What do children's global ratings of oral health and well-being measure?
To explore the constructs children incorporate in the responses to global ratings of their oral health (OH) and OH-related overall well-being (OWB). Data were collected as part of a project to validate the Child Perceptions Questionnaire for ages 11-14 (CPQ11-14), a self-report measure of OH-related quality of life. Its 37 questions are organized in the symptoms, functional limitations, emotional and social well-being domains. Children were recruited from paediatric dentistry, orthodontic and orofacial dental clinics. To identify the CPQ11-14 domain scores and questions predicting the global ratings, correlation and multiple regression analyses were used. Of the 123 children, 22.8% rated their OH as 'Fair/Poor' and 30.1% reported that their OWB was affected by their oral/orofacial condition. Positive significant correlations were observed between the OH ratings and the CPQ11-14 oral symptoms and emotional well-being domains, and between the OWB ratings and all four CPQ11-14 domains. The number of the CPQ11-14 questions significantly correlated with the OH and OWB ratings were 8 and 19, respectively. Only the symptoms domain entered the model for the OH (R2=0.05), while age, functional limitations and emotional well-being domains predicted the OWB (R2=0.18). The OH model included three questions (R2=0.13) and the OWB model included age and six questions (R2=0.25). In both models all but one of the questions came from the emotional and social well-being domains. These findings suggest that children view OH and its impact on well-being as multidimensional concepts. Further research, including qualitative studies, is needed to better understand the referents children use when responding to global ratings and the factors that determine their responses.


Water movement within the unsaturated zone in four agricultural areas of the United States.
Millions of tons of agricultural fertilizer and pesticides are applied annually in the USA. Due to the potential for these chemicals to migrate to groundwater, a study was conducted in 2004 using field data to calculate water budgets, rates of groundwater recharge and times of water travel through the unsaturated zone and to identify factors that influence these phenomena. Precipitation was the only water input at sites in Indiana and Maryland; irrigation accounted for about 80% of total water input at sites in California and Washington. Recharge at the Indiana site (47.5 cm) and at the Maryland site (31.5 cm) were equivalent to 51 and 32%, respectively, of annual precipitation and occurred between growing seasons. Recharge at the California site (42.3 cm) and Washington site (11.9 cm) occurred in response to irrigation events and was about 29 and 13% of total water input, respectively. Average residence time of water in the unsaturated zone, calculated using a piston-flow approach, ranged from less than 1 yr at the Indiana site to more than 8 yr at the Washington site. Results of bromide tracer tests indicate that at three of the four sites, a fraction of the water applied at land surface may have traveled to the water table in less than 1 yr. The timing and intensity of precipitation and irrigation were the dominant factors controlling recharge, suggesting that the time of the year at which chemicals are applied may be important for chemical transport through the unsaturated zone.


Testicular postgenomics: targeting the regulation of spermatogenesis.
Sperm are, arguably, the most differentiated cells produced within the body of any given species. This is owing to the fact that spermatogenesis is an intricate and highly specialized process evolved to suit the individual particularities of each sexual species. Despite a vast diversity in method, the aim of spermatogenesis is always the same, the idealized transmission of genetic patrimony. Towards this goal certain requirements must always be met, such as a relative twofold reduction in ploidy, repackaging of the chromatin for transport and specialized enhancements for cell motility, recognition and fusion. In the past 20 years, the study of molecular networks coordinating male germ cell development, particularly in mammals, has become more and more facilitated thanks to large-scale analyses of genome expression. Such postgenomic endeavors have generated landscapes of data for both fundamental and clinical reproductive biology. Continuous, large-scale integration analyses of these datasets are undertaken which provide access to very precise information on a myriad of biomolecules. This review presents commonly used transcriptomic and proteomic workflows applied to various testicular germ cell studies. We will also provide a general overview of the technical possibilities available to reproductive genomic biologists, noting the advantages and drawbacks of each technique.


Renal oncocytoma in a 13-year-old girl: A case report and literature review.
Renal oncocytoma is a benign renal neoplasm which has mostly been reported in adults. Occurrence in children is infrequent. To date, there are only six pediatric cases of renal oncocytoma reported previously. Herein, we report a 13-year-old girl presented with hematuria for a week. Abdominal computed tomography showed a well-defined heterogeneous solid mass with a stellate central scar in the left kidney. The patient underwent a nephron sparing surgery. Histopathological and immunohistochemical findings confirmed the diagnosis of renal oncocytoma. Though uncommon, renal oncocytoma should be considered as the differential diagnosis of renal tumor in children. In addition, intranuclear inclusions were firstly described in this pediatric patient with unclear significance, which need a large cohort to summarize and analyze.


Characterization of two novel mutations in IL-12R signaling in MSMD patients.
Mendelian Susceptibility to Mycobacterial Disease (MSMD) is a rare syndrome with infections-among other complications-after Bacillus Calmette-Guerin (BCG) vaccination in children. We focused on the IL-12/IFN-γ pathway to identify new mutations in our patients. This study included 20 patients by vulnerability to mycobacteria and clinical manifestations of severe, recurrent infections. Blood samples were activated with BCG, BCG + IL-12 and BCG + IFN-γ. Cytokine levels were analyzed by ELISA. Measurements of IL-12Rβ1 and IL-12Rβ2 on the surface of peripheral blood mononuclear cells were performed by flow cytometry. To detect genetic defects, next-generation sequencing was performed by Thermo Fisher immunodeficiency panel. Flow cytometry analysis of 20 patients indicated reduction in IL-12R (β1/β2) expression in seven patients who showed incomplete production of IFN-γ by ELISA. In the patient with reduced IL-12 production, IFN-γR and IL-12R (β1/β2) expression levels were normal. Mutation analysis showed three previously reported mutations, two novel mutations in IL-12 R (β1/β2), and one previously reported mutation in IL-12.


Roles of heme oxygenase-1 in the antiproliferative and antiapoptotic effects of nitric oxide on Jurkat T cells.
Nitric oxide (NO) has been shown to exert antiproliferative and antiapoptotic effects on human T cells. Heme oxygenase-1 (HO-1), which degrades heme into biliverdin, free iron (Fe(2+)), and carbon monoxide (CO), has also been known to have antiproliferative and antiapoptotic effects. Recent evidence suggests that HO-1 is an important cellular target of NO; whether HO-1 expression contributes to the antiproliferative and/or antiapoptotic effects mediated by NO remains to be investigated. In the present study, we examined the effects of NO on HO-1 expression and possible roles of HO-1 in T cell proliferation and apoptosis. Using human Jurkat T cells, we found that the NO donor sodium nitroprusside (SNP) induced HO-1 expression and that preincubation with SNP suppressed T cell proliferation induced by concanavalin A and apoptosis triggered by anti-Fas antibody. Suppressions of T cell proliferation and apoptosis comparable with SNP were also observed when the T cells were preincubated with the HO-1 inducer cobalt protoporphyrin. A phosphorothioate-linked HO-1 antisense oligonucleotide blocked HO-1 expression, and subsequently abrogated the antiproliferative and antiapoptotic effects of SNP. Overexpression of the HO-1 gene after transfection into Jurkat T cells resulted in significant decreases in T cell proliferation and apoptosis. The CO donor tricarbonyldichlororuthenium (II) dimer mimicked the antiproliferative effect of SNP, and the Fe(2+) donor FeSO(4) blocked anti-Fas-induced apoptosis. Taken together, our results suggest that NO induces HO-1 expression in T cells and that suppressions of T cell proliferation and apoptosis afforded by NO are associated with an increased expression of HO-1 by NO.


Understanding the work of case managers in Australian community aged care: a longitudinal time and motion study.
Objective The aim of this study was to quantify the work activities of community aged care case managers and assess changes following consumer-directed policy reforms. Methods A longitudinal, time and motion study was performed, with direct observation (n=339h) of case managers undertaking work in the office or in the community. We compared the distribution of proportions of time spent across seven broad work task categories during May-August 2014 (P1) and May-October 2016 (P2). Results Office time was primarily consumed by communication (43.7%) and documentation (33.3%) tasks. Documentation increased substantially from P1 to P2 (29.4% vs 37.0% respectively; P<0.001), with more time spent on the subtask of recording information (18.0% vs 24.5% respectively; P=0.039). Travel (45.9%) and communication (41.0%) accounted for most community time. Time in communication increased from P1 to P2 (37.3% vs 48.4% respectively; P=0.047), with more time allocated to client communication (14.6% vs 31.7%; P<0.001). Case managers spent 33.6% of community time in clients' homes (median 25.2min per client; 22.8 vs 30.1min in P1 and P2 respectively) and visited a median of two clients per day (3 vs 1 visits per day in P1 and P2 respectively). Conclusions This study provides the first quantification of task-time distribution among this workforce and how work patterns have changed during a time of significant policy reform and operational changes within the community aged care sector. What is known about the topic? Early qualitative studies gauging case managers' perceptions of the effect of consumer-directed care reforms on their work activities indicate an increase in time spent working directly with aged care clients. However, there is no existing quantitative evidence examining changes to case managers' work activities. What does this paper add? By capturing timed, multidimensional data, this study provides new quantitative evidence of how case managers distribute their time on work activities in office and community settings. Further, the results provide an indication of changes in work task-time distribution over a 2-year period when significant policy reforms and operational changes occurred. Amid a changing aged care landscape, how and with whom case managers spend their time was found to shift, with an increase in time spent recording information and communicating with clients identified. What are the implications for practitioners? This study demonstrates that direct observational studies provide important evidence of the ways in which policy and organisational changes affect community aged care case managers' work activities in practice. Triangulating this quantitative evidence with existing qualitative accounts of policy impact can further allow assessment of how complex reforms may affect everyday work. For policy makers and aged care organisations, such evidence can help discern whether policies and changes are having their desired effects, as well as providing insights as to why or why not.


Biological activity of activating thyroid-stimulating hormone receptor mutants depends on the cellular context.
Activating TSH receptor (TSHR) mutations are a major cause of toxic thyroid adenoma and familial hyperthyroidism, and more than 37 such mutations have been described. Previously their functional activity had been assessed in terms of cAMP and inositol phosphate production and predominantly in transiently transfected COS-7 (monkey embryonic kidney cells), a model that does not reflect effects on thyrocyte proliferation and function. Here we have performed a systematic comparison of wild-type and seven gain-of-function TSHR mutants, introduced into rat FRTL-5 and human thyrocytes, using retroviral vectors. Our results show that 1) biological potency of TSHR mutants in thyroid cells does not correlate with their cAMP levels in transfected COS cells, highlighting the importance of cellular context and level of expression when assessing biological effects of oncogenic mutations; 2) dissociation between stimulation of function and growth occurs with thyrocyte differentiated functions more readily stimulated than growth; 3) TSHR mutants show a similar order of potency in FRTL-5 cells and human thyrocytes; 4) mutants inducing the highest stimulation of adenylyl cyclase may paradoxically fail to induce proliferation; and 5) biological effects of cAMP activating TSHR mutants are attenuated by complex counterregulatory mechanisms at least at the level of phosphodiesterases and cAMP regulatory element modulator isoforms.


Clinical Efficacy of Tinnitus Retraining Therapy Based on Tinnitus Questionnaire Score and Visual Analogue Scale Score in Patients with Subjective Tinnitus.
Tinnitus is the annoying sensation of sound perception without acoustic stimulus. Tinnitus retraining therapy (TRT) is the habituation therapy used for the management of chronic subjective tinnitus. The objective of the study is to describe TRT and to evaluate its efficacy in patients with subjective tinnitus. In total, 58 patients with tinnitus who did not respond to medications were enrolled in the TRT program. TRT included counseling as described in the neurophysiological model of tinnitus and sound therapy (aided or unaided) for six months. The tinnitus severity grade (TSG) 1-5, based on a validated tinnitus questionnaire score (TQS), and the visual analogue scale (VAS) score were documented before and after therapy. Before TRT, 53 patients (91.3%) exhibited TSG 3-5, and the average VAS score was 6.7±2.1. After TRT for two months, 49 patients (84.4%) showed TSG 1-3, and the average VAS score was 3.2±2.4. After six months of TRT, most of the patients found remarkable improvement in the symptoms, and 51 patients (87.9%) exhibited TSG 1-2, and the average VAS score was 2.1±2.6. Statistically significant difference was found in TSG and VAS score before and after TRT. Statistically significant correlation was observed between TSG and VAS score. TRT is an useful approach for amelioration of tinnitus. TQS is a very effective, cheap, and easy method to help otologists to grade the patients as per the severity of symptoms.


Supplementing diet with blackberry extract causes a catabolic response with increments in insulin sensitivity in rats.
Blackberry (Rubus sp.) fruit has a high content of anthocyanins, but its health benefits have not been sufficiently explored in healthy individuals. Thus, the aim of the study was to determine the effects of blackberry extract on lipid and glucose variables in female and male rats. Sprague Dawley rats were given a standard pellet (SD) or cafeteria (CD) diet supplemented (SD+R and CD+R) or not with Rubus extract for 80 days. Female rats given SD+R had lower body and liver weights than SD females; both sexes given SD+R showed lower plasma glucose and insulin, higher plasma NEFA, glycerol and 3-hydroxybutyrate, and higher liver concentration of triacylglycerols than SD rats. The homeostasis model of insulin resistance (HOMA) was lower in SD+R rats than in SD rats, but higher in CD rats. No effects of Rubus extract were observed in CD rats. In conclusion, Rubus extract, in rats given SD, decreased glycemia and increased insulin sensitivity. It also increased lipid breakdown in adipose tissue. The effects were greater in females than in males. No effect was seen in rats given CD, probably as a result of their high insulin resistance.


Potential of creatine supplementation for improving aging bone health.
Aging subsequently results in bone and muscle loss which has a negative effect on strength, agility, and balance leading to increased risks of falls, injuries, and fractures. Resistance training is an effective strategy for maintaining bone mass, possibly by increasing activity of cells involved in bone formation and reducing activity of cells involved in bone resorption. However, bone loss is still evident in older adults who have maintained resistance training for most of their life, suggesting that other factors such as nutrition may be involved in the aging bone process. Emerging evidence suggests that creatine supplementation, with and without resistance training, has the potential to influence bone biology. However, research investigating the longer-term effects of creatine supplementation and resistance training on aging bone is limited.


Biopsychosocial Predictors of Quality of Life Outcomes in Pediatric Congenital Heart Disease.
The purpose of this prospective multi-center cross-sectional study was to identify key biopsychosocial factors that impact quality of life (QOL) of youth with congenital heart disease (CHD). Patient-parent pairs were recruited at a regular hospital follow-up visit. Patient- and parent-proxy-reported QOL were assessed using the Pediatric Cardiac Quality of Life Inventory (PCQLI). Wallander's and Varni's disability-stress coping model guided factor selection, which included disease factors, educational impairment, psychosocial stress, child psychological and parent/family factors. Measures utilized for these factors included the Pediatric Inventory for Parents, Self-Perception Profile for Children/Adolescents, Child Behavior Checklist, Revised Children's Manifest Anxiety Scale, Child PTSD Symptom Scale, State-Trait Anxiety Inventory, and Posttraumatic Diagnostic Scale. Ordinary least squares regression was applied to test the theoretical model, with backwards stepwise elimination process. The models accounted for a substantial amount of variance in QOL (Patient-reported PCQLI R 2 = 0.58, p < 0.001; Parent-proxy-reported PCQLI R 2 = 0.60, p < 0.001). For patient-reported QOL, disease factors, educational impairment, poor self-esteem, anxiety, patient posttraumatic stress, and parent posttraumatic stress were associated with lower QOL. For parent-proxy-report QOL, disease factors, educational impairment, greater parental medical stress, poorer child self-esteem, more child internalizing problems, and parent posttraumatic stress were associated with lower QOL. The results highlight that biopsychosocial factors account for over half the variance in QOL in CHD survivors. Assessing and treating psychological issues in the child and the parent may have a significant positive impact on QOL.


Attitudes and risk perceptions of stakeholders in a nuclear waste siting issue.
Stakeholders are often regarded as a critically important group in such issues as the siting of nuclear facilities. In this article, stakeholders were identified on the basis of self-reported activities with regard to a nuclear waste siting issue under debate in four communities. Data were obtained in an extensive mailed survey from a total of 2,548 respondents, approximately an equal number from each community. The overall response rate was 43.9%. Some of the results and telephone interviews with a sample of the nonrespondents indicated that the data are reasonably representative of the respective populations. Stakeholder activities were measured by 20 questions and combined with an index of stakeholder activity level, dichotomized at the 90th percentile. Stakeholders were found to have a higher level of education than others, but otherwise they did not differ in demographics. They did not tend to see risks in general as high, but were quite interested and involved in the nuclear waste siting issue. The stakeholder activity level correlated with risk perception and attitudes in the waste siting issue, but with different signs for those who were for and those who were opposed: stakeholders of both types had more extreme views than others, but in different directions. In addition, stakeholder opponents were much more likely to strongly espouse extreme statements regarding the project than were supporters who also were stakeholders. Implications for risk management and communication are discussed.


Treatment of systemic lupus erythematosus: new therapeutic options.
Systemic lupus erythematosus (SLE) is a systemic autoimmune inflammatory disease of unknown cause, with heterogeneity in its clinical presentation, as well as variability in its clinical course and prognosis. The current goal of treatment is to achieve disease remission or a state of low activity, and thereby improve the patient's quality of life. Biological therapy in lupus, unlike other entities, although it has not been fully established, in recent years it has burst onto the scene with important therapeutic novelties. This review aims to update the therapeutic tools for the treatment of SLE focusing on the new molecules that have achieved the objectives of their clinical trials.


Mitochondrial fatty acid utilization increases chromatin oxidative stress in cardiomyocytes.
The inability of adult mammalian cardiomyocytes to proliferate underpins the development of heart failure following myocardial injury. Although the newborn mammalian heart can spontaneously regenerate for a short period of time after birth, this ability is lost within the first week after birth in mice, partly due to increased mitochondrial reactive oxygen species (ROS) production which results in oxidative DNA damage and activation of DNA damage response. This increase in ROS levels coincides with a postnatal switch from anaerobic glycolysis to fatty acid (FA) oxidation by cardiac mitochondria. However, to date, a direct link between mitochondrial substrate utilization and oxidative DNA damage is lacking. Here, we generated ROS-sensitive fluorescent sensors targeted to different subnuclear compartments (chromatin, heterochromatin, telomeres, and nuclear lamin) in neonatal rat ventricular cardiomyocytes, which allowed us to determine the spatial localization of ROS in cardiomyocyte nuclei upon manipulation of mitochondrial respiration. Our results demonstrate that FA utilization by the mitochondria induces a significant increase in ROS detection at the chromatin level compared to other nuclear compartments. These results indicate that mitochondrial metabolic perturbations directly alter the nuclear redox status and that the chromatin appears to be particularly sensitive to the prooxidant effect of FA utilization by the mitochondria.


Mutations in collagen, type XVII, alpha 1 (COL17A1) cause epithelial recurrent erosion dystrophy (ERED).
Corneal dystrophies are a clinically and genetically heterogeneous group of inherited disorders that bilaterally affect corneal transparency. They are defined according to the corneal layer affected and by their genetic cause. In this study, we identified a dominantly inherited epithelial recurrent erosion dystrophy (ERED)-like disease that is common in northern Sweden. Whole-exome sequencing resulted in the identification of a novel mutation, c.2816C>T, p.T939I, in the COL17A1 gene, which encodes collagen type XVII alpha 1. The variant segregated with disease in a genealogically expanded pedigree dating back 200 years. We also investigated a unique COL17A1 synonymous variant, c.3156C>T, identified in a previously reported unrelated dominant ERED-like family linked to a locus on chromosome 10q23-q24 encompassing COL17A1. We show that this variant introduces a cryptic donor site resulting in aberrant pre-mRNA splicing and is highly likely to be pathogenic. Bi-allelic COL17A1 mutations have previously been associated with a recessive skin disorder, junctional epidermolysis bullosa, with recurrent corneal erosions being reported in some cases. Our findings implicate presumed gain-of-function COL17A1 mutations causing dominantly inherited ERED and improve understanding of the underlying pathology.


[Age peculiarities of combined maxillofacial injuries treatment].
Experience of help to 399 patients with combined craniofacial traumas of different age groups was shown. Some algorithm of help to such patients was suggested, interaction of craniofacial trauma components were demonstrated. Some scheme of pathogenetic based treatment of patients with combined craniofacial injuries was grounded upon it.


Analysis of schizophrenia-related genes and electrophysiological measures reveals ZNF804A association with amplitude of P300b elicited by novel sounds.
Several genes have recently been identified as risk factors for schizophrenia (SZ) by genome-wide association studies (GWAS), including ZNF804A which is thought to function in transcriptional regulation. However, the downstream pathophysiological changes that these genes confer remain to be elucidated. In 143 subjects (68 clinical high risk, first episode or chronic cases; 75 controls), we examined the association between 21 genetic markers previously identified by SZ GWAS or associated with putative intermediate phenotypes of SZ against three event-related potential (ERP) measures: mismatch negativity (MMN), amplitude of P300 during an auditory oddball task, and P300 amplitude during an auditory novelty oddball task. Controlling for age and sex, significant genetic association surpassing Bonferroni correction was detected between ZNF804A marker rs1344706 and P300 amplitude elicited by novel sounds (beta=4.38, P=1.03 × 10(-4)), which is thought to index orienting of attention to unexpected, salient stimuli. Subsequent analyses revealed that the association was driven by the control subjects (beta=6.35, P=9.08 × 10(-5)), and that the risk allele was correlated with higher novel P300b amplitude, in contrast to the significantly lower amplitude observed in cases compared to controls. Novel P300b amplitude was significantly correlated with a neurocognitive measure of auditory attention under interference conditions, suggesting a relationship between novel P300b amplitude and higher-order attentional processes. Our results suggest pleiotropic effects of ZNF804A on risk for SZ and neural mechanisms that are indexed by the novel P300b ERP component.


The combined effects of job demand and control, effort-reward imbalance and work-family conflicts on the risk of major depressive episode: a 4-year longitudinal study.
Work-related psychosocial factors may precipitate the onset of depression. In occupational mental health research, there are three widely used theoretical models, namely, job demand and control (JD-C), effort-reward imbalance (ERI) and work-family conflicts (WFC). However, the interaction between these models and their combined effect on the risk of major depression in the workplace is largely unknown. The aim of this study is to examine the longitudinal combined effects of JD-C, ERI and WFC on the risk of major depression in the working population. Longitudinal data (2008-2013) were collected on randomly selected participants (n=4200) from the working population of the province of Alberta, Canada, at baseline and 1-, 2-, 3- and 4-year follow-up. Data about JD-C, ERI, WFC and major depression were collected by trained interviewers using a computer-assisted telephone interviewing method. Generalised estimating equations for longitudinal modelling were used. There was an independent association between high ERI and high WFC at tx and major depression at tx+1 (OR 1.56, 95% CI 1.25 to 1.96; OR 1.33, 95% CI 1.16 to 1.52), respectively. The combined effects of JD-C and ERI, ERI and WFC, and WFC and JD-C on the risk of major depression were as follows: OR 1.71, 95% CI 1.22 to 2.42, OR 2.47, 95% CI 1.99 to 3.49 and OR 2.21, 95% CI 1.48 to 3.30, respectively. The relative excess risks attributable to the interactions were statistically non-significant. Work-related psychosocial factors are associated with increased risk of major depression over time, but their combined effect is not synergistic. The effects of the factors depicted in the three occupational health models on the risk of major depression appear to be additive.


Assessment of hepatic VX2 tumors of rabbits with second harmonic imaging under high and low acoustic pressures.
To investigate the possible clinical application value of second harmonic imaging under low acoustic pressure. Six New Zealand rabbits, averaging 2.7+/-0.4 kg, were selected and operated upon to construct hepatic VX2 tumor carrier model. Hepatic VX2 tumors were imaged with B mode Ultrasonography (US), and second harmonic imaging (SHI) under high mechanic index (1.6) and low mechanic index (0.1). Echo agent was intravenously injected through ear vein at a dose of 0.01 mL/kg under B mode US and high MI SHI, and 0.05 mL/kg under low MI SHI, and then the venous channel was cleaned with sterilized saline. All the images were recorded by magnetic optics (MO), and they were analyzed further by at least two independent experienced sonographers. Totally 6 hypoechoic and 3 hyperechoic lesions were found in the six carrier rabbits with a mean size about 2.1+/-0.4 under B mode ultrasound, they were oval or round in shape with a clear outline or a hypoechoic halo at the margin of the lesions. Contrast agent could not change the echogenicity of the lesions under B mode US and SHI under high acoustic pressure. However, it could greatly increase the real time visualization sensitivity of the lesions with SHI under low acoustic pressure. Our results suggest that contrast enhanced SHI with low MI and a bubble non-destructive method would be much more helpful than conventional SHI in our future clinical applications.


Osteomyelitis associated with peripheral vascular disease secondary to diabetes mellitus.
Diabetes mellitus and arteriosclerotic vascular disease have been found to be the predisposing factors of osteomyelitis associated with peripheral vascular disease (10). A diabetic person is more susceptible to osteomyelitis because of the microangiopathy, peripheral neuropathy and decreased resistance to infection. In diabetes mellitus there can be microangiopathy which results from the proliferation of the endothelium of the intima and thickening of the basement membrane. This further contributes to a sluggish blood flow. In the patient with arteriosclerotic vascular disease, the lumens of the arterioles and arterioles are compromised by the atheromatous plaques. The anatomic structure of the blood supply to bone along with the pathologic membrane thickening, allows for slowing of blood. This slowing of blood flow causes micro-thrombi and enhances bacterial growth. In diabetes mellitus it has been shown that there is a decreased immunologic response which, along with the above, contributes to the sheltering and proliferation of bacteria in the small bones of the foot.


Xenopus Cdc42 regulates convergent extension movements during gastrulation through Wnt/Ca2+ signaling pathway.
Rho GTPases are molecular switches that regulate many essential cellular processes, including actin dynamics, cell adhesion, cell-cycle progression, and transcription. We have isolated the Xenopus homolog of Rho GTPase Cdc42 and examined its potential role during gastrulation movements in early Xenopus embryos. XCdc42 is expressed in tissues undergoing extensive morphogenetic changes, such as the deep layers of involuting mesoderm and posterior neuroectoderm during gastrulation, and somitic mesoderm at neurula stages. Overexpression of either wild-type (WT) or dominant-negative (DN) XCdc42 interferes with convergent extension movements in intact embryos, activin-stimulated animal caps, and dorsal marginal zone explants. These effects occur without affecting mesodermal specification. Overexpression of WT or DN XCdc42 leads to the decrease and increase of cell adhesiveness of blastomeres, respectively, as demonstrated by the cell adhesion assay. In addition, when overexpressed, PKC-alpha, XWnt-5a, and Mfz-3 inhibit activin-induced convergent extension in animal cap explants. This inhibition can be rescued by coexpression of DN XCdc42, implying that XCdc42 acts downstream of the Wnt/Ca2+ signaling pathway involving PKC activation. XCdc42 also lies downstream of XWnt-5a in the regulation of Ca2+-dependent cell adhesion. Taken together, our results suggest that XCdc42 plays a role in the regulation of convergent extension movements during gastrulation through the protein kinase C-mediated Wnt/Ca2+ pathway.


Hypertrophic obstructive cardiomyopathy causing severe right and left ventricular outflow tract obstruction.
An 18-year-old male patient presented with a 3-year history of exertional dyspnea, dizziness, and angina. Echocardiography showed advanced hypertrophy of the left ventricle (LV), right ventricle (RV) free wall, and interventricular septum. There were apparent muscular bundles especially at the level of the right ventricular outflow tract (RVOT). Maximal pressure gradients across the RVOT and left ventricular outflow tract (LVOT) were 141 mmHg and 66 mmHg, respectively. There was also grade 2 aortic regurgitation. Transesophageal echocardiography and cardiac magnetic resonance imaging confirmed these findings. Despite treatment with propranolol and cibenzoline, the patient remained symptomatic with unchanged pressure gradients. Corrective surgery including an extensive muscular resection of the RVOT, minimal resection of the LVOT, and interposition of a graft patch in the RVOT resulted in complete disappearance of the RVOT gradient and a significant decrease to 28 mmHg in the LVOT gradient. During a year follow-up, aortic valvular insufficiency remained clinically stable and the patient was asymptomatic. This is the first case of hypertrophic obstructive cardiomyopathy with predominant RVOT obstruction treated by myectomy and patch graft interpositioning.


[Implementation of respiratory rehabilitation in the municipalities of Valparaíso, Viña del Mar, Quilpué and Villa Alemana in 2013].
Pulmonary rehabilitation is a keystone in the treatment of patients with Chronic Obstructive Pulmonary Disease. Significantly reduces the costs to the health system, the use of health resources by reducing hospital stay and consultations to emergency services. Describe the current condition of respiratory rehabilitation in primary care centers located in the region of Valparaíso. A closed survey in the respiratory centers of primary health care was applied. The sample consisted of 32 health centers corresponding to the communes of Valparaíso, Viña del Mar, Quilpué and Villa Alemana. 9 centers (28%) of the total sample performed pulmonary rehabilitation and the same number have a structured rehabilitation program. In 15 (47%) of the centers there is a Nutritionist in the health team. In 100% of hospitals patients assessed by spirometry and dyspnea scales. Most centers (89%) training upper and lower extremities. Among the factors that limit the performance of respiratory rehabilitation, 20 (63%) report that the schedule are one of the most limiting factors, while 23 (72%) report that centers do not have adequate space and 22 (69%) centers relate not have the minimum equipment necessary. Our findings suggest that most respiratory rehabilitation center did not performed as part of the treatment of patients with chronic obstructive pulmonary disease, mainly due to problems of human, material and infrastructure.


Total structural determination of alloyed Au15.37Cu16.63(S-Adm)20 nanoclusters with double superatomic chains.
Thiolated-alloy nanocluster Au15.37Cu16.63(S-Adm)20 ((AuCu)32 for short) has been synthesized. Single crystal X-ray crystallography (SC-XRD) proved that this cluster contains a Au14Cu6 core, which is composed of double superatom chains, two M4(SR)5 (M = Au/Cu) motifs, four Cu(SR)2 monomer staples and two SR molecules at the waist. The composition of this nanocluster is confirmed by SC-XRD and further verified by XPS, EDX and 2H-NMR. Surprisingly, double superatom chains connect to each other only via two Au-Au bonds, which makes the kernel resemble a tunnel. Combined with DFT calculation and electronic structure analysis, it is further proved that the (AuCu)32 nanocluster contains six 2e alloy superatomic Au3Cu2+ units. This work is the first report showing that superatom units (CuAu32+) self-assembling to a hollow kernel maintain the superatom characteristic of metal nanoclusters, which enriches the fundamental knowledge of metal superatom clusters. The stable electronic structure of the nanocluster provides an experimental basis for theoretical analysis in the future. In addition, the hollow structure may be promising in catalytic applications.


Long noncoding RNA Chaer mediated Polycomb Repressor Complex 2 (PRC2) activity to promote atherosclerosis through mTOR signaling.
Recent studies highlighted long noncoding RNAs (lncRNAs) have been implicated in many biological processes and diseases. However, atherosclerosis is a major risk factor for cardiovascular disease, but the detailed mechanism of atherosclerosis progression remained unclear. In this study, we mainly focused on the role of lncRNA Chaer in atherosclerosis. RT-PCR was used to detect the expression of lncRNA Chaer in atherosclerosis patients and animal model. Moreover, the expression of Chaer in vascular smooth muscle cell dysfunction model was also measured. Proliferation ability was tested by CCK-8 and cyclin D1 assay, through loss- and gain-of-function approaches. Western-blot was used to measure the expression of H3 lysine 27 methylation, when Chaer was in different levels. RIP and ChIP assay discovered an interaction between Chaer and PRC2 through mTOR signaling. Here we identified a heart-enriched long non-coding RNA, named Cardiac Hypertrophy Associated Epigenetic Regulator (Chaer). We found that the Chaer was highly expressed in serum samples from 28 patients with atherosclerosis, compared with 28 healthy volunteers. Chaer was dramatically upregulated in atherosclerotic plaques of ApoE-/- mice. We also found that the expression of Chaer was upregulated in vascular smooth muscle cell injury model. Through loss- and gain-of-function approaches, we showed that Chaer promotes cell proliferation and induces apoptosis in vitro. Mechanistically, Chaer interacts with Polycomb Repressor Complex 2 (PRC2) through inhibiting histone H3 lysine 27 methylation. Further, this interaction is induced upon mTOR signaling pathway. According to the results, we found that lncRNA Chaer was closely related to the progression of atherosclerosis, which could be a previously uncharacterized lncRNA-dependent epigenetic checkpoint.


Mutagenicity of industrial compounds. VII. Styrene and styrene oxide: II. Point mutations, chromosome aberrations and DNA repair induction analyses.
The possible genetic effects produced by styrene have been investigated by means of different methodologies in several biological organisms: (a) the induction of point mutation has been investigated in Salmonella typhimurium (reverse mutation), in the yeast Schizosaccharomyces pombe (forward mutation), both in vitro and in vivo, in the host-mediated assay of mice, and in the Chinese hamster cell line grown in vitro (V-79) (forward mutation); (b) the induction of chromosome mutation has been investigated in vivo, in mice, through the analysis of the presence of chromosome aberrations in bone marrow cells of treated animals; (c) the production of DNA (deoxyribonucleic acid) damage and the stimulation of DNA repair synthesis have been evaluated from measurements of unscheduled DNA synthesis in a heteroploid human cell line (EUE) and gene-conversion produced in the yeast Saccharomyces cerevisiae treated in vitro and in vivo (host-mediated assay). All the in vitro studies have been developed by the testing of the styrene in the presence of a metabolic activating system obtained with a mouse liver microsomal preparation. Styrene oxide, one of the in vivo metabolites of styrene with electrophilic properties towards DNA molecules, have also been tested in similar systems. Styrene was not mutagenic in all the systems tested; styrene oxide, on the contrary, was shown to be an active mutagen, independently of the genetic system under evaluation.


Psoriatic Dermal-derived Mesenchymal Stem Cells Reduce Keratinocyte Junctions, and Increase Glycolysis.
Although it is known that psoriatic dermal-derived mesenchymal stem cells (DMSCs) dysregulate keratinocyte proliferation, the biological activity profile of keratinocytes influenced by psoriatic DMSCs remain unknown. In the present study, we assessed the impact of psoriatic DMSCs on keratinocyte proliferation, differentiation, and glucose metabolism in normal human epidermal keratinocytes co-cultured with or without psoriatic DMSCs. Co-culture of normal human epidermal keratinocytes with psoriatic DMSCs downregulated expression levels of proteins associated with cell junction assembly (alpha-actinin-1, catenin beta-1, poliovirus receptor-related protein 4 and procollagen-lysine, 2-oxoglutarate 5-dioxygenase 2), while upregulating proteins associated with keratinocyte proliferation and differentiation (involucrin, isoform 2 of Histone-binding protein, isoform 3 of Telomeric repeat-binding factor 2 and keratin 13). Moreover, co-culture of normal human epidermal keratinocytes with psoriatic DMSCs stimulated keratinocyte proliferation and glycolysis, but reduced keratinocyte junctions. Taken together, these results demonstrate that psoriatic DMSCs increase keratinocyte proliferation and glycolysis, and reduce cell junctions, suggesting a pathogenic role of psoriatic DMSCs in epidermal hyperplasia, aberrant differentiation, and reduction in turnover time of keratinocytes in psoriasis.


[Diagnosis and treatment of nephroptosis in flying personnel].
Fifty human subjects of flying personnel and 25 human subjects of ground personnel suffered from nephroptosis mean age of which was 28.7 +/- 0.9 years have been under study. Dynamics observation of flying personnel for a period of 1-8 years revealed that the persons suffered from nephroptosis of the 1st stage are capable of performing the flying activity without limitations and need such observation and performance of the appropriate treatment- and--prophylactic measures. With the nephroptosis of stage II (27 pilots), the early operative treatment for eliminating the nephroptosis is indicated. The post-operative supervision of such patients is mastered. The nephropexy has been performed in 24 pilots; more recently, 23 persons were allowed to perform flying activities without restrictions, there were no nephroptosis recurrences. In the patients group of ground servicing personnel (26 persons) there have effectively been performed 20 nephropexies. Thus, it has been possible to overcome the nephroptosis and to improve the functional state of the kidneys. The operative treatment results allow one to recommend the early operative treatment of the stage II nephroptosis in the flying personnel even in the absence of the complicated nephroptosis and pronounced disorder of the kidney function.


Isoniazid-induced reduction in GABAergic neurotransmission alters the function of the cerebellar cortical circuit.
The cerebellar cortex contributes to the control of movement, coordination, and certain cognitive functions. The cerebellar network is composed of five different types of neurons that are wired together in a repetitive module. Given that four of these five neurons synthesize and release GABA, this inhibitory neurotransmitter plays a central role in regulation of the excitability and correct functioning of the cerebellar cortex. We have now used isoniazid, an inhibitor of glutamic acid decarboxylase, the enzyme responsible for the synthesis of GABA, to evaluate the contribution of GABAergic transmission in different types of cerebellar cortical neurons to the functioning of the cerebellar circuit. Parasagittal cerebellar slices were prepared from 28- to 40-day-old male rats and were subjected to patch-clamp recording in the voltage- or current-clamp mode. Exposure of the tissue slices to isoniazid (10 mM) resulted in a decrease in the level of GABAergic transmission in Purkinje cells and a consequent increase in the firing rate of spontaneous action potentials that was apparent after 40 min. In granule neurons, isoniazid reduced both tonic and phasic GABAergic currents and thereby altered the flow of information across the cerebellar cortex. Our data support the notion that the amount of GABA at the synaptic level is a major determinant of the excitability of the cerebellar cortex, and they suggest that isoniazid may be a useful tool with which to study the function of the cerebellar network.


Unplanned admissions to a pediatric cardiac critical care unit: a review of 2 years' experience.
Unplanned admissions to the pediatric cardiac ICU may be a large and high-risk group. Our study describes the frequency of unplanned pediatric cardiac ICU admissions, their admission data, and outcomes. All admissions to a pediatric cardiac ICU over 2 years were reviewed and those that were unplanned were identified for a detailed chart abstraction. Demographic, laboratory, diagnostic, and outcome data were collected. Readmission or admission for adverse event was noted. Single, tertiary, pediatric cardiac center. All patients admitted unexpectedly to the pediatric cardiac critical care unit between May 2008 and May 2010. None. There were 1,203 admissions to the cardiac ICU, and 426 (35%) were unplanned. The most common reasons for admission were new heart disease (25%), infection (19%), arrhythmia (13%), and congestive heart failure (11%). The majority of unplanned admissions (62%) occurred at night. Shock was present at admission in 18.5% of patients. Structural heart disease was present in 79%, and 39% of those were patients with single ventricle. Overall mortality among unplanned admissions was 7.3%, which is higher than that reported for elective surgical admissions. Mortality for the subset of patients readmitted within 30 days was 5.5%. Mean creatinine at admission was higher among nonsurvivors (0.7) than survivors (0.5). Unplanned admissions accounted for over one third of all admissions and had a high mortality rate. The majority of these occur at night, which may affect staffing models. Acute deterioration leading to unplanned admission, rather than readmission status, may be the driving factor in increased mortality. However, the risk of readmission, lower renal function, or other indices may identify patients at higher risk of an unplanned admission. Continued efforts to identify patients at risk for unplanned admissions are warranted given the outcomes in this cohort.


Utilization of MEDFILE--a preprinted medical literature filing system.
To facilitate the creation of a personal medical literature filing system, we developed MEDFILE, a noncomputerized, preprinted medical literature filing system. A graduating medical school class that had access to MEDFILE and a control group of incoming interns were studied to ascertain satisfaction, usage, utility, and implementation of MEDFILE in comparison with traditional literature filing systems. Data were obtained from 52 recent graduates of the site school and 25 graduates of other institutions. MEDFILE users had a significantly higher satisfaction level (7.3 +/- 1.5 vs 4.5 +/- 2.7, p less than .0001, two-tailed t-test), a more extensive filing system (p less than .02, chi square), and greater confidence that their filing system would remain useful during residency (p less than .0001, Fisher's exact test) than new graduates who had created their own filing systems. The data indicate that MEDFILE is an efficient, effective, and inexpensive method of organizing medical reprints. It may be particularly useful for physicians entering primary care disciplines that require information processing over a wide range of clinical topics.


HECTOR: a parallel multistage homopolymer spectrum based error corrector for 454 sequencing data.
Current-generation sequencing technologies are able to produce low-cost, high-throughput reads. However, the produced reads are imperfect and may contain various sequencing errors. Although many error correction methods have been developed in recent years, none explicitly targets homopolymer-length errors in the 454 sequencing reads. We present HECTOR, a parallel multistage homopolymer spectrum based error corrector for 454 sequencing data. In this algorithm, for the first time we have investigated a novel homopolymer spectrum based approach to handle homopolymer insertions or deletions, which are the dominant sequencing errors in 454 pyrosequencing reads. We have evaluated the performance of HECTOR, in terms of correction quality, runtime and parallel scalability, using both simulated and real pyrosequencing datasets. This performance has been further compared to that of Coral, a state-of-the-art error corrector which is based on multiple sequence alignment and Acacia, a recently published error corrector for amplicon pyrosequences. Our evaluations reveal that HECTOR demonstrates comparable correction quality to Coral, but runs 3.7× faster on average. In addition, HECTOR performs well even when the coverage of the dataset is low. Our homopolymer spectrum based approach is theoretically capable of processing arbitrary-length homopolymer-length errors, with a linear time complexity. HECTOR employs a multi-threaded design based on a master-slave computing model. Our experimental results show that HECTOR is a practical 454 pyrosequencing read error corrector which is competitive in terms of both correction quality and speed. The source code and all simulated data are available at: http://hector454.sourceforge.net.


Ehrlichiosis--"spotless spotted fever".
Ehrlichia Canis, a canine rickettsia, produces an acute infection in humans characterized by thrombocytopenia, leukopenia, and anemia. Patients should be closely questioned and examined for tick bites. Rash is not prominent, leading to the interesting if somewhat inaccurate label of "spotless spotted fever." The diagnosis is made by clinical presentation, absence of positive Lyme disease or Rocky Mounted Spotted Fever (RMSF) serology, and positive E. canis titers. Tetracyclines are preferred treatment. Ehrlichiosis should be considered in the differential diagnosis of fevers of unknown origin, Lyme disease, idiopathic thrombocytopenia, and hypoplastic anemia.


Comparison of Muscle Activity in Three Single-Joint, Hip Extension Exercises in Resistance-Trained Women.
The aim of the study was to compare neuromuscular activation in the gluteus maximus, the biceps femoris and the erector spinae from the Romanian deadlift, the 45-degree Roman chair back extension and the seated machine back extension. Fifteen resistance-trained females performed three repetitions with 6-RM loading in all exercises in a randomized and counterbalanced order. The activation in the whole movement as well as its lower and upper parts were analyzed. The results showed that the Romanian deadlift and the Roman chair back extension activated the gluteus maximus more than the seated machine back extension (94-140%, p < 0.01). For the biceps femoris the Roman chair elicited higher activation compared to both the Romanian deadlift and the seated machine back extension (71-174%). Further, the Romanian deadlift activated the biceps femoris more compared to the seated machine back extension (61%, p < 0.01). The analyses of the different parts of the movement showed that the Roman chair produced higher levels of activation in the upper part for both the gluteus maximus and the biceps femoris, compared to the other exercises. There were no differences in activation of the erector spinae between the three exercises (p = 1.00). In conclusion, both the Roman deadlift and the Roman chair back extension would be preferable to the seated machine back extension in regards to gluteus maximus activation. The Roman chair was superior in activating the biceps femoris compared to the two other exercises. All three exercises are appropriate selections for activating the lower back muscles. For overall lower limb activation, the Roman chair was the best exercise.


Genetic Deficiency of the Long Pentraxin 3 Affects Osteogenesis and Osteoclastogenesis in Homeostatic and Inflammatory Conditions.
The long pentraxin 3 (PTX3) is a soluble glycoprotein made by immune and nonimmune cells endowed with pleiotropic functions in innate immunity, inflammation, and tissue remodeling. PTX3 has recently emerged as a mediator of bone turnover in both physiological and pathological conditions, with direct and indirect effects on osteoblasts and osteoclasts. This notwithstanding, its role in bone biology, with major regard to the osteogenic potential of osteoblasts and their interplay with osteoclasts, is at present unclear. Here, we investigated the contribution of this pentraxin to bone deposition in the osteogenic lineage by assessing collagen production, mineralization capacity, osteoblast maturation, extracellular matrix gene expression, and inflammatory mediators' production in primary osteoblasts from the calvaria of wild-type (WT) and Ptx3-deficient (Ptx3-/-) mice. Also, we evaluated the effect of PTX3 on osteoclastogenesis in cocultures of primary osteoblasts and bone marrow-derived osteoclasts. Our investigations were carried out both in physiological and inflammatory conditions to recapitulate in vitro aspects of inflammatory diseases of the bone. We found that primary osteoblasts from WT animals constitutively expressed low levels of the protein in osteogenic noninflammatory conditions, and genetic ablation of PTX3 in these cells had no major impact on collagen and hydroxyapatite deposition. However, Ptx3-/- osteoblasts had an increased RANKL/OPG ratio and CD44 expression, which resulted in in enhanced osteoclastogenesis when cocultured with bone marrow monocytes. Inflammation (modelled through administration of tumor necrosis factor-α, TNF-α) boosted the expression and accumulation of PTX3 and inflammatory mediators in WT osteoblasts. In these conditions, Ptx3 genetic depletion was associated with reduced collagen deposition and immune modulators' production. Our study shed light on the role of PTX3 in osteoblast and osteoclast biology and identified a major effect of inflammation on the bone-related properties of this pentraxin, which might be relevant for therapeutic and/or diagnostic purposes in musculoskeletal pathology.


Association of glucocorticoid receptor haplotypes with body composition and metabolic parameters in HIV-infected patients from the FRAM study.
HIV infection has been associated with dyslipidemia, insulin resistance, and changes in body composition, including loss of subcutaneous fat and skeletal muscle, with relative sparing of upper trunk and visceral fat. Because of its resemblance to Cushing's syndrome, caused by glucocorticoid excess, we hypothesized that variations in the glucocorticoid receptor (GR) gene, associated with changes in sensitivity to glucocorticoids, may be associated with such abnormalities in HIV-infected patients. This was a cross-sectional genetic association study. GR polymorphisms were determined in HIV-infected participants from the study of Fat Redistribution and Metabolic Change in HIV Infection (FRAM). We created haplotypes in 754 participants and assessed the associations with fasting metabolic parameters and body composition by MRI. After stratification for ethnicity, we found no consistent pattern of associations between the described GR haplotypes and body composition or metabolic parameters in HIV-infected patients. However, we found a new haplotype comprising the Tth111I polymorphism in African-Americans. Heterozygous carriers of this haplotype (n=24) had significantly higher levels of high-density lipoprotein cholesterol compared with age-matched and sex-matched noncarriers (n=96) (median 55 vs. 44 mg/dl, P=0.026) and a tendency toward lower glucose (-5 mg/dl) and triglyceride (-21 mg/dl) levels and lower visceral adipose tissue mass (-0.22 l). CD4 count as well as skeletal muscle mass were also lower in carriers of this haplotype (-154 cells/μl and -1.6 l, respectively). Although our cohort included only a small number of carriers of the new Tth111I haplotype, these results are suggestive that this GR haplotype may be associated with a healthier metabolic profile in African-Americans with HIV infection.


Intermittent Exothermic and Self-Healing Hydrated Salt Gels for Advanced Thermal Management of Underfloor Radiant Heating System.
Phase change materials (PCMs) have great prospects in thermal management applications because they can store and release latent heat. However, they are not suitable for on-demand heating as they can only release heat once. Herein, this work reports the intermittent exothermic of PCMs based on a supersaturated salt solution, exhibiting fully controlled long-term storage of energy, releasing and suspending heat on demand. Due to the high energy barrier, it is difficult for the supersaturated salt solution to nucleate; thus, it can store energy for a long time. Contact with seeds or other foreign objects can destroy the metastable state of the supersaturated salt solution and promote the formation of crystal nuclei, enabling crystallization and heat release on demand. The release of crystallization heat can be interrupted using scissors dip in water. Additionally, self-healing behavior allows it to be recycled and last longer, due to the presence of Fe3+ , inducing strong dynamic reversible non-covalent crosslinking through metal coordination bonds. Furthermore, the hydrated salts gels are applied for thermal management of underfloor radiant heating system, demonstrating four types of intermittent exotherms sequences amazingly. Further, the intermittent exothermic hydrated salts gels provide a more user-friendly thermal management of underfloor radiant heating systems.


[Management of infections in palliative and terminal cancer care].
Patients with cancer are highly susceptible to infections. There is a lack of evidencebased guidelines or protocols for their management in palliative and endoflife care. To define an optimal dia-gnostic approach and therapeutic management of infections in patients with palliative and terminal cancer care. Along with thromboembolic disease and cancer progression, infections are the most frequent causes of death in oncology. Besides the impact on mortality, they are accompanied with a myriad of symptoms decreasing the quality of life. High incidence of infectons is due to a malignancy itself, the oncolgical therapy and host factors. There is a lack of evidencebased guidelines and protocols for the therapy of infections in palliative and terminal cancer care. Most of available studies are retrospective in nature, with diverse methods and cohorts. Incidence of infections in these patient oscillates between 16- 55% in specialized palliative units, and rises up to 83% in acute care hospitals. From the epidemiologic viewpoint, urinary (39- 42%) and respiratory infections (22- 36%) are the most frequent cases, followed by soft tissue and skin infections (6- 12%) and bacteremias (5- 14%). At present, the antibio-tic treatment does not seem to have a positive impact on the survival rate. Symptom control antibio-tic therapy as a means of symptom control still remains controversial, since it meets this purpose only in a few percents of studies. The most successful is the symtom control in urinary tract infections (60- 79%), in contrast to other sites of infection (30- 43%). In the last week of life there the symptom control is achieved only in 10% of patient. One should always consider the prognosis, actual preformance status and patients preferences when it comes to the management of dia-gnostics and therapy of infections. If the prognosis counts in weeks or months the dia-gnostics and therapy should not differ from the approach to any other oncological patient. In terminal cancer care the antibio-tics should be spared strictly for the purpose of symptom control and with a palliative intent. This article reviews current knowledge of dia-gnostics and therapy of infections in palliative cancer care and includes an algorithm for their management.


Changes in experiences with discrimination across pregnancy and postpartum: age differences and consequences for mental health.
We aimed to contribute to growing research and theory suggesting the importance of examining patterns of change over time and critical life periods to fully understand the effects of discrimination on health, with a focus on the period of pregnancy and postpartum and mental health outcomes. We used hierarchical linear modeling to examine changes across pregnancy and postpartum in everyday discrimination and the resulting consequences for mental health among predominantly Black and Latina, socioeconomically disadvantaged young women who were receiving prenatal care in New York City. Patterns of change in experiences with discrimination varied according to age. Among the youngest participants, discrimination increased from the second to third trimesters and then decreased to lower than the baseline level by 1 year postpartum; among the oldest participants, discrimination decreased from the second trimester to 6 months postpartum and then returned to the baseline level by 1 year postpartum. Within-subjects changes in discrimination over time predicted changes in depressive and anxiety symptoms at subsequent points. Discrimination more strongly predicted anxiety symptoms among participants reporting food insecurity. Our results support a life course approach to understanding the impact of experiences with discrimination on health and when to intervene.


Observational Cross-Sectional Study on Mediterranean Diet and Sperm Parameters.
Infertility, affecting 15 to 25% of couples in the most developed countries, is recognized by the World Health Organization as a public health issue at a global level. Different causes are acknowledged to reduce fertility in both sexes. In particular, about 40-50% of cases recognize a male factor. Dietary habits and lifestyle are acknowledged to influence sperm quality and are therefore important modifiable factors in male reproductive health. Conditions such as overweight/obesity, impaired glucose metabolism and determinants of metabolic syndrome, together with unhealthy lifestyle behavior, i.e., smoking cigarettes and physical inactivity, are suggested to have a negative impact on male fertility. While individual elements and characteristics of the Western diet and habits are considered risk factors for male infertility, the Mediterranean diet (MD) seems to promote reproductive potential for improving sperm quality. It is also interesting to note that previous observational studies reported a positive correlation between the consumption of the single food classes of the MD pattern (i.e., vegetables and fruits, poultry, fish and seafood, whole grains, low-fat dairy products) and the quality of several sperm parameters. To evaluate the relationship between sperm parameters and MD adherence, we performed a cross-sectional study on the seminal data of 300 males (mean age 34.6 ± 9.1 years) who spontaneously referred to our center of reproductive medicine. The evaluation of adherence to MD was performed with a validated 14-point Mediterranean Diet Adherence Screener (MEDAS) questionnaire. Our findings showed that sperm parameters such as sperm count, motility, viability and normal morphology are significantly and positively correlated with MEDAS, independently of BMI and age. In addition, the application of an ROC curve on MEDAS value vs. seminal alterations identified 6.25 as the score threshold value below which altered sperm parameters were more likely to occur [AUC = 0.096 (CI: 0.059-0.133; p < 0.00)]. Therefore, adhering to the MD with at least a MEDAS score of 6.26 increases the probability of normozoospermia. Moreover, subjects who had a MEDAS value lower than 6.25 had an Odds Ratio of 6.28 (CI = 3.967-9.945) for having at least one altered sperm parameter compared to those who were more adherent to the MD. In conclusion, our findings show that a higher adherence to the MD is associated with better semen parameters, in particular in relation to sperm count, sperm concentration, typical sperm morphology, and sperm progressive motility.


Challenges in Preloss Care to Parents Facing Their Child's End-of-Life: A Qualitative Study From the Clinicians Perspective.
Bereavement care for parents predominantly focuses on care after child loss. However, Health Care Professionals (HCPs) feel responsible for supporting parents who are grieving losses in their child's end-of-life. Preloss care is tailored to the parents' needs, thus highly varying. To better understand the nature of preloss care, this study aims to gain insight into the challenges HCPs encounter while providing care for parents during their child's end-of-life. Exploratory qualitative research using semistructured interviews with physicians and nurses working in neonatology and pediatrics in 3 university pediatric hospitals and 1 child home care service. A multidisciplinary team thematically analyzed the data. Twenty-two HCPs participated in this study. From the HCPs' inner perspective, three dyadic dimensions in preloss care delivery were identified that create tension in HCPs: sustaining hope versus realistic prospects, obtaining emotional closeness versus emotional distance, and exploring emotions versus containing emotions. Throughout preloss care delivery, HCPs weighed which strategies to use based on their perception of parental needs, the situation, and their own competencies. HCPs remained with lingering uncertainties on whether the preloss care they provide constituted optimal care. As a result of the experienced tension, HCPs are at risk for prolonged distress and possibly even compassion fatigue. In order to maintain a positive emotional balance in HCPs, education should focus on adapting positive coping strategies and provide hands-on training. Furthermore, on an institutional level a safe environment should be fostered and well-being could be enhanced through learning by sharing as a team.


A study to evaluate the met and unmet needs of members belonging to Young Stroke groups affiliated with the Stroke Association.
To examine the met and unmet needs of young people with stroke who accessed services run by the Stroke Association. One hundred and thirty-five out of 200 members of 14 participating Young Stroke groups completed and returned the postal version of the Southampton Needs Assessment Questionnaire for Stroke questionnaire. Young Stroke group members had a median of five unmet needs. An analysis of these needs showed that information about the person's stroke, help with finances, assistance with non-care activities (e.g. help with social activities) and help with maintaining intellectual fulfilment were the four most frequently reported ones. There was no association between the number of unmet needs reported and factors such as age, time since stroke and social class. Young Stroke group members may be more aware of what their unmet needs are and have better knowledge in accessing existing health and social service resources. Nevertheless, these findings show that people with stroke considered the provision of information geared to their own needs as important. Statutory services should personalize information to individual's specific situation and should also tackle other problems, not only physical ones, experienced by young people with strokes.


Observational study of the clinical performance of a public-private partnership national referral hospital network in Lesotho: Do improvements last over time?
Public-private partnerships (PPP) may increase healthcare quality but lack longitudinal evidence for success. The Queen 'Mamohato Memorial Hospital (QMMH) in Lesotho is one of Africa's first healthcare PPPs. We compare data from 2012 and 2018 on capacity, utilization, quality, and outcomes to understand if early documented successes have been sustained using the same measures over time. In this observational study using administrative and clinical data, we assessed beds, admissions, average length of stay (ALOS), outpatient visits, and patient outcomes. We measured triage time and crash cart stock through direct observation in 2013 and 2020. Operational hospital beds increased from 390 to 410. Admissions decreased (-5.3%) while outpatient visits increased (3.8%). ALOS increased from 5.1 to 6.5 days. Occupancy increased from 82% to 99%; half of the wards had occupancy rates ≥90%, and Neonatal ward occupancy was 209%. The proportion of crash cart stock present (82.9% to 73.8%) and timely triage (84.0% to 27.6%) decreased. While overall mortality decreased (8.0% to 6.5%) and neonatal mortality overall decreased (18.0% to 16.3%), mortality among very low birth weight neonates increased (30.2% to 36.8%). Declines in overall hospital mortality are promising. Yet, continued high occupancy could compromise infection control and impede response to infections, such as COVID-19. High occupancy in the Neonatal ward suggests that the population need for neonatal care outpaces QMMH capacity; improvements should be addressed at the hospital and systemic levels. The increase in ALOS is acceptable for a hospital meant to take the most critical cases. The decline in crash cart stock completeness and timely triage may affect access to emergency treatment. While the partnership itself ended earlier than anticipated, our evaluation suggests that generally the hospital under the PPP was operational, providing high-level, critically needed services, and continued to improve patient outcomes. Quality at QMMH remained substantially higher than at the former Queen Elizabeth II hospital.


Accessing source information in analogical problem-solving.
Several studies showed that people presented with source information fail to apply it to an analogous target problem unless they are instructed to use the source. Seven experiments were carried out to assess whether such a lack of spontaneous transfer occurs because individuals do not activate the source during the target task or because they do not realize the source-target relationship. Experiment 1 compared a condition in which the source was activated with no cue about the source-target connection to conditions in which subjects were informed about this connection. Results suggested that the lack of spontaneous transfer does not depend on failure in activating source information. Experiments 2, 3, and 4 were devised to falsify this finding by activating the source closer and closer to the target and by focusing participants' attention toward the relevant aspects of the source. Experiments 5, 6, and 7 were aimed at stressing source-target correspondences by introducing surface similarities. All experiments showed that the mere activation of the source does not facilitate analogical transfer. Results suggested that two processes should be distinguished in the access phase of analogical problem-solving: Source retrieval and identification of the source-target connection.


[Colorectal cancer screening based on quantitative determining of fecal hemoglobin and transferrin].
To reduce mortality rate from cancer there has been developed a program of colorectal cancer screening. It was conducted a pilot implementation of the methodology of colorectal cancer screening based on quantitative immunochemical determination of fecal hemoglobin and transferrin with colonoscopy. The study included 10307 men and women aged 50 years and older without symptoms of the disease who received containers for a 2-day collection of stool samples. There were returned 9455 sets with samples (91.8%). Of these an excess hemoglobin level and/or transferrin above the threshold was in 1354 (14.3%). 1164 patients (86% of positive) underwent colonoscopy. Colon diseases were found in 662 patients including polyps in 237. The efficiency of a 2-day test to detect polyps was significantly higher compared to a 1-day. Colorectal cancer was revealed in 23 people--2.4 per 1000 patients. 87% of patients had cancer of stages I and II, 13%--in stage III. The results of the introduction of screening program confirm the possibility of its use in practical public health.


Isolation and sequence of the gene for ferredoxin I from the cyanobacterium Anabaena sp. strain PCC 7120.
The structural gene for ferredoxin I, petF, from the cyanobacterium Anabaena sp. strain PCC 7120 has been isolated from a recombinant lambda library. Mixtures of tetradecanucleotides and heptadecanucleotides, each containing all possible DNA sequences corresponding to two separate regions of the ferredoxin amino acid sequence, were synthesized and used as hybridization probes to identify a genomic clone containing the coding sequence for the petF gene. The sequence of the entire petF coding region and portions of the 3'- and 5'-flanking regions was determined. The DNA sequence of petF suggests that, in contrast to the nucleus-encoded plant protein, cyanobacterial apoferredoxin is not synthesized as a higher-molecular-weight precursor. The Anabaena petF gene is a single-copy gene. During growth on complete medium it was transcribed into a monocistronic mRNA species of approximately 500 bases that initiated 100 base pairs upstream from the petF coding region.


Grid computing for improving conformational sampling in NMR structure calculation.
Methods for automatic nuclear magnetic resonance (NMR) structure determination need to face a high level of ambiguity encountered in NMR spectra recorded by solid-state NMR and by solution NMR of partially unfolded proteins, leading to time-consuming calculations. The software package Ambiguous Restraints for Iterative Assignment (ARIA) allows for straightforward parallelization of the calculation, as the conformers can be generated in parallel on many nodes. Due to its architecture, the adaptation of ARIA to grid computing can be easily achieved by using the middleware glite and JDL (Job Description Language) scripts. This adaptation makes it possible to address highly ambiguous datasets, because of the much larger conformational sampling that can be generated by use of the grid computational power. The version 2.3.1 of ARIA implemented on the grid is freely available from the ARIA web site: aria.pasteur.fr/downloads.


Managing Menopausal Symptoms and Associated Clinical Issues in Breast Cancer Survivors.
Review evidence to guide management of menopausal signs and symptoms in women after breast cancer and make recommendations accordingly. Randomized controlled clinical trials, observational studies, evidence-based guidelines, and expert opinion from professional societies. Symptoms and clinical problems associated with estrogen depletion-sleep disorders, vulvovaginal atrophy (VVA), vasomotor symptoms (VMS), mood changes, depressive symptoms, cardiovascular disease, osteopenia, and osteoporosis-confront the estimated 9.3 million breast cancer survivors globally. Following breast cancer, women should not generally be treated with menopausal hormone therapy or tibolone but should optimize lifestyle. Women with moderate to severe symptoms may benefit from mind-brain behavior or nonhormone, pharmacologic therapy. The selective serotonin/noradrenaline reuptake inhibitors and gabapentenoid agents improve VMS and quality of life. For osteoporosis, nonhormonal agents are available. Treatment of VVA remains an area of unmet need. Low-dose vaginal estrogen is absorbed in small amounts with blood levels remaining within the normal postmenopausal range but could potentially stimulate occult breast cancer cells, and although poorly studied, is not generally advised, particularly for those on aromatase inhibitors. Intravaginal dehydroepiandrosterone and oral ospemiphene have been approved to treat dyspareunia, but safety after breast cancer has not been established. Vaginal laser therapy is being used for VVA but efficacy from sham-controlled studies is lacking. Therapies undergoing development include lasofoxifene, neurokinin B inhibitors, stellate ganglion blockade, vaginal testosterone, and estetrol. Nonhormone options and therapies are available for treatment of estrogen depletion symptoms and clinical problems after a diagnosis of breast cancer. Individualization of treatment is essential.


Fetal omphalocele detected early in pregnancy: associated anomalies and outcomes.
To detect omphalocele and associated anomalies at ultrasonography (US) early in pregnancy and to describe the outcomes in fetuses with isolated and nonisolated omphalocele. Fetal endovaginal US was performed in 43,896 pregnant women at 12-16 weeks gestation. The women found to have fetal omphalocele were offered an amniocentesis to determine the fetal karyotype. For parents who decided to continue the pregnancy, repeat targeted transabdominal fetal US was performed at 20-24 weeks gestation. Additional follow-up US examinations performed until delivery were recommended. Postnatal pediatric examinations were performed in all of these fetuses. For the pregnancies in which no anomaly was detected at early US, the women were advised to undergo repeat US at about 24 weeks gestation for the detection of late-manifesting fetal anomalies. For pregnancies in which the baby was not delivered at the authors' affiliated hospital, the woman, her obstetrician, and her pediatrician were asked to inform the authors of any detected anomaly. Omphalocele was visualized at US in 38 fetuses, who were categorized into two groups. One group consisted of 22 (58%) fetuses with associated structural anomalies. According to the karyotype determined for 18 of these fetuses, 11 of them also had chromosomal anomalies. The pregnancy was terminated at the parents' request in 19 of these 22 cases. There were two cases of missed abortion, and a small omphalocele in one fetus disappeared at 21 weeks gestation. The second group consisted of 16 (42%) fetuses with a normal karyotype and an omphalocele as an isolated US finding. In eight of these fetuses, the omphalocele disappeared at 20-24 weeks gestation and no defect was seen at delivery. In six other fetuses, omphalocele was identified at delivery. There was one case each of missed abortion and pregnancy termination. There were no false-negative diagnoses of omphalocele. Isolated omphalocele diagnosed during the early stages of gestation typically has a good prognosis. In cases of a small defect, the anomaly may disappear later in the pregnancy.


Platelet toll-like receptors in thromboinflammation.
Besides their undiscussed role in hemostasis and thrombosis, platelets are also key effector cells capable of assisting and modulating inflammatory reactions and immune responses. Platelets play a sentinel role in immune surveillance by recognizing danger signals from pathogens and cell damage through the expression of toll-like receptors (TLRs) on its surface and internal compartments. Platelets express all 10 TLRs transcripts and its signalosome, including adaptor proteins and transcription factors. The activation of these receptors in platelets triggers hemostatic and inflammatory responses which participate in the host's response to bacterial and viral infections, linking thrombosis with infection and immunity. Among the responses elicited by the activation of platelet TLRs are platelet adhesion and aggregation, formation of mixed platelet-leukocyte aggregates, expression and secretion of cytokines and quemokines, and thrombin generation. TLRs also are expressed in megakaryocytes, and their activation regulates not only platelet biogenesis, but also pro-inflammatory and antiviral responses. This review will focus on work that has shown the role of platelet TLRs, mainly in thromboinflammatory responses elicited by platelets and megakaryocytes.


Wnt and hedgehog signaling pathways in bone development.
Cell-cell signaling is a major strategy that vertebrate embryos employ to coordinately control cell proliferation, differentiation, and survival in many developmental processes. Similar cell signaling pathways also control adult tissue regeneration and repair. We demonstrated in the developing skeletal system that the Wnt/beta-catenin signaling controls the differentiation of progenitor cells into either osteoblasts or chondrocytes. Genetic ablation of beta-catenin in the developing mouse embryo resulted in ectopic formation of chondrocytes at the expense of osteoblast differentiation during both intramembranous and endochondral ossification. Conversely, ectopic upregulation of the canonical Wnt signaling led to suppression of chondrocyte formation and enhanced ossification. As other signaling pathways also play critical roles in controlling skeletal development, to gain a full picture of the molecular regulatory network of skeletal development, we investigated how the Wnt/beta-catenin signaling is integrated with Indian hedgehog (Ihh) signaling in controlling various aspects of skeletal development. We found that Wnt signaling acts downstream of Ihh signaling and is required in osteoblasts after Osterix expression to promote osteoblast maturation during endochondral bone formation. Since similar controlling mechanisms of osteoblast proliferation and differentiation may be employed by adult mesenchymal progenitor cells during fracture repair, these studies suggest that, to enhance fracture repair or bone formation, Ihh signaling needs to be enhanced at early stages, whereas Wnt signaling should be upregulated slightly later in differentiated osteoblasts.


Trunk strength effect on track wheelchair start: implications for classification.
The T54 wheelchair racing class comprises athletes with normal arm muscle strength and trunk strength ranging from partial to normal. Paralympic sports classes should comprise athletes who have impairments that cause a comparable degree of activity limitation. On the basis of this criterion, the purpose of this study was to determine whether the T54 class is valid by assessing the strength of association between trunk strength and wheelchair acceleration. Participants were 10 male and 3 female international wheelchair track athletes with normal arm strength. Six were clinically assessed as having normal trunk strength, and seven had impaired trunk strength. Measures included isometric arm and trunk strength and distance covered at 1, 2, and 3 s in an explosive start from standstill on a regulation track, as well as on a custom-built ergometer with four times normal rolling resistance. No significant differences were observed between male athletes with and without full trunk strength in distance covered after 1, 2, and 3 s. Correlations between isometric trunk strength and wheelchair track acceleration were nonsignificant and low (0.27-0.32), accounting for only 7%-10% of variance in performance. Correlations between trunk strength and distance pushed under high resistance were also nonsignificant, although values were almost double (r = 0.41-0.54), accounting for 18%-28% of the variance in performance. These results provide evidence that impairment of trunk strength has minimal effect on wheelchair acceleration and indicate the T54 class is valid. Results do not infer that athletes with no trunk strength should compete with those who have partial or full trunk strength.


Nuclear receptor COUP-TFII-expressing neocortical interneurons are derived from the medial and lateral/caudal ganglionic eminence and define specific subsets of mature interneurons.
Neocortical GABAergic interneurons in rodents originate from subpallial progenitor zones. The majority of mouse neocortical interneurons are derived from the medial and caudal ganglionic eminences (MGE and CGE, respectively) and the preoptic area (POA). It is controversial whether the lateral ganglionic eminence (LGE) also generates neocortical interneurons. Previously it was shown that the transcription factor COUP-TFII is expressed in the CGE; here we show that COUP-TFII is also expressed in the dorsal MGE, dorsal LGE (dMGE and dLGE, respectively), and POA. In the adult neocortex, COUP-TFII+/somatostatin (SOM)+ interneurons are mainly located in layer V. Using a genetic fate-mapping approach (Shh-Cre and Nkx2.1-Cre), we demonstrate that the POA and ventral MGE do not give rise to COUP-TFII+ neocortical interneurons, suggesting that the dMGE is the source of COUP-TFII+/SOM+ neocortical interneurons. We also observed a migratory stream of COUP-TFII+/Sp8+ cells emanating from the dLGE and CGE to the neocortex mainly through the subventricular zone at later embryonic stages. Slice culture experiments in which dLGE progenitors were labeled with BrdU provided additional evidence that the dLGE generates neocortical interneurons. While earlier-born dMGE-derived COUP-TFII+ interneurons occupy cortical layer V, later-born dLGE- and CGE-derived COUP-TFII+ ones preferentially occupy superficial cortical layers. A similar laminar distribution was observed following neonatal transplantation of embryonic day (E)14.5 dMGE and E15.5 dLGE. These results provide novel information about interneuron fate and position from spatially and temporally distinct origins in the ganglionic eminences.


Ion Sensor Properties of Fluorescent Schiff Bases Carrying Dipicolylamine Groups. A Simple Spectrofluorimetric Method to Determine Cu (II) in Water Samples.
Four fluorescent Schiff bases carrying dipicolylamine groups were designed and synthesized to determine their ion sensor properties in partial aqueous solution. The corresponding amine compound and the aldehyde compounds such as 1-naphthaldehyde, 9-anthraldehyde, phenanthrene-9-carboxaldehyde and 1-pyrenecarboxaldehyde were used to prepare the new Schiff bases. The influence of many metal cations and anions on the spectroscopic properties of the ligands was investigated in ethanol-water (1:1) by means of emission spectrometry. From the spectrofluorimetric titrations, the complexation stoichiometry and complex stability constants of the ligands with Cd2+, Zn2+, Cu2+ and Hg2+ ions were determined. The ligands did not interact with the anions. However, the Schiff base derived from phenanthrene-9-carboxaldehyde showed sensitivity for Cu2+ among the tested metal ions. The phenanthrene-based Schiff base was used as analytical ligand for the simple and fast determination of Cu2+ ion in water samples. A modified standard addition method was used to eliminate matrix effect. The linear range was from 0.3 mg/L to 3.8 μg/L. Detection and quantification limits were 0.14 and 0.43 mg/L, respectively. Maximum contaminant level goal (MCLG) for copper in drinking water according to EPA is 1.3 mg/L. The proposed method has high sensitivity to determine copper in drinking waters.


GAMUT: A genomics big data management tool.
Efficient analysis of Single Nucleotide Polymorphisms (SNPs) across genomic samples enable in deciphering the relationship between genotype and phenotype. The core principle behind SNP comparison is to arrive at a probable list of variants that can differentiate two sets of data (populations). Such SNPs have direct applications in array design, genotype imputation and in cataloging of variants in regions of interest. We have developed GAMUT (Genomics bigdAta Management Tool), a big data-based solution for efficient run-time comparison of SNPs across large datasets based on partition of samples belonging to different populations taking into account user-defined splits. The tool is based on client-server architecture with MongoDB at the back-end and JSF with PrimeFaces as the front-end. It is readily deployable on wild-fly server as well as a docker container. Spark-based parallel data uploader enables optimal loading times. GAMUT enables dynamic querying of the large datasets consisting of multiple samples using text-based, chromosome position-based as well as gene-name based options. Various charting options like bar and pie charts along with tabular formats are available to ease the analysis of the queried data. The resultant data pertaining to comparison of genomewide SNPs can also be downloaded in different formats like text, html, json for further stand-alone analysis. GAMUT is available for download at: https://github.com/bioinformatics-cdac/gamut.


Update on the role of Pentraxin 3 in atherosclerosis and cardiovascular diseases.
Pentraxin 3 (PTX3) is an acute-phase protein that was recently demonstrated to play pleiotropic activities in cardiovascular (CV) diseases. Tumor necrosis factor and interleukins up-regulates PTX3 transcription in different cell types (i.e. endothelial cells, phagocytes, smooth muscle cells, fibroblasts and glial cells) involved in atherogenesis. By interacting with numerous ligands, PTX3 acts as a modulatory molecule of complement system, inflammatory response, angiogenesis, and vascular/tissue remodeling. Experimental data point to a beneficial role of PTX3 in atherosclerotic plaque development and vulnerability. Animal studies indicated a protective role of PTX3 signaling in ischemic/reperfusion injury and failing heart. Clinical studies have so far provided contrasting results, highlighting a debated role of PTX3 as an active mediator of endothelial dysfunction, atherosclerotic plaque vulnerability and worse outcome after ischemic events. Therefore, substantial evidence suggests a dual role of PTX3 as modulator or amplifiers of the innate immune response. The final result of PTX3 activation might be determined by a fine tuning of time, space and environmental signals. The aim of this review is to provide an overview of biological properties of PTX3 in CV diseases and to discuss the ability of PTX3 to act as a crossroad between pro- and anti-inflammatory pathways.


Laparoscopic placement of distal ventriculoperitoneal shunt catheters.
Ventriculoperitoneal shunts (VPSs) are commonly placed into the peritoneal cavity via a small laparotomy or blindly by using a split trocar. Larger patients require larger incisions, and placement is made more difficult by previous abdominal operations and obesity. For general surgeons, laparoscopy has become the first-choice approach for abdominal procedures, using 1 or several very small incisions. The authors discuss their pediatric series of patients in whom laparoscopy was used to place distal shunt catheters. The authors reviewed the medical records accrued over a 9-year period, noting VPS operations performed using laparoscopy. Complications, morbidity, and alterations of planned management were noted. One hundred thirty-seven VPS operations in 126 patients were identified, 92 performed by the senior author (M.H.H.) alone and 45 conducted with the assistance of a general surgeon. A second port was placed for lysis of adhesions or retrieval of old catheters in 7 cases. There were no immediate complications. The infection rate was 6.6%, comparable with the institutional norm (6.3%) over an 8-year period. There were 3 early failures due to abdominal malabsorption without infection. Five catheters later broke at the level where they were introduced into the abdomen due to shearing by the abdominal trocar. Laparoscopic placement of distal VPS catheters is relatively safe and allows insertion via inconspicuous incisions. It can allow for inspection or lysis of adhesions and removal of foreign bodies, help determine if and where the abdomen can absorb shunt fluid, and make VPS surgery in the obese patient easier.


Restoration of Mitochondrial Function Is Essential in the Endothelium-Dependent Vasodilation Induced by Acacetin in Hypertensive Rats.
Mitochondrial dysfunction in the endothelium contributes to the progression of hypertension and plays an obligatory role in modulating vascular tone. Acacetin is a natural flavonoid compound that has been shown to possess multiple beneficial effects, including vasodilatation. However, whether acacetin could improve endothelial function in hypertension by protecting against mitochondria-dependent apoptosis remains to be determined. The mean arterial pressure (MAP) in Wistar Kyoto (WKY) rats, spontaneously hypertensive rats (SHR) administered with acacetin intraperitoneally for 2 h or intragastrically for six weeks were examined. The endothelial injury was evaluated by immunofluorescent staining and a transmission electron microscope (TEM). Vascular tension measurement was performed to assess the protective effect of acacetin on mesenteric arteries. Endothelial injury in the pathogenesis of SHR was modeled in HUVECs treated with Angiotensin II (Ang II). Mitochondria-dependent apoptosis, the opening of Mitochondrial Permeability Transition Pore (mPTP) and mitochondrial dynamics proteins were determined by fluorescence activated cell sorting (FACS), immunofluorescence staining and western blot. Acacetin administered intraperitoneally greatly reduced MAP in SHR by mediating a more pronounced endothelium-dependent dilatation in mesenteric arteries, and the vascular dilatation was reduced remarkably by NG-nitro-L-arginine methyl ester (L-NAME), an inhibitor of NO synthesis. While acacetin administered intragastrically for six weeks had no apparent effect on MAP, it improved the endothelium-dependent dilatation in SHR by activating the AKT/eNOS pathway and protecting against the abnormalities of endothelium and mitochondria. Furthermore, acacetin remarkably inhibited Ang II induced apoptosis by inhibiting the increased expression of Cyclophilin D (CypD), promoted the opening of mPTP, ROS generation, ATP loss and disturbance of dynamin-related protein 1 (DRP1)/optic atrophy1 (OPA1) dynamics in HUVECs. This study suggests that acacetin protected against endothelial dysfunction in hypertension by activating the AKT/eNOS pathway and modulating mitochondrial function by targeting mPTP and DRP1/OPA1-dependent dynamics.


1H NMR-based Investigation of Metabolic Response to Electro-Acupuncture Stimulation.
Acupuncture is a traditional Chinese medicine therapy that has been found useful for treating various diseases. The treatments involve the insertion of fine needles at acupoints along specific meridians (meridian specificity). This study aims to investigate the metabolic basis of meridian specificity using proton nuclear magnetic resonance (1H NMR)-based metabolomics. Electro-acupuncture (EA) stimulations were performed at acupoints of either Stomach Meridian of Foot-Yangming (SMFY) or Gallbladder Meridian of Foot-Shaoyang (GMFS) in healthy male Sprague Dawley (SD) rats. 1H-NMR spectra datasets of serum, urine, cortex, and stomach tissue extracts from the rats were analysed by multivariate statistical analysis to investigate metabolic perturbations due to EA treatments at different meridians. EA treatment on either the SMFY or GMFS acupoints induced significant variations in 31 metabolites, e.g., amino acids, organic acids, choline esters and glucose. Moreover, a few meridian-specific metabolic changes were found for EA stimulations on the SMFY or GMFS acupoints. Our study demonstrated significant metabolic differences in response to EA stimulations on acupoints of SMFY and GMFS meridians. These results validate the hypothesis that meridian specificity in acupuncture is detectable in the metabolome and demonstrate the feasibility and effectiveness of a metabolomics approach in understanding the mechanism of acupuncture.


Treating viral venereal infections with the CO2 laser.
Viral venereal infections caused by herpes simplex virus 2 and papillomavirus (wart) are epidemic diseases in the United States. Unfortunately, these two infections have eluded conventional therapy to date. Therefore, 306 women were treated for viral venereal diseases with the CO2 laser. Two hundred twenty-eight patients were treated for condyloma acuminatum and 78 for genital herpes. All the patients who underwent treatment for herpes were enrolled in an investigative protocol. Since the viral organisms of both diseases replicate in either the basal or prickle cell layers of the epithelium, deep laser treatment is not necessary; treatment to a depth of 1 to 2 mm is adequate. The average power densities ranged from 311 to 660 w/cm2. Herpes patients responded with relief of pain and elimination of viral infectivity for that cycle. Patients with primary herpes were "cured" in 83% of cases. C. acuminatum could be eliminated with the CO2 laser in virtually every woman.


Community perceptions of bloody diarrhoea in an urban slum in South Asia: implications for introduction of a Shigella vaccine.
Understanding local perceptions of disease causation could help public health officials improve strategies to prevent bloody diarrhoea. A cross-sectional survey was conducted in Dhaka, Bangladesh to elicit community beliefs about the causes of and prevention strategies for bloody diarrhoea. Between March and June 2003, we interviewed 541 randomly selected respondents. Overall, 507 (93%) respondents perceived that a vaccine could prevent bloody diarrhoea. If a vaccine provided lifetime protection, 445 (83%) respondents stated that they would opt to get the vaccine and would pay a median of $0·05 (range U.S.$0·01-0·15) for it, equivalent to <1% of their median weekly income. There was almost universal perception that an effective vaccine to prevent bloody diarrhoea was highly beneficial and acceptable. While respondents valued a vaccine for prevention of bloody diarrhoea, they were only willing to pay minimally for it. Therefore, achieving a high rate of Shigella vaccine coverage may require subsidy of vaccine purchase.


[Municipal health conferences in North Rhine-westphalia. Experience and perspectives].
Health conferences are established structural elements in the field of health prevention and health-care in North Rhine-Westphalia. This applies to the state level (state health conferences) as well as to the municipal and city levels of government (local health conferences). After being tested in a pilot project in the period 1995-1998, the foundation of local conferences became obligatory in all municipalities when the public health service act of 1998 came into effect. The present article describes the relevant structures, developments and results.