmune thyroiditis (AT) in celiac disease (CD) has been well documented among adults, CD in AT has been less reported in children. We aimed to investigate the frequency of CD in children with AT. Materials and Methods : This prospective study was carried out from October 2015 to August 2016 and included 66 patients with AT. Firstly, total IgA and tissue transglutaminase antibody (tTG) IgA levels were measured. Those with increased level of tTG IgA were tested for anti-endomysium IgA antibodies (EMA). Patients with positive EMA underwent gastroduodenoscopy for a definitive diagnosis of CD. Sixty-six patients with AT (52 female) with mean age of 14.68 ± 3.18 years were enrolled. IgA deficiency was found in four patients. Only three of 66 patients (4.5%) were positive for tTG IgA. Patients positive for tTG IgA were then tested for EMA, and only one of them (1.5%) had positive EMA antibodies. Gastroduodenoscopy was performed in this patient. The result of pathological investigation was compatible with CD. Furthermore, one patient with AT had been diagnosed with CD previously. Two (3.0%) of 66 patients with AT were found to have CD. According to the results, we assume that there is a close relationship between CD and AT disease. However, there is a need for multicentric, prospective studies that would support our findings.


Local Fluxionality of Surface-Deposited Cluster Catalysts: The Case of Pt7 on Al2O3.
Subnano surface-supported catalytic clusters can be generally characterized by many low-energy isomers accessible at elevated temperatures of catalysis. The most stable isomer may not be the most catalytically active. Additionally, isomers may interconvert across barriers, i.e., exhibit fluxionality, during catalysis. To study the big picture of the cluster fluxional behavior, we model such a process as isomerization graph using bipartite matching algorithm, harmonic transition state theory, and paralleled nudged elastic band method. All the minimal energy paths form a minimum spanning tree (MST) of the original graph. Detailed inspection shows that, at temperatures typical for catalysis, the cluster geometry changes frequently within several regions in the MST, while transition across regions is less likely. As a further confirmation, the structural similarity analysis was additionally performed based on molecular dynamics trajectories. This local fluxionality picture provides a new perspective on understanding finite-temperate catalytic processes.


Sustained hypoxia enhances chondrocyte matrix synthesis.
Articular cartilage is an avascular tissue with chondrocytes in the deeper zones existing under conditions of sustained hypoxia. Using a hypoxic chamber to provide controlled hypoxia, this study was performed to determine whether sustained hypoxia enhances the production of cartilage matrix proteins. Freshly isolated primary bovine articular chondrocytes were encapsulated in three-dimensional alginate beads and maintained at 2% oxygen with media changes using media pre-equilibrated to 2% oxygen. Immunolocalization of HIF-1alpha was performed to verify hypoxic conditions. Sustained hypoxia resulted in an increase in proteoglycan synthesis after only 1 day, as measured by 35S-sulfate incorporation. This increase was maintained for the duration of the 17 day study. After 17 days of hypoxic culture, increases in total type II collagen and COL2A1 gene expression were probed by indirect immunofluorescence, type II collagen ELISA, and real-time qPCR; in addition, increased glycosaminoglycan deposition was observed as determined by chemical analysis. These studies show that sustained hypoxia enhances articular chondrocyte matrix synthesis and viability in three-dimensional alginate culture.


Analgesic Effect of Intra-articular Morphine or Dexmedetomidine Added with Levobupivacaine in Arthroscopic Knee Surgeries - A Comparative Evaluation.
Knee arthroscopy is associated with variable amount of postoperative pain. In an attempt to improve postoperative analgesia, intra-articular injection of local anaesthetic in combination with other agent have been studied. However, the best combination is not known. To compare the analgesic efficacy of intra-articular injection of morphine and dexmedetomidine when added with levobupivacaine in arthroscopic knee surgeries. Seventy eight patients, scheduled to undergo elective arthroscopic procedure under spinal anaesthesia were recruited for the study. All the patients received 18 ml of 0.25% levobupivacaine however in addition to this Group M patients received 8 mg (2 ml) morphine, Group D patients received 100μg (2 ml) of dexmedetomidine while Group C patients received 2 ml of isotonic saline intra-articularly. Postoperatively the intensity of pain was assessed using Numerical Rating Scale (NRS). Rescue analgesia was given at NRS ≥ 4. The duration of analgesia and total diclofenac consumption was noted. The mean duration of analgesia was longest in Group M (576.20±67.09 minutes) followed by Group D (460.93±38.95 minutes) and Group C (370.27±58.80 minutes) statistically this difference was found to be highly significant (p-value < 0.001). Total consumption of diclofenac in 24 hours was found lowest in group M (86.25±27.48 mg) followed by group D (110.87±44.48 mg) and group C (141.35±44.13 mg) this difference was found to be highly significant (p-value < 0.001). Morphine when added with levobupivacaine in patients undergoing arthroscopic knee surgery improves the quality and prolongs the duration of postoperative analgesia.


Affinity parameters of amino acid derivative binding to molecularly imprinted nanospheres consisting of poly[(ethylene glycol dimethacrylate)-co-(methacrylic acid)].
The binding of L-Boc-phenylalanine anilide (BFA) and L-Boc-phenylalanine (phe) to molecularly imprinted and non-imprinted polymer nanoparticles consisting of poly[(ethylene glycol dimethacrylate)-co-(methacrylic acid)] has been investigated by adsorption experiments and mathematical modeling. The experimental isotherms have been mathematically adapted following the models of Freundlich, Langmuir, Langmuir-Freundlich, Bi-Langmuir, and extended Langmuir. The extended Langmuir model differentiated between specific and nonspecific binding of the ligand to the receptor nanoparticles and rendered excellent fitting of the experimental data. It delivered a thermodynamic and kinetic parameter set on the experimental association curves of L-BFA by L-BFA-imprinted nanospheres in suspension experiments with the equilibrium constant KD= 4.09 +/- 0.69 micromol L(-1) and the kinetic association rate constant Ka= 5.60 mL micromol(-1) min(-1).


Study of the Correlation between the Level of CRP and Chemerin of Serum and the Occurrence and Development of DN.
The aim of the study was to find the correlation between CRP and chemerin in development of DN. We choose 90 type-2 diabetic patients between February 2010 and February 2013, who were then divided into DN group and healthy control group. The results of BP showed that there is no difference in SBP and DBP of patients in the three groups. HDL-C of patients in diabetic group and DN group is lower compared with control. CRP in diabetic group and DN group is higher than that of patients in control group. Comparing the patients in DN group with that in diabeteic group, CRP was significantly higher. Chemerin level in the diabetic group and DN group is higher than control group. When comparing the patients in DN group with those in diabeteic group, serum level of chemerin was significantly higher. Serum level of chemerin is negatively correlated with HDL-C and positively correlated with FPG, HbA1c, LDL-C, BUN and Scr. Serum CRP is negatively correlated with HDL-C and positively correlated with FPG, HbA1c, LDL-C, BUN and Scr. Serum level of chemerin is positively correlated with CRP (r=0.701, P<0.05). CRP and chemerin of the DN patients rose significantly, and may participate in the occurrence and development of DN.


The vortex: families' experiences with death in the intensive care unit.
Lack of communication from healthcare providers contributes to the anxiety and distress reported by patients' families after a patient's death in the intensive care unit. To obtain a detailed picture of the experiences offamily members during the hospitalization and death of a loved one in the intensive care unit. A qualitative study with 4 focus groups was used. All eligible family members from 8 intensive care units were contacted by telephone; 8 members agreed to participate. The experiences of the family members resembled a vortex: a downward spiral of prognoses, difficult decisions, feelings of inadequacy, and eventual loss despite the members' best efforts, and perhaps no good-byes. Communication, or its lack, was a consistent theme. The participants relied on nurses to keep informed about the patients' condition and reactions. Although some participants were satisfied with this information, they wishedfor more detailed explanations ofprocedures and consequences. Those family members who thought that the best possible outcome had been achieved had had a physician available to them, options for treatment presented and discussed, andfamily decisions honored. Uncertainty about the prognosis of the patient, decisions that families make before a terminal condition, what to expect during dying, and the extent of a patient s suffering pervade families' end-of-life experiences in the intensive care unit. Families' information about the patient is often lacking or inadequate. The best antidote for families' uncertainty is effective communication.


Cutaneous adverse effects of antiepileptic drugs.
Antiepileptic drugs (AED) are widely used in therapy. They are mainly indicated in the treatment of epilepsy and some psychiatric pathologies as well as for their analgesic action. Their cutaneous adverse effects (CAE) are common, often mild but sometimes serious. The aim of this work was to study the epidemiological and clinical features of CAE occurring in adults and elderly patients (aged over 20 years-old) and to identify the most implicated AED. We conducted a descriptive retrospective study over a period of five years from January 2017 to December 2022 about CAE of AED in adults and elderly patients notified to The National Center Chalbi Belkahia of Pharmacovigilance (Tunis,Tunisia). All cases were analyzed according to the updates French methods of imputability. We collected 71 cases of patients aged over 20 years old who presented CAE to AED. The age ranged from 20 to 79 years (mean age=44.8 years). The sex ratio F/M was 0.7. AED were indicated for neurological pathology in 70.5% of cases, for psychiatric pathology in 15.9% of cases and for their analgesic action in 12.9% of cases. Epilepsy was the first indication (51.1% of cases). The most notified CAE in our study were drug reaction with eosinophilia and systemic symptoms (DRESS syndrome; 34% of cases), maculopapular exanthema (MPE; 26% of cases), erythematous rash (8% of cases) and photosensitivity in 5% of cases. Severe cutaneous adverse reactions were accounted for 37% of all CAE. The most implicated AED were carbamazepine (52%), phenobarbital (24%) and lamotrigine (18%). However, further study with a larger number of patients and in collaboration with prescribing physicians are needed to better clarify features of CAE associated with AED intake and specify the risk factors, specific to our Tunisian population.


Rapid jetting status inspection and accurate droplet volume measurement for a piezo drop-on-demand inkjet print head using a scanning mirror for display applications.
Despite the inherent fabrication simplicity of piezo drop-on-demand inkjet printing, the non-uniform deposition of colourants or electroluminescent organic materials leads to faulty display products, and hence, the importance of rapid jetting status inspection and accurate droplet volume measurement increases from a process perspective. In this work, various jetting status inspections and droplet volume measurement methods are reviewed by discussing their advantages and disadvantages, and then, the opportunities for the developed prototype with a scanning mirror are explored. This work demonstrates that jetting status inspection of 384 fictitious droplets can be performed within 17 s with maximum and minimum measurement accuracies of 0.2 ± 0.5 μm for the fictitious droplets of 50 μm in diameter and -1.2 ± 0.3 μm for the fictitious droplets of 30 μm in diameter, respectively. In addition to the new design of an inkjet monitoring instrument with a scanning mirror, two novel methods to accurately measure the droplet volume by amplifying a minute droplet volume difference and then converting to other physical properties are suggested and the droplet volume difference of ±0.3% is demonstrated to be discernible using numerical simulations, even with the low measurement accuracy of 1 μm. When the fact is considered that the conventional vision-based method with a CCD camera requires the optical measurement accuracy less than 25 nm to measure the volume of an in-flight droplet in the nominal diameter of 50 μm at the same volume measurement accuracy, the suggested method with the developed prototype offers a whole new opportunity to inkjet printing for display applications.