Amplification of the proliferative response to alloantigen by a factor present in an extract of syngeneic thymic lymphoid cells.
A synergistic interaction in the proliferative response to alloantigen has been previously noted when intact thymus cells are cultured with post-thymic (peripheral) lymphoid cells. In the present study, a factor extracted from the thymus has been shown to similarly enhance the reactivity of syngeneic lymph node cells and thus to retain the amplifier activity of intact thymus cells. The factor has no effect on lymphoid cell proliferation in the absence of alloantigen. Cells with amplifier activity are found in highest concentration in the thymus but also may be detected in spleen cells that are nonadherent to nylon wool. The factor is shown in these experiments to be derived from thymic lymphoid cells and to act primarily upon post-thymic (peripheral) lymphoid cells. As such, this factor appears to be distinct from various other thymus factors that have been localized to thymic reticuloepithelial elements and that are thought to effect predominantly the differentiation of T-cell precursors.


PDA workshop on "Quality by Design for Biopharmaceuticals: Concepts and Implementation", May 21-22, 2007, Bethesda, Maryland.
Janet Woodcock, MD, Deputy Commissioner for Operations/Chief Medical Officer at FDA, closed the workshop. She stated that, "QbD represents an evolution and not a revolution" that is in response to the increasing cost pressures on both the regulatory agencies and industry to control the escalation of drug prices. She acknowledged that the successful implementation will require efforts and cooperation between industry and the FDA. She also said that the realization of the full benefits of implementing QbD will require changes in the way industry operates and in the regulations, and thus will take time. The issue of the lack of harmonization of these concepts across different regulatory agencies was recognized as a significant deterrent for companies to implement QbD. FDA is working with other major regulatory agencies to seek better alignment. The Agency also acknowledged that the concepts and associated flexibility of QbD has not yet reached the inspectional arena. The establishment of a "Pharmaceutical Inspectorate" that would standardize an approach and hopefully become an international organization was suggested as a potential outcome of the ongoing efforts.


Variables affecting the fracture toughness of resin-based inlay/onlay systems.
The fracture toughness of five different resin-based inlay/onlay materials was investigated by means of critical stress intensity factor (KIC) using the SEN three-point bending test procedure (BS 5447: 1977). KIC values were determined from specimens prepared by both the direct and indirect techniques. Tests were performed immediately, after 1 day, 1 month and 3 month time intervals. Also, fractured surfaces of specimens were observed using SEM photographs.


Heat induced superfast diclofenac removal in Cu(II)-activated peracetic acid system: Mediation from non-radical to radical pathway.
A Cu(II)/heat coactivated peracetic acid (PAA) system for enhancing diclofenac (DCF) degradation was proposed in this work. The superiority of this synergetic activation strategy for PAA, working reactive species, catalytic mechanism and effects of reaction parameters on DCF elimination in this system were simultaneously investigated. Based on our results, the DCF loss rate in Cu(II)-heat/PAA process at pH 8.0 was about 49.3 and 4.2 times of that in Cu(II)/PAA and heat/PAA processes, respectively. Increasing the reaction temperature to 60 оC not only motivated the conversion of Cu(II) to Cu(I) but also facilitated the one-electron transfer between Cu(I) and PAA, boosting the generation of radicals. Organic radicals (mainly CH3C(O)O• and CH3C(O)OO•) were evidenced to be the core oxidizing substances dominating in the destruction of DCF while hydroxyl radical (•OH) made a minor contribution in this system by electron paramagnetic resonance (EPR) method together with scavenging experiments. This study broads the eyes into enhanced PAA activation initiated by homogenous Cu(II), providing a simple but efficient tool to degrade micropollutants.


Mechanisms Mediating Pediatric Severe Asthma and Potential Novel Therapies.
Although a rare disease, severe therapy-resistant asthma in children is a cause of significant morbidity and results in utilization of approximately 50% of health-care resources for asthma. Improving control for children with severe asthma is, therefore, an urgent unmet clinical need. As a group, children with severe asthma have severe and multiple allergies, steroid resistant airway eosinophilia, and significant structural changes of the airway wall (airway remodeling). Omalizumab is currently the only add-on therapy that is licensed for use in children with severe asthma. However, limitations of its use include ineligibility for approximately one-third of patients because of serum IgE levels outside the recommended range and lack of clinical efficacy in a further one-third. Pediatric severe asthma is thus markedly heterogeneous, but our current understanding of the different mechanisms underpinning various phenotypes is very limited. We know that there are distinctions between the factors that drive pediatric and adult disease since pediatric disease develops in the context of a maturing immune system and during lung growth and development. This review summarizes the current data that give insight into the pathophysiology of pediatric severe asthma and will highlight potential targets for novel therapies. It is apparent that in order to identify novel treatments for pediatric severe asthma, the challenge of undertaking mechanistic studies using age appropriate experimental models and airway samples from children needs to be accepted to allow a targeted approach of personalized medicine to be achieved.


Definitive Hematopoiesis in the Yolk Sac Emerges from Wnt-Responsive Hemogenic Endothelium Independently of Circulation and Arterial Identity.
Adult-repopulating hematopoietic stem cells (HSCs) emerge in low numbers in the midgestation mouse embryo from a subset of arterial endothelium, through an endothelial-to-hematopoietic transition. HSC-producing arterial hemogenic endothelium relies on the establishment of embryonic blood flow and arterial identity, and requires β-catenin signaling. Specified prior to and during the formation of these initial HSCs are thousands of yolk sac-derived erythro-myeloid progenitors (EMPs). EMPs ensure embryonic survival prior to the establishment of a permanent hematopoietic system, and provide subsets of long-lived tissue macrophages. While an endothelial origin for these HSC-independent definitive progenitors is also accepted, the spatial location and temporal output of yolk sac hemogenic endothelium over developmental time remain undefined. We performed a spatiotemporal analysis of EMP emergence, and document the morphological steps of the endothelial-to-hematopoietic transition. Emergence of rounded EMPs from polygonal clusters of Kit(+) cells initiates prior to the establishment of arborized arterial and venous vasculature in the yolk sac. Interestingly, Kit(+) polygonal clusters are detected in both arterial and venous vessels after remodeling. To determine whether there are similar mechanisms regulating the specification of EMPs with other angiogenic signals regulating adult-repopulating HSCs, we investigated the role of embryonic blood flow and Wnt/β-catenin signaling during EMP emergence. In embryos lacking a functional circulation, rounded Kit(+) EMPs still fully emerge from unremodeled yolk sac vasculature. In contrast, canonical Wnt signaling appears to be a common mechanism regulating hematopoietic emergence from hemogenic endothelium. These data illustrate the heterogeneity in hematopoietic output and spatiotemporal regulation of primary embryonic hemogenic endothelium.


Structural Covariance of the Prefrontal-Amygdala Pathways Associated with Heart Rate Variability.
The neurovisceral integration model has shown a key role of the amygdala in neural circuits underlying heart rate variability (HRV) modulation, and suggested that reciprocal connections from amygdala to brain regions centered on the central autonomic network (CAN) are associated with HRV. To provide neuroanatomical evidence for these theoretical perspectives, the current study used covariance analysis of MRI-based gray matter volume (GMV) to map structural covariance network of the amygdala, and then determined whether the interregional structural correlations related to individual differences in HRV. The results showed that covariance patterns of the amygdala encompassed large portions of cortical (e.g., prefrontal, cingulate, and insula) and subcortical (e.g., striatum, hippocampus, and midbrain) regions, lending evidence from structural covariance analysis to the notion that the amygdala was a pivotal node in neural pathways for HRV modulation. Importantly, participants with higher resting HRV showed increased covariance of amygdala to dorsal medial prefrontal cortex and anterior cingulate cortex (dmPFC/dACC) extending into adjacent medial motor regions [i.e., pre-supplementary motor area (pre-SMA)/SMA], demonstrating structural covariance of the prefrontal-amygdala pathways implicated in HRV, and also implying that resting HRV may reflect the function of neural circuits underlying cognitive regulation of emotion as well as facilitation of adaptive behaviors to emotion. Our results, thus, provide anatomical substrates for the neurovisceral integration model that resting HRV may index an integrative neural network which effectively organizes emotional, cognitive, physiological and behavioral responses in the service of goal-directed behavior and adaptability.


Influence of myofascial pain on the pressure pain threshold of masticatory muscles in women with migraine.
To evaluate the influence of myofascial pain on the Pressure Pain Threshold (PPT) of masticatory muscles in women with migraine. The sample comprised 101 women, ages ranging from 18 to 60 years, with an episodic migraine diagnosis previously confirmed by a neurologist. All patients were evaluated using Research Diagnostic Criteria for Temporomandibular Disorders to determine the presence of myofascial pain and were divided into 2 groups: group I (n=56), comprising women with a migraine, and group II (n=45), comprising women with a migraine and myofascial pain. Two more groups (49 asymptomatic women and 50 women with myofascial pain), matched for sex and race, obtained from a previous study, were added to this study. The PPT values of masseter and temporalis (anterior, middle, and posterior regions) muscles were recorded bilaterally using a pressure algometer. One-way analysis of variance and the Tukey test for pairwise comparisons were used in statistical analysis with a 5% significance level. We found that all groups had significantly lower PPT values compared with asymptomatic women, with lower values seen in group II (women with migraine and myofascial pain). Women with a migraine and myofascial pain showed significantly lower PPT values compared with women with a migraine only, and also when compared with women with myofascial pain only. Migraine, especially when accompanied by myofascial pain, reduces the PPT of masticatory muscles, suggesting the importance of masticatory muscle palpation during examination of patients with migraine.


Evidence that actomyosin cross bridges contribute to "passive" tension in detrusor smooth muscle.
Contraction of detrusor smooth muscle (DSM) at short muscle lengths generates a stiffness component we termed adjustable passive stiffness (APS) that is retained in tissues incubated in a Ca(2+)-free solution, shifts the DSM length-passive tension curve up and to the left, and is softened by muscle strain and release (strain softened). In the present study, we tested the hypothesis that APS is due to slowly cycling actomyosin cross bridges. APS and active tension produced by the stimulus, KCl, displayed similar length dependencies with identical optimum length values. The myosin II inhibitor blebbistatin relaxed active tension maintained during a KCl-induced contraction and the passive tension maintained during stress-relaxation induced by muscle stretch in a Ca(2+)-free solution. Passive tension was attributed to tension maintaining rather than tension developing cross bridges because tension did not recover after a rapid 10% stretch and release as it did during a KCl-induced contraction. APS generated by a KCl-induced contraction in intact tissues was preserved in tissues permeabilized with Triton X-100. Blebbistatin and the actin polymerization inhibitor latrunculin-B reduced the degree of APS generated by a KCl-induced contraction. The degree of APS generated by KCl was inhibited to a greater degree than was the peak KCl-induced tension by rhoA kinase and cyclooxygenase inhibitors. These data support the hypothesis that APS is due to slowly cycling actomyosin cross bridges and suggest that cross bridges may play a novel role in DSM that uniquely serves to ensure proper contractile function over an extreme working length range.


Evaluation of the Potential of Fungal Biopesticides for the Biological Control of the Seed Bug, Elasmolomus pallens (Dallas) (Hemiptera: Rhyparochromidae).
Elasmolomus pallens is a post-harvest insect pest of groundnuts which causes severe yield loss to farmers, particularly in Africa and Asia. Resistance to synthetic chemicals has been on the rise among insects and is a constraint on insecticides regulations. In view of the drive for alternative approaches to synthetic insecticides, this study evaluated the potential of biopesticides based on entomopathogenic fungi against E. pallens under laboratory conditions. Fungal isolates from the bug cadaver including Fusarium proliferatum F1, Aspergillus tamarii F2, A. flavus F3, Trichoderma atroviride F4, A. niger F4, and Metarhizium anisopliae (Meschn.) Sorokin, originating from the cadaver of Zonocerus variegatus were screened for virulence against the bug. Adult bugs were dipped briefly in conidial concentration 1 × 108 conidial mL-1 and observed at 25 ± 2 °C, 80 ± 10 RH and 14: 10 L:D for 10 days. The fungal isolates caused mortality ranging from 48 to 100% based on their potential to infect and kill the bug. Five conidial concentrations (1 × 104 to 1 × 108 conidia mL-1) were evaluated against adult bugs in the multiple-dose virulence bioassay. Lethal concentrations (LC50 and LC90) values of 6.75 × 106 and 4.42 × 109 conidia mL-1 were obtained for A. flavus F3 while M. anisopliae had 8.0 × 106 and 6.14 × 108 conidia mL-1 respectively. Lethal time (LT50 and LT90) values were 3.3 and 6.2 days for A. flavus F3 compared to 3.6 and 5.6 days for M. anisopliae, respectively. Thus, A. flavus F3 showed potential against E. pallens; and can be considered as an ideal isolate for incorporation into formulations for field applications.


[Reversible pulmonary hypertension as a consequence of dasatinib treatment in a patient with chronic myeloid leukemia and scleroderma].
Pulmonary hypertension may be associated with many clinical conditions, including connective tissue diseases. We present a case of a patient with sclerodermia and chronic myeloid leukemia, who developed severe symptoms of pulmonary hypertension. Atypical clinical course of pulmonary hypertension, including complete remission of clinical symptoms and hemodynamic improvement provoked critical approach to the etiology of pulmonary hypertension. Taking into account the temporal coincidence with the use of dasatinib (a tyrosine kinase inhibitor) and a few case reports in the literature, it appears that reversible pulmonary hypertension in our patient was associated with the use of dasatinib. Sclerodermia in a previous medical history, an acknowledged risk factor for pulmonary hypertension, initially delayed the correct diagnosis. Reclassification changes the clinical prognosis of pulmonary hypertension in this specific case and allowed to terminate of specific treatment of pulmonary hypertension with good results.


Polyamines in rat hepatocyte cultures.
In rat hepatocytes cultured for 120 h polyamine content was markedly modified. Putrescine concentration reached a maximum at 48 h, spermidine increased for 48 h and then remained constant, spermine after a decrease returned to its initial values. Total polyamine amount was increased by 75%. Both ornithine decarboxylase and the retroconversion pathway were responsible for these modifications. The possible correlation between polyamine metabolism and retrodifferentiation process was investigated by studying them in conditions which are known to preserve differentiated functions.


Prevalence of drug-resistant and nonsubtype B HIV strains in antiretroviral-naïve, HIV-infected individuals in New York State.
The duration of HIV infection is usually unknown for most patients entering into HIV care. Data on the frequency at which resistance mutations are detected in these patients are needed to support practical guidance on the use of resistance testing in this clinical situation. Furthermore, little is known about HIV subtype diversity in much of the United States. Therefore, we analyzed the prevalence of drug resistance mutations and nonsubtype B strains of HIV among antiretroviral-naïve individuals presenting for HIV care in New York State between September 2000 and January 2004. Sequences were obtained using a commercial HIV genotyping assay. Seventeen of 151 subjects (11.3%; 95% confidence interval 7.2%-17.3%) had at least one drug-resistance mutation, including 5 subjects with fewer than 200 CD4(+) T cells, indicative of advanced infection. Nucleoside reverse transcriptase inhibitor, non-nucleoside reverse transcriptase inhibitor, and protease inhibitor resistance mutations were detected in 6.6%, 5.3%, and 0.7% of subjects, respectively. Subjects from New York City-based clinics were less likely to have resistant virus than subjects from clinics elsewhere in New York State. Nonsubtype B strains of HIV were detected in 9 (6.0%) individuals and were associated with heterosexual contact. Two nonsubtype B strains from this cohort also carried drug-resistance mutations. These data indicate that drug-resistant virus is frequently detected in antiretroviral-naïve individuals entering HIV care in New York State. Furthermore, a diverse set of nonsubtype B strains were identified and evidence suggests that nonsubtype B strains, including those carrying drug-resistance mutations, are being transmitted in New York State.


No Influence of bcl-2, p53, and p21waf1 protein expression on the outcome of pediatric Hodgkin lymphomas.
In Argentina, lymphomas account for 13.6% of all pediatric tumors and 47% of them are Hodgkin lymphoma. Previous studies of lymphoma series have reported the expression of apoptotic and cell cycle proteins. Our aim was to study these markers in our pediatric patients and correlate them with their outcome. Immunohistochemical staining with monoclonal antibodies anti-p53, bcl-2, p21, and mdm2 were performed on formalin-fixed paraffin-embedded Hodgkin lymphoma lymph node biopsies from 54 pediatric patients. The analyzed oncogenes p53, bcl-2, p21, and mdm2 exhibited 81%, 44%, 76%, and 90% positive staining, respectively. The most prevalent p53/p21 expression pattern was p53+/p21+, in 57% of cases, whereas concerning p53/mdm2 expression pattern p53+/mdm2+ was observed in 61% of cases. We failed to find any statistically significant correlation between oncogene expression and patient's survival. It seems that p53 plays an important role in lymphomagenesis in our studied population, because it is overexpressed in 81% of Hodgkin lymphoma cases and in more than 50% of cases, it might be able to activate its cellular effectors. Bcl-2 staining observed in 44% of our cases could represent a failure in bcl-2 down-regulation that leads to a rescue event in defective germinal center B-cells, that allows them to develop into Reed-Sternberg and Hodgkin cells.


Recent Progress of Nano-drug Delivery System for Liver Cancer Treatment.
Liver cancer is one of serious diseases which threaten human life and health. Studies on the treatment of liver cancer have attracted widespread attention. Application of nano-drug delivery system (NDDS) can not only improve selective drug delivery to liver tissue and improve the bioavailability of drug, but also can reduce the side effects of drugs when it is specially modified in the respects of structure modification or specific target molecules decoration. This review will address the latest development of liver-targeted drug delivery system.


High prevalence of erectile dysfunction in diabetes: a systematic review and meta-analysis of 145 studies.
Erectile dysfunction may be common among men with diabetes, but its prevalence is still debated. We aimed to assess the relative prevalence of erectile dysfunction in diabetes searching major databases from inception to November 2016 for studies reporting erectile dysfunction in men with Type 1 and Type 2 diabetes mellitus. We conducted a meta-analysis of the prevalence [and 95% confidence intervals (95% CIs)] of erectile dysfunction in diabetes compared with healthy controls, calculating the relative odds ratios (ORs) and 95% CIs. A random effect model was applied. From 3747 initial hits, 145 studies were included representing 88 577 men (age: 55.8 ± 7.9 years). The prevalence of erectile dysfunction in diabetes overall was 52.5% (95% CI, 48.8 to 56.2) after adjusting for publication bias, and 37.5%, 66.3% and 57.7% in Type 1, Type 2 and both types of diabetes, respectively (P for interaction < 0.0001). The prevalence of erectile dysfunction was highest in studies using the Sexual Health Inventory for Men (82.2%, 17 studies, P for interaction < 0.0001). Studies with a higher percentage of people with hypertension moderated our results (beta = 0.03; 95% CI, 0.008 to 0.040; P = 0.003; R2 = 0.00). Compared to healthy controls (n = 5385) men with diabetes (n = 863) were at increased odds of having erectile dysfunction (OR 3.62; 95% CI, 2.53 to 5.16; P < 0.0001; I2 = 67%, k = 8). Erectile dysfunction is common in diabetes, affecting more than half of men with the condition and with a prevalence odds of approximately 3.5 times more than controls. Our findings suggest that screening and appropriate intervention for men with erectile dysfunction is warranted.


Co-infection by Semliki forest virus and malarial parasite modulates viral multipucation, pathogenesis and cytokines in mice.
Environmental, technological and societal factors continue to have a dramatic effect on infectious diseases worldwide and are considered to be facilitating the emergence of several infectious diseases at a time. Co-infection with different species of viral and malaria infections are currently emerging problems of dual infection in the developing as well as developed countries. Understanding of interactions between the host, malaria and virus infection is of current concern and we have initiated studies to delineate the mechanisms involved during the progression of Semliki forest virus (SFV) and Plasmodium yoelii (P. yoelii) infection in mice. Enhanced virus multiplication and up-regulation of cytokine mRNA level in P. yoelii and SFV co-infected mice were observed on day 4 post-infection compared to respective controls. Collectively, our observations indicate that malaria infection may influence virus multiplication, pathogenesis and up-regulation of cytokine mRNA during co-infection in mice.


A case study: the initiative to improve RN scheduling at Hamilton Health Sciences.
In 2003, Hamilton Health Sciences embarked on an initiative to improve and standardize nursing schedules and scheduling practices. The scheduling project was one of several initiatives undertaken by a corporate-wide Nursing Resource Group established to enhance the work environment and patient care and to ensure appropriate utilization of nursing resources across the organization's five hospitals. This article focuses on major activities undertaken in the scheduling initiative. The step-by-step approach described, plus examples of the scheduling resources developed and samples of extended-tour schedules, will all provide insight, potential strategies and practical help for nursing administrators, human resources (HR) personnel and others interested in improving nurse scheduling.


Bowel diversion should be used with caution in stenosing anal Crohn's disease.
Proximal diversion has commonly been used for severe perianal Crohn's disease in an attempt to relieve local symptoms, whether the primary intestinal disease is in the colon or small bowel. Two patients are presented in whom diversion led to severe symptomatic disease in the previously normal defunctioned bowel. In each case the development of colonic disease was associated with increasing anal stenosis leading to retention of purulent fluid within the bowel lumen. Faecal stream diversion should be used with caution in stenosing anal Crohn's disease.


Evidence for a glucose effect on N-acetylglucosamine catabolism in Candida albicans.
Two strains of Candida albicans were examined for a glucose effect on the catabolism of N-acetylglucosamine. It was shown that the induction of N-acetylglucosamine uptake capacity was almost completely blocked by glucose at 0.5% (w/v), whereas that of N-acetylglucosamine kinase was partially repressed.


Omalizumab in children and adolescents with chronic spontaneous urticaria: Case series and review of the literature.
The recent EAACI/GA2 LEN/EDF/WAO guidelines recommend omalizumab (anti-IgE) for the management of patients aged ≥12 years with chronic urticaria unresponsive to high-doses second-generation H1 -antihistamines (antiH1 ). However, there is little published information on the success of omalizumab for such a treatment in children. We reported our experience of six patients with chronic spontaneous urticaria (CSU) treated with omalizumab. Mean age of our case series was 14.7 years (range 11-16 years) with a prevalence of male gender (66.7%). All six patients were treated with at least one 6-months course of omalizumab. The average follow-up period was 13 ± 6 months. Only one patient was no responder to omalizumab therapy. Thus far, two patients have experienced a complete CSU regression over 12 months after the final omalizumab administration. The remaining three patients needed a second course of treatment. Our experience demonstrates that omalizumab is effective and safe as treatment option for CSU unresponsive to antiH1 , even in adolescent age.


Accelerated prenatal diagnosis of fragile X syndrome by polymerase chain reaction restriction fragment detection.
Prenatal diagnosis of fragile X syndrome requires detection of the full FMR1 mutation in chorionic villus or amniotic fluid cell samples. Although analysis of genomic DNA restriction fragment pattern is a highly reliable technique for identification of the full FMR1 mutation, standard Southern blot determination of this pattern requires significantly more genomic DNA than is initially available from a prenatal sample. To overcome this limitation we developed a method that determines the diagnostic pattern of genomic restriction fragments from a fraction of a prenatal specimen. The prenatal DNA sample is first digested with EcoRI and EagI, and after agarose gel electrophoresis, the 2- to 10-kb region of the gel is serially sectioned and amplified by polymerase chain reaction. Analysis of prenatal samples from an unaffected male and from a full mutation male showed that this approach generated a diagnostic pattern comparable with a Southern blot of 100-fold more material. This innovation enables laboratories to prenatally diagnose the full FMR1 mutation sooner than standard techniques.


Seven Challenges for the Dehumanization Hypothesis.
Propagandists often compare members of stigmatized out-groups to nonhuman entities such as rats, lice, and snakes. Drawing on these horrifying descriptions, the dehumanization hypothesis proposes that out-group members are viewed as less than human and that being viewed as less than human renders them vulnerable to harm. I offer seven challenges to the dehumanization hypothesis. I argue that, even in supposedly prototypical examples of extreme dehumanization, out-group members are not treated like nonhuman entities. Furthermore, although out-group members may be denied some human qualities and states, they are attributed others. I also argue that there is reason to doubt the hypothesized causal connection between being viewed as less than human and being at risk of harm-some nonhuman organisms are treated with great care, and some groups are harmed because of how their uniquely human qualities are perceived. I close by offering an alternative account of why out-group members are sometimes referred to as nonhuman entities.


FHOD1 regulates cytoplasmic actin-based spindle migration for mouse oocyte asymmetric cell division.
FHOD1 is a member of Diaphanous-related formins (DRFs) which belongs to the Formin family. Previous studies have shown that the DFRs might affect several cellular functions such as morphogenesis, cytokinesis, cell polarity, and embryonic differentiation. However, there is no evidence showing the functions of FHOD1 during oocyte meiosis. This study is aimed at exploring the roles of FHOD1 during the mammalian oocyte maturation. Immunofluorescent staining showed that FHOD1 was restricted to the nucleus in germinal vesicle (GV) stage of the oocytes, after the GV breakdown FHOD1 was primarily located at two poles of the spindle at both metaphases I and II stages. Knockdown of FHOD1 by siRNA injection did not affect polar body extrusion but generated the large polar bodies. In addition, we observed the spindle migration failure in metaphase I oocytes, with a large number of meiotic spindles anchoring in the center of cytoplasm. The expression level of cytoplasmic actin but not cortex actin was significantly reduced, indicating that FHOD1 regulates cytoplasmic actin distribution for the spindle movement. Furthermore, we found that the disruption of ROCK (the Rho-dependent protein kinase) with inhibitor Y-27632 caused the decreased FHOD1 protein expression. Therefore, our data indicate that FHOD1 is regulated by ROCK for cytoplasm actin assembly and spindle migration during mouse oocyte meiosis.


Antiparasitic activity of nine pyrazole derivatives against Trichomonas vaginalis, Entamoeba invadens and Plasmodium berghei.
Nine nitropyrazole derivatives were prepared and tested against Trichomonas vaginalis in vitro and in vivo, Entamoeba invadens in vitro and Plasmodium berghei in vivo. Three of the compounds, 4-4-nitropyrazole, 1-methyl-4-nitropyrazole and 4,4'-dinitro-1,1'-methylenedipyrazole, have an activity similar to that of metronidazole (used as the reference compound) against T. vaginalis and E. invadens after 48 hours of incubation. All the compounds tested were inactive against P. berghei.


Ovarian Manson's Schistosomiasis: Rare Diagnosis or Underestimated Prevalence?
The occurrence of Manson's schistosomiasis in organs of the female reproductive tract is an uncommon event, given that the etiological agent for this disease is a blood parasite that inhabits the mesenteric veins. In this case report, a 45-year-old female patient reported that her first symptoms had been strong pain in the left iliac region around two years earlier. An endovaginal pelvic ultrasonography showed that the left ovary was enlarged, and the report suggested that this finding might be correlated with clinical data and tumor markers. After being examined at several healthcare services, the patient was referred to an oncology service due to suspected neoplasia, where she underwent a left ovariectomy. The result from the histopathological examination showed the presence of granulomatous inflammatory processes surrounding both viable and calcified eggs of Schistosoma mansoni. There was no evidence of any neoplastic tissue. The patient was medicated and followed-up as an outpatient.


[Pd8(CH3COO)8(NO)8]: solution from X-ray powder diffraction data.
The water-insoluble title compound, octakis(mu-acetato-kappa2O:O)octakis(mu-nitroso-kappa2N:O)octapalladium(II), [Pd8(CH3COO)8(NO)8], was precipitated as a yellow powder from a solution of palladium nitrate in nitric acid by adding acetic acid. Ab initio crystal structure determination was carried out using X-ray powder diffraction techniques. Patterson and Fourier syntheses were used for atom locations, and the Rietveld technique was used for the final structure refinement. The crystal structure is of a molecular type. The skeleton of the [Pd8(CH3COO)8(NO)8] molecule is constructed as a tetragonal prism with Pd atoms at the vertices. The eight NO- groups are in bridging positions along the horizontal edges of the prism. The N and O atoms of each nitroso group coordinate two different Pd atoms. The vertical edges present PdPd contacts with a short distance of 2.865 (1) A. These Pd atoms are bridged by a pair of acetate groups in a cis orientation with respect to each other. The complex has crystallographically imposed 4/m symmetry; all C atoms of the acetate groups are on mirror planes. The unique Pd atom lies in a general position and has square-planar coordination, consisting of three O and one N atom.


Predictors of Low Cardiac Output Syndrome in Infants After Open-Heart Surgery.
To evaluate the predictors of low cardiac output syndrome (LCOS) in infants with congenital heart disease (CHD) after cardiopulmonary bypass (CPB). A total of 217 infants were enrolled and classified according to whether they developed LCOS after cardiac surgery. Each infant's preoperative and intraoperative clinical variables were collected. The incidence of LCOS was 28.11% in our study. The univariate analysis showed that the LCOS group was younger than the non-LCOS group (25.69 ± 25.01 days vs. 44.45 ± 26.97 days, P < 0.001), with a higher proportion of neonates (60.7 vs. 27.6%, P < 0.001) and a higher proportion of patients with a RACHS-1 score ≥4 (50.8 vs. 17.9%, P < 0.001). A lower weight (3.70 ± 0.74 vs. 4.23 ± 1.10 kg, P = 0.001), longer ACC time (61.96 ± 21.44 min vs. 41.06 ± 18.37 min, P < 0.001) and longer CPB time (131.54 ± 67.21 min vs. 95.78 ± 62.67 min, P < 0.001) were found in the LCOS group. The levels of free triiodothyronine (FT3) (4.55 ± 1.29 pmol/L vs. 5.18 ± 1.42 pmol/L, P = 0.003) and total triiodothyronine (TT3) (1.80 ± 0.56 nmol/L vs. 1.98 ± 0.54 nmol/L, P = 0.026) were also lower in the LCOS group. The multivariate binary logistic regression analysis and receiver operating characteristic (ROC) indicated that the ACC time, FT3 level and body weight were independent predictors of LCOS. In our patient population, we first propose that preoperative FT3 can predict the occurrence of postoperative LCOS. ACC time, FT3 level and body weight are independent predictors of LCOS and maybe helpful in reducing the incidence of postoperative LCOS in the future.


Anagrelide: a decade of clinical experience with its use for the treatment of primary thrombocythaemia.
Primary thrombocythaemia (PT) is the most frequent among the rare chronic myeloproliferative disorders. Life expectancy is determined by thromboembolic and haemorrhagic complications, which can be prevented by cytoreductive therapy. For a long time, hydroxyurea has been considered as the therapeutic gold standard. However, hydroxyurea treatment is not lineage-specific, may not be tolerated because of adverse effects (skin, gastrointestinal tract) and is leukaemogenic when sequentially used with other DNA-targeting drugs. Hence, anagrelide was welcomed in 1988 when it was first described as being efficient at normalising elevated platelet counts, specific for megakaryocytes and non-mutagenic. Since then, anagrelide has been approved in the US and Canada (Agrylin), Shire Pharmaceuticals) as well as in Austria and other countries of the EU (Thromboreductin), AOP Orphan Pharmaceuticals). Clinical Phase III trials (PT1 and ANAHYDRET) are underway to directly compare the efficacy and safety of anagrelide and hydroxyurea.


Changes in Swallowing-related Quality of Life After Endoscopic Treatment For Zenker's Diverticulum Using SWAL-QOL Questionnaire.
Dysphagia affects the most cardinal of human functions: the ability to eat and drink. The aim of this prospective study was to evaluate swallowing dysfunction in patients diagnosed with Zenker's diverticulum using the Swallowing Quality of Life (SWAL-QOL) questionnaire preoperatively. In addition, SWAL-QOL was used to assess changes in the outcome of swallowing function after endoscopic treatment of Zenker's diverticulum compared to baseline. Pre- and postoperative SWAL-QOL data were analyzed in 25 patients who underwent endoscopic treatment of Zenker's diverticulum between January 2011 and December 2013. Patients were treated by different endoscopic techniques, depending on the size of the diverticulum: CO2 laser technique or stapler technique, or the combination of both techniques used in larger diverticula. Their mean age was 69 years, and 28% of patients were female. The mean interval between endoscopic surgery and completion of the postoperative SWAL-QOL was 85 days. The median (min-max) preoperative total SWAL-QOL score was 621 (226-925) out of 1100, indicating the perception of oropharyngeal dysphagia and diminished quality of life. Following endoscopic treatment of Zenker's diverticulum, significant improvement was demonstrated in the postoperative total SWAL-QOL score of 865 (406-1072) out of 1100 (p < 0.001). On the majority of subscales of SWAL-QOL there was significant improvement between pre- and postoperative scores. To the authors' knowledge, this is the first report in the literature on the changes in pre- and postoperative SWAL-QOL scores for patients with Zenker's diverticulum before and after treatment. The results of this study indicate that endoscopic treatment of Zenker's diverticulum leads to significant symptom relief as documented by significant changes in the majority of the SWAL-QOL domains.


The effectiveness of standardized versus individualized hypnotic suggestions: a brief communication.
The results of a number of studies indicate that hypnotizability is a relatively stable trait that has some predictive value for therapy outcome. Some authors argue, however, that hypnotizability scores are artifacts of standardized test procedures, and that more people will benefit from hypnosis when a broader range of suggestions is used. The present study was designed to investigate the effectiveness of standardized versus individualized suggestions. In a crossover design, counterbalanced for order of presentation, 48 Ss were tested twice: once with the Stanford Hypnotic Clinical Scale: Adult (SHCS: Adult) of Morgan and J. R. Hilgard (1975) and once with an individualized equivalent of SHCS: Adult. The results of this comparison showed no significant differences between the 2 methods. The present study does not support the concept of hypnotizability scores as artifacts of standardized measurements.


Involvement of central nervous system in diabetes mellitus.
Brainstem auditory evoked responses were recorded in 22 diabetic patients with a variable duration of illness (mean 5.8 years) and 14 normal healthy controls of comparable age. The initial 10 millisecond components, found to be most consistent and reproducible, were analysed. Variations in the form of individual wave latency, interpeak latencies and V wave amplitude were compared in both the groups. No difference was found in any of the parameters. It was concluded that central neural pathways are not involved at least initially in diabetes mellitus.


Bleeding complications in BCR-ABL negative myeloproliferative neoplasms: prevalence, type, and risk factors in a single-center cohort.
The BCR-ABL1-negative myeloproliferative neoplasms (MPN) share an increased risk of thrombotic and hemorrhagic complications. Risk factors for hemorrhage are less well defined than those for thrombosis. Because patients with CALR mutations have higher platelet counts compared to JAK2 V617F-mutated patients, bleeding rates may be increased in this group. Our aim was to retrospectively evaluate whether acquired von Willebrand disease (AvWD), thrombocytosis, mutational status, or treatment history are associated with bleeding in a cohort of MPN patients. Using an electronic database, MPN patients seen between 2005 and 2013 were retrospectively identified using ICD-9 codes and billing records. A bleeding event was defined as one that was identified in the medical record and graded based on the Common Terminology Criteria for Adverse Event (CTCAE) version 4.0. Among 351 MPN patients, 15.6 % experienced 64 bleeding event types. There was no association of bleeding with mutational status, gender, MPN subtype, aspirin use, prior thrombosis, or platelet count at presentation. There was an association between bleeding and older age at diagnosis. aVWD was identified in six patients. In this single-center retrospective study, bleeding events were identified in 15 % of patients, and associated with older age at diagnosis. aVWD was rarely tested for in this cohort.


Use of DNA barcode in the identification of fish eggs in tributaries of the Paranapanema River basin.
Fish eggs are often excluded from identification analysis since at this stage of development there are few morphological characters. The correct identification of eggs can provide important information about spawning areas of species. The current work aimed to identify fish eggs in the Tibagi and Cinzas Rivers using the DNA barcode to obtain information on richness and diversity, adding to the existing data in the area. Of the 928 sequences analyzed using the BOLD Systems database, 99.78% were able to be identified at a specific level, demonstrating a high success rate for egg identification. The samples resulted in 25 species, 11 families, and 2 orders. Of the 25 species found, more than half (60%) present reproductive migration behavior, indicating that the tributaries of the Capivara reservoir are being used as a migratory route by these species. Eggs of rare and endangered species were found, indicating these tributaries as spawning grounds for these species. The results demonstrate the importance of identifying fish eggs in reservoir-influenced environments to recognize breeding areas of native and endangered species, as well as the importance of the Tibagi and Cinzas Rivers for the maintenance of native fish species in the Paranapanema River.


A method for in situ visualization of Protein-Nascent RNA interactions in single cell using Proximity Ligation Assay (IPNR-PLA) in mammalian cells.
Proximity ligation assay (PLA) is an immunofluorescence assay, which determines in situ interaction of two biomolecules present within 40 nm close proximity. Here, we describe a modification of PLA for visual detection of in situ protein interactions with nascent RNA in a single cell (IPNR-PLA). In IPNR-PLA, nascent RNA is labeled by incorporating 5-fluorouridine (FU), a uridine nucleotide analogue, followed by covalent cross-linking of the interacting partners in proximity to newly synthesized RNA. By using combination of anti-BrdU antibody, which specifically binds to FU, and primary antibody against a protein of interest, the IPNR reaction results in fluorescent puncta as a positive signal, only if the candidate proteins are in proximity to nascent RNA. We have validated this method by demonstrating known CDK9 and elongating RNA pol II interaction with nascent RNA. Finally, we used this method to test for the presence of DNA double strand breaks as well as Poly (ADP-ribose) polymerase 1 (PARP1), an RNA binding protein, in the vicinity of nascent RNA in cancer cells. The capability of performing parallel IF labeling and quantifiable multiparameter measurements within heterogeneous cell populations makes IPNR-PLA very attractive for use in biological studies. Overall, we have developed the IPNR-PLA method for analysis of protein association with nascent RNA with single-cell resolution, which is highly sensitive, quantitative, efficient, and requires little starting experimental material.


Fluctuations in Parkinson's disease and personalized medicine: bridging the gap with the neuropsychiatric fluctuation scale.
Neuropsychiatric fluctuations (NpsyF) are frequent and disabling in people with Parkinson's disease (PD). In OFF-medication, NpsyF entail minus neuropsychiatric symptoms (NPS) like anxiety, apathy, sadness, and fatigue. In ON-medication, NpsyF consist in plus NPS, such as high mood, hypomania, and hyperactivity. Accurate identification of these NpsyF is essential to optimize the overall PD management. Due to lack of punctual scales, the neuropsychiatric fluctuation scale (NFS) has been recently designed to assess NpsyF in real time. The NFS comprises 20 items with two subscores for plus and minus NPS, and a total score. To evaluate the psychometric properties of the NFS in PD. PD patients with motor fluctuations and healthy controls (HC) were assessed. In PD patients, the NFS was administrated in both the ON-and OFF-medication conditions, together with the movement disorders society-unified Parkinson disease rating scale parts I-IV. Depression (Beck depression scale II), apathy (Starkstein apathy scale) and non-motor fluctuations items of the Ardouin scale of behaviour in PD (ASBPD OFF and ON items) were also assessed. NFS internal structure was evaluated with principal component analysis consistency (PCA) in both medication conditions in PD patients and before emotional induction in HC. NFS internal consistency was assessed using Cronbach's alpha coefficient. NFS convergent and divergent validity was measured through correlations with BDI-II, Starktein, and ASBPD OFF and ON non motor items. Specificity was assessed comparing NFS global score between the HC and PD populations. Sensitivity was evaluated with t-student test comparing the ON-and the OFF-medication conditions for NFS global score and for minus and plus subscores. In total, 101 consecutive PD patients and 181 HC were included. In PD patients and HC, PCA highlighted one component that explained 32-35 and 42% of the variance, respectively. Internal consistency was good for both the NFS-plus (alpha =0.88) and NFS-minus items (alpha =0.8). The NFS showed a good specifity for PD (p < 0.0001) and a good sensitivity to the medication condition (p < 0.0001). The satisfactory properties of the NFS support its use to assess acute neuropsychiatric fluctuations in PD patients, adding to available tools.


[Plastic Surgical Correction of Buried Penis].
A "buried penis" causes functional problems and embarrassment. In the past, this complex condition was only seen in extremely overweight patients or as a result of severe inflammations in this region. More recently, this problem has also been observed in patients with massive weight loss following bariatric surgery. In these patients there is an abundance of extremely flaccid skin in the suprapubic region, which covers the penis and causes it to "disappear". This leads to balanitis and, in turn, further retraction of the penis. The only solution to this condition is a sophisticated surgical approach in 3 phases: At first, suprapubic tissues must be lifted. Secondly, the penis must be completely denuded and debrided and the correct penopubic/penoscrotal angles must be reconstructed. The last phase includes a strainless coverage of the remaining defect of the penis. This condition has not been widely described in the literature. The general incidence and prevalence in the postbariatric population is unknown, probably due to patients' embarrassment and lack of knowledge on the physicians' end. Nevertheless, the buried penis can be successfully exposed through careful, structured surgical treatment and an interdisciplinary approach between plastic surgeons and urologists.


Morphometric comparison of the human corpus callosum in professional musicians and non-musicians by using in vivo magnetic resonance imaging.
The purpose of this study was to determine the possible morphometrical differences of the corpus callosum between professional musicians and non-musicians. Certain callosal dimensions and areas were measured in 20 professional musicians and compared with 20 age-, sex- and handedness-matched control group by using in vivo magnetic resonance imaging (MRI). Sagittal T1-weighted midsagittal sections were traced with the digitizer and the metric scale of the system was used for the measurements. Results were statistically analysed by independent t test. There were significant differences between the two groups both for the anterior and posterior areas of the corpus callosum. Furthermore, significant differences between the two groups were found in the thicknesses of certain parts of the corpus callosum. Our results support the hypothesis that brain morphology is prone to plastic changes caused by environmental factors.


Comprehensive transcriptional analysis of pig facial skin development.
Skin development is a complex process that is influenced by many factors. Pig skin is used as an ideal material for xenografts because it is more anatomically and physiologically similar to human skin. It has been shown that the skin development of different pig breeds is different, and some Chinese pig breeds have the characteristics of skin thickness and facial skin folds, but the specific regulatory mechanism of this skin development is not yet clear. In this study, the facial skin of Chenghua sows in the four developmental stages of postnatal Day 3 (D3) , Day 90 (D90) , Day 180 (D180), and Year 3 (Y3) were used as experimental materials, and RNA sequencing (RNA-seq) analysis was used to explore the changes in RNA expression in skin development at the four developmental stages, determine the differentially expressed messenger RNAs (mRNAs), long noncoding RNAs (lncRNAs), microRNAs (miRNAs), and circular RNAs (circRNAs), and perform functional analysis of related genes by Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. A pairwise comparison of the four developmental stages identified several differentially expressed genes (DEGs) and found that the number of differentially expressed RNAs (DE RNAs) increased with increasing developmental time intervals. Elastin (ELN) is an important component of the skin. Its content affects the relaxation of the epidermis and dermal connection, and its expression is continuously downregulated during the four developmental stages. The functions of DEGs at different developmental stages were examined by performing GO and KEGG analyses, and the GO terms and enrichment pathways of mRNAs, lncRNAs, miRNAs, and circRNAs highly overlapped, among which the PPAR signaling pathway, a classical pathway for skin development, was enriched by DEGs of D3 vs. D180, D90 vs. D180 and D180 vs. Y3. In addition, we constructed lncRNA-miRNA-mRNA and circRNA-miRNA interaction networks and found genes that may be associated with skin development, but their interactions need further study. We identified a number of genes associated with skin development, performed functional analyses on some important DEGs and constructed interaction networks that facilitate further studies of skin development.


Neurological and neurophysiological examinations of workers exposed to arsenic levels exceeding hygiene standards.
The assessment of the neurotoxic effect of arsenic (As) and its inorganic compounds is still the subject of interest due to a growing As application in a large array of technologies and the need to constantly verify the principles of prevention and technological parameters. The aim of this study was to determine the status of the nervous system (NS) in workers exposed to As at concentrations exceeding hygiene standards (Threshold Limit Values (TLV) - 10 μg/m(3), Biological Exposure Index (BEI) - 35 μg/l) and to analyze the relationship between the NS functional state, species of As in urine and As levels in the workplace air. The study group comprised 21 men (mean age: 47.43±7.59) employed in a copper smelting factory (mean duration of employment: 22.29±11.09). The control group comprised 16 men, matched by age and work shifts. Arsenic levels in the workplace air (As-A) ranged from 0.7 to 92.3 μg/m(3); (M = 25.18±28.83). The concentration of total arsenic in urine (As(tot)-U) ranged from 17.35 to 434.68 μg/l (M = 86.82±86.6). Syndrome of peripheral nervous system (PNS) was manifested by extremity fatigue (28.6%), extremity pain (33.3%) and paresthesia in the lower extremities (33.3%), as well as by neuropathy-type mini-symptoms (23.8%). Electroneurographic (ENeG) tests of peroneal nerves showed significantly decreased response amplitude with normal values of motor conduction velocity (MCV). Stimulation of sural nerves revealed a significantly slowed sensory conduction velocity (SCV) and decreased sensory potential amplitude. Neurophysiological parameters and the results of biological and environmental monitoring showed a relationship between As(tot), As(III) (trivalent arsenic), the sum of iAs (As(III)+As(V) (pentavalent arsenic))+MMA (monomethylarsonic acid) concentration in urine and As levels in the air. The results of the study demonstrate that occupational exposure to inorganic arsenic levels exceeding hygiene standards (TLV, BEI) generates disorders typical of peripheral neuropathy.


Development of alternative herbals remedy for gastric cancer based on transcriptomic analysis of immune infiltration and ferroptosis.
Objective: Screening out potential herbal medicines and herbal ingredients for the treatment of gastric cancer based on transcriptomic analysis of immune infiltration and ferroptosis. Methods: Gene expression profiles of gastric tumour tissues and normal tissue samples were obtained from the GEO database and the samples were analysed for immune cell infiltration condition and differential expressed genes of ferroptosis. Key genes were screened by protein-protein interaction (PPI) and enrichment analysis, and molecular docking was used to predict and preliminary validate potential herbal and traditional Chinese medicine components for gastric cancer based on the key genes. Finally, RT-QPCR was used to validate the prediction results. Results: Immune cell infiltration analysis revealed high levels of infiltration of activated CD4 memory T cells, monocytes, M0 macrophages in gastric tumor tissues, while plasma cells and resting mast cells had higher levels of infiltration in the paraneoplastic tissues. Differential gene expression analysis identified 1,012 upregulated genes and 880 downregulated genes, of which 84 immune related differentially expressed genes such as CTSB, PGF and PLAU and 10 ferroptosis-related differentially expressed genes such as HSF1, NOX4 and NF2 were highly expressed in gastric cancer tissues. The results of enrichment analysis showed that they mainly involve 343 biological processes such as extracellular matrix organization and extracellular structural organization; 37 cellular components such as complexes of collagen trimer and basement membrane; 35 molecular functions such as signal receptor activator activity and receptor ligand activity; 19 regulatory pathways such as cytokine-cytokine receptor interactions and retinol metabolism. Finally, two key genes, TLR4 and KRAS, were selected and 12 herbal medicines such as Radix Salviae liguliobae, Rhizoma Coptidis, Rhizoma Polygoni cuspidati and 27 herbal ingredients such as resveratrol, salvianolic acid b were predicted on the basis of key genes. Molecular docking results showed that KRAS binds tightly to coumarin and magnolol, while TLR4 can bind tightly to resveratrol, curcumin, salvianolic acid b, shikonin. Subsequently, the effect of resveratrol and magnolol was experimentally verified. Conclusion: Herbal medicines such as S. liguliobae, Rhizoma Coptidis, Rhizoma P. cuspidati and herbal ingredients such as resveratrol, curcumin, salvianolic acid b may provide research directions and alternative therapeutic approaches for immunomodulation of TME and ferroptosis of tumour cells in gastric cancer.


Intestinal peptide and protein delivery: novel bioadhesive drug-carrier matrix shielding from enzymatic attack.
We have been developing a novel bioadhesive drug-carrier matrix that protects embedded therapeutic peptides and proteins from degradation by the most abundant intestinal proteases. Increasing amounts of the Bowman-Birk inhibitor (BBI) were thereby covalently linked to chitosan-EDTA. The bioadhesive properties of the resulting polymer-BBI conjugates and their inhibitory effect toward trypsin (EC 220.127.116.11), chymotrypsin (EC 188.8.131.52), elastase (126.96.36.199), carboxypeptidase A (EC 220.127.116.11), and aminopeptidase N (EC 184.108.40.206) were evaluated in vitro. Whereas unmodified chitosan-EDTA exhibited under our experimental conditions an adhesive strength of 54.4 +/- 7.7 mN, it was determined to be 21.0 +/- 3.8 mN for the comparably most adhesive polymer-BBI conjugate (mean +/- SD; n = 5). All polymer-BBI conjugates showed a strong inhibitory activity toward the serine proteases trypsin and chymotrypsin. However, the protective effect toward elastase was markedly lower. Due to the high binding affinity of chitosan-EDTA toward zinc, which represents an essential cofactor for carboxypeptidase A and aminopeptidase N, all polymer-BBI conjugates displayed additionally a strong protective effect toward these exopeptidases. The novel bioadhesive polymer-BBI conjugates described in this study seem to be very useful drug-carrier matrixes in overcoming the enzymatic barrier to orally administered peptide and protein drugs.


Using pulse oximetry in the home.
As complex patients require more sophisticated nursing care and equipment to stay at home, home care nurses must be able to make detailed, objective assessments. Pulse oximetry provides a tool to objectively assess oxygenation in the home. This article reviews how pulse oximetry works, how to interpret the results based on the patient's blood oxygen-carrying capacity, and technical aspects of using pulse oximetry in the home, including sources of inaccuracy in measurements and basic troubleshooting. These pulse oximetry principles are applied in the home care setting in three case studies.


Cardiovascular actions of microinjections of angiotensin II in the brain stem of rats.
The blood pressure and heart rate responses to microinjection of angiotensin II (ANG II) into the brain stem of urethan-anesthetized rats were studied. Microinjection of ANG II into the area postrema (AP) resulted in significant elevation of blood pressure and significant reduction of heart rate. Microinjection into the region of the nucleus tractus solitarius (NTS) yielded a significant dose-dependent elevation in blood pressure and consistent increases in heart rate. The response to microinjection of ANG II into the region of the NTS was not due to leakage into the peripheral circulation, since intravenous administration of the ANG II antagonist, saralasin, did not attenuate the response. In fact, the cardiovascular response was increased after peripheral ANG II blockade, and the heart rate, which was consistently but not significantly elevated by NTS injection alone, was significantly elevated after saralasin pretreatment. Thermal ablation of the AP did not change the heart rate or the pressor response to microinjection of ANG II into the region of the NTS, indicating that the response was not mediated through the AP.


Effects of aging on tensile fatigue strength of bovine dentin.
The effects of aging on the tensile fatigue strength of bovine dentin were investigated. Tensile tests and tensile fatigue tests were performed in 37 degrees C water with bovine dentin specimens of two different age groups. The tensile strengths of the young group and the adult group were 74.0 MPa and 72.7 MPa, respectively; there was no significant difference between the young and the adult group. However, the tensile fatigue strength of the adult group, 46.9 MPa, was significantly weaker than that of the young group, 51.0 MPa. There was a obvious difference between the tensile fracture surface and the tensile fatigue fracture surface; a smooth surface of the peritubular dentin and an uneven surface of the intertubular dentin were clearly distinct in the fatigue fracture surface. Plugged dentinal tubules and narrower dentin tubules were commonly observed in the adult group. These morphological changes were suggested to be the reason for the decrease in the tensile fatigue strength with aging.


Surgical outcomes of laparoscopic vs. open surgery for rectal carcinoma--a matched case-control study.
The present study evaluated the short- and middle-term surgical outcomes of laparoscopic surgery (LS) for rectal carcinoma in comparison with a case-control series of open surgery (OS). Between February 1998 and December 2004, 47 patients with rectal carcinoma underwent LS. These patients were compared with a conventional OS group matched for age, gender, location of tumor, surgical procedure, extent of resection and pathological stage. The median follow-up period for the LS group and the OS group was 25 and 49 months, respectively. In the LS group, median operative time was significantly longer but median blood loss was lower than those in the OS group. There was one requiring conversion to OS. Postoperative intervals until liquid and solid intakes, and hospital stay were significantly shorter in the LS group. Postoperative complications rates are similar and anastomotic leakage occurred in one patient in each group. In the LS group, the levels of white blood cell count on postoperative day 1 and C-reactive protein on postoperative days 1 and 2 were significantly lower than those in the OS group. LS for rectal carcinoma provides benefits during the early postoperative period without increase in morbidity or mortality.


Coronary artery anatomy in children with congenital heart disease by computed tomography.
To evaluate electron beam computed tomography (EBCT) for recognition of coronary artery patterns in children with congenital heart diseases. Institutional review board approval was obtained; informed consents were not required. A total of 226 children diagnosed with Tetralogy of Fallot (n=122), double outlet right ventricle (n=52), transposition of the great arteries (n=34), and congenitally corrected transposition (n=18) who had undergone cardiac EBCT at our institution between 1995 and 2002 were identified. Iodinated contrast medium was injected with arterial phase acquisition. The two radiologists and one pediatric cardiologist that interpreted the EBCT images and cardiac angiograms, respectively, were blinded to each other's results. Surgical and cardiac angiogram findings were compared to the EBCT results. Descriptive statistics were used to compare efficacy. Numerous aberrant patterns were clearly identified on the EBCT images. Pattern IX occurred in most patients with Tetralogy of Fallot or double outlet right ventricle. Patterns I and 0 are the most common coronary artery types in transposition of the great arteries and congenitally corrected transposition, respectively. Overall diagnostic accuracy for all disease groups was 82.7%. The diagnostic accuracy of the coronary arterial anatomy by EBCT increased with older age, and was more than 90% in individuals aged over 3 months. EBCT is effective for identification of the coronary anatomy of children with specific congenital heart diseases, except for neonates and small infants less than 3 months of age.


Determination of Acyclovir in Human Plasma Samples by HPLC Method with UV Detection: Application to Single-Dose Pharmacokinetic Study.
The aim of this study is estimation of pharmacokinetic parameters: Cmax, tmax, t1/2, AUC0-t and AUC0-∞ with the two-way analysis of variance, single observation (ANOVA) for two preparations containing acyclovir. In order to evaluate pharmacokinetic study of acyclovir, method for quantitative determination of acyclovir in human plasma should be simple, rapid and reproducible. Therefore, the method is developed, validated and applied for analysis of acyclovir in plasma samples obtained from healthy volunteers. High performance liquid chromatographic (HPLC) method with UV-detection for the determination of acyclovir in human plasma is presented. This method involves protein precipitation with 20 % (V/V) perchloric acid. The chromatographic separation was accomplished on a reversed phase C8 column with a mobile phase composed of 0.1 % (V/V) triethylamine in water (pH 2.5). No internal standard is required. UV detection was set at 255 nm. The method was successfully applied for the evaluation of pharmacokinetic profiles of acyclovir tablets in 24 healthy volunteers. The validation results shows that proposed method is rugged, precise (RSDs for intra- and inter-day precision ranged from 1.02 to 8.37 %) and accurate (relative errors are less than 6.66 %). The calibration curve was linear in the concentration range of 0.1-2.0 µg/ml and the limit of quantification was 0.1 µg/ml. The Cmax, tmax and AUCs for the two products were not statistically different (p>0.05), suggesting that the plasma profiles generated by Zovirax were comparable to those produced by acyclovir manufactured by Jaka 80 company. Good precision, accuracy, simplicity, sensitivity and shorter time of analysis of the method makes it particularly useful for processing of multiple samples in a limited period of time for pharmacokinetic study of acyclovir.


[Self-efficacy predictiveness and its determinants among preschoolers].
Precision of self-efficacy predictions on a ball-throwing task was compared between the younger group (3-year-olds; N = 40) and the older group (5-year-olds; N = 40). Three factors underlying the development of accurate efficacy expectations were examined. They were the effect of experience, the complexity of the task, and information of task performance. Results indicated that the predictions of the older group were more accurate than those of the younger group, and their predictions were significantly related to subsequent performance. They did more realistic efficacy predictions by using information of task performance and experience. The younger group showed no accuracy of self-efficacy predictions. But the presentation of information about task performance enabled them to make realistic efficacy predictions.


Sweat electrolyte loss in asthmatic children during exercise in the heat.
This study assessed sweat electrolyte concentration and losses in asthmatic children during exercise in the heat. Eleven asthmatics (AG; 11 +/- 2 years old) and 11 nonasthmatics (CG; 10 +/- 1 year old) underwent a maximal progressive cycleergometer test. During a second session, participants cycled in the heat (35 degrees C, 60% RH) of a climatic chamber for 30 min at 50-60% of maximal workload. Sweat was collected using sweat patches attached to the dorsal region. No differences were observed in sweat [Na+] (AG = 35 +/- 12.9 and CG = 43.4 +/- 18 mmol/L) and [Cl-] (AG = 27.3 +/- 10.4 and CG = 38.5 +/- 19.1 mmol/L). There was no difference in sweat Na+ losses (AG = 0.47 +/- 0.36 and CG = 0.66 +/- 0.68 mmol/kg/h) and Cl- losses (AG = 0.37 +/- 0.29 and CG = 0.59 +/- 0.62 mmol/kg/h) between groups. Asthmatic children did not differ from nonasthmatics in their sweat electrolyte concentrations and electrolyte losses.


Predictors of sickness absence in patients with a new episode of low back pain in primary care.
This study examines predictors of sickness absence in patients presenting to a health practitioner with acute/ subacute low back pain (LBP). Aims of this study were to identify baseline-variables that detect patients with a new LBP episode at risk of sickness absence and to identify prognostic models for sickness absence at different time points after initial presentation. Prospective cohort study investigating 310 patients presenting to a health practitioner with a new episode of LBP at baseline, three-, six-, twelve-week and six-month follow-up, addressing work-related, psychological and biomedical factors. Multivariate logistic regression analysis was performed to identify baseline-predictors of sickness absence at different time points. Prognostic models comprised 'job control', 'depression' and 'functional limitation' as predictive baseline-factors of sickness absence at three and six-week follow-up with 'job control' being the best single predictor (OR 0.47; 95%CI 0.26-0.87). The six-week model explained 47% of variance of sickness absence at six-week follow-up (p<0.001). The prediction of sickness absence beyond six-weeks is limited, and health practitioners should re-assess patients at six weeks, especially if they have previously been identified as at risk of sickness absence. This would allow timely intervention with measures designed to reduce the likelihood of prolonged sickness absence.


Clock gene expression is altered in veterans with sleep apnea.
Clock gene dysregulation has been shown to underlie various sleep disorders and may lead to negative cardio-metabolic outcomes. However, the association between sleep apnea (SA) and core clock gene expression is unclear. We performed a cross-sectional analysis of 49 Veterans enrolled in a study of SA outcomes in veterans with chronic kidney disease, not selected for SA or sleep complaints. All participants underwent full polysomnography and next morning whole blood collection for clock gene expression. We defined SA as an apnea-hypopnea index ≥15 events/h; nocturnal hypoxemia(NH) was defined as ≥10% of total sleep time spent at <90% oxygen saturation. We used quantitative real-time PCR to compare the relative gene expression of clock genes between those with and without SA or NH. Clock genes studied were Bmal1, Ck1δ, Ck1ε, Clock, Cry1, Cry2, NPAS2, Per1, Per2, Per3, Rev-Erb-α, RORα, and Timeless. Our cohort was 90% male, mean age was 71 yr (SD 11), mean body mass index was 30 kg/m2 (SD 5); 41% had SA, and 27% had NH. Compared with those without SA, Per3 expression was reduced by 35% in SA ( P = 0.027). Compared with those without NH, NPAS2, Per1, and Rev-Erb-α expression was reduced in NH (50.4%, P = 0.027; 28.7%, P = 0.014; 31%, P = 0.040, respectively). There was no statistical difference in expression of the remaining clock genes by SA or NH status. Our findings suggest that SA or related NH and clock gene expression may be interrelated. Future study of 24 h clock gene expression in SA is needed to establish the role of clock gene regulation on the pathway between SA and cardio-metabolic outcomes.


Bacterial transformation of dietary lignans in gnotobiotic rats.
The bioactivity of lignans depends on their transformation by gut bacteria. The intestinal bacteria Clostridium saccharogumia, Eggerthella lenta, Blautia producta and Lactonifactor longoviformis convert the plant lignan secoisolariciresinol diglucoside via secoisolariciresinol (SECO) into the bioactive enterolignans enterodiol (ED) and enterolactone (EL). While the in vitro conversion of lignans by these bacteria has already been demonstrated, it is unclear whether this defined community is also capable of catalysing lignan transformation in vivo. We therefore associated germ-free rats with these four species. Germ-free rats served as a control. All animals were fed a diet containing 5% ground flaxseed. The caecal contents of rats associated with the four lignan-activating bacteria (ALB rats) contained SECO, ED and EL. The maximal EL formation rate from lignans in the pooled caecal contents of ALB rats was 7.52 nmol min(-1) g(-1) dry matter. The ALB rats excreted EL, but no SECO and ED, in their urine. The caecal contents of germ-free rats contained SECO, but no ED and EL. Their urine was devoid of lignans. Hence, the presence of enterolignans in the ALB rats, but not in the germ-free rats, demonstrates that this defined microbial community is capable of transforming plant lignans into EL in vivo.


Assessment of psychopathology in 2- to 5-year-olds: Applying the Infant-Toddler Social Emotional Assessment.
The information provided by parents is indispensable for the early identification of psychopathology; for this reason, developmentally appropriate, reliable, and valid questionnaires are needed to gather their information. This study was designed to examine the utility of the Infant Toddler Social Emotional Assessment (ITSEA), a parent-report questionnaire covering a wide range of behavior and emotional problems and competencies, in preschoolers referred for child psychiatric evaluation. The fathers and mothers of 85 children (23.2% girls; age 15-57 months) with autism spectrum, externalizing, or internalizing disorders completed the ITSEA, the Child Behavior Checklist (CBCL/2-3 and 4-18 versions), and the child domain of the Parenting Stress Index (PSI). The ITSEA showed good interrater reliability between parents, and validity was supported by significant correlations with corresponding CBCl and PSI domains. Evidence supporting the validity of the ITSEA for psychopathology was mixed across scales, with good diagnostic accuracy at the level of the broader psychiatric syndromes being achieved by the combination of subscales within the Externalizing, Internalizing, and Competence domains. The value of the ITSEA lies in the ability to systematically evaluate a wide range of problem behaviors and competencies. The ITSEA may be useful to create profiles of children's functioning in preschoolers referred for psychiatric assessment.


Simple pulse compression scheme based on filtering self-phase modulation-broadened spectrum and its application in an optical time-division multiplexing system.
We propose a simple and stable pulse compression scheme based on a filtering self-phase modulation broadened spectrum in a highly nonlinear fiber. It is found experimentally that under offset filtering the compressed pulse has a better quality compared with center filtering, such as a no pulse pedestal. Furthermore, numerical simulations reveal that the scheme has the potential to improve the pulse extinction ratio during compression. Finally, based on the obtained pulse train the 4 x 10 Gbits/s optical time-division multiplexing system is studied for verification of the high pulse quality. The compression scheme has the advantages of simple configuration, being pedestal-free, and having a high pulse extinction ratio.


[Influence of ionizing radiation of low intensity on the processes of reproduction, aging and dying off of Escherichia coli bacteria].
The influence of 60Co gamma-ray irradiation of low intensity (0.1-0.4, 0.76 x 10(3) microGy/h) on the processes of reproduction, aging and dying off of E. coli B/r and E. coli BS-1 bacteria have been investigated. It was shown that the reproduction of this bacteria strains was not dependent on the dose rate in the range 0.1-0.4 microGy/h. It was shown in comparison with the irradiated E. coli B/r cells dynamics of the aging and dying off of the irradiated E. coli BS-1 is decreased in the process of prolonged (about 190 days) irradiation with a dose rate of 0.76 x 10(3) microGy/h. It is proposed the relationship between the revealed phenomenon of the decrease in the intensity of the irradiated E. coli BS-1 cell aging and dying and the Vavilov-Cerenkov emission.


A path integral influence functional for excess electron in fluids: Density-functional formulation.
In this paper, we propose a path integral influence functional from a solvent to determine a self-correlation function of a quantum particle in classical simple fluid. It is shown that the influence functional is related to a grand potential functional of the pure solvent under a three-dimensional external field arising from a classical isomorphic polymer, on which the quantum particle is mapped. The influence functional can be calculated from the self-correlation function, the solute-solvent and the solvent-solvent pair correlation function. The obtained equation of the self-correlation function is applied to an excess electron problem in fluid helium. The Fourier path-integral Monte Carlo method is employed to perform the path integral of the electron. The solute-solvent pair correlation function is estimated from a reference interaction site model integral equation. These results obtained form our proposed influence functional and from that proposed by Chandler, Singh, and Richardson are compared with those provided by a path integral Monte Carlo simulation with the explicit helium solvent.


[Deep venous thrombosis of the upper extremities].
Deep vein thrombosis of the upper extremity is rare. While its pathogenesis is not always evident, it often occurs in connection with tumors, thoracic outlet syndrome or intravenous catheter therapy. Acute thrombosis of the subclavian vein usually is a clinical diagnosis, but in doubtful cases diagnostic tests such as Doppler ultrasound and/or plethysmography may be useful. If necessary, verification of subclavian vein thrombosis can be done by phlebography. Considering the incidence of thromboembolic complications such as pulmonary embolism, anticoagulation is indicated in all cases of acute thrombosis. Under standard conservative treatment residual symptoms following the venous occlusion are few and the prognosis is favorable. Therefore, invasive treatment such as thrombectomy or thrombolysis should be considered only in special cases.


DRESS syndrome with hepatic involvement in a patient with depressive disorder.
We present a 31-year-old woman with a depressive disorder admitted in the Infectious Diseases Department with high fever, cervical lymphadenopathy, generalized rash and progressive jaundice. Sepsis with hepatic involvement was initially suspected, but the bacteriological and serological profiles for viral and bacterial pathogens remained negative. The exposure to antidepressant medication including lamotrigine, an aromatic anticonvulsant molecule, raised the suspicion of Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) Syndrome. The antidepressants were withdrawn and methylprednisolone therapy was started with a favorable outcome and lent recovery after two months. This case highlights a rare drug allergic complication to antidepressant medication evolving as a sepsis with hepatic dysfunction.


Immunoglobulin binding by mouse intestinal epithelial cell receptors.
The IgG receptors involved in transporting maternal antibodies to the blood stream of the young mouse were studied by feeding internally labeled mouse myeloma proteins and enzymatically generated specific fragments of these proteins. The data obtained from competition experiments showed the following: 1) intestinal receptors have a single specificity which is directed against IgG Fc determinants; 2) IgG subclass proteins differ in their affinities for the receptors and thus have similar but not identical Fc recognition sites; 3) the order of affinities of the IgG subclass proteins for the receptors correlates with the relative concentrations of the four subclass proteins in mouse milk; and 4) several subfractions of the Fc fragment were inactive in binding to the receptors. In many of their properties the intestinal receptors resemble the Fc receptors on other cell types, but they are apparently unique in their ability to bind tightly non-aggregated IgG molecules.


Metabolism of the phosphatidylglycerol molecular species in Escherichia coli.
The fractionation, turnover and biosynthesis of the phosphatidylglycerol molecular species of Escherichia coli were studied. Monoacetyldiglycerides derived from phosphatidylglycerol were separated into five subfractions; cis-vaccenyl-palmitoleyl, cis-vaccenyl-cis-vaccenyl, palmityl-palmitoleyl, palmityl-cis-vaccenyl and the disaturated molecular species on a silica gel plate impregnated with silver nitrate. Individual molecular species had different turnover rates. The palmityl-cis-vaccenyl species was metabolized faster than the others. Disaturated species were rather stable. Various phosphatidylglycerol molecular species were synthesized in the presence of sn-glycerol 3-phosphate, palmityl-CoA, palmitoleyl-CoA, cis-vaccenyl-CoA and CTP by the E. coli membrane particulate fraction. When only the proportion of palmityl-CoA among the three acyl-CoAs was increased, the molecular species containing the palmityl residue were increased. Similar results were obtained with the other acyl-CoAs. However, a temperature-sensitive incorporation of unsaturated and saturated fatty acids into phosphatidylglycerol molecular species was observed with no change in the proportions of the three acyl-CoAs, completely reflecting the in vivo unsaturated/saturated ratio.


Nerve grafting.
For a long period, nerve grafting was used as a last resort when other means to manage a nerve defect failed. All attempts to apply allografts were disappointing. With the development of a new technique based on microsurgery, free nerve grafting has become a reliable method. The results are close to the results achieved by neurorrhaphy under favorable conditions and better than the results achieved by neurorrhaphy under tension. Today, this fact is recognized by nearly all surgeons. Discussion is limited only to the length of defect that still permits application of neurorrhaphy or represents an indication for nerve grafting. It is logical that different surgeons have different results, according to their training, their background, and the cases they have to treat. If the material contains more fresh cases, neurorrhaphy will be favored; if it contains more late secondary cases, nerve grafts will be applied in a higher frequency. The vascularized nerve graft is a new technique that certainly will have its indication in selected cases. If the immunologic problems connected with nerve grafting will be solved in one or the other way, a new era of nerve grafting will commence.


Exercise Increases Human Skeletal Muscle Insulin Sensitivity via Coordinated Increases in Microvascular Perfusion and Molecular Signaling.
Insulin resistance is a major health risk, and although exercise clearly improves skeletal muscle insulin sensitivity, the mechanisms are unclear. Here we show that initiation of a euglycemic-hyperinsulinemic clamp 4 h after single-legged exercise in humans increased microvascular perfusion (determined by contrast-enhanced ultrasound) by 65% in the exercised leg and 25% in the rested leg (P < 0.05) and that leg glucose uptake increased 50% more (P < 0.05) in the exercised leg than in the rested leg. Importantly, infusion of the nitric oxide synthase inhibitor l-NG-monomethyl-l-arginine acetate (l-NMMA) into both femoral arteries reversed the insulin-stimulated increase in microvascular perfusion in both legs and abrogated the greater glucose uptake in the exercised compared with the rested leg. Skeletal muscle phosphorylation of TBC1D4 Ser318 and Ser704 and glycogen synthase activity were greater in the exercised leg before insulin and increased similarly in both legs during the clamp, and l-NMMA had no effect on these insulin-stimulated signaling pathways. Therefore, acute exercise increases insulin sensitivity of muscle by a coordinated increase in insulin-stimulated microvascular perfusion and molecular signaling at the level of TBC1D4 and glycogen synthase in muscle. This secures improved glucose delivery on the one hand and increased ability to take up and dispose of the delivered glucose on the other hand.


A comparison of the vertical infraclavicular and axillary approaches for brachial plexus anaesthesia.
This prospective, randomized study compared the efficacy of the vertical infraclavicular and axillary approaches using a single injection blockade of the brachial plexus. The primary endpoint was complete blockade in dermatomes C5-Th1, while secondary endpoints included onset time, motor block, block performance time, surgical success rate, patient satisfaction, and side-effects/complications. Sixty patients, American Society of Anesthesiologists physical status I or II, scheduled for surgery of the forearm or hand received either a vertical infraclavicular (n = 30) or an axillary block (n = 30). A single injection of 0.5 ml/kg ropivacaine 7.5 mg/ml was made after electrolocalization of nerve fibres corresponding to the median nerve at maximum 0.5 mA (2 Hz, 0.1 ms). Onset and distribution of analgesia and motor block were assessed at 5, 10, 15, 20, 30 and 60 min after the local anaesthetic injection. A complete block was defined as analgesia in all dermatomes (C5-Th1) at 60 min post-injection. The vertical infraclavicular approach provided complete blockade in 29 patients (97%) and the axillary approach in 23 patients (77%). Analgesia in C5-C6 dermatomes and corresponding motor block occurred significantly more frequently in the vertical infraclavicular approach, which also had the shortest onset time. Block procedure was quicker in the axillary approach. Side-effects were similar in both groups, and there were no permanent sequelae. Patient satisfaction was equally high in both groups. The vertical infraclavicular approach provides a more complete block than the axillary approach when using a single injection technique and equal volumes/doses of local anaesthetic.


Preliminary evaluation of a particle-enhanced turbidimetric immunoassay (PETIA) for the determination of serum cystatin C-like immunoreactivity in dogs.
Serum cystatin C often is used in humans as a rapid and more sensitive marker than serum creatinine for glomerular filtration rate. The purpose of the present study was to evaluate whether cystatin C-like immunoreactivity (CLI) could be measured reliably in canine serum and to investigate whether dogs with clinical renal insufficiency had higher CLI levels than did clinically healthy dogs and dogs with nonrenal diseases. A commercially available particle-enhanced turbidimetric immunoassay (PETIA) for human serum cystatin C was used to measure canine serum CLI in a linear and proportional manner, with a mean recovery of 104% +/- 7.5% and coefficients of variation of 1.7 to 9.6%. The assay was then applied to serum samples from 17 clinically healthy dogs, 12 dogs with nonrenal diseases, and 8 dogs with renal insufficiency. Serum CLI was significantly higher in dogs with renal insufficiency (median serum CLI = 5.01 mg/L) than in clinically healthy dogs and dogs with nonrenal diseases (median serum CLI = 1.06 mg/L and 1.62 mg/L, respectively). Thus, canine serum CLI could be reliably measured using a commercially available PETIA designed for human serum cystatin C, and dogs with clinical renal insufficiency had, as expected, significantly higher serum CLI levels.


[The characteristic of proliferative activity of thymocytes and peripheral blood lymphocytes in the offspring of females with experimental chronic liver diseases of various aetiology].
The aim of the study was a comparative analysis of the proliferative activity of thymocytes and peripheral blood lymphocytes in the offspring of female rats with chronic liver pathology of various genesis. In adult female Wistar rats toxic and autoimmune forms of liver lesions were modeled. The offspring of these experimental animals was studied at different time points of postnatal ontogenesis. Proliferative activity of thymocytes and lymphocytes was estimated by counting the proportion of cells with multiple nucleolar organizing regions (AgNORs) and using the cytofluorometric method with acridine orange. In the offspring of experimental animals, the depression of proliferative activity of thymocytes as well as the increase of the proliferative activity of peripheral blood lymphocytes were found at all the time points studied. This was indicated by a change in a relative number of AgNORs-activated cells and a decrease of nucleic acid content in cortical thymocytes.


Fluorescence studies on nyctinasty which suggest the existence of genus-specific receptors for leaf-movement factor.
Periodic leaf-movement of legumes is called nyctinasty and has been known since the age of Alexander the Great. We found that nyctinasty is controlled by a periodic change of the internal concentration of leaf-opening and leaf-closing substances in the plant body. Now, we have developed novel fluorescent probes (1) based on the structure of cis-p-coumaroylagmatine (3), which was isolated as a leaf-opening substance of Albizzia juribrissin Durazz. Binding experiments using probe 1 showed that Albizza plants have receptors for a leaf-opening substance in their motor cells. By using probes 1 we then found that genus-specific receptors are involved in nyctinasty.


Fluctuating environments during early development can limit adult phenotypic flexibility: insights from an amphibious fish.
The interaction between developmental plasticity and the capacity for reversible acclimation (phenotypic flexibility) is poorly understood, particularly in organisms exposed to fluctuating environments. We used an amphibious killifish (Kryptolebias marmoratus) to test the hypotheses that organisms reared in fluctuating environments (i) will make no developmental changes to suit any one environment because fixing traits to suit one environment could be maladaptive for another, and (ii) will be highly phenotypically flexible as adults because their early life experiences predict high environmental variability in the future. We reared fish under constant (water) or fluctuating (water-air) environments until adulthood and assessed a suite of traits along the oxygen cascade (e.g. neuroepithelial cell density and size, cutaneous capillarity, gill morphology, ventricle size, red muscle morphometrics, terrestrial locomotor performance). To evaluate the capacity for phenotypic flexibility, a subset of adult fish from each rearing condition was then air-exposed for 14 days before the same traits were measured. In support of the developmental plasticity hypothesis, traits involved with O2 sensing and uptake were largely unaffected by water-air fluctuations during early life, but we found marked developmental changes in traits related to O2 transport, utilization and locomotor performance. In contrast, we found no evidence supporting the phenotypic flexibility hypothesis. Adult fish from both rearing conditions exhibited the same degree of phenotypic flexibility in various O2 sensing- and uptake-related traits. In other cases, water-air fluctuations attenuated adult phenotypic flexibility despite the fact that phenotypic flexibility is hypothesized to be favoured when environments fluctuate. Overall, we conclude that exposure to environmental fluctuations during development in K. marmoratus can dramatically alter the constitutive adult phenotype, as well as diminish the scope for phenotypic flexibility in later life.


Transcriptional inactivation of secreted frizzled-related protein 1 by promoter hypermethylation as a potential biomarker for non-small cell lung cancer.
Epigenetic silencing of secreted frizzled-related protein (SFRP) genes, antagonists of the WNT pathway, contributes to the pathogenesis of several cancers including non-small cell lung cancer (NSCLC). We hypothesize that methylation analysis of SFRPs family could improve their use as a panel of biomarkers for diagnosing and staging of NSCLC in China. The expression of four SFRP members (SFRP1, 2, 4, and 5) in NSCLC samples was screened by RT-PCR and quantitative real-time PCR. Only SFRP1 was significantly downregulated in NSCLC, as compared to adjacent normal tissues and benign pulmonary disease tissues (P=0.006). Promoter hypermethylation of SFRP1 was found in 32.1% (25/78) NSCLC specimens and was closely correlated with loss of expression, besides SFRP1 hypermethylation was associated with lymph metastasis (P=0.039) and disease progression within one year (P=0.027). Furthermore, methylated SFRP1 was detected in 28.2% (22/78) of plasma samples from NSCLC patients while only 4% (2/50) in cancer-free controls, and the concordance of SFRP1 methylation status in tumor tissues and corresponding plasmas was satisfactory (P <0.001). In conclusion, epigenetic inactivation of SFRP1 is a common event contributing to lung carcinogenesis and maybe used as a potential biomarker for NSCLC in Chinese population.


Blockade of deubiquitylating enzyme Rpn11 triggers apoptosis in multiple myeloma cells and overcomes bortezomib resistance.
Proteasome inhibition is an effective therapy for multiple myeloma (MM) patients; however, the emergence of drug resistance is common. Novel therapeutic strategies to overcome proteasome inhibitor resistance are needed. In this study, we examined whether targeting deubiquitylating (DUB) enzymes upstream of 20S proteasome overcomes proteasome inhibitor resistance. Gene expression analysis, immunohistochemical studies of MM patient bone marrow, reverse transcription-PCR and protein analysis show that Rpn11/POH1, a DUB enzyme upstream of 20S proteasome, is more highly expressed in patient MM cells than in normal plasma cells. Importantly, Rpn11 expression directly correlates with poor patient survival. Loss-of-function studies show that Rpn11-siRNA knockdown decreases MM cell viability. Pharmacological inhibition of Rpn11 with O-phenanthroline (OPA) blocks cellular proteasome function, induces apoptosis in MM cells and overcomes resistance to proteasome inhibitor bortezomib. Mechanistically, Rpn11 inhibition in MM cells activates caspase cascade and endoplasmic stress response signaling. Human MM xenograft model studies demonstrate that OPA treatment reduces progression of tumor growth and prolongs survival in mice. Finally, blockade of Rpn11 increases the cytotoxic activity of anti-MM agents lenalidomide, pomalidomide or dexamethasone. Overall, our preclinical data provide the rationale for targeting DUB enzyme Rpn11 upstream of 20S proteasome to enhance cytotoxicity and overcome proteasome inhibitor resistance in MM.


Point-of-care urine tenofovir testing to predict HIV drug resistance among individuals with virologic failure.
We sought to evaluate the utility of a point-of-care (POC) urine tenofovir (TFV) assay, developed to objectively assess adherence, to predict HIV drug resistance (HIVDR) in people failing first-line antiretroviral therapy (ART). We retrospectively analyzed TFV levels as a biomarker of adherence in urine specimens collected during a clinical trial that enrolled adults with virologic failure on first-line ART in Uganda and South Africa. Urine specimens were analyzed from participants on TFV-containing regimens who had a viral load >1000 copies/ml and paired genotypic resistance test (GRT) results. We assessed recent ART TFV adherence with a qualitative POC lateral flow urine assay with a cut-off value of 1500 ng/ml. We then calculated performance characteristics of the POC urine TFV assay to predict HIVDR, defined as intermediate or high-level resistance to any component of the current ART regimen. Urine specimens with paired plasma GRT results were available from 283 participants. The most common ART regimen during study conduct was emtricitabine, tenofovir disoproxil fumarate, and efavirenz. The overall prevalence of HIVDR was 86% ( n = 243/283). Of those with TFV detected on the POC assay, 91% ( n = 204/224) had HIVDR, vs. only 66% ( n = 39/59) among those with no TFV detected ( P- value < 0.001). Positive and negative predictive values of the assay to predict HIVDR were 91% and 34%, respectively. In populations with a high prevalence of HIVDR, the POC urine TFV assay can provide a low-cost, rapid method to guide requirements for confirmatory resistance testing and inform the need for regimen change.


In situ STM observation of morphological changes of the Pt(111) electrode surface during potential cycling in 10 mM HF solution.
In the present study, we have performed in situ STM observation of the surface oxidation-reduction process at Pt(111) surface in 10 mM HF solution under N(2) atmosphere in a stainless-steel chamber. We have for the first time demonstrated the dynamic process of the roughening of the Pt(111) surface during the potential cycles. At E < 0.8 V vs. RHE, no distinct change was observed in the positive-going potential sweep, even though surface oxidation is expected to commence in the so-called butterfly peak region at 0.6 V. At E > or = 0.9 V, tiny spots with a height of 0.08 nm appeared on the terraces, which can be attributed to adsorbed oxygen species rather than Pt ad-atoms. When the electrode potential reached 1.3 V, the electrode surface became bumpy with small corrugations (<0.1 nm) due to oxygen atoms becoming incorporated into the subsurface, without any additional layer formation. In the negative-going potential sweep, the electrode surface was suddenly covered with monoatomic islands, as well as pits, while the tiny spots disappeared at the moment that the electrode potential reached 0.5 V, at which the surface reduction was completed. During the repetitive potential cycles, the formation and growth of the Pt islands were found to occur only around 0.5 V in each negative-going potential sweep back from 1.3 V.


Antifungal antibiotic hamycin increases susceptibility of Candida albicans to phagocytosis by murine macrophages.
Hamycin is an antifungal antibiotic produced by Streptomyces pimprina Thirum. In the present study, the effect of hamycin on (a) the phagocytosis of Candida albicans by murine peritoneal macrophages and (b) the cell surface hydrophobicity (CSH) of C. albicans was investigated. Addition of hamycin to the culture of macrophages and Candida cells increased the susceptibility of Candida cells to the phagocytosis by macrophages. Pretreatment of Candida cells with hamycin increased their vulnerability to killing by macrophages. Examination of physico-chemical properties of Candida cell surface showed a significant decrease in the CSH. These findings suggest that the binding of hamycin to Candida cells induces biochemical/physico-chemical alterations of the surface, so that it becomes more susceptible to phagocytosis by murine macrophages.