Erythropoietin improves object placement recognition memory in a time dependent manner in both, uninjured animals and fimbria-fornix-lesioned male rats.
An increasing number of reports sustain a possible role of erythropoietin (EPO) as neuroprotective agent. In two previous articles we have evaluated EPO as plasticity promoting agent, and to contribute the restoration of brain function affected by acquired damage. We have shown that EPO is able to induce an increased synaptic efficacy in vivo along with a plasticity promoting effect. In the Morris water maze EPO administration to fimbria-fornix lesioned male rats induces a significant improvement of their spatial memory, affected by the lesion. Singularly, EPO was only effective when administered shortly after training (10 min) but not after several hours (5 h), suggesting a specific EPO effect on time dependent plasticity process. In the present paper we have expanded this line of evidence using a low stress paradigm of object placement recognition in lesioned and healthy male rats. The memory trace in this model is short-lasting; animals could recognize the change in object position when tested 24 h after, but not 48 or 72 h after the acquisition session. EPO administration 10 min after acquisition significantly prolongs retention to, at least, 72 h in healthy rats. No effect was seen if EPO was administered 5 h after training, suggesting a specific EPO modulatory effect on the consolidation process. Remarkably, early EPO treatment to fimbria fornix lesioned animals reverts the memory deficit caused by the lesion. An increased expression of the plasticity related gene arc, was also confirmed in the hippocampus and the prefrontal cortex, that is likely to be involved in the behavioral improvement observed.


Intestinal Enteroids Model Guanylate Cyclase C-Dependent Secretion Induced by Heat-Stable Enterotoxins.
Enterotoxigenic Escherichia coli (ETEC) causes ∼20% of the acute infectious diarrhea (AID) episodes worldwide, often by producing heat-stable enterotoxins (STs), which are peptides structurally homologous to paracrine hormones of the intestinal guanylate cyclase C (GUCY2C) receptor. While molecular mechanisms mediating ST-induced intestinal secretion have been defined, advancements in therapeutics have been hampered for decades by the paucity of disease models that integrate molecular and functional endpoints amenable to high-throughput screening. Here, we reveal that mouse and human intestinal enteroids in three-dimensional ex vivo cultures express the components of the GUCY2C secretory signaling axis. ST and its structural analog, linaclotide, an FDA-approved oral secretagog, induced fluid accumulation quantified simultaneously in scores of enteroid lumens, recapitulating ETEC-induced intestinal secretion. Enteroid secretion depended on canonical molecular signaling events responsible for ETEC-induced diarrhea, including cyclic GMP (cGMP) produced by GUCY2C, activation of cGMP-dependent protein kinase (PKG), and opening of the cystic fibrosis transmembrane conductance regulator (CFTR). Importantly, pharmacological inhibition of CFTR abrogated enteroid fluid secretion, providing proof of concept for the utility of this model to screen antidiarrheal agents. Intestinal enteroids offer a unique model, integrating the GUCY2C signaling axis and luminal fluid secretion, to explore the pathophysiology of, and develop platforms for, high-throughput drug screening to identify novel compounds to prevent and treat ETEC diarrheal disease.


RIGHT-SIDED COLITIS.
The term ;right-sided colitis' has been used to describe a lesion in which the right half of the colon shows maximal inflammatory changes; although the terminal ileum is always involved, the rectum is normal or shows minimal inflammatory changes. Some of these cases appear to be of atypical Crohn's disease, whilst the others resemble chronic ulcerative colitis. The high incidence of Jewish people in this series suggests a racial tendency towards this distribution of the inflammatory change. The right-sided nature of the lesion has led to unnecessarily prolonged medical treatment, to right hemicolectomy, and to ileorectal anastomosis. The results of such procedures have been disappointing, all the more so because the rectum was almost normal and hence would seem ideally suited for ileorectal anastomosis. These patients have progressed very well with ileostomy.


Age changes in motor skills during childhood and adolescence.
Reports dating back to the 1920s have unequivocally established that efficiency of movement improves during infancy and childhood, and generally through adolescence. The inclination from 1940 to 1960 to record movement in quantitative values has given way during the last two decades to a reemphasis of qualitative assessment. Investigators commonly agree that movement skills change in an orderly manner, but controversy continues over the degree of accuracy obtainable with the various descriptive forms, and over the utility of products resulting from such assessments. Comparison of the quantitative changes in movement skills of children is difficult because standardized procedures of test administration have not been applied. When comparisons are possible because of similar or identical testing protocols, improvement in selected motor tests is evident in both boys and girls until adolescence. At approximately 13 years of age the performance of girls in some tests reaches a plateau, and may even decline thereafter, while boys continue to improve in skills requiring strength, power, and muscular endurance. Exceptions to these generalizations occurred in arm and shoulder girdle muscular endurance, as measured by the flexed-arm hang, where boys had superior performances beginning at age 7, and in flexibility, as measured by the sit and reach test, where girls excelled at age 5 and thereafter. Stability of motor performance was greater for tasks that required all-out effort than for those emphasizing accuracy or total body coordination. Relationships between successive measures taken during early and middle childhood are likely to decline more rapidly than those taken after adolescence. Girls generally were more stable in motor performance than boys, except in the Motor Performance Study, where the values for boys across a range of 5 to 6 years were clearly more stable. This review underscores the need for careful documentation of the conditions under which data on motor performance are obtained. Numerous reports were examined and excluded by the authors because information that would have qualified the data for comparative analysis was not available. Essential ingredients in such reports are descriptions of the sampling techniques and the manner of calculating chronological ages, socioeconomic status, ethnic and racial characteristics, evidence of secular changes, geographic and environmental characteristics, and a detailed account of the testing procedures. Differences in maturational age for a given chronological age, and accompanying assumptions about body size, may account for differences in motor skills that might otherwise be attributed to changes in p


Hematological malignancies during pregnancy.
Hematological malignancy during pregnancy is a rare event, therefore most data on this issue is based on case studies, retrospective studies and expert opinion. The purpose of the present narrative review was to provide an overview of the diagnosis and recommended management of the most common hematological malignancies during pregnancy, based on current literature, with clinical cases, and discussion of the diagnostic and therapeutic options. The therapeutic consensus while coping with hematological malignancies in pregnancy is to salvage the mother, while trying to preserve pregnancy and avoid treatment-related-toxicity to the fetus. In most scenarios, particularly during late trimesters, the goal is to administer the same treatment as outside of pregnancy, if possible. Further research is needed for better evidence-based management.


The humoral response of mouse spleen cells to two types of sheep erythrocytes. I. Genetic control of the response to H and L SRBC.
Some strains of mice discriminate between two types of sheep erythrocytes (H or L-SRBC) and others do not. It is proposed that there are shared antigen(s) common to both H and L extra antig(s) present only in H. It shown that individual clones of antibody-forming cells make antibody to either the shared or extra antigens. These antigenic differences are not found to correlate with any of the known major sheep erythrocyte antigens. The genetic control of the ability to discriminate between these two types of red cell was investigated by an analysis of response of F1, F2 and backcross mice. The results suggest that the response is under multigene control. BL/6 mice give high responses to the extra antigens and low responses to the shared (high discriminator). DBA/2 gives high responses to the extra antigen (nondiscriminator). F1 mice give high responses to both extra and shared antigen but still discriminate between the two types of erythrocytes (low discriminator). Additional phenotypes appear in the F2 and backcross mice.


Identification of greA encoding a transcriptional elongation factor as a member of the carA-orf-carB-greA operon in Pseudomonas aeruginosa PAO1.
A homolog of the transcriptional elongation factor, GreA, was identified in Pseudomonas aeruginosa PAO1. The deduced amino acid sequence for GreA from this organism exhibits 65.2% identity to its counterpart in Escherichia coli K-12. The nucleotide sequence of greA from P. aeruginosa overlaps by four bases the 3' terminus of carB which encodes the large subunit of carbamoylphosphate synthetase. S1 nuclease experiments showed that level of the greA transcript is elevated approximately 10-fold under conditions of pyrimidine limitation, consistent with the conclusion that transcription is initiated from the previously identified pyrimidine-sensitive promoter upstream of the carA-orf-carB-greA operon. Transcriptional fusion experiments showed the presence of an additional weak promoter within the carB sequence. A greA insertional mutant of Pseudomonas aerugionsa was constructed by gene replacement. The mutant derivative grew well in rich medium but did not grow in minimal medium supplemented by arginine and nucleosides. The greA phenotype was suppressed by secondary mutations at a relatively high rate, consistent with the notion of an important physiological role for GreA.


Impact of Selenium Supplementation in Neutropenia and Immunoglobulin Production in Childhood Cancer Patients.
Essential to human health, selenium (Se) has enzymatic functions of fundamental importance to human biology due to its effects on DNA damage repair, its antioxidant properties, and cancer prevention. The best studied relationships between Se and the immune system is its role in the functions of neutrophils and of lymphocytes. Despite these observations, it is not yet clear by which mechanism Se is able to modify the immune status. This was a double-blind, crossover study: Group 1 received Se and Group 2 received placebo (30 days). After this, Group 1 received placebo and Group 2 received Se (30 days). Every 30 days, blood samples were collected for white blood cell count, red blood cell count, and Ig level measurement (IgA, IgG, IgE, IgM). Of the 36 patients, 17 were suffering from leukemia/lymphomas (LL) and 19 from solid tumors (ST). In the ST group's leukogram, a significant increase in neutrophils was observed after Se usage (P = .0192). During the analyzed period, Se minimized the triggering of neutropenia cases in both groups. IgA and IgG levels in ST patients were significantly higher than those identified in LL patients after Se usage (P = .0051 and P = .0055). For IgA, a significant increase in its production, after Se usage, was observed in the ST group when compared to the LL (P = .0011). The same did not occur to the IgM and IgE immunoglobulins. In our study, the supplementation with Se reduced the neutropenic cases (LL and ST patients) and reduced IgG and IgA levels in LL and increased in ST group.


Review of salvage therapy for biochemically recurrent prostate cancer: the role of imaging and rationale for systemic salvage targeted anti-prostate-specific membrane antigen radioimmunotherapy.
Despite local therapy with curative intent, approximately 30% of men suffer from biochemical relapse. Though some of these PSA relapses are not life threatening, many men eventually progress to metastatic disease and die of prostate cancer. Local therapy is an option for some men, but many have progression of disease following local salvage attempts. One significant issue in this setting is the lack of reliable imaging biomarkers to guide the use of local salvage therapy, as the likely reason for a low cure rate is the presence of undetected micrometastatic disease outside of the prostate/prostate bed. Androgen deprivation therapy is a cornerstone of therapy in the salvage setting. While subsets may benefit in terms of delay in time to metastatic disease and/or death, research is ongoing to improve salvage systemic therapy. Prostate-specific membrane antigen (PSMA) is highly overexpressed by the majority of prostate cancers. While initial methods of exploiting PSMA's high and selective expression were suboptimal, additional work in both imaging and therapeutics is progressing. Salvage therapy and imaging modalities in this setting are briefly reviewed, and the rationale for PSMA-based systemic salvage radioimmunotherapy is described.


Flocculation of low algae concentration water using polydiallyldimethylammonium chloride coupled with polysilicate aluminum ferrite.
The combined application of polydiallyldimethylammonium chloride (PDADMAC) and polysilicate aluminum ferrite (PSFA) was investigated to treat low algae density water samples, in which Microcystis aeruginosa is one of the dominant species. coagulation performance of M. aeruginosa was studied with regard to algal removal, Algal density was evaluated by determining the change in the optical density of the algal culture suspension at 680 nm and chlorophyll a. The dissolved organic matter, cellular morphology, viability, and recovery of M. aeruginosa cells after flocculation and sedimentation were also included. In addition, the effects of pH and addition order of PSFA and PDADMAC on algal removal were investigated. The removal efficiency of algae coagulated using combined PDADMAC and PSFA was improved by 34.5% and 19.3%, respectively. The organic matter removal was also enhanced. The optimum pH range for algal removal is 7.0-10.0, and the preferable addition sequence is the simultaneous addition of PDADMAC and PSFA. Scanning electron microscopy observation indicated that the combined usage of PDADMAC and PSFA caused no damage to the algal cell. Moreover, the experiment on algal recovery demonstrated that PDADMAC has bacteriostatic ability.


Oxidative damage in alveolar macrophages exposed to cigarette smoke extract and participation of nitric oxide in redox balance.
Nitric oxide (NO) acts in both pathological and biological processes. We investigated the role of NO in the regulation of cigarette smoke-induced oxidative stress in rat alveolar macrophages (RAM). RAM collected from Wistar rats were cultured in 5% concentration cigarette smoke extract (CSE) for 1h. RAM exposed to CSE were then co-incubated with L-NAME (LN), L-arginine (LA), N-acetylcysteine (NAC) and both LN and NAC. RAM cultured only with medium was considered as control group. Biochemical analysis were performed to measure cellular metabolism (MTT), nitrite levels, superoxide dismutase (SOD) and glutathione peroxidase activities, reduced glutathione (GSH) and oxidized (GSSG), malondialdehyde and myeloperoxidase activity. During exposure to CSE, increased NO levels were not only associated with an increase of cell activation, but also affected MTT levels in RAM. CSE exposure resulted in significant redox imbalance in RAM. NAC administration affected SOD antioxidant profile regardless NO levels; however nitrite values were associated with GSH/GSSG ratio. In addition, lipid peroxidation appeared to be nitric-oxide dependent. Furthermore, the use of NAC significantly reduced the expression of NFkB normally observed in RAM exposed to CSE. The present results show that NO appeared to be involved in RAM activation, oxidative status maintenance and lipid peroxidation process during exposure to CSE.


Tear Cytokine Levels in Sicca Syndrome-Related Dry Eye: A Meta-Analysis.
Sjogren's syndrome (SS) is an autoimmune disease that affects exocrine glands, mainly salivary and lacrimal glands. Several studies have investigated cytokine profiles in tears in order to understand the pathogenesis of SS and find additional diagnostic markers. This systematic review and meta-analysis aimed to analyze cytokines in tears of SS patients. A systematic literature search of the Cochrane, Medline via PubMed, Scopus, and Web of Science databases was conducted using key terms related to "Sjögren's syndrome" and "tears" combined with "biomarker", "cytokines", "interleukin", and "chemokines", following PRISMA guidelines. Article selection was subjected to certain eligibility criteria. A total of 17 articles (from 1998 and 2022) were selected for the quantitative and qualitative analysis. When compared to controls, concentrations of IFN-γ, TNF-α, IL-1α, IL-1 Ra, IL-4, IL-6, IL-8, IL-10, IL-17, IL-21 and IL-22 were consistently higher; however, IL-23 was significantly lower in patients with SS compared to the controls. Tear levels of some cytokines were significantly elevated among SS groups compared to control groups. Therefore, these cytokines could be potential biomarkers of SS. However, standardization of sample collection and analytical methods is necessary in order to translate these findings into clinical practice.


Brief communication: intraperitoneal galactosamine misdosing as a possible interpretation for responder/nonresponder phenotypes.
Previous reports investigating the mechanisms of galactosamine toxicity have discussed the presence of responders and nonresponders after intraperitoneal (IP) administration of a toxic dose. The incidence of nonresponders has been reported to be as high as 47%. To rule out inadvertent intestinal, solid organ, or subcutaneous injection as at least a partial cause for the variability, we performed midline incisions and dosed 10 rats via a flexible catheter, with a toxic dose of galactosamine. Results were compared to a previous range finding study with IP-injected rats. As opposed to the IP-injected rats that had a roughly 50% response rate (based on serum alanine aminotransferase [ALT] elevation) and 100% of the midline incision catheter-instilled rats had elevations in ALT. Saline controls had no elevations. Histopathologic examination of livers from 5 midline-incisioned rats euthanized 48 hr after dosing with the lowest ALT responses revealed portal eosinophilic infiltrates and biliary hypertrophy/hyperplasia contiguous with areas of necrosis. Examination of 5 rats with the highest ALT elevations euthanized 10 days post dose revealed similar lesions to be resolving. We conclude that a significant contribution to variability in response to IP-injected galactosamine and possibly other investigative drugs is inadvertent misinjection of all or part of the dose.


Inhibitory neurotransmission in the nucleus tractus solitarii: implications for baroreflex resetting during exercise.
Inhibitory neurotransmission plays a crucial role in the processing of sensory afferent signals in the nucleus of the solitary tract (NTS). The aim of this review is to provide a critical overview of inhibitory mechanisms that may be responsible for altering arterial baroreflex function during physical activity or exercise. Over a decade ago, the view of reflex control of cardiovascular function during exercise was revised because of the finding that the arterial baroreflex is reset in humans, enabling continuous beat-to-beat reflex regulation of blood pressure and heart rate. During the ensuing decade, many investigators proposed that resetting was mediated by central neural mechanisms that were intrinsic to the brain. Recent experimental data suggest that rapid and reversible changes in gamma-aminobutyric acid (GABA) inhibitory neurotransmission within the NTS play a fundamental role in this process. The hypothesis will be presented that baroreflex resetting by somatosensory input is mediated by: (1) selective inhibition of barosensitive NTS neurones; and (2) excitation of sympathoexcitatory neurones in the rostral ventrolateral medulla. Current research findings will be discussed that support an interaction between GABA and substance P (SP) signalling mechanisms in the NTS. An understanding of these mechanisms may prove to be essential for future detailed analysis of the cellular and molecular mechanisms underlying sensory integration in the NTS.


Determinants of intravascular resistance in Indian diabetic nephropathy patients: a hospital-based study.
Aims and Objectives. Metabolic dysregulation has failed to explain clinical variability of patients with diabetic nephropathy and hence a renewed interest emerged in haemodynamic factors as determinant of progression and development of diabetic nephropathy. We therefore studied for various factors which can correlate with raised renal vascular resistance in diabetic nephropathy. Material and Methods. Renal vascular resistance was measured in patients with established and incipient diabetic nephropathy and compared with controls using noninvasive color Doppler examinations of intrarenal vasculature. Results. Renal vascular resistance correlated with age, duration of disease, GFR, serum creatinine, and stage of retinopathy. Renal vascular resistance was significantly reduced in patients on treatment with RAAS inhibitors and insulin, than those on OHA and antihypertensives other than RAAS inhibitors. Conclusion. The study implies that renal vascular resistance may help identify diabetics at high risk of developing nephropathy, and these set of patients could be candidates for RAAS inhibition and early insulin therapy even in patients without albuminuria.


Epidemiology of Helicobacter pylori infection among the healthy population in Iran and countries of the Eastern Mediterranean Region: a systematic review of prevalence and risk factors.
To investigate the epidemiology of Helicobacter pylori (H. pylori) infection among the healthy asymptomatic population in Iran and countries of the Eastern Mediterranean Region. A computerized English language literature search of PubMed, ISI Web of Science, Scopus, and Google Scholar was performed in September 2013. The terms, "Eastern Mediterranean Regional Office (EMRO)" and "Helicobacter pylori", "H. pylori" and "prevalence" were used as key words in titles and/or abstracts. A complementary literature search was also performed in the following countries: Afghanistan, Bahrain, Djibouti, Egypt, Iran, Iraq, Jordan, Kuwait, Lebanon, Libya, Morocco, Oman, Pakistan, Palestine, Qatar, Saudi Arabia, Somalia, Sudan, Syria, Tunisia, The United Arab Emirates, and Yemen. In the electronic search, a total of 308 articles were initially identified. Of these articles, 26 relevant articles were identified and included in the study. There were 10 studies from Iran, 5 studies from the Kingdom of Saudi Arabia, 4 studies from Egypt, 2 from the United Arab Emirates, and one study from Libya, Oman, Tunisia, and Lebanon, respectively. The overall prevalence of H. pylori infection in Iran, irrespective of time and age group, ranged from 30.6% to 82%. The overall prevalence of H. pylori infection, irrespective of time and age group, in other EMRO countries ranged from 22% to 87.6%. The prevalence of H. pylori in EMRO countries is still high in the healthy asymptomatic population. Strategies to improve sanitary facilities, educational status, and socioeconomic status should be implemented to minimize H. pylori infection.


Research on How Emotional Expressions of Emotional Labor Workers and Perception of Customer Feedbacks Affect Turnover Intentions: Emphasis on Moderating Effects of Emotional Intelligence.
Previous studies have used various external variables and parameters as well as moderator variables such as emotional intelligence have been to understand emotional labor and its related problems. However, a comprehensive model to study such variables' correlations with each other and their overall effect on emotional labor has not yet been established. This study used a structural equation model to understand the relationship between employees' expression of emotional labor and perception of customer feedbacks. The study also looked at how the perception of customer feedback affects emotional exhaustion in order to understand how emotional exhaustion affects job satisfaction and turnover intentions. Further, in order to fully understand the effects of emotion on emotional labor at the service contact points, this study developed and tested a model of emotional labor with four factors of emotional intelligence as moderating factors. Five hundred and seventy nine emotional labor workers in service industries in the United States were collected and 577 valid survey results have been analyzed. The result shows that there exists moderating effects of emotional intelligence on how employees' Deep Acting and Surface Acting recognize customers' reactions, both positive and negative, that would affect employees' Emotional Exhaustion and Job Satisfaction, and hence, Turnover Intention. The result suggests that employees with better understanding of their own emotions, although they are more likely to recover from emotional exhaustion, experience a greater negative effect when there is a discrepancy between what they feel and how they should act.


[Nevoid basal cell carcinoma syndrome].
Nevoid Basal Cell Carcinoma Syndrome (NBCCS) is an autosomal-dominant disorder characterized by multiple basal cell carcinomas, jaw cysts, palmar/plantar pits, calcification of the falx cerebri, and spine and rib anomalies. The combination of clinical, imaging, and histological findings is helpful in identifying NBCCS patients. Imaging plays a crucial role in evaluation of these patients. We present a wide variety of clinical and radiological findings characteristic of this disease.


Localization of abnormal parathyroid tissue with use of technetium-99m-sestamibi.
To evaluate the efficacy of "double-phase" technetium-99m-sestamibi scanning in the localization of abnormal parathyroid tissue in patients with hyperparathyroidism. We present a prospective review of patients with hyperparathyroidism seen at a university teaching hospital between June 1994 and May 1997. Twenty-four patients entered into the study underwent preoperative localization with double-phase technetium-99m-sestamibi. The nuclear medicine results were compared with the operative findings. The Tc-99m-sestamibi scan correctly identified the location of single parathyroid adenomas in 22 patients (100%). Of the other two patients, both with diffuse parathyroid hyperplasia, one had a negative sestamibi scan and one had only the two inferior parathyroid glands localized on the sestamibi scan. One patient with recurrent hypercalcemia, who previously underwent total parathyroidectomy and parathyroid autotransplantation into the left forearm, had activity localized to that forearm but not to the neck. Subsequently, hyperplastic parathyroid tissue was successfully removed from the transplantation site. Another patient, who had previously undergone two unsuccessful surgical explorations prompted by hyperparathyroidism, had sestamibi localization of an adenoma inferior and medial to the right submandibular gland. The third surgical exploration disclosed a large adenoma medial to the carotid artery, just below the angle of the jaw. In two elderly, debilitated women with positive scans, adenomas were removed with use of local anesthesia. Of 22 patients in whom long-term follow-up was available, 21 remained normocalcemic for a mean period of 11.4 +/- 1.7 months postoperatively. One patient in whom hyperplastic parathyroid tissue had been removed from the left forearm had recurrence of hypercalcemia 1 year after operation. Technetium-99m-sestamibi scanning is a reliable method for identifying parathyroid adenomas but not as helpful in localizing hyperplastic parathyroid glands. The precise localization of an adenoma simplifies surgical exploration and in selected patients may allow excision of the adenoma under local anesthesia. Tc-99msestamibi scanning has become the preferred method for noninvasive localization of abnormal parathyroid glands.


Paradoxical hypotension and bradycardia after intravenous arginine vasopressin.
Standard therapy for variceal bleeding includes endoscopic sclerotherapy and esophageal balloon tamponade. In addition, pharmacologic therapies, including arginine vasopressin (AVP), are frequently used in hemodynamically unstable patients or where sclerotherapy has been unsuccessful. A case is described herein of a 30-year-old woman with a history of ethanol abuse, hematemeisis, and biopsy-proven hepatic cirrhosis in which the addition of AVP to an antivariceal regimen of octreotide was associated with a paradoxical episode of hypotension, bradycardia, and hypoxia. Indeed, within 15 minutes after initiation of an AVP infusion, the patient exhibited hypotension with a systolic blood pressure of 80 mmHg, a relative bradycardia to 76 beats per minute, and a desaturation of blood oxygen to 84%. The AVP infusion was discontinued 2 hours later and blood pressure, heart rate, and oxygen saturation rapidly returned to baseline. This temporal correlation between the onset and termination of the physiologic effects and the initiation and discontinuation of the AVP infusion suggests a causal relationship. The paradoxical physiologic effects might reflect cardiac ischemia secondary to vasospasm and/or central suppression of the autonomic nervous system induced by AVP.


Detection of disease-causing mutations in prostate cancer by NGS sequencing.
Gene mutations may affect the fate of many tumors including prostate cancer (PCa); therefore, the research of specific mutations associated with tumor outcomes might help the urologist to identify the best therapy for PCa patients such as surgical resection, adjuvant therapy or active surveillance. Genomic DNA (gDNA) was extracted from 48 paraffin-embedded PCa samples and normal paired tissues. Next, gDNA was amplified and analyzed by next-generation sequencing (NGS) using a specific gene panel for PCa. Raw data were refined to exclude false-positive mutations; thus, variants with coverage and frequency lower than 100× and 5%, respectively were removed. Mutation significance was processed by Genomic Evolutionary Rate Profiling, ClinVar, and Varsome tools. Most of 3000 mutations (80%) were single nucleotide variants and the remaining 20% indels. After raw data elaboration, 312 variants were selected. Most mutated genes were KMT2D (26.45%), FOXA1 (16.13%), ATM (15.81%), ZFHX3 (9.35%), TP53 (8.06%), and APC (5.48%). Hot spot mutations in FOXA1, ATM, ZFHX3, SPOP, and MED12 were also found. Truncating mutations of ATM, lesions lying in hot spot regions of SPOP and FOXA1 as well as mutations of TP53 correlated with poor prognosis. Importantly, we have also found some germline mutations associated with hereditary cancer-predisposing syndrome. gDNA sequencing of 48 cancer tissues by NGS allowed to detect new tumor variants as well as confirmed lesions in genes linked to prostate cancer. Overall, somatic and germline mutations linked to good/poor prognosis could represent new prognostic tools to improve the management of PCa patients.


Personalized Dosimetry for Radionuclide Therapy Using Molecular Imaging Tools.
For treatment of systemic malignancies, when external radiation therapy is not applicable, radionuclide therapy can be an alternative. In this form of therapy, radionuclides are administered to the patient, often in a form where the radionuclide is labelled to a molecule that plays the active part in the localization of the tumor. Since the aim is to impart lethal damage to tumor cells while maintaining possible side-effects to normal tissues at tolerable levels, a proper and accurate personalized dosimetry should be a pre-requisite. In radionuclide therapy, there is a need to measure the distribution of the radiopharmaceutical in vivo, as well as its re-distribution over time, in order estimate the total energy released in radioactive decays and subsequent charged-particle interactions, governing the absorbed dose to different organs and tumors. Measurements are usually performed by molecular imaging, more specifically planar and SPECT (Single-Photon Emission Computed Tomography) imaging, combined with CT. This review describes the different parts in the dosimetry chain of radionuclide therapy. Emphasis is given to molecular imaging tools and the requirements for determining absorbed doses from quantitative planar and SPECT images. As example solutions to the different problems that need to be addressed in such a dosimetric chain, we describe our tool, Lundadose, which is a set of methods that we have developed for personalized dosimetry.


The role and treatment of inflammation in dry eye disease.
Dry eye syndrome is a common ocular surface problem, affects 10-30 % of the population, especially in those who are older than 40 years. As a consequence of the demographic pressure created by the aging population, its prevalence is expected to increase as well as its burden on ophthalmologic practices. Thus, understanding the complex underlying mechanisms and development of thoughtful, effective strategies that involve these mechanisms are critical. Many factors causing ocular surface damage and inflammation have been shown to contribute to the etiopathogenesis. Increased osmolarity induces ocular surface inflammation leading to disruption of both the quality and quantity of tears. Pathologic tear function and the ocular surface inflammation affects the neural arcade and increases apoptosis in the ocular surface cells thus creating a viscous cycle for dry eye by causing unstable and hyperosmolar tears. Thus, the treatment objective is to prevent severe dry eye complications via preventing inflammation and apoptosis of the ocular surface cells. The ultimate target is a normalized ocular surface, increased tear stability, and decreased osmolarity of the tear film. In the light of current literature, this review aims to elucidate the role of inflammation as the main etiological factor in dry eye disease and discuss current therapeutic approaches to overcome it.


Effects of electroacupuncture combined with interleukin‑10 on chronic sinusitis in mice.
Electroacupuncture (EA) has been documented as a form of therapy for chronic sinusitis (CRS). The present study aimed to assess the effects of EA combined with interleukin‑10 (IL‑10) overexpression on CRS in mice, and to investigate the associated mechanisms. A mouse model of CRS was established by the administration of ovalbumin (OVA), and overexpression of IL‑10 was induced using virus‑encoded IL‑10. The experimental groups were as follows: i) Control group; ii) OVA group; iii) OVA + EA group; iv) OVA + empty vector group; v) OVA + vector + EA group; vi) OVA + IL‑10 group; and vii) OVA + IL‑10 + EA group. Pathological changes and nasal mucus were analyzed using hematoxylin and eosin staining. Interferon‑γ (IFN‑γ) and IL‑10 were detected via reverse‑transcription quantitative PCR and western blot analyses. The pseudostratified epithelium of the mucosa of the nasal sinus was impaired following the induction of CRS. Treatment with EA and/or IL‑10 reversed the injury. Combination treatment with EA and IL‑10 induced synergistic effects. No infiltration of inflammatory cells was observed in the submucosa following EA and IL‑10 treatment. Compared with the control group, the expression of IFN‑γ and IL‑10 in the OVA group was reduced. By contrast, EA or the overexpression of IL‑10 inhibited this reduction. Furthermore, the combined application of EA and IL‑10 had a significantly more potent inhibitory effect on the reduction of IFN‑γ expression, but not IL‑10. Collectively, EA combined with IL‑10 induced specific effects on CRS in mice, likely through the upregulation of IFN‑γ and IL‑10. The current study presented mechanistic implications for the application of EA as an alternative treatment for CRS.


Intramural hematoma of the cecum: report of two cases.
Intramural hematoma of the cecum is a rare complication of blunt abdominal trauma. We report two patients who presented with cecal hematoma after a fall and a traffic accident, respectively. Diagnosis was by abdominal computed tomographic scan. Patients were operated on 24 and 36 hours after the injury because of sudden clinical deterioration and hemoperitoneum, respectively. The patients had a large cecal intramural hematoma that progressed to the ascending colon by dissection of the teniae coli. Emergency right hemicolectomy was followed by uneventful recovery in both patients. Only six previously reported cases of cecal intramural hematoma were found, and in all cases a right hemicolectomy was performed. In conclusion, in contrast to hematomas located in other sections of the gastrointestinal tract, early surgical treatment for intramural hematoma of the cecum is recommended.


The use of estrogen in older women.
The menopause is associated with a relatively abrupt decline in the ovarian production of estrogen that results in a state of estrogen deficiency. This estrogen deficiency state is associated with an accelerated expression of cardiovascular disease, osteoporosis, urogenital atrophy, dermal aging, an increased expression of colorectal cancer, an alteration in the expression of breast cancer that results in more malignant forms of the disease, and the loss of neurons from the brain that is associated with a more rapid decline in cognitive function, balance, and an earlier expression of Alzheimer's disease. Macular degeneration and cataract formation may be additional consequences of the estrogen deficiency state. Thus the estrogen deficiency state may be characterized as a state of accelerated aging. The abrupt transition from the reproductive state of multiple estrogen-dependent neural systems within the brain may affect their function as manifested by the typical menopausal symptoms of hot flashes, mood changes, sleep disturbance, and cognitive impairment. This transition may trigger a cascade of events that contributes to the acceleration of brain aging and the expression of neurodegenerative processes as Alzheimer's disease. This article discusses the use of estrogen to prevent these age-related changes.


Enhancement of Focused Liquid Jets by Surface Bubbles.
We investigate the enhancement of the velocity of focused liquid jets by surface bubbles preformed on the inner surface of the container. The focused jets are created from the impact on a liquid-filled cylindrical tube at cavitation numbers of 0.37 (strong impact where cavitation is likely to occur on unprocessed surfaces) and 2.1 (weak impact where cavitation does not occur from the impact). The bubbles with a base diameter up to hundreds of micrometers were formed via the process of solvent exchange using air-equilibrated ethanol and water. Our measurements by high-speed imaging show that at both cavitation numbers, the jet velocities with preformed bubbles are significantly higher than those without preformed bubbles. Furthermore, our results show that after the process of solvent exchange, a large number of expanding bubbles are observed at cavitation number of 0.37, indicating that possibly both sub-millimeter and sub-micrometer bubbles on the surface contribute to the jet velocity enhancement. At the cavitation number of 2.1, the surface bubbles are observed to oscillate immediately after the impact. The measurements of the liquid pressure after the impact reveal that at both cavitation numbers, the negative pressure is damped by the preformed surface bubbles, contributing to the increase of the jet velocity. This work sheds light on the crucial role of surface bubbles on the impulsive motion of liquids. Our findings have significant implications for the focusing jet technology, opening the opportunities for jetting fragile samples such as biological samples.


Immunodeficiencies associated with sulphasalazine therapy in inflammatory arthritis.
Abnormalities in serum immunoglobulin levels (Igs) are documented in a series of 350 patients with rheumatoid arthritis (RA) and other inflammatory joint diseases treated with sulphasalazine (SASP) for up to 10 years. Low Ig levels occurred in just over 10% of patients after therapy. Three per cent developed selective IgA deficiency between 8 and 20 weeks after starting SASP. Low IgG levels occurred in 2% at 4-52 weeks and low IgM levels in 5% after 3-7 months. One per cent developed panhypogammaglobulinaemia (hypo gamma) 3-7 months after commencing therapy. Most immunodeficiencies were not accompanied by other toxic reactions and SASP was continued in all but one patient with a rash and thrombocytopenia. A good clinical response was observed in most patients particularly those with selective IgA deficiency and hypo gamma. Two patients with hypo gamma developed chest infections which responded to antibiotics. A low level of individual Igs is not usually an indication to stop SASP unless accompanied by other reactions. Panhypo gamma is potentially serious and should be monitored carefully and replacement therapy should be considered in these patients if infections occur.


Effects of Dietary Resistant Starch on the Wnt Signaling Pathway and Preneoplastic Cells in the Colons of Azoxymethane-Treated Rats.
Dietary resistant starch (RS) has been suggested to reduce colonic neoplasia. To determine the effects of digestion-resistant cornstarch on colonic carcinogenesis and Wnt signaling in azoxymethane (AOM)-treated F344 rats, diets containing naturally occurring RS from corn lines derived partially from Guat209 (GUAT), AR16035 (AR), or a hybrid (ARxGUAT), containing 34.5 ± 2.0, 0.2 ± 0.1, and 1.9 ± 0.1% RS, respectively, were fed at 55% of the diet. GUAT-fed rats had increased cecal content and tissue weight and decreased cecal pH compared with AR- or ARxGUAT-fed rats. Numbers of aberrant crypt foci (ACF) were not different among diet groups. Increased numbers of crypts/focus were observed in AOM-injected rats fed GUAT compared with rats fed other diets. β-catenin mRNA expression of the crypts was significantly increased in GUAT-fed rats injected with AOM relative to those injected with saline. These findings suggest that selected dietary RSs may at some level further enhance colonocyte proliferation and differentiation in an AOM-treated colon.


Palatal flap in bilateral inferior partial maxillectomy.
Maxillectomy is done for a variety of disease conditions. Reconstruction following maxillectomy is done to restore the form and function. One of the important goals that are to be achieved in reconstruction is the separation of the oral and nasal cavities. In this article, we report the use of palatal flap by preserving the descending palatine artery during bilateral inferior partial maxillectomy, for separating the nasal cavity from the oral cavity. This technique eliminates the need for an obturator or another free or local flap for this purpose.


Curculigo orchioides Gaertn Effectively Ameliorates the Uro- and Nephrotoxicities Induced by Cyclophosphamide Administration in Experimental Animals.
Background Curculigo orchioides Gaertn is an ancient medicinal plant (Family: Amaryllidaceae), well known for its immunomodulatory and rejuvenating effects. Cyclophosphamide (CPA) is an alkylating agent widely used for treating a variety of human malignancies, but associated with different toxicities too. Our previous reports regarding the hemoprotective and hepatoprotective effects of the plant against CPA toxicities provide the background for the present study, which is designed to analyze the ameliorative effect of the methanolic extract of C orchioides on the urotoxicity and nephrotoxicity induced by CPA. Methods CPA was administered to male Swiss albino mice at a single dose of 1.5 mmol/kg body weight to induce urotoxicity after 5 days of prophylactic treatment with C orchioides extract (20 mg/kg body weight). Mesna (2-mercaptoethanesulfonate) was used as a control drug. Serum, tissue, and urine levels of kidney function markers and antioxidant levels were checked along with the serum cytokine levels. Results The plant extract was found to be effective in ameliorating the urotoxic and nephrotoxic side effects of CPA. Upregulation of serum interferon-γ and interleukin-2 levels were observed with C orchioides treatment, which was decreased by CPA administration. Besides these, serum tumor necrosis factor-α level was also downregulated by C orchioides treatment. Conclusion Curculigo orchioides was found to be effective against the CPA-induced bladder and renal toxicities by its antioxidant capability and also by regulating the pro-inflammatory cytokine levels.


Metacaspase-binding peptide inhibits heat shock-induced death in Leishmania (L.) amazonensis.
Leishmania (Leishmania) amazonensis is an important agent of cutaneous leishmaniasis in Brazil. This parasite faces cell death in some situations during transmission to the vertebrate host, and this process seems to be dependent on the activity of metacaspase (MCA), an enzyme bearing trypsin-like activity present in protozoans, plants and fungi. In fact, the association between MCA expression and cell death induced by different stimuli has been demonstrated for several Leishmania species. Regulators and natural substrates of MCA are poorly known. To fulfill this gap, we have employed phage display over recombinant L. (L.) amazonensis MCA to identify peptides that could interact with the enzyme and modulate its activity. Four peptides were selected for their capacity to specifically bind to MCA and interfere with its activity. One of these peptides, similar to ecotin-like ISP3 of L. (L.) major, decreases trypsin-like activity of promastigotes under heat shock, and significantly decreases parasite heat shock-induced death. These findings indicate that peptide ligands identified by phage display affect trypsin-like activity and parasite death, and that an endogenous peptidase inhibitor is a possible natural regulator of the enzyme.


Comparative transcriptomic analysis of the response to cold acclimation in Eucalyptus dunnii.
Eucalyptus dunnii is an important macrophanerophyte with high economic value. However, low temperature stress limits its productivity and distribution. To study the cold response mechanisms of E. dunnii, 5 cDNA libraries were constructed from mRNA extracted from leaves exposed to cold stress for varying lengths of time and were evaluated by RNA-Seq analysis. The assembly of the Illumina datasets was optimized using various assembly programs and parameters. The final optimized assembly generated 205,325 transcripts with an average length of 1,701 bp and N50 of 2,627 bp, representing 349.38 Mb of the E. dunnii transcriptome. Among these transcripts, 134,358 transcripts (65.4%) were annotated in the Nr database. According to the differential analysis results, most transcripts were up-regulated as the cold stress prolonging, suggesting that these transcripts may be involved in the response to cold stress. In addition, the cold-relevant GO categories, such as 'response to stress' and 'translational initiation', were the markedly enriched GO terms. The assembly of the E. dunnii gene index and the GO classification performed in this study will serve as useful genomic resources for the genetic improvement of E. dunnii and also provide insights into the molecular mechanisms of cold acclimation in E. dunnii.


Methylammonium-free, high-performance, and stable perovskite solar cells on a planar architecture.
Currently, perovskite solar cells (PSCs) with high performances greater than 20% contain bromine (Br), causing a suboptimal bandgap, and the thermally unstable methylammonium (MA) molecule. Avoiding Br and especially MA can therefore result in more optimal bandgaps and stable perovskites. We show that inorganic cation tuning, using rubidium and cesium, enables highly crystalline formamidinium-based perovskites without Br or MA. On a conventional, planar device architecture, using polymeric interlayers at the electron- and hole-transporting interface, we demonstrate an efficiency of 20.35% (stabilized), one of the highest for MA-free perovskites, with a drastically improved stability reached without the stabilizing influence of mesoporous interlayers. The perovskite is not heated beyond 100°C. Going MA-free is a new direction for perovskites that are inherently stable and compatible with tandems or flexible substrates, which are the main routes commercializing PSCs.


Accelerating forward genetics for cell wall deconstruction.
The elucidation of the genes involved in cell wall synthesis and assembly remains one of the biggest challenges of cell wall biology. Although traditional genetic approaches, using simple yet elegant screens, have identified components of the cell wall, many unknowns remain. Exhausting the genetic toolbox by performing sensitized screens, adopting chemical genetics or combining these with improved cell wall imaging, hold the promise of new gene discovery and function. With the recent introduction of next-generation sequencing technologies, it is now possible to quickly and efficiently map and clone genes of interest in record time. The combination of a classical genetics approach and cutting edge technology will propel cell wall biology in plants forward into the future.


A prospective case series of women with estrogen receptor-positive breast cancer: levels of tamoxifen metabolites in controlled ovarian stimulation with high-dose tamoxifen.
Controlled ovarian stimulation (COS) in women with estrogen receptor (ER)-positive breast cancer is potentially harmful because of the increase in serum estrogen levels. During COS for cryopreservation of oocytes or embryos, these women may receive high doses of tamoxifen (60 mg) to modulate the ER and prevent extra growth of estrogen responsive tumours during COS. However, it is unknown whether adequate serum concentrations of endoxifen, the most important metabolite of tamoxifen, can be reached. The aim of this study is to evaluate whether the tamoxifen dose used in a tamoxifen-COS combined schedule for women with ER-positive breast cancer is high enough to reach endoxifen levels that are considered therapeutically effective to inhibit breast cancer growth. The four women with ER-positive breast cancer who underwent COS for cryopreservation of oocytes were prospectively studied at the Academic Medical Centre, Amsterdam, the Netherlands. Throughout COS, blood samples were collected and tamoxifen and endoxifen levels were determined by a validated high-performance liquid chromatography tandem mass spectrometry assay. The four women with ER-positive breast cancer underwent a total of five COS cycles, while additionally using tamoxifen 60 mg daily. The tamoxifen and endoxifen levels showed a large variability between the women, with endoxifen levels during the whole period of ovarian stimulation varying between 3.96 and 41.0 ng/ml. The average number of vitrified oocytes was 11 (5-14). Therapeutically effective endoxifen serum levels can be reached when tamoxifen is used to counteract estrogen levels during COS for fertility preservation, but not in all women. Large variations of tamoxifen and endoxifen levels between the women were observed.


A Case Report of Decreased Fetal Movement During Fetomaternal Hemorrhage.
Fetomaternal hemorrhage is a rare, potentially catastrophic event for a fetus. Leakage of the fetus's blood into the mother's circulation can cause fetal anemia, hydrops, and even death. The prevailing symptom is decreased fetal movement, and signs can include a sinusoidal electronic fetal monitor pattern, a positive Kleihauer-Betke test, or changes in fetal Doppler blood flow. A mother's report or perception of decreased fetal movement coupled with a nonreactive nonstress test or abnormal ultrasound findings should prompt an investigation into underlying causes.


Fluorescent in situ hybridization (FISH): A useful diagnostic tool for childhood conjunctival melanoma.
Conjunctival melanoma is extremely rare in children and has low rates of resolution. Definitive histopathological diagnosis based exclusively on microscopic findings is sometimes difficult. Thus, early diagnosis and adequate treatment are essential to improve clinical outcomes. We present the first case in which the fluorescent in situ hybridization (FISH) diagnostic technique was applied to a 10-year-old boy initially suspected of having amelanotic nevi in his right eye. Based on the 65% of tumor cells with 11q13 (CCND1) copy number gain and 33% with 6p25 (RREB1) gain as measured by the FISH analysis, and on supporting histopathological findings, the diagnosis of conjunctival melanoma could be made. Following a larger re-excision, adjuvant therapy with Mitomycin C (MMC), cryotherapy and an amniotic membrane graft, the patient has remained disease-free during 9 years of long-term follow-up. Every ophthalmologist should remember to consider and not forget the possibility of using FISH analyses during the differential diagnosis of any suspicious conjunctival lesions. Genetic techniques, such as FISH, have led to great advances in the classification of ambiguous lesions. Evidence-based guidelines for diagnosing conjunctival melanoma in the pediatric population are needed to determine the most appropriate strategy for this age group.


The use of the diary as a data collection technique.
The initiation of a research project requires many decisions, not the least of which is the selection of a method for data collection. This decision is, in large measure, guided by the nature of the research question which generally prescribes the selection of a strategy for data collection from among an array of possible alternatives. This article addresses the use of a diary for data collection. Although diaries have traditionally been used in social science and health research, their use in nursing research is more recent. The article begins with a brief discussion of the rationale for using the diary to gather data in a study of personal and professional caregiving. A brief review of the use of diaries in previous studies follows, along with a description of the use of a diary in the caregiving study and a discussion of the possible threats to high quality data as well as measures used to ensure the collection of high quality data. The article concludes with a discussion of the strengths and weaknesses of the diary and makes recommendations regarding its use in nursing research.


Activation of double-stranded RNA-activated protein kinase in HeLa cells after poliovirus infection does not result in increased phosphorylation of eucaryotic initiation factor-2.
Protein kinase activity in general is stimulated at least 5- to 10-fold in ribosomal salt wash preparations from poliovirus-infected HeLa cells compared with those from mock-infected cells. The stimulation of kinase activity is manifested by increased phosphorylation of ribosome-associated polypeptides having approximate molecular weights of 135,000, 120,000, 85,000, 68,000, 65,000, 40,000, 28,000, 25,000, and 21,000. The Mr 68,000 phosphoprotein is structurally identical to the interferon-induced, double-stranded RNA-activated protein kinase (P1) which phosphorylates the alpha subunit of eucaryotic initiation factor-2 (eIF-2). A similar protein of Mr 68,000 is more phosphorylated in poliovirus-infected cells than in mock-infected cells. Increased phosphorylation of P1 protein in poliovirus-infected cells, however, does not result in an increased phosphorylation of the alpha subunit of endogenous or exogenously added eIF-2, both in vitro and in vivo. These results suggest that a mechanism must exist in poliovirus-infected HeLa cells which prevents further phosphorylation of eIF-2 by the activated kinase.


Psychotropic drug use during pregnancy: weighing the risks.
Although psychotropic drugs have not been tested or approved by the Food and Drug Administration for use during pregnancy, some women continue to take these medications while they are pregnant, particularly since mood and anxiety disorders cluster in women during childbearing years. The relative risks and benefits of drug therapy for these women must be weighed with each patient and treatment limited to those situations in which risks to mother and fetus from the disorder are presumed to exceed the risk of drug treatment. Risks of psychotropic drug use during pregnancy include teratogenic effects, direct neonatal toxicity, and the potential for longer term neurobehavioral sequelae. Of growing concern is the risk of untreated psychiatric disorder as it may potentially affect fetoplacental integrity and fetal central nervous system development. Coordination of care with the patient, her husband or partner, and the obstetrician is essential, as is careful medical record documentation when treating pregnant patients with psychiatric disorders.


[Successful cumulative treatment with pre/post-operative interferon-alpha, nephrectomy, and surgical resection of metastasis in advanced renal cell carcinoma : a case report].
A 55-year-old man was admitted with cough and sputum. Computed tomography revealed a left renal tumor, 7 cm in diameter, and multiple lung tumors with left pleural effusion. We considered nephrectomy impossible given his poor performance status. He received 500 x 104 IU/day of interferon alpha subcutaneously three times a week. Five months after the start of interferon alpha therapy, the renal and lung tumors were markedly reduced in size. Because of improvement of his condition and downsizing of tumors, radical nephrectomy was performed. In addition, interferon alpha therapy was continued for seven more months. At that point, all metastatic pulmonary lesions but one had disappeared. Interferon alpha therapy was then continued for one more year. About five years after the first admission, he is alive without evidence of disease.


Brief Maternal Separation Inoculates Against the Effects of Social Stress on Depression-Like Behavior and Cocaine Reward in Mice.
Exposure to intermittent repeated social defeat (IRSD) increases the vulnerability of mice to the rewarding effects of cocaine in the conditioned place preference (CPP) paradigm. According to the "inoculation of stress" hypothesis, a brief period of maternal separation (MS) can provide protection against the negative effects of IRSD. The aim of the present study was to assess whether exposure to a brief episode of MS prevents the subsequent short-term effects of IRSD on depression- and anxiety-like behaviors and to explore its long-term effects on cocaine CPP in mice. Four groups of male C57BL/6 mice were employed; two groups were separated from their mother [6 h on postnatal day (PND) 9], while the other two groups were not (controls). On PND 47, 50, 53 and 56, mice that had experienced MS were exposed to social defeat in the cage of an aggressive resident mouse (MS + IRSD group) or were allowed to explore an empty cage (MS + EXPL group). The same procedure was performed with control mice that had not experienced MS (CONTROL + IRSD and CONTROL + EXPL groups). On PND57-58, all the mice performed the elevated plus maze and the hole-board, social interaction and splash tests. Three weeks after the last episode of defeat, all the mice underwent the CPP procedure with cocaine (1 mg/kg). Irrespective of whether or not MS had taken place, a reduction in open arms measures, dips, and social interaction was observed in mice that experienced IRSD. A higher latency of grooming and acquisition of cocaine-induced CPP were observed only in mice exposed to IRSD alone (CONTROL + IRSD). These results suggest that exposure to a brief episode of stress early in life increases the subsequent resilience of animals to the effects of social stress on vulnerability to cocaine.


The lncRNA MALAT1, acting through HIF-1α stabilization, enhances arsenite-induced glycolysis in human hepatic L-02 cells.
Accelerated glycolysis, a common process in tumor cells called the Warburg effect, is associated with various biological phenomena. However, the role of glycolysis induced by arsenite, a well-established human carcinogen, is unknown. Long non-coding RNAs (lncRNAs) act as regulators in various cancers, but how lncRNAs regulate glucose metabolism remains largely unexplored. We have found that, in human hepatic epithelial (L-02) cells, arsenite increases lactate production; glucose consumption; and expression of glycolysis-related genes, including HK-2, Eno-1, and Glut-4. In L-02 cells exposed to arsenite, the lncRNA, metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), and hypoxia inducible factors (HIFs)-α, the transcriptional regulators of cellular response to hypoxia, are over-expressed. In addition, HIF-1α, not HIF-2α, is involved in arsenite-induced glycolysis, and MALAT1 enhances arsenite-induced glycolysis. Although MALAT1 regulates HIF-α and promotes arsenite-induced glycolysis, MALAT1 promotes glycolysis through HIF-1α, not HIF-2α. Moreover, arsenite-increased MALAT1 enhances the disassociation of Von Hippel-Lindau (VHL) tumor suppressor from HIF-1α, alleviating VHL-mediated ubiquitination of HIF-1α, which causes accumulation of HIF-1α. In sum, these findings indicate that MALAT1, acting through HIF-1α stabilization, is a mediator that enhances glycolysis induced by arsenite. These results provide a link between the induction of lncRNAs and the glycolysis in cells exposed to arsenite, and thus establish a previously unknown mechanism for arsenite-induced hepatotoxicity.


Fixation of experimental osteotomy of the distal femur with biodegradable thread in rabbits.
A distal femoral osteotomy on 24 rabbits was fixed with biodegradable polyglycolic acid (PGA) thread pulled through drill holes made on both sides of the osteotomy. Follow-up times were one, three, six, 12 and 24 weeks. The distal part of each femur was removed, fixed in alcohol, embedded in methylmethacrylate, sawed to 80 microns thick for oxytetracycline (OTC)-labeling studies and microradiography, and sectioned at 5 microns for histologic studies. As judged by histologic microradiographic, and OTC-labeling studies, 19 of 24 osteotomies were healing normally; after six weeks of follow-up examination, union of 11 of 14 osteotomies was observed on radiographs. On the basis of the present study, PGA threads may be promising for the fixation of osteotomies of the metaphyseal cancellous bone in rabbits.


In vitro and in vivo cholesterol lowering ability of Lactobacillus pentosus KF923750.
Lactobacillus pentosus KF923750 was characterised for probiotic related properties and then characterised for cholesterol uptake in vitro as well as in vivo using rabbits fed a high-cholesterol diet. The survival percentage of L. pentosus KF923750 was 100% at pH 3, 52.18% at pH 2 and 36.21% at pH 2 plus pepsin. Similarly, this strain appeared resistant to bile (0.1% [98.42%], 0.3% [88.52%], 0.5% [75.60%] and 1% [71.15%]), after 4 h exposure. Moreover, L. pentosus KF923750 controlled growth of Escherichia coli ATCC 25922 and Staphylococcus aureus ATCC 25923 through the production of a bacteriocin-like inhibitory substance and anti-adhesive capabilities. L. pentosus KF923750 was non-cytotoxic to eukaryotic cells but sensitive to some antibiotics. Compared with rabbits fed a high-cholesterol diet but without L. pentosus KF923750 supplementation, the plasma total cholesterol, low-density lipoprotein cholesterol and triglycerides levels were significantly decreased in L. pentosus KF923750-fed rabbits by 11.54, 16.00 and 18.00%, respectively, with no significant change in high-density lipoprotein cholesterol levels. The histological sections of livers revealed lesions in all the rabbits that were fed a high-cholesterol diet, but these were less pronounced in rabbits ingesting L. pentosus KF923750. This study highlights the potential of lactobacilli, such as L. pentosus KF923750, in the treatment or prevention of hypercholesterolemia.


[Chronic multivessel disease: past, present and future].
Public health predictions indicate that the prevalence of cardiovascular disease will reach epidemic levels throughout the world in coming years, principally because of increasing obesity and diabetes in the general population. Numerous studies have confirmed that diabetes will affect morbidity and mortality in patients with complex multivessel disease. The magnitude of the public health problem and the enormous economic costs associated with the treatment and hospitalization of these patients make it essential that clinical studies designed to elucidate the pathophysiological mechanisms underlying the development of clinical atherosclerosis from its subclinical form are carried out, with the aim of identifying treatment that can lead to disease regression. Moreover, it is important that evidence from patient registries, and not only from large clinical studies, is interpreted correctly, so that the most effective therapies can be implemented. Registries are not subject to the same patient inclusion biases as studies and they contain information that is not included in clinical studies. Recent evidence from patient registries indicates that the physician's judgment is a predictive variable for a successful clinical outcome. In addition, clinical studies confirm that medical treatment, when it is well monitored and implemented aggressively, can provide similar benefits to surgery. Using the knowledge that has been gained over the last few decades, we have designed a study, named FREEDOM, that will enable us to use high-resolution imaging to reliably and reproducibly correlate plaque characteristics, including the level of inflammation and the so-called <<disease burden>>, with the effectiveness of medical treatment aimed at promoting endogenous defense mechanisms. In this way, we hope to be able to influence atherosclerotic disease in high-risk groups from its early silent phase onwards, to slow its spread, and to alter its clinical epidemiology.


Central 5-alpha reduction of testosterone is required for testosterone's inhibition of the hypothalamo-pituitary-adrenal axis response to restraint stress in adult male rats.
In rodents, the hypothalamo-pituitary-adrenal (HPA) axis is controlled by a precise regulatory mechanism that is influenced by circulating gonadal and adrenal hormones. In males, gonadectomy increases the adrenocorticotropic hormone (ACTH) and corticosterone (CORT) response to stressors, and androgen replacement returns the response to that of the intact male. Testosterone (T) actions in regulating HPA activity may be through aromatization to estradiol, or by 5α-reduction to the more potent androgen, dihydrotestosterone (DHT). To determine if the latter pathway is involved, we assessed the function of the HPA axis response to restraint stress following hormone treatments, or after peripheral or central treatment with the 5α-reductase inhibitor, finasteride. Initially, we examined the timecourse whereby gonadectomy alters the CORT response to restraint stress. Enhanced CORT responses were evident within 48 h following gonadectomy. Correspondingly, treatment of intact male rats with the 5α-reductase inhibitor, finasteride, for 48 h, enhanced the CORT and ACTH response to restraint stress. Peripheral injections of gonadectomized male rats with DHT or T for 48 h reduced the ACTH and CORT response to restraint stress. The effects of T, but not DHT, could be blocked by the third ventricle administration of finasteride prior to stress application. These data indicate that the actions of T in modulating HPA axis activity involve 5α-reductase within the central nervous system. These results further our understanding of how T acts to modulate the neuroendocrine stress responses and indicate that 5α reduction to DHT is a necessary step for T action.


Drain amylase monitoring for early diagnosis of anastomotic leakage in sleeve gastrectomy An animal study.
Sleeve gastrectomy(SG) is a popular bariatric surgery procedure with rare but dreaded complications. Although drain amylase levels are a reliable early predictor of anastomosis leakage in oesophagectomy and pancreaticoduodenectomy, for SG have not yet been studied. We aimed to monitor drain amylase levels to ascertain their applicability for early diagnosis of gastric leakage in SG. Twenty-four rats were randomly divided into three groups: Group A: only laparotomy and abdominal drain; Group B: laparotomy, SG, and drain; Group C: laparotomy, SG with fistula,and drain. On postoperative days 0,1,2,3, and 4, drain lavage samples were collected to measure amylase. Groups were compared in pairs. Preoperative weights were not significantly different in any comparison. On postoperative days 0,1,2,3, and 4, drain amylase levels were found to be significantly lower in Group A than in Group B as well as in Group A than in Group C but were significantly higher in Group C than in Group B. For postoperative day 1, a receiver operating characteristic curve was done. Drain amylase levels over 1514 IU were statistically significant for leakage. Drain amylase levels were significantly high in sleeve gastrectomy with fistula. This indicates that drain amylase level monitoring might be an easy and cheap alternative for determining staple-line leakage for high risk patients with Body Mass Index(BMI)>50kg/m2 in whom we cannot use radiological imaging. Animal Experimental Study, Bariatric Surgery, Drain amylase, Sleeve gastrectomy, Staple-line leakage.


Cost of applying the K/DOQI guidelines for bone metabolism and disease to a cohort of chronic hemodialysis patients.
Hyperphosphatemia is a common feature of advanced chronic kidney disease (CKD) and is treated routinely with oral calcium-based phosphate binders. In 2003, the National Kidney Foundation Kidney Disease Outcomes and Quality Initiative (K/DOQI) published Clinical Practice Guidelines (CPGs) for the treatment of Bone Metabolism and Disease in CKD. These advocate broad usage of expensive non-calcium-based phosphate binders such as sevelamer. This study was designed to determine the cost of implementation of the K/DOQI CPGs as they pertain to phosphate binding in a large Canadian hemodialysis (HD) unit. Laboratory and medication data for all chronic HD patients at the Ottawa Hospital were reviewed (n=416). Patients meeting each of the relevant K/DOQI guidelines were identified. Where guidelines would recommend a switch to non-calcium binders, equivalent sevelamer doses were estimated. The cost of implementing each guideline was then calculated individually and an estimate total cost of implementing all the guidelines was derived. Overall, 53% (222) patients fulfilled at least one criterion for sevelamer use. The yearly cost of implementation of the K/DOQI guidelines at this center was estimated at 500,605 dollars (American dollars). Given the significant cost, widespread adoption of the K/DOQI CPGs for Bone Metabolism and Disease should await the publication of compelling data demonstrating significant improved outcomes in patients treated with sevelamer.


2,3-diphosphoglycerate phosphatase activity of phosphoglycerate mutase: stimulation by vanadate and phosphate.
The binding of inorganic vanadate (Vi) to rabbit muscle phosphoglycerate mutase (PGM), studied by using 51V nuclear magnetic resonance spectroscopy, shows a sigmoidal dependence on vanadate concentration with a stoichiometry of four vanadium atoms per PGM molecule at saturating [Vi]. The data are consistent with binding of one divanadate ion to each of the two subunits of PGM in a noncooperative manner with an intrinsic dissociation constant of 4 X 10(-6) M. The relevance of this result to other studies which have shown that the Vi-stimulated 2,3-diphosphoglycerate (2,3-DPG) phosphatase activity of PGM has a sigmoidal dependence on [Vi] with a Hill coefficient of 2.0 is discussed. At pH 7.0, inorganic phosphate has little effect on the 2,3-DPG phosphatase activity of PGM, even at concentrations as high as 50 mM. Similarly, 25 microM Vi has little effect on the phosphatase activity. However, in the presence of 25 microM Vi, a phosphate concentration of 20 mM increases the phosphatase activity by more than 3-fold. This behavior is rationalized in terms of activation of the phosphatase activity by a phosphate/vanadate mixed anhydride. This interpretation is supported by the observation of strong activation of the phosphatase activity by inorganic pyrophosphate. A molecular mechanism for the observed effects of vanadate is proposed, and the relevance of this study to the possible use of vanadate as a therapeutic agent for the treatment of sickle cell anemia is discussed.


Comparative study of the effect of two different doses of intravenous labetalol on the cardiovascular response to endotracheal extubation.
Providing a stable hemodynamic in extubation is important. We aimed to compare the effect of two different doses of intravenous labetalol on the cardiovascular response to endotracheal extubation. This double-blind randomized trial was performed in 2019-2020 in Isfahan on 72 patients under general anesthesia. Patients using Random Allocation software were divided into three groups and received 0.1 mg/ kg or 0.2 mg/kg labetalol and normal saline intravenously 10 min before extubation. Hemodynamic variables including heart rate (HR), Systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), and peripheral blood oxygen saturation(SPO2) was measured for each patient before induction of anesthesia and 1, 3, 5 and 10 minutes after extubation. SBP changes were significantly different between the three groups at 1, 3, 5 minutes after extubation (P=0.036, P=0.009, P=0.005 respectively) unlike the other two groups, patients who received 0.2 mg/kg labetalol did not have an increase in DBP after extubation (P>0.05). DBP was significantly different between the three groups one minute after extubation (P=0.03). At minutes 1 and 3 following extubation, there was a significant difference in the MAP between the three groups. (P=0.029 and P=0.012 respectively). There was no significant difference between the three groups regarding heart rate (P>0.05). Tracheal extubation is usually associated with an increase in hemodynamic variables. Both doses of labetalol attenuate the hemodynamic response accompanying tracheal extubation. But labetalol 0.2 mg/kg in reducing hemodynamic response to extubation acted more effectively than labetalol 0.1mg/kg.


Modulation of let-7 miRNAs controls the differentiation of effector CD8 T cells.
The differentiation of naive CD8 T cells into effector cytotoxic T lymphocytes upon antigen stimulation is necessary for successful antiviral, and antitumor immune responses. Here, using a mouse model, we describe a dual role for the let-7 microRNAs in the regulation of CD8 T cell responses, where maintenance of the naive phenotype in CD8 T cells requires high levels of let-7 expression, while generation of cytotoxic T lymphocytes depends upon T cell receptor-mediated let-7 downregulation. Decrease of let-7 expression in activated T cells enhances clonal expansion and the acquisition of effector function through derepression of the let-7 targets, including Myc and Eomesodermin. Ultimately, we have identified a novel let-7-mediated mechanism, which acts as a molecular brake controlling the magnitude of CD8 T cell responses.


Outcome of plantar fasciitis treatment using monochrome infrared irradiation.
Plantar fasciitis is one of the most common causes of heel pain. Conservative treatment yields a good result, but it takes long time to accomplish the goal. Physical therapy modality, i.e. Infrared ray is one of the options that maybe help for quicker recovery. To study the results of infrared rays for the treatment of plantar fasciitis. 70 patients with diagnosis of plantar fasciitis at Phramongkutklao Hospital were divided in 2 groups. First group received a conservative treatment by NSAIDS, achiles tendon stretching. The second group is like the first group, with addition of infrared rays. The pain was measured at initial and 6 months post treatment using visual analog scale (VAS). In control group, 34 from 39 feet had lower VAS at 6 months, from 8.41 to 5.28. In the studied group, 35 from 44 feet had lower VAS at 6 months, from 8.70 to 3.38. No patient had the worse symptoms since the using of infrared rays. Application of infrared rays for the treatment of plantar fasciitis is effective. Infrared rays are safe and easy to use.


Workshop Proceedings: Streamlined Development of Safety Assessment Programs Supporting Orphan/Rare Diseases-Are We There Yet?
A workshop entitled "Streamlined Development of Safety Assessment Programs Supporting Orphan/Rare Diseases-Are We There Yet?" was held at the 36th Annual Meeting of the American College of Toxicology in Summerlin, Nevada. The workshop was sponsored by Shire and Ultragenyx and was designed to present the nonclinical considerations for the development of various products for rare diseases. A panel of experts from industry and government highlighted the nonclinical considerations in developing toxicology programs supporting rare disease therapeutics, challenges in preclinical safety assessment, reviewed the current guidance, and presented the progress that has been made to date. The main learning from the workshop was that nonclinical testing of therapeutics targeting rare disease warrants special considerations, and early collaboration between sponsors and health authorities may help optimize the scope and timing of the supportive studies. Specific examples for nonclinical development programs for enzyme replacement therapy (ERT) were presented. Although the symposium focused on ERTs, the concepts are broadly applicable.


Curious Behavior of Fe3+-As3+ Chemical Interactions and Nucleation of Clusters in Aqueous Medium.
The simultaneous presence of Fe3+ and As3+ ions in groundwater (higher ppb or lower ppm level concentrations at circumneutral pH) as well as in acid mine drainages (AMDs)/industrial wastewater (up to few thousand ppm concentration at strongly acidic pH) are quite common. Therefore, understanding the chemical interactions prevalent between Fe3+ and As3+ ions in aqueous medium leading to nucleation of ionic clusters/solids, followed by aggregation and growth, is of great environmental significance. In the present work, we attempt to probe the nucleation process of Fe3+-As3+ clusters in solutions of various concentrations and pHs (from AMD to groundwater-like) using a combination of experimental and theoretical techniques. Interestingly, our study reveals nucleation of primary FeAs clusters in nearly all of them independent of concentration or pH. Theoretical studies employed density functional theory (DFT) to predict the primary clusters as stable Fe4As4 units. The surprising resemblance of these clusters with known Fe3+-As3+ minerals at the local level was observed experimentally, which provides an important clue about solid-phase growth from a range of Fe3+-As3+ solutions. Our experimental findings are further supported by a stepwise reaction mechanism established from detailed DFT studies.


Chromatin stiffening underlies enhanced locus mobility after DNA damage in budding yeast.
DNA double-strand breaks (DSBs) induce a cellular response that involves histone modifications and chromatin remodeling at the damaged site and increases chromosome dynamics both locally at the damaged site and globally in the nucleus. In parallel, it has become clear that the spatial organization and dynamics of chromosomes can be largely explained by the statistical properties of tethered, but randomly moving, polymer chains, characterized mainly by their rigidity and compaction. How these properties of chromatin are affected during DNA damage remains, however, unclear. Here, we use live cell microscopy to track chromatin loci and measure distances between loci on yeast chromosome IV in thousands of cells, in the presence or absence of genotoxic stress. We confirm that DSBs result in enhanced chromatin subdiffusion and show that intrachromosomal distances increase with DNA damage all along the chromosome. Our data can be explained by an increase in chromatin rigidity, but not by chromatin decondensation or centromeric untethering only. We provide evidence that chromatin stiffening is mediated in part by histone H2A phosphorylation. Our results support a genome-wide stiffening of the chromatin fiber as a consequence of DNA damage and as a novel mechanism underlying increased chromatin mobility.


Droplet-Confined Electroless Deposition of Silver Nanoparticles on Ordered Superhydrophobic Structures for High Uniform SERS Measurements.
Surface-enhanced Raman scattering spectroscopy (SERS) is a nondestructive testing technique. To increase reproducibility of the SERS measurement is the key issue for improving the performance of SERS. In this article, we demonstrate an efficient method to improve the reproducibility, using confined silver nanoparticles (AgNPs) as a substrate. The AgNPs are formed uniformly on the tops of the prepared nanopillars by droplet-confined electroless deposition on the hydrophobic Si nanopillar arrays. The AgNPs present an excellent reproducibility in Raman measurement; the relative standard deviation is down to 3.40%. There exists a great linear correlation between the concentration of Rhodamine 6G (R6G) and the Raman intensity in the log-log plot; R2 is 0.998, indicating that this SERS substrate can be applied for the quantitative SERS analysis. Meanwhile, the minimum detection concentration is down to 10-11 M on the hydrophobic substrate, with R6G as a probe molecule.


[Hemorrhagic digestive metastases from testicular choriocarcinoma].
The metastasis of testicular choriocarcinoma are often hemorrhagic, primarily of cerebral or pulmonary seat. The secondary digestive localizations are rare and of bad forecast when they bleed. The surgical operation by laparotomy allows the topographic diagnosis and the treatment, but was made responsible for hemorrhagic decompensation of other metastatic localizations engaging the vital forecast.


A case of rectal metastatic tumor in the soft tissue of the hand.
Hand metastases occur infrequently, and metastatic tumors in the soft tissue of the hand caused by rectal cancer are extremely rare. We report a case here. The patient was a 76-year old man. He underwent Miles operation for rectal cancer located in the lower portion of the rectum. Histopathologically, the resected specimen showed well-differentiated adenocarcinoma. Six years postoperatively, a tumor involving the soft tissue of the palma was found in his left hand. The tumor was resected, and pathological examination showed a well-differentiated adenocarcinoma similar to the primary rectal carcinoma. Immunohistochemical examination demonstrated that this hand tumor had metastasized from rectal cancer. Fifteen cases of colorectal metastatic tumors in the hand have been documented, of which three were soft-tissue metastases. This report describes the fourth case.


Expression and characterization of recombinant human lactoferrin in edible alga Chlamydomonas reinhardtii.
Lactoferrin (LF) is a naturally occurring iron-binding glycoprotein with a variety of biological functions. It has increasing demand every year and huge market potential. In this study, we explored the feasibility of expressing human LF (hLF) in edible algae C. reinhardtii. A codon-optimized hLF gene was synthesized, inserted into pCAMBIA-1301C and transformed into C. reinhardtii SP strain. In total, 7 hLF-expressing clones were selected with clone 121 exhibiting the highest expression level. The hLF-containing algal extract significantly inhibited the growth of bacteria such as Escherichia coli and Klebsiella variicola. During acute toxicity experiment no acute toxicity was detected, especially on changes of the body weight and histopathology of organs. The recombinant hLF possessed a similar or modestly reduced stability compared to commercial hLF standard. Our data indicated that expression of hLF in C. reinhardtii is feasible and paved a way to commercial production of lactoferrin using edible Chlamydomonas expression system. Abbreviations: atrazine chlorohydrolase gene (atzA); bovine serum albumin (BSA); human LF (hLF); lactoferrin (LF); Luria-Bertani (LB); quantitative reverse transcriptase PCR (qRT-PCR) ; SDS polyacrylamide gel electrophoresis (SDS-PAGE); Tris-acetate phosphate (TAP); western blotting (WB).


Frequent occurrence of low-level positive autoantibodies in chronic hepatitis C.
Evidence of autoimmune disease associated with hepatitis C virus (HCV)-infection has important clinical implications. A systematic profile of these autoantibodies in relevant clinical cohorts relative to healthy controls is needed to better inform current standard of care for chronic hepatitis C. Samples from an Australian cohort of chronic HCV-infected subjects (n=127) were tested for the presence of 19 diagnostic autoantibodies and compared with data available from a control cohort representing a general Caucasian population (n=198). Chronic HCV-infected individuals had a greater number of autoantibodies than controls (p<0.0001). Anti-nuclear antibodies (ANA) followed by anti-smooth muscle antibodies (SMA) were the most frequently detected autoantibodies within the HCV cohort and significantly more than in the control cohort (p<0.0001 and p=0.006, respectively). However, for most autoantibody assays the 95th percentile approximated the reference value for positivity. None of the autoantibodies were significantly associated with age or sex for the HCV cohort, except SMA positivity that was significantly higher in chronic HCV-infected male subjects (p<0.0001). Autoantibodies found in chronic HCV-infected subjects were commonly low positive and not disease-specific. Accordingly, general screening for autoimmunity in HCV-infected subjects should not be performed unless there is high clinical suspicion of an underlying autoimmune disease.


Effects of androgen disruption by DDE on the development and functioning of the immune system in Japanese quail.
We hypothesized that immunosuppression in birds that is caused by exposure to antiandrogenic chemicals occurs mainly through disruption of the development of the androgen-sensitive avian lymphoid organ, the bursa of Fabricius. Injections of 20.0 or 40.0 mug of p,p'-DDE [ethylene, 1,1-dichloro-2,2-bis(p-chlorophenyl)], an antiandrogen, were administered at embryonic day 1. Bursas from only chicks treated with DDE were larger than, had fewer follicles, and exhibited vacuolization within follicles compared with controls; spleens were unaffected. No differences in either immune response test were observed. This study demonstrates that the bursa may play a role in androgen-active endocrine disrupting chemical-induced immunosuppression.


Characteristics of Chinese patients with Wegener's granulomatosis with anti-myeloperoxidase autoantibodies.
Cytoplasmic antineutrophil cytoplasmic autoantibodies (cANCA)/proteinase-3(PR3)-ANCA was considered the serologic diagnostic marker for Wegener's granulomatosis (WG). However, Chinese patients with MPO-ANCA positive WG were frequently diagnosed. We now analyze the characteristics of patients with MPO-ANCA positive WG and investigate the difference between patients with MPO-ANCA and PR3-ANCA. Patients with WG were selected according to both Chapel Hill Consensus Conference definition and American College of Rheumatology (ACR) classification criteria in 500 Chinese patients with ANCA-associated systemic vasculitides. The clinical manifestions were compared between patients with MPO-ANCA and with PR3-ANCA. Eight-nine patients fulfilled the diagnostic criteria of WG: 54/89(60.7%) were MPO-ANCA positive, 34/89(38.2%) were PR3-ANCA positive. Patients with MPO-ANCA were predominantly female compared with patients with PR3-ANCA. Patients with MPO-ANCA also had multisystem involvement. However, the prevalences of arthagia, skin rash, ophthalmic and ear involvement were significantly lower in patients with MPO-ANCA than those in patients with PR3-ANCA (46.3% vs. 70.6%, P < 0.05; 20.4% vs. 44.1%, P < 0.05; 27.8% vs. 58.8%, P < 0.01; 40.7% vs. 67.6%, P < 0.05, respectively). The prevalence of elevated initial serum creatinine was significantly higher in patients with MPO-ANCA than that in patients with PR3-ANCA (81.5% vs. 61.8%, chi(2) = 4.20, P < 0.05). Patients with MPO-ANCA positive WG were not rare in Chinese.


Salivary alpha-amylase activity: a possible indicator of pain-induced stress in orthodontic patients.
Pain, a common experience reported by orthodontic patients, has its intensity assessed with the help of subjective scales, which have a limited and disputable value. Such unpleasant experience, which may raise stress levels, is reflected by an increase in the salivary concentration of alpha-amylase. Assess the correlation between the salivary levels of alpha-amylase and pain intensity reported by patients during orthodontic treatment. Twenty male patients (11-37 years of age) were assessed daily, before treatment, after bracket bonding, and after initial arch wire insertion. Saliva was sampled for alpha-amylase analysis, and pain intensity was measured with the visual analog scale. There was no correlation between alpha-amylase concentrations in the saliva and pain intensity, although the patients had a significant and progressive increase of alpha-amylase levels during the assessment period. The findings may reflect the psychological stress caused by the presence and activation of the fixed appliance.


Substance P stimulates production of inflammatory cytokines in human disc cells.
Laboratory study. The aims of this study were as follows: (1) to confirm that Substance P (SP) is expressed by nucleus pulposus (NP) and annulus fibrosus (AF) cells; (2) to determine the effect of SP on expression of inflammatory mediators in human disc cells and the effect of inflammatory mediators on the expression of SP; and (3) to characterize the relative expression of SP receptor isoforms in disc tissue and describe whether exposure to SP changes receptor expression. SP, classically described as a neurotransmitter, acts as an inflammatory regulator in other tissue types, but its role within the intervertebral disc has not been characterized. Human AF and NP cells from 7 individuals were expanded in monolayer and maintained in alginate bead culture. Cells were treated with SP or interleukin (IL)-1β/tumor necrosis factor-α (TNF-α). After treatment, the cells were recovered and then RNA was isolated and transcribed into cDNA. Quantitative reverse-transcriptase polymerase chain reaction was performed to evaluate expression of inflammatory mediators and SP and its receptors. Disc cells treated with SP demonstrated significant upregulation of IL-1β, IL-6, and IL-8 in NP and AF cells whereas significant upregulation of RANTES and TNF occurred only in the AF cells. AF and NP cells expressed SP at low levels; expression did not change significantly with SP treatment but was significantly upregulated after treatment with IL-1β/TNF-α. Both SP receptor isoforms were expressed by NP and AF cells. SP upregulates inflammatory mediators in disc cells. SP and its receptors were expressed in both NP and AF cells, and expression did not change after treatment with SP but increased after treatment with IL-1β/TNF-α. SP likely acts in an autocrine or paracrine manner in intervertebral disc cells and may be involved in "crosstalk" between disc cells and neurons, providing a potential mechanism for transmission of painful discogenic stimuli.


The outcome of decompression alone for lumbar spinal stenosis with degenerative spondylolisthesis.
Lumbar spinal stenosis in the presence of degenerative spondylolisthesis is generally treated by means of surgery. The role of lumbar decompression without fusion is not clear. Therefore, the aim of this study was to assess whether patients who undergo decompression alone have a favourable outcome without the need for a subsequent fusion. This is a prospective cohort study with single blinding of 83 consecutive patients with lumbar stenosis and degenerative spondylolisthesis treated by decompression, without fusion, using a spinous process osteotomy. Blinded observers collected pre- and post-operative Oswestry Disability Index (ODI), EuroQol Five Dimensions (EQ-5D), and visual analogue scale (VAS) for back and leg pain scores prospectively. Failures for this study were those patients who required a subsequent lumbar fusion procedure at the decompressed levels. Statistical analysis was performed using paired t test and Mann-Whitney test. There were 36 males and 47 females with a mean age of 66 years (range 35-82). The mean follow-up was 36 months (range 19-48 months). The mean pre-operative ODI, EQ-5D, and VAS scores were 52 [standard deviation (SD) 18], 0.25 (SD 0.30), and 61 (SD 22), respectively. All mean scores improved post-operatively to 38 (SD 23), 0.54 (SD 0.34) and 36 (SD 27), respectively. There was a statistically significant improvement in all scores (p ≤ 0.0001). Nine patients (11 %) required a subsequent fusion procedure and five patients (6 %) required revision decompression surgery alone. Our study's results show that a lumbar decompression procedure without arthrodesis in a consecutive cohort of patients with lumbar spinal stenosis with degenerative spondylolisthesis had a significant post-operative improvement in ODI, EQ-5D, and VAS. The rate of post-operative instability and subsequent fusion is not high. Only one in 10 patients in this group ended up needing a subsequent fusion at a mean follow-up of 36 months, indicating that fusion is not always necessary in these patients.


Plasmon-induced transparency in coupled triangle-rod arrays.
We demonstrate polarization-dependent plasmon-induced transparency in coupled triangle-rod arrays. The observed phenomenon is the result of the destructive interference between the bright and dark resonators in this coupled system, which is verified through the numerical simulations using the finite-difference time-domain (FDTD) method. By precisely controlling the structural parameters of the coupled triangle-rod system, the plasmon-induced transparency can be effectively manipulated. This plasmonically coupled nanostructure could be potentially useful for designing and developing artificial plasmonic molecules and metamaterials with desired functions, which may further find promising applications in biosensing, nanoparticle trapping and optical filters.


Consolidation of Sleep-Dependent Appetitive Memory Is Mediated by a Sweet-Sensing Circuit.
Sleep is a universally conserved physiological state which contributes toward basic organismal functions, including cognitive operations such as learning and memory. Intriguingly, organisms can sometimes form memory even without sleep, such that Drosophila display sleep-dependent and sleep-independent memory in an olfactory appetitive training paradigm. Sleep-dependent memory can be elicited by the perception of sweet taste, and we now show that a mixed-sex population of flies maintained on sorbitol, a tasteless but nutritive substance, do not require sleep for memory consolidation. Consistent with this, silencing sugar-sensing gustatory receptor neurons in fed flies triggers a switch to sleep-independent memory consolidation, whereas activating sugar-sensing gustatory receptor neurons results in the formation of sleep-dependent memory in starved flies. Sleep-dependent and sleep-independent memory relies on distinct subsets of reward signaling protocerebral anterior medial dopaminergic neurons (PAM DANs) such that PAM-β'2mp DANs mediate memory in fed flies whereas PAM-α1 DANs are required in starved flies. Correspondingly, we observed a feeding-dependent calcium increase in PAM-β'2mp DANs, but not in PAM-α1 DANs. Following training, the presence of sweet sugars recruits PAM-β'2mp DANs, whereas tasteless medium increases calcium in PAM-α1 DANs. Together, this work identifies mechanistic underpinnings of sleep-dependent memory consolidation, in particular demonstrating a role for the processing of sweet taste reward signals.SIGNIFICANCE STATEMENT Sleep is essential for encoding and consolidating memories, but animals must often suppress sleep for survival. Consequently, Drosophila have evolved sleep-independent consolidation that allows retention of essential information without sleep. In the presence of food, sleep is required for memory, but mechanisms that transmit signals from food cues to regulate the need for sleep in memory are largely unknown. We found that sweet-sensing neurons drive the recruitment of specific reward signaling dopaminergic neurons to establish sleep-dependent memory. Conversely, in the absence of a sweet stimulus, different neurons are activated within the same dopaminergic cluster for sleep-independent memory consolidation. Therefore, the processing of sleep-dependent memory relies on the presence of sweet sugars that signal through reward circuitry.


Current Status of MR-Linac System.
Current status of MR-Linac System was reported. First, we introduced the history of development about MR-Linac System. We discussed the advantage of MR-Linac for radiotherapy. Next, we explained the electron return effect caused by magnetic field, resulting in different dose distribution, compared to dose distribution with no magnetic field. Our explanation about MR-Linac will help for understanding this system.