Metabolic correction: a functional biochemical mechanism against disease--Part 1: concept and historical background.
Human physiology depends on countless biochemical reactions, numerous of which are co-dependent and interrelated. The speed and level of completion of reactions usually depend on the availability of precursors and enzymes. The enzymatic activity depends on the bioavailability of micronutrient cofactors such as vitamins and minerals. In order to achieve a healthy physiological state, the organism requires that biochemical reactions occur at a controlled rate. To achieve this state it is required that metabolic reactions reach what can be considered an optimal metabolic equilibrium. A combination of genetic makeup, dietary patterns, trauma, disease, toxins, medications, and environmental stressors can elevate the demand for the nutrients needed to reach this optimal metabolic equilibrium. In this, part 1, the general concept of metabolic correction is presented with an elaboration explaining how this concept is increasing in importance as we become aware of the presence of genetic variants that affect enzymatic reactions causing metabolic disturbances that themselves favor or promote the disease state. In addition, part 1 reviews how prominent scientists have contributed in fundamental ways to our understanding of the importance of micronutrients in health and disease and in the development of the metabolic correction concept.


TAILoR (TelmisArtan and InsuLin Resistance in Human Immunodeficiency Virus [HIV]): An Adaptive-design, Dose-ranging Phase IIb Randomized Trial of Telmisartan for the Reduction of Insulin Resistance in HIV-positive Individuals on Combination Antiretroviral Therapy.
Combination antiretroviral therapy results in metabolic abnormalities which increase cardiovascular disease risk. We evaluated whether telmisartan reduces insulin resistance in human immunodeficiency virus (HIV)-positive individuals on antiretrovirals. We conducted a multicenter, randomized, open-label, dose-ranging controlled trial of telmisartan. Participants with HIV infection receiving combination antiretroviral therapy were randomized equally to either no intervention (control) or 20, 40, or 80 mg telmisartan once daily. The adaptive design allowed testing of all dose(s) of telmisartan in stage I, with the promising dose(s) being taken into stage II. The primary outcome measure was reduction in homeostasis model assessment of insulin resistance (HOMA-IR) at 24 weeks. A total of 377 patients were recruited. In stage I, 48, 49, 47, and 45 patients were randomized to control and 20, 40, and 80 mg telmisartan, respectively (total n = 189). At the interim analysis, 80 mg telmisartan was taken forward into stage II. At the end of stage II (n = 105, control; 106, 80-mg arm), there were no differences in HOMA-IR (estimated effect, 0.007; SE, 0.106) at 24 weeks between the telmisartan (80 mg) and nonintervention arms. Longitudinal analysis over 48 weeks showed no change in HOMA-IR, lipid or adipokine levels. There were significant (P ≤ .05), but marginal, improvements in revised Quantitative Insulin Sensitivity Check Index (QUICKI) (0.004) and plasma hs-CRP (-0.222 mg/L) and reduction in liver fat content (1.714 mean reduction; P = .005). No significant effect of telmisartan was demonstrated on the primary outcome (HOMA-IR), but there were marginal improvements with some secondary outcome measures. Further studies in this population are warranted to identify novel strategies for preventing cardiovascular morbidity and mortality. ISRCTN registry (51069819).


[Basics of spatial diagnostic acoustic analysis of ocular and orbital tissues by the example of a study on local changes in systemic sarcoidosis].
The study enrolled 39 patients (78 orbits) with verified sarcoidosis. Acoustic analysis of pathological changes in ocular and orbital tissues was performed in all cases. A new evaluation method based on a combination of different modes of digital ultrasound techniques has been proposed. New data on intravital changes in sarcoidosis has been obtained. Formerly unknown deformities of acoustic images of the globe, lacrimal gland, vitreous, optic nerve, and ophthalmic artery, that could be recommended to ophthalmologists and other specialists studying sarcoidosis, have been identified.


Components involved in virally mediated membrane fusion and permeability changes.
1. Intact F glycoprotein is required to induce permeability changes in Lettrée cells or in erythrocytes. Some HN glycoproteins may also be required. Permeability changes thus offer a simple, accurate and rapid means of assaying the integrity of F glycoprotein in certain viral preparations. 2. The '1-day' virus (which contains intact F glycoprotein but which differs morphologically from '3 day' virus) does not cause permeability changes; it can be rendered active by various physical treatments. It is concluded that the environment in which F glycoprotein is embedded is a determining factor for permeability changes. 3. The entry of fluorescently labelled peptides into cells made permeable by virus has been measured. Peptides having a molecular weight in excess of 1000 enter poorly, suggesting a 'pore' size of approx. 1 nm in diameter. 4. Two novel assay methods concerned with virus--cell fusion are described. The first measures the fluorescence enhancement that occurs when anthroylstearate is transferred from anthroylstearate-labelled virus to cells. The second measures the giant-cell formation that occurs when partially fused erythrocytes are exposed to hypo-osmotic treatment. The '1-day' virus is active in these assays. In contrast with permeability changes, virus--cell fusion is insensitive to changes in external Ca2+-concentration. 5. The results are compatible with a model [Knutton & Pasternak (1979) Trends Biochem. Sci. 4, 220--223; Impraim, Foster, Micklem & Pasternak (1980) Biochem. J. 186, 847--860] in which virus--cell fusion is a prerequisite for permeability changes, and in which permeability changes are the cause of haemolysis and giant-cell (polykaryon) formation.


Prevalence of low back pain in children and adolescents: a meta-analysis.
Low back pain (LBP) is common in children and adolescents, and it is becoming a public health concern. In recent years there has been a considerable increase in research studies that examine the prevalence of LBP in this population, but studies exhibit great variability in the prevalence rates reported. The purpose of this research was to examine, by means of a meta-analytic investigation, the prevalence rates of LBP in children and adolescents. Studies were located from computerized databases (ISI Web of Knowledge, MedLine, PEDro, IME, LILACS, and CINAHL) and other sources. The search period extended to April 2011. To be included in the meta-analysis, studies had to report a prevalence rate (whether point, period or lifetime prevalence) of LBP in children and/or adolescents (≤ 18 years old). Two independent researchers coded the moderator variables of the studies, and extracted the prevalence rates. Separate meta-analyses were carried out for the different types of prevalence in order to avoid dependence problems. In each meta-analysis, a random-effects model was assumed to carry out the statistical analyses. A total of 59 articles fulfilled the selection criteria. The mean point prevalence obtained from 10 studies was 0.120 (95% CI: 0.09 and 0.159). The mean period prevalence at 12 months obtained from 13 studies was 0.336 (95% CI: 0.269 and 0.410), whereas the mean period prevalence at one week obtained from six studies was 0.177 (95% CI: 0.124 and 0.247). The mean lifetime prevalence obtained from 30 studies was 0.399 (95% CI: 0.342 and 0.459). Lifetime prevalence exhibited a positive, statistically significant relationship with the mean age of the participants in the samples and with the publication year of the studies. The most recent studies showed higher prevalence rates than the oldest ones, and studies with a better methodology exhibited higher lifetime prevalence rates than studies that were methodologically poor. Future studies should report more information regarding the definition of LBP and there is a need to improve the methodological quality of studies.


Object memory effects on figure assignment: conscious object recognition is not necessary or sufficient.
In three experiments we investigated whether conscious object recognition is necessary or sufficient for effects of object memories on figure assignment. In experiment 1, we examined a brain-damaged participant, AD, whose conscious object recognition is severely impaired. AD's responses about figure assignment do reveal effects from memories of object structure, indicating that conscious object recognition is not necessary for these effects, and identifying the figure-ground test employed here as a new implicit test of access to memories of object structure. In experiments 2 and 3, we tested a second brain-damaged participant, WG, for whom conscious object recognition was relatively spared. Nevertheless, effects from memories of object structure on figure assignment were not evident in WG's responses about figure assignment in experiment 2, indicating that conscious object recognition is not sufficient for effects of object memories on figure assignment. WG's performance sheds light on AD's performance, and has implications for the theoretical understanding of object memory effects on figure assignment.


Nickel-catalyzed regioselective arylation of aromatic amides with aryl iodides enabled by an N,O-bidentate directing group.
A bidentate directing group enabled regioselective arylation of C(sp2)-H bonds in aromatic carboxamides with aryl iodides under nickel-catalysis is reported, which provides the corresponding products in moderate to good yields. This protocol using the inexpensive and low-toxic Ni catalyst can tolerate a wide range of functional groups.


Yeast histone genes show dosage compensation.
The copy number of yeast histone genes was increased by inserting an extra H2A,H2B gene pair into the haploid genome by the technique of yeast transformation. The presence of this extra gene copy has no detectable effect on cell growth. The steady-state levels of histone H2A,H2B mRNAs are not elevated in transformed strains, and they correspond to the levels measured for the parental strain. The transcription rate is increased in these strains, however, and the parental steady-state levels of histone mRNAs are maintained by increased turnover of histone transcripts. These results demonstrate that yeast histone genes display dosage compensation through the operation of posttranscriptional controls. They also suggest that maintainance of a constant ratio between histone mRNA concentration and the rate of chromosome replication may be of general importance to histone mRNA metabolism.


On the difficulties involved in the segmentation of pictures.
The problem of picture segmentation is widely believed to be practically unsolvable in its more general case formulation. However, as far as the authors know no formal argumentation has yet been given to this belief related to the segmentation problem. This correspondence provides some theoretical aspects of this phenomenon.


Advancing Equity in the Farm Bill: Opportunities for the Gus Schumacher Nutrition Incentive Program (GusNIP).
The Gus Schumacher Nutrition Incentive Program (GusNIP) is a federally funded grant program that provides nutrition incentives-subsidies for purchasing fruits and vegetables (FV)-to Supplemental Nutrition Assistance Program (SNAP) participants. GusNIP currently advances nutrition equity by improving FV access for people with low incomes, yet inequities exist within GusNIP. We sought to identify inequities in GusNIP at the community, organization, partner, and individual levels and develop recommendations for farm bill provisions to make the program more equitable. In Spring 2021, a group of nutrition incentive experts (n = 11) from across the country convened to discuss opportunities to enhance equity in GusNIP. The iterative recommendation development process included feedback from key stakeholders (n = 15) and focus group participants with GusNIP lived experience (n = 12). Eleven recommendations to advance equity in GusNIP in the farm bill emerged across six categories: (1) increase total GusNIP funding, (2) increase funding and support to lower-resourced organizations and impacted communities, (3) eliminate the match requirement, (4) support statewide expansion, (5) expand and diversify retailer participation, and (6) expand program marketing. Including these recommendations in the upcoming and future farm bills would equitably expand GusNIP for SNAP participants, program grantees, and communities across the country.


N-terminal truncation of Lats1 causes abnormal cell growth control and chromosomal instability.
The tumor suppressors Lats1 and Lats2 are mediators of the Hippo pathway that regulates tissue growth and proliferation. Their N-terminal non-kinase regions are distinct except for Lats conserved domains 1 and 2 (LCD1 and LCD2), which may be important for Lats1/2-specific functions. Lats1 knockout mice were generated by disrupting the N-terminal region containing LCD1 (Lats1(ΔN/ΔN)). Some Lats1(ΔN/ΔN) mice were born safely and grew normally. However, mouse embryonic fibroblasts (MEFs) from Lats1(ΔN/ΔN) mice displayed mitotic defects, centrosomal overduplication, chromosomal misalignment, multipolar spindle formation, chromosomal bridging and cytokinesis failure. They also showed anchorage-independent growth and continued cell cycles and cell growth, bypassing cell-cell contact inhibition similar to tumor cells. Lats1(ΔN/ΔN) MEFs produced tumors in nude mice after subcutaneous injection, although the tumor growth rate was much slower than that of ordinary cancer cells. Yap, a key transcriptional coactivator of the Hippo pathway, was overexpressed and stably retained in Lats1(ΔN/ΔN) MEFs in a cell density independent manner, and Lats2 mRNA expression was downregulated. In conclusion, N-terminally truncated Lats1 induced Lats2 downregulation and Yap protein accumulation, leading to chromosomal instability and tumorigenesis.


Years of Life Lost due to Opioid Overdose in Ohio: Temporal and Geographic Patterns of Excess Mortality.
The aim of the study was to quantify the burden of premature mortality because of opioid overdose in Ohio, document the role of fentanyl poisoning in contribution to this evolving epidemic, examine geographic, demographic, and temporal patterns of mortality burden within Ohio, and measure the effect of opioid overdose on lifespan in the state. A serial cross-sectional analysis was performed for all fatal opioid poisonings (N = 12,782) in the state of Ohio between January 1, 2010 and December 31, 2016. The burden of fatal opioid overdose was calculated in Years of Life Lost (YLL). YLL were mapped with respect to geographic and cultural region. The geographic spread of fentanyl poisoning was also mapped, and the shifting contribution of fentanyl poisoning to overall opioid mortality burden was assessed over time. Finally, the negative effect of opioid overdose on average lifespan was calculated. Opioid overdose resulted in 508,451 total YLL. In the year 2016 alone, there were 136,679 YLL attributable to opioid poisoning. Fentanyl-related YLL rose from 7.5% of all YLL because of opioid overdose in 2010 to 69.0% in 2016. In the same year, opioid overdose lowered the lifespan of an average Ohioan by 0.97 years. Fatal opioid overdose accounted for over half a million YLL in Ohio during the 7-year study period. Opioid overdose mortality rose annually. Fentanyl involved overdoses accounted for a growing proportion of excess mortality. Burden was not equally distributed within the state. Two distinct geographical clusters of excess mortality were identified in the northeast and south.


Coordination of care: stage one in assessing rural managed care.
This article provides a framework for assessing the role of managed care in optimizing the mix of services to advance the health of rural populations. Mindful of limited organizational and financial resources in many rural areas, such assessments must carefully weigh the contribution of these resources to effective management of care. The framework presented emphasizes the different populations and different health conditions that a variety of care coordinators may address more or less effectively. Attention to issues having to do with organizational architecture and financial accountability of managed care should flow from prior to consideration of care management.


CPP-115, a vigabatrin analogue, decreases spasms in the multiple-hit rat model of infantile spasms.
Infantile spasms (IS) have poor outcomes and limited treatment options, including vigabatrin, a γ-aminobutyric acid (GABA) aminotransferase inactivator. Vigabatrin has been associated with retinal toxicity. A high affinity vigabatrin analogue (CPP-115; Catalyst Pharmaceutical Partners, Inc., Coral Gables, FL, U.S.A.) has shown lower risk of retinal toxicity. Here, we test the efficacy of CPP-115 in reducing spasms and its tolerability in the multiple-hit rat model of IS, in which daily vigabatrin reduced spasms for only one day, but was not well tolerated. Male rats were treated with the protocol of the multiple-hit model of IS on postnatal day 3 (PN3). Using a randomized, blinded, vehicle-controlled, dose-response study design, CPP-115 (0.1, 1, or 5 mg/kg intraperitoneally [i.p.]) or vehicle was given daily (PN4-12) or as a single injection (PN7) after spasm onset. Intermittent video- or video-electroencephalography (EEG) monitoring was done. Secondary end points included the following: daily weights, survival, performance on open field activity, surface righting time, and negative geotaxis (PN3-20), horizontal bar (PN13-20), and Barnes maze (PN16-19). Statistics used a linear mixed model of raw or normalized log-transformed data, taking into account the repeated observations on each animal. The lower CPP-115 doses (0.1-1 mg/kg/day, PN4-12) reduced spasms between PN6 and 7 without increasing mortality. CPP-115 at 5 mg/kg/day (PN4-12) reduced spasms earlier (PN5), but was eventually lethal. A single CPP-115 injection (1 mg/kg, i.p.) decreased electroclinical spasms acutely but transiently. CPP-115 transiently improved the probability to >50% reduction of spasms, but did not accelerate spasm cessation. CPP-115 did not alter neurodevelopmental outcomes or visuospatial learning. We provide proof-of-concept evidence that CPP-115, a vigabatrin analogue, decreases spasms in the multiple-hit rat model of IS at considerably lower and better tolerated doses than vigabatrin did in our previous studies. Further optimization of the treatment protocol is needed. CPP-115 may be a promising new candidate treatment for IS with better tolerability than vigabatrin.


Metabolic Syndrome Is Associated With Altered mRNA and miRNA Content in Human Circulating Extracellular Vesicles.
As mediators of intercellular communication, circulating extracellular vehicles (EVs) can modulate tissue and cellular pathways by altering transcription profiles in recipient cells, and their content may reflect the status of their parent cells. However, whether their cargo is altered in the metabolic syndrome (Mets) remains unclear. We hypothesized that MetS altered mRNAs and miRNAs packed within circulating-EVs. EVs were collected from plasma of patients with MetS or age-matched Lean controls (n=4 each). RNA sequencing was performed to identify dysregulated mRNAs and miRNAs, and analyze genes targeted by miRNAs, top pathways, and diseases associated with MetS-EVs. MetS patients showed elevated body weight, blood pressure, glucose, insulin, and liver injury markers levels. 1,446 mRNAs were downregulated and 32 upregulated in MetS- compared to Lean-EVs, whereas 40 miRNAs were selectively enriched and 10 downregulated in MetS-EVs. MetS upregulated in EVs genes involved in apoptosis, mitochondrial regulation, transport, and lipoproteins, but downregulated vessel and heart development, protein complex biogenesis, and angiogenesis. MetS also upregulated miRNAs targeting genes implicated in cellular processes, including oxidation-reduction, and downregulated miRNAs capable of modulating catalytic activity, as well as heart, blood vessel, and skeletal development, transcriptional regulation, apoptosis, and cell cycle. Our study, thus, indicates that human subjects with MetS show modified cargo of circulating EVs, which in turn may modulate several critical cellular functions and fate. These EVs may reflect the anomalous status of their parent cells, and potentially serve as important regulators, biomarkers, and targets in the progression and treatment of MetS.


A systematic neuro-fuzzy modeling framework with application to material property prediction.
A systematic neural-fuzzy modeling framework that includes the initial fuzzy model self-generation, significant input selection, partition validation, parameter optimization, and rule-base simplification is proposed in this paper. In this framework, the structure identification and parameter optimization are carried out automatically and efficiently by the combined use of a sell-organization network, fuzzy clustering, adaptive back-propagation learning, and similarity analysis-based model simplification. The proposed neuro-fuzzy modeling approach has been used for nonlinear system identification and mechanical property prediction in hot-rolled steels from construct composition and microstructure data. Experimental studies demonstrate that the predicted mechanical properties have a good agreement with the measured data by using the elicited fuzzy model with a small number of rules.


The phenotype of limb-girdle muscular dystrophy type 2I.
Mutations in the fukutin-related protein gene FKRP cause limb-girdle muscular dystrophy (LGMD2I) as well as a form of congenital muscular dystrophy (MDC1C). To define the phenotype in LGMD2I. The authors assessed 16 patients from 14 families with FKRP gene mutations and LGMD and collected the results of mutation analysis, protein studies, and respiratory and cardiac investigations. Thirteen patients, most with adult presentation, were homozygous for the common C826A mutation in FKRP. The three other cases were compound heterozygotes for C826A and two of them presented in childhood, with more progressive disease. The pattern of muscle involvement, frequently including calf hypertrophy, was similar to dystrophinopathy. Complications in patients with LGMD2I were common and sometimes out of proportion to the skeletal muscle involvement. Six patients had cardiac involvement, and 10 had respiratory impairment: five required nocturnal respiratory support. All patients had serum creatine kinase at least 5 to 70 times normal. The most consistent protein abnormality found on muscle biopsy was a reduction of laminin alpha2 immunolabeling, either on muscle sections or immunoblotting alone. LGMD2I due to FKRP mutations appears to be a relatively common cause of LGMD, with respiratory and cardiac failure as prominent complications.


Effects of PROtein enriched MEDiterranean Diet and EXercise on nutritional status and cognition in adults at risk of undernutrition and cognitive decline: the PROMED-EX Randomised Controlled Trial.
Undernutrition leading to unplanned weight loss is common in older age and has been linked to increased dementia risk in later life. Weight loss can precede dementia by a decade or more, providing a unique opportunity for early intervention to correct undernutrition and potentially prevent or delay cognitive impairment. The combined effects of diet and exercise on undernutrition have not yet been evaluated. The objective of this trial is to determine the effect of a protein-enriched Mediterranean diet, with and without exercise, on nutritional status and cognitive performance in older adults at risk of undernutrition and cognitive decline. One hundred and five participants aged 60 years and over at risk of undernutrition and with subjective cognitive decline will be recruited to participate in a 6-month, single-blind, parallel-group randomised controlled trial. Participants will be block randomised into one of three groups: group 1-PROMED-EX (diet+exercise), group 2-PROMED (diet only) and group 3-standard care (control). The primary outcome is nutritional status measured using the Mini Nutritional Assessment. Secondary outcomes include cognitive function, nutritional intake, body composition, physical function and quality of life. Mechanistic pathways for potential diet and exercise-induced change in nutritional status and cognition will be explored by measuring inflammatory, metabolic, nutritional and metabolomic biomarkers. The study is approved by the UK Office for Research Ethics Committee (ref: 21/NW/0215). Written informed consent will be obtained from participants prior to recruitment. Research results will be disseminated to the public via meetings and media and the scientific community through conference presentations and publication in academic journals. ClinicalTrials.gov Registry (NCT05166564).


Inhibition of the Nuclear Export Receptor XPO1 as a Therapeutic Target for Platinum-Resistant Ovarian Cancer.
Purpose: The high fatality-to-case ratio of ovarian cancer is directly related to platinum resistance. Exportin-1 (XPO1) is a nuclear exporter that mediates nuclear export of multiple tumor suppressors. We investigated possible clinicopathologic correlations of XPO1 expression levels and evaluated the efficacy of XPO1 inhibition as a therapeutic strategy in platinum-sensitive and -resistant ovarian cancer.Experimental Design: XPO1 expression levels were analyzed to define clinicopathologic correlates using both TCGA/GEO datasets and tissue microarrays (TMA). The effect of XPO1 inhibition, using the small-molecule inhibitors KPT-185 and KPT-330 (selinexor) alone or in combination with a platinum agent on cell viability, apoptosis, and the transcriptome was tested in immortalized and patient-derived ovarian cancer cell lines (PDCL) and platinum-resistant mice (PDX). Seven patients with late-stage, recurrent, and heavily pretreated ovarian cancer were treated with an oral XPO1 inhibitor.Results: XPO1 RNA overexpression and protein nuclear localization were correlated with decreased survival and platinum resistance in ovarian cancer. Targeted XPO1 inhibition decreased cell viability and synergistically restored platinum sensitivity in both immortalized ovarian cancer cells and PDCL. The XPO1 inhibitor-mediated apoptosis occurred through both p53-dependent and p53-independent signaling pathways. Selinexor treatment, alone and in combination with platinum, markedly decreased tumor growth and prolonged survival in platinum-resistant PDX and mice. In selinexor-treated patients, tumor growth was halted in 3 of 5 patients, including one with a partial response, and was safely tolerated by all.Conclusions: Taken together, these results provide evidence that XPO1 inhibition represents a new therapeutic strategy for overcoming platinum resistance in women with ovarian cancer. Clin Cancer Res; 23(6); 1552-63. ©2016 AACR.


Reference intervals for leukocyte subsets in adults: Results from a population-based study using 10-color flow cytometry.
Reference intervals for leukocyte subsets from peripheral blood are helpful for the understanding of disease states and therapy effects. We performed in-depth immunophenotyping for 608 healthy German adults from the Leipzig region from 40 to 79 years by 10-color flow cytometry (FCM) to gain reference information for various leukocyte subsets including subsets of granulocytes, monocytes and lymphocytes. First, we derived gender- and age-specific reference intervals for males and females from 40 to 59 and from 60 to 79 years, respectively. Second, we further investigated the influence of gender and age on leukocyte counts. We found significantly higher cell counts for monocytes (P < 0.001) and NK cells (P < 0.001) in men, whereas women had higher counts for B cells (P < 0.001), Th cells (P < 0.001) and regulatory T cells (P = 0.008). Furthermore, with increasing age, a decrease in Tc cells (about 8% within 5 years) and an increase in NK cells (<4% within 5 years) were observed. In future research, it should be investigated whether these are real ageing effects that can be confirmed in longitudinal studies. Furthermore, it is important to understand if the Tc cell count drop is functionally compensated by the increase of NK cells.


The in vitro effects of H-89, a specific inhibitor of protein kinase A, in the human colonic carcinoma cell line Caco-2.
H-89 is a compound characterized in vitro as a potent and selective inhibitor of protein kinase A. In the present study, we observed that H-89 induced morphological transformation and caused growth inhibition of the human colon cancer cell line Caco-2 in a dose-dependent manner. However, another protein kinase A inhibitor, H-8, had no effect on Caco-2 cells. To evaluate the possible molecular mechanism of H-89-evoked effects in Caco-2 cells, we analysed the capacity of H-89 to regulate the protein kinase B (Akt/PKB) signalling pathway. H-89 treatment led to an activation of Akt/PKB in Caco-2 cells. This activation was phosphatidylinositol 3 (PI3)-kinase-dependent and promoted survival of Caco-2 cells because the PI3 kinase inhibitor LY294002 inhibited the Akt/PKB activation and induced apoptosis of Caco-2 cells. To test whether Akt/PKB activity promoted resistance to H-89-induced effects, LY294002 was added in combination with H-89. LY294002 greatly potentiated the H-89-induced growth inhibition and apoptosis of Caco-2 cells. These results suggest that the H-89-induced growth inhibition of Caco-2 cells is associated with phosphorylation of Akt/PKB protein and that the cells become more sensitive to H-89 and die by apoptosis upon inhibition of the PI3K/Akt pathway.


Gender-related ADL performance of old people recently admitted to a Swiss nursing home. A cross-sectional study.
The aim of this paper was to establish gender-specific associations between the characteristics of residents recently admitted to Swiss nursing homes (NH) and their activities of daily living (ADL) performance. A sample of 17'331 NH residents living in 90 Swiss NHs received a Resident Assessment Instrument Minimum Data Set (RAI-MDS) shortly after NH entry, in the period from 1997 to 2007. ADL performance was assessed using the MDS-ADL long-form scale that measures self-performance in the seven following tasks: bed mobility, transfer, locomotion, dressing, eating, toilet use and personal hygiene. Associations between ADL performance and health and personal characteristics of the residents were then investigated using bivariate and multivariate analyses. A total of 40% of the residents recently admitted to Swiss NHs were completely dependent for ADL. Absence of physical activity and having been admitted to a NH before 2003 were gender-specific variables associated with poorer ADL. Incontinence, poor balance, impaired cognition and vision as well as low BMI were important factors associated with poorer ADL performance in both genders. The general scheme of ADL impairment was quite similar for both genders, but females tended to do slightly but significantly better than males. Overall, strategies improving balance, continence, cognition and sensory function including treatment of vision impairment, promoting healthy nutrition as well as physical activity--particularly among elderly women with musculoskeletal conditions--may facilitate care in recently admitted residents and/or delay NH admission.


Long-term effects on bone of postnatal immunization against GHRH in female and male rats.
The effects of neonatal passive immunization against GHRH on bone was examined in male and female rats. Pups were treated subcutaneously with GHRH-antiserum (GHRH-Ab) from day 1 to day 10 of age. Bone mineral content (BMC) and bone mineral density (BMD) were evaluated at monthly intervals until 7 months. Markers of bone resorption (urinary lysylpyridinoline, LP), bone formation (serum osteocalcin, OC) and serum IGF-I were measured at 2, 3 and 7 months. In male rats, GHRH-Ab did not modify BMC and BMD when compared with controls. In contrast, female rats demonstrated lower whole body and femoral BMC and BMD from 2 to 7 months of age. Reduced bone growth in the females was associated with lower IGF-I levels than controls at 2 and 3 months of age, whereas in males IGF-I titers did not change during the period of the study. LP excretion was higher in GHRH-Ab-treated rats at 2 and 3 months in both sexes. In females, no difference in OC values was recorded, whereas in GHRH-Ab-treated males, there was an increase in OC levels at 2 and 3 months. These data indicate that transient GHRH deprivation induces an osteopenic effect in female rats which is not evident in male rats.


[Roles of phenylalanine ammonia-lyase in low temperature tolerance in cucumber seedlings].
To reveal the roles of phenylalanine ammonia-lyase (PAL) in low temperature tolerance in cucumber seedlings, a specific PAL inhibitor (AOPP) was sprayed to the seedlings, and then the stress tolerance was determined. The results suggested that both gene expression and enzymatic activity of PAL in cucumber leaves were induced under low temperature. The seedlings pretreated with AOPP showed lower PAL activity and less accumulation of phenolics and flavonoids. Low temperature caused damages in cucumber seedlings, and pretreatment of AOPP aggravated these damages. Compared to the control, the seedlings pretreated with AOPP showed significantly higher relative electrolyte leakage and MDA production, lower maximum photochemical efficiency of PSII (Fv/Fm) but higher photo-chemical quenching coefficient Y(NO), and reduced expression of low temperature-responsive genes (PR1-la, COR47, P5CS and HSP70). In cucumber seedlings, low temperature stress induced the accumulation of H2O2, increased the contents of ascobate (AsA) but decreased the contents of dehydroascobate (DHA), and thus reduced the value of AsA: DHA. In the AOPP-pretreated seedlings, the activities of antioxidant enzymes (CAT and APX) were significantly repressed, and excess H2O2 accumulated. The value of AsA: DHA was also lower than the control. Furthermore, co-application of H2O2 scavenger alleviated the low temperature-induced damages in the AOPP-pretreated seedlings, while coapplication of a CAT inhibitor made the seedlings more sensitive to low temperature stress. These results indicated that under low temperature stress, the enhanced activities of PAL could increase the biosynthesis of phenylpropanoid compounds and activate the cellular antioxidant enzymes, which could scavenge the excess ROS and maintain the cellular redox status, and thereby reduce the photo- and oxidative damages caused by low temperature stress.


MINFLUX monitors rapid molecular jumps with superior spatiotemporal resolution.
Compared with localization schemes solely based on evaluating patterns of molecular emission, the recently introduced single-molecule localization concept called MINFLUX and the fluorescence nanoscopies derived from it require up to orders of magnitude fewer emissions to attain single-digit nanometer resolution. Here, we demonstrate that the lower number of required fluorescence photons enables MINFLUX to detect molecular movements of a few nanometers at a temporal sampling of well below 1 millisecond. Using fluorophores attached to thermally fluctuating DNA strands as model systems, we demonstrate that measurement times as short as 400 microseconds suffice to localize fluorescent molecules with ∼2-nm precision. Such performance is out of reach for popular camera-based localization by centroid calculation of emission diffraction patterns. Since theoretical limits have not been reached, our results show that emerging MINFLUX nanoscopy bears great potential for dissecting the motions of individual (macro)molecules at hitherto-unattained combinations of spatial and temporal resolution.


Is Gout Associated with Pyoderma Gangrenosum? A Population-Based Case-Control Study.
The coexistence of pyoderma gangrenosum (PG) and gout has been reported in individual patients; however, the association between these conditions has not been investigated. We aimed to assess the association between PG and gout and to examine whether the presence of gout predisposes to the development of PG. A population-based case-control study was conducted comparing PG patients (n = 302) with age-, sex-, and ethnicity-matched control subjects (n = 1497) with respect to the presence of preceding gout. Logistic regression models were utilized for univariate and multivariate analyses. The prevalence of preceding gout was greater in patients with PG than in control subjects (3.7% vs. 0.7%, respectively; p < 0.001). Gout was associated with a more than fivefold increase in the risk of PG (OR, 5.15; 95% CI, 2.21-11.98). After adjusting for confounding factors, gout emerged as a significant independent predictor of PG (adjusted OR, 4.08; 95% CI, 1.69-9.80). Gout preceded the diagnosis of PG by a median latency of 4.6 years. Patients with gout-associated PG were older, predominantly male, and had a higher prevalence of metabolic syndrome than other patients with PG. In conclusion, gout increases the risk of developing PG by more than fivefold. Physicians managing patients with gout and PG should be aware of this emerging association.


Expression of epidermal growth factor receptor (EGF-R), vascular endothelial growth factor receptor (VEGF-R) and fibroblast growth factor receptor (FGF-R) systems in porcine oviduct and endometrium during the time of implantation.
The oviduct and uterus provide the environment for the establishment of pregnancy. Among others, growth factor systems are involved in functional signaling interactions at the pre- and peri-implantation maternal-conceptus interface in pigs. Distinct regulation of epidermal growth factor Receptor (EGF-R), vascular endothelial growth factor receptor (VEGF-R) and fibroblast growth factor receptor (FGF-R) systems and of bioactivation of EGF-R in porcine oviduct and endometrium during the estrous cycle, early pregnancy and during steroid replacement in ovariectomized gilts is summarized. Remarkable influences of ovarian steroids and EGF on the expression of specific markers of transcription and translation in these tissues are discussed. Known biological effects of the EGF, VEGF and FGF are related to cellular differentiation and angiogenesis. This suggests their involvement in the transformation of the endometrium into a decidua subsequently leading towards successful establishment of pregnancy. Peripheral steroids may exert their effects on epithelial cells both in a direct genomic manner or through mediators such as growth factors. The aim of our study was to draw specific attention to the paracrine regulation in the porcine endometrium especially during the implantation window.


[Structural organization of chromatin as a factor determining the rate of its endonucleolysis in irradiated and nonirradiated thymocytes].
A study was made of chromatin endonucleolysis in hypotonic thymocytes incubated in digestive buffers containing different concentrations of potassium, magnesium, calcium, and mercaptoethanol. Inhibition of endonucleolysis by univalent cation during the first 20 min of incubation was followed by intensive chromatin degradation. A decrease in free potassium content retarded chromatin degradation and enhanced the inhibiting effect of the univalent cations. The regularities of changes in the rate of chromatin endonucleolysis in different digestive buffers were similar with both exposed and intact thymocytes.


Thrombin generation and activity in multiple sclerosis.
The coagulation cascade and immune system are intricately linked, highly regulated and respond cooperatively in response to injury and infection. Increasingly, evidence of hyper-coagulation has been associated with autoimmune disorders, including multiple sclerosis (MS). The pathophysiology of MS includes immune cell activation and recruitment to the central nervous system (CNS) where they degrade myelin sheaths, leaving neuronal axons exposed to damaging inflammatory mediators. Breakdown of the blood-brain barrier (BBB) facilitates the entry of peripheral immune cells. Evidence of thrombin activity has been identified within the CNS of MS patients and studies using animal models of experimental autoimmune encephalomyelitis (EAE), suggest increased thrombin generation and activity may play a role in the pathogenesis of MS as well as inhibit remyelination processes. Thrombin is a serine protease capable of cleaving multiple substrates, including protease activated receptors (PARs), fibrinogen, and protein C. Cleavage of all three of these substrates represent pathways through which thrombin activity may exert immuno-regulatory effects and regulate permeability of the BBB during MS and EAE. In this review, we summarize evidence that thrombin activity directly, through PARs, and indirectly, through fibrin formation and activation of protein C influences neuro-immune responses associated with MS and EAE pathology.


The effect of chemotherapy with 5-fluorouracil, bleomycin and cisplatin in the healing of colonic anastomoses in rats.
Chemotherapeutic factors are known to affect healing on the postoperative patient. The aim of the present experimental study was to evaluate the effect of intraperitoneal infusion of 5-fluorouracil, bleomycin and cisplatin on the healing of colonic anastomoses in rats. Forty Albino-Wistar male rats were randomly divided into two groups, a control and a chemotherapy (CT) group. In both, an end-to-end colonic anastomosis was performed. collagen, In the control group, 2cc saline was administered intraperitoneally during the operation and daily postoperatively until the sacrifice. In the CT group, rats were administered a solution of 5-fluorouracil (20mg/kg b.w.), bleomycin (4mg/kg b.w.) and cisplatin (0.7 mg/kg b.w.) in an amount of 2cc intraperitoneal intraoperatively and afterwards daily postoperatively until the seventh postoperative day when they were sacrificed. At sacrifice, adhesion presence was calculated and the anastomoses were resected and macroscopically examined. Bursting pressures were calculated and histological features were graded. Hydroxyproline concentrations were evaluated. No deaths or wound infections were observed until sacrifice. Bodyweight was significantly decreased in the CT group (p=0.005). Bursting pressures (p=0.001) were significantly lower in the chemotherapy group, whereas adhesions were significantly increased (p=0.001). Hydroxyproline concentrations were not significantly different (p=0.401). All histological parameters appeared significantly decreased in the CT group: inflammation (p<0.008), neoangiogenesis (p<0.001), and fibroblast activity (p=0.001) and collagen deposition (p<0.001). The use of chemotherapeutic agents had negative effects on the healing process of colonic anastomosis in rats. The decreased inflammatory response depicts in more frequent anastomotic dehiscence, ruptures and bodyweight loss postoperatively. Adhesion, Bursting pressure, Collagen, Hydroxyproline, Inflammation, Neoangiogenesis.


Integrating Population-Wide Laboratory Testing Data with Audit and Feedback Reports for Ontario Physicians.
Audit and feedback reports, distributed by Health Quality Ontario to consenting primary care physicians, provide doctors with a confidential summary of how they manage patients with diabetes; these reports currently lack clinical information. We examined the feasibility of linking the Ontario Laboratories Information System (OLIS), a large provincial database of laboratory test results, with the existing provincial audit and feedback reporting structure to integrate measures of glycemic and cholesterol control among patients with diabetes. We found that we could ascertain glycated hemoglobin (69.9%) and low-density lipoprotein cholesterol (64.1%) test results in the previous year for most patients and that there was wide variation among physicians in the proportion of patients who exceeded clinical thresholds for these measures. Our study highlights the potential value of reporting more clinically rich information to physicians to improve diabetes care and management and demonstrates the feasibility of using OLIS data at the population level to enhance ongoing research and quality improvement.


Endovascular management of poor-grade aneurysmal subarachnoid hemorrhage in the geriatric population.
The incidence of poor-grade (Hunt and Hess grade IV and V) subarachnoid hemorrhage (SAH) is higher in elderly patients (>70 years) than in younger groups. The aim of this retrospective study was to analyze the outcome of these poor grade elderly patients after endovascular treatment. We retrospectively reviewed the clinical records of 27 patients older than 70 years who underwent endovascular treatment for aneurysmal SAH between January 1996 and July 2002. Thirteen patients with SAH and a poor Hunt and Hess grade at initial presentation had been treated by endovascular means. Their outcomes were assessed by the using the Glasgow Outcome Scale (GOS). Two patients (15%) had a good outcome according to the GOS. Three patients (23%) were moderately disabled, two (15%) were severely disabled at the time of discharge from the hospital, and six (47%) died. Five patients (38%) developed clinical vasospasm and underwent balloon angioplasty. Three procedure-related deaths occurred (23%). Endovascular treatment has modified the management of poor-grade SAH in elderly patients, most of whom are high-risk surgical candidates. Endovascular treatment can be administered early after the initial ictus, reducing the risk of rebleeding and providing an option to pursue aggressive triple-H therapy. Symptomatic vasospasm can also be treated by endovascular means in the initial setting.


The effects of pregnancy and parturition on phosphorus metabolites in rat uterus studied by 31P nuclear magnetic resonance.
Concentrations of phosphorus metabolites and intracellular pH have been measured in non-pregnant, late-pregnant and post-partum rat uterus using 31P nuclear magnetic resonance (31P n.m.r.). Intact uterine tissue was superfused with oxygenated de-Jalon solution at 4, 20 or 37 degrees C while inside the n.m.r. spectrometer. The phosphocreatine concentration [PCr], was higher and the inorganic phosphate concentration [Pi], lower than values determined by chemical analysis of extracts from both pregnant and non-pregnant rat uterus. [PCr] was 1.4-fold greater in late-pregnant than in non-pregnant rat uterus. Following parturition, large changes were observed in [PCr], [Pi] and in an unidentified metabolite in the phosphomonoester (PME) region of the n.m.r. spectrum. The time course of the recovery of these metabolites to prepregnant values was determined. The [PCr] remained below the non-pregnant value for at least 1 week post-partum and the [Pi] was elevated, compared to the non-pregnant value, during this period. More rapid changes were seen in the [PME], which doubled on day 0 post-partum but almost returned to its non-pregnant value on day 1 post-partum. No significant difference was observed between intracellular pH values in late-pregnant and non-pregnant rat uterus; however, there was a large acid shift following parturition. Intracellular pH depended upon the temperature at which the tissue was maintained. The effect of muscular work during parturition was investigated by comparing Caesarian-sectioned uteri with uteri which had undergone normal parturition. Uteri examined 1 day after Caesarian operation showed no differences in metabolite levels from normal, 1 day post-partum uteri. We conclude that concentrations of phosphorus metabolites depend upon the physiological state of the uterus. We suggest that the changes following parturition are not a consequence of the mechanical work performed by the uterus, but must be caused by some other event associated with parturition such as hormonal changes.


Prediction and prevention of thromboembolic events with enoxaparin in cancer patients with elevated tissue factor-bearing microparticles: a randomized-controlled phase II trial (the Microtec study).
Elevated levels of circulating tissue factor-bearing microparticles (TFMP) have been associated with an increased risk of developing venous thromboembolism (VTE) in cancer patients. We performed a randomized phase II study to evaluate the cumulative incidence of VTE in advanced cancer patients with lower levels of TFMP not receiving thromboprophylaxis and those with higher levels of circulating TFMP randomized to enoxaparin or observation. The cumulative incidence of VTE at 2 months in the higher TFMP group randomized to enoxaparin (N = 23) was 5·6% while the higher TFMP group observation arm (N = 11) was 27·3% (Gray test P = 0·06). The cumulative incidence of VTE in the low TFMP was 7·2% (N = 32). No major haemorrhages were observed in the enoxaparin arm. The median survival for patients with higher levels of TFMP followed by observation was 11·8 months compared with 17·8 months on enoxaparin (P = 0·58). In a prospective randomized trial, increased numbers of circulating TFMP detected by impedance flow cytometry identified cancer patients with a high incidence of VTE. Enoxaparin demonstrated a clear trend towards reducing the rate of VTE in patients with elevated levels of TFMP, with an overall rate of VTE similar in magnitude to the lower TFMP group.


Clinical outcomes after MRI connectivity-guided radiofrequency thalamotomy for tremor.
Radiofrequency thalamotomy (RF-T) is an established treatment for refractory tremor. It is unclear whether connectivity-guided targeting strategies could further augment outcomes. The aim of this study was to evaluate the efficacy and safety of MRI connectivity-guided RF-T in severe tremor. Twenty-one consecutive patients with severe tremor (14 with essential tremor [ET], 7 with Parkinson's disease [PD]) underwent unilateral RF-T at a single institution between 2017 and 2020. Connectivity-derived thalamic segmentation was used to guide targeting. Changes in the Fahn-Tolosa-Marin Rating Scale (FTMRS) were recorded in treated and nontreated hands as well as procedure-related side effects. Twenty-three thalamotomies were performed (with 2 patients receiving a repeated intervention). The mean postoperative assessment time point was 14.1 months. Treated-hand tremor scores improved by 63.8%, whereas nontreated-hand scores deteriorated by 10.1% (p < 0.01). Total FTMRS scores were significantly better at follow-up compared with baseline (mean 34.7 vs 51.7, p = 0.016). Baseline treated-hand tremor severity (rho = 0.786, p < 0.01) and total FTMRS score (rho = 0.64, p < 0.01) best correlated with tremor improvement. The most reported side effect was mild gait ataxia (n = 11 patients). RF-T guided by connectivity-derived segmentation is a safe and effective option for severe tremor in both PD and ET.


Validation of a current definition of early allograft dysfunction in liver transplant recipients and analysis of risk factors.
Translational studies in liver transplantation often require an endpoint of graft function or dysfunction beyond graft loss. Prior definitions of early allograft dysfunction (EAD) vary, and none have been validated in a large multicenter population in the Model for End-Stage Liver Disease (MELD) era. We examined an updated definition of EAD to validate previously used criteria, and correlated this definition with graft and patient outcome. We performed a cohort study of 300 deceased donor liver transplants at 3 U.S. programs. EAD was defined as the presence of one or more of the following previously defined postoperative laboratory analyses reflective of liver injury and function: bilirubin >or=10mg/dL on day 7, international normalized ratio >or=1.6 on day 7, and alanine or aspartate aminotransferases >2000 IU/L within the first 7 days. To assess predictive validity, the EAD definition was tested for association with graft and patient survival. Risk factors for EAD were assessed using multivariable logistic regression. Overall incidence of EAD was 23.2%. Most grafts met the definition with increased bilirubin at day 7 or high levels of aminotransferases. Of recipients meeting the EAD definition, 18.8% died, as opposed to 1.8% of recipients without EAD (relative risk = 10.7 [95% confidence interval: 3.6, 31.9] P < 0.0001). More recipients with EAD lost their grafts (26.1%) than recipients with no EAD (3.5%) (relative risk = 7.4 [95% confidence interval: 3.4, 16.3] P < 0.0001). Donor age and MELD score were significant EAD risk factors in a multivariate model. In summary a simple definition of EAD using objective posttransplant criteria identified a 23% incidence, and was highly associated with graft loss and patient mortality, validating previously published criteria. This definition can be used as an endpoint in translational studies aiming to identify mechanistic pathways leading to a subgroup of liver grafts with clinical expression of suboptimal function.


Dietary Restriction Delays But Cannot Heal Irradiation-Induced Hair Graying by Preserving Hair Follicle Stem Cells in Quiescence.
DNA damage represents one of the cell intrinsic causes of stem cell aging, which leads to differentiation-induced removal of damaged stem cells in skin and blood. Dietary restriction (DR) retards aging across various species, including several strains of laboratory mice. Whether, DR has the potential to ameliorate DNA damage-driven stem cell exhaustion remains incompletely understood. In this study, we show that DR strongly extends the time to hair graying in response to γ-irradiation (ionizing radiation [IR])-induced DNA damage of C57BL/6 J mice. The study shows that DR prolongs resting phase of hair follicles. DR-mediated prolongation of hair follicle stem cell (HFSC) quiescence blocks hair growth and prevents the depletion of HFSCs and ckit+ melanoblasts in response to IR. However, prolongation of HFSC quiescence also correlates with a suppression of DNA repair and cannot prevent melanoblast loss and hair graying in the long run, when hair cycling is reinitiated even after extended periods of time. Altogether, these results support a model indicating that nutrient deprivation can delay but not heal DNA damage-driven extinction of melanoblasts by stalling HFSCs in a prolonged state of quiescence coupled with inhibition of DNA repair. Disconnecting these two types of responses to DR could have the potential to delay stem cell aging.


Spatial Distribution of Megacopta cribraria (Hemiptera: Plataspidae) Adults, Eggs and Parasitism by Paratelenomus saccharalis (Hymenoptera: Platygastridae) in Soybean.
Since 2014, populations of the kudzu bug, Megacopta cribraria (F.) (Hemiptera: Plataspidae), have declined in the southeastern United States and seldom require treatment. This decline follows the discovery of Paratelenomus saccharalis (Dodd; Hymenoptera: Platygastridae), a non-native egg parasitoid. The objective of this project was to observe the temporal and spatial dynamics of P. saccharalis parasitism of kudzu bug egg masses in commercial soybean fields. Four fields were sampled weekly for kudzu bugs and egg masses at a density of one sample per 0.6 ha. Sampling commenced when soybean reached the R2 maturity stage and continued until no more egg masses were present. Responses including kudzu bugs, egg masses, and parasitism rates were analyzed using ANOVA, Spatial Analysis by Distance Indices (SADIE), and SaTScan spatial analysis software. Egg masses were collected from the field, held in the lab and monitored for emergence of kudzu bug nymphs or P. saccharalis. Kudzu bug populations were generally lower than previously reported in the literature and spatial aggregation was not consistently observed. Egg parasitism was first detected in early July and increased to nearly 40% in mid-August. Significant spatial patterns in parasitism were observed with spatio-temporal clusters being loosely associated with clusters of egg masses. There were no significant differences in parasitism rates between field margins and interiors, suggesting that P. saccharalis is an effective parasitoid of kudzu bug egg masses on a whole-field scale.


Comparison of four induced molting methods based on subsequent performance and welfare of Single Comb White Leghorn hens.
A total of 400 Single Comb White Leghorn hens at 80 weeks of age were used in present study. Four treatment groups that were consisted of six replications with 10 hens per each replication were considered. In the first treatment, food and water were removed for the first 2, 4, 6 and 8 days. However, on days 3, 5, 7, 9 and on day 10 until day 28 hens were fed 45 g of food per hen (ON-OFF group). In the second and third groups, food was withdrawn for 10, 14 days, respectively and oyster shell and water were provided for ad libitum until day 28 (California and North Carolina treatments (CAL, NC groups)). The last group (full-food treatments (FF group)) was the hens that were non-food-deprived and were fed corn molt diet for 28 days ad libitum. In all treatment groups at day 29, hens were returned to a full food layer ration and received 16 h of light day(-1). Body weight, egg production, egg weight, relative eggshell weight, internal egg quality, egg specific gravity and mortality were determined. Differential leukocyte count and antibody response were also measured. The results demonstrated that induced molting increased egg production according to pre-molt egg production. There was not a significant difference in the rate of egg production during the peak period of post molt production for treatments. No significant differences were detected in differential leukocyte counts and antibody response against Sheep Red Blood Cell (SRBC) between treatments at pre molt and post molt of the experiment. This study indicated that diets with high corn level (FF groups) are effective and simplified nonfood removal procedure for welfare molting hens.


Thickness Distribution of Glenohumeral Joint Cartilage.
High-resolution 3-dimensional cartilage-specific magnetic resonance imaging (MRI) was performed at 3 T to test the following hypotheses: (1) there is a nonuniform cartilage thickness distribution both on the proximal humerus and on the glenoid surface and (2) the glenohumeral joint as a combined system is congruent with the level of the joint cartilage surface without substantial radial mismatch. Inclusion of 38 volunteers (19 females, mean age 24.34 ± 2.22 years; range 21-29 years) in a prospective study. Measurements of: cartilage thickness in 3 regions and 3 zones; radius of both circles (glenoid and humeral cartilage) for congruency calculation using 3-T MRI with 3-dimensional dual-echo steady-state sequence with water excitation. A homogenous mean cartilage thickness (1.2-1.5 mm) and slightly higher values for the glenoidal articulating surface radii both in the mid-paracoronar section (2.4 vs. 2.1 cm, P < 0.001) and in the mid-paraaxial section (2.4 vs. 2.1 cm, P < 0.001) compared with the humeral side were observed. The concept of a radial mismatch between the humeral head and the glenoid in healthy human subjects can be confirmed. This study provides normative data for the comparison of joint cartilage changes at the shoulder for future studies.


The functional connectivity between the locust leg pattern generators and the subesophageal ganglion higher motor center.
Higher motor centers and central pattern generators (CPGs) interact in the control of coordinated leg movements during locomotion throughout the animal kingdom. The subesophageal ganglion (SEG) is one of the insect head ganglia reported to have a role in the control of walking behavior. Here we explored the functional relations between the SEG and the thoracic leg CPGs in the desert locust. Backfill staining revealed about 300 SEG descending interneurons (DINs) altogether. Recordings from an in-vitro isolated chain of thoracic ganglia, with intact or severed connections to the SEG, during pharmacological activation were used to determine how the SEG affects the centrally generated motor output to the legs. The SEG was demonstrated to both activate leg CPGs and synchronize their bilateral activity. The role of the SEG in insect locomotion is discussed in light of these findings.


Comparison of FDG-PET and dynamic contrast-enhanced MRI in the evaluation of suggestive breast lesions.
The aim of our study was a direct comparison of the ability of positron-emission tomography with FDG-PET and of magnetic resonance imaging (MRI) to determine whether breast lesions were benign or malignant and of the two imaging methods capability of depicting eventual multifocal disease. We performed both PET and MRI in 36 patients (40 lesions) who were scheduled for surgery because of suggestive mammographic, sonographic and/or clinical findings. A final histological classification was available for all lesions. Tumour size ranged from 5 to 45 mm (mean 16.7 mm). Sensitivity for lesions, sensitivity for patients, specificity for lesions and specificity for patients were 68.0%, 76.2%, 73.3%, and 73.3% for PET and 92.0%, 95.2%, 73.3%, and 73.3% for MRI, respectively. MRI was more sensitive than FDG-PET in disclosing malignant breast tumours and was also more accurate than FDG-PET in the assessment of multifocal disease. The lower sensitivity of FDG-PET than of MRI seems to be due to difficulties in reliable imaging of carcinomas smaller than 10 mm and of lobular carcinomas.


[Comparison of raster mammography and real time sonography with histology in carcinoma of the breast].
In a retrospective study, the results of real-time sonography and grid mammography in 161 patients with histologically confirmed breast cancer were analyzed and compared with the histopathologic characteristics of the tumours to assess the diagnostic accuracy of these preoperative image-producing methods. The results showed the determination of the tumour size as obtained by the image-producing methods to correlate closely with the histopathologic findings. Furthermore, both real-time sonography and mammography yielded certain indications allowing prognostically valuable conclusions in respect of malignancy and invasiveness of the carcinomas. Taking into account the different but complementing diagnostic results of both methods, the combination of grid mammography and real-time sonography must be considered as the presently most reliable preoperative diagnostic procedure.


Chlamydia trachomatis infection during pregnancy associated with preterm delivery: a population-based prospective cohort study.
Chlamydia trachomatis infection is the most prevalent bacterial sexually transmitted infection and may influence pregnancy outcome. This study was conducted to assess the effect of chlamydial infection during pregnancy on premature delivery and birthweight. Pregnant women attending a participating midwifery practice or antenatal clinic between February 2003 and January 2005 were eligible for the study. From 4,055 women self-administered questionnaires and urine samples, tested by PCR, were analysed for C. trachomatis infection. Pregnancy outcomes were obtained from midwives and hospital registries. Gestational ages and birthweights were analysed for 3,913 newborns. The C. trachomatis prevalence was 3.9%, but varied by age and socio-economic background. Chlamydial infection was, after adjustment for potential confounders, associated with preterm delivery before 32 weeks (OR 4.35 [95% CI 1.3, 15.2]) and 35 weeks gestation (OR 2.66 [95% CI 1.1, 6.5]), but not with low birthweight. Of all deliveries before 32 weeks and 35 weeks gestation 14.9% [95% CI 4.5, 39.5] and 7.4% [95% CI 2.5, 20.1] was attributable to C. trachomatis infection. Chlamydia trachomatis infection contributes significantly to early premature delivery and should be considered a public health problem, especially in young women and others at increased risk of C. trachomatis infection.


Combined invariants to similarity transformation and to blur using orthogonal Zernike moments.
The derivation of moment invariants has been extensively investigated in the past decades. In this paper, we construct a set of invariants derived from Zernike moments which is simultaneously invariant to similarity transformation and to convolution with circularly symmetric point spread function (PSF). Two main contributions are provided: the theoretical framework for deriving the Zernike moments of a blurred image and the way to construct the combined geometric-blur invariants. The performance of the proposed descriptors is evaluated with various PSFs and similarity transformations. The comparison of the proposed method with the existing ones is also provided in terms of pattern recognition accuracy, template matching and robustness to noise. Experimental results show that the proposed descriptors perform on the overall better.


Temperature driven reactant solubilization synthesis of BiCuOSe.
Phase-pure BiCuOSe, which is isostructural to the layered p-type transparent conductor LaCuOS, has been synthesized in high yield by a single-step hydrothermal reaction at low temperature (250 degrees C) and pressure (<20 atm). A moderate reaction temperature of 250 degrees C was sufficiently high to solubilize both Bi2O3 and Cu2O and stabilize monovalent copper and low enough to impede the oxidation of dianionic selenium. BiCuOSe exhibits a relatively high electrical conductivity (sigma approximately 3.3 S cm(-1)) and a reduced band gap (E(g) = 0.75 eV), which compare favorably with the optoelectronic properties of BiCuOS and the cerium-based oxysulfides, CeAgOS and CeCuOS.


Ankylosed primary molars.
The prevalence of ankylosis of primary molars was found to be 3.7% of the sample subjects. Eighty-two of the 2234 children examined exhibited ankylosis. The prevalence of ankylosis among the black children in the sample was much lower (0.93%) than that of the white children (4.10%). The mandibular first primary molar was ankylosed at an earlier age and more frequently than any other tooth. The frequency of ankylosis of the second primary molar increased in older children. The high incidence of ankylosed primary teeth was seen in children between seven and eleven years of age. Treatment should be based on the evaluation of growth potential jeopardized by the condition. Early extraction and subsequent space management, especially in the younger patient, is recommended.


How internal and external cues for bedtime affect sleep and adaptive functioning in adolescents.
To determine whether the main reason for bedtime is associated with sleep and adaptive functioning in adolescents. Participants were 1374 adolescents (X age = 16.8 years, SD = 0.58; 33.6% male) from Helsinki, Finland. Adolescents completed a questionnaire battery including the Munich Chronotype Questionnaire, Strengths and Difficulties Questionnaire, Beck Depression Inventory, and items drawn from the School Sleep Habits Survey, and the Pittsburgh Sleep Quality Index. On school nights, adolescents whose parents set their bedtime, and those who went to bed when they were tired went to bed earlier, obtained more sleep and had earlier midpoint of sleep than adolescents who went to bed when they have finished messaging/socializing or when their television show had finished. Adolescents who went to bed when they had finished their homework had sleep that fell in between these groups. On weekends, adolescents whose parents set their bedtime went to bed earlier and had an earlier midpoint of sleep. However, there were no differences between groups in terms of sleep duration once the need to rise for school in the morning was removed. Adolescents who went to bed on school nights when they were tired or once their homework was finished had better adaptive functioning. These results provide support for two very different approaches to help optimize the sleep of adolescents: either by implementing parental regulation of bedtimes across adolescence, or by encouraging adolescents to use their bodily cues to indicate when it is time for bed, rather than relying on an external cue.


Methylprednisolone disposition in rabbits. Analysis, prodrug conversion, reversible metabolism, and comparison with man.
Methodology was evolved for comparison of methylprednisolone disposition in man and rabbit. Methylprednisolone, methylprednisone, and methylprednisolone hemisuccinate ester concentrations in plasma were measured by HPLC methodology after iv administration of each compound to rabbits. Methylprednisolone hemisuccinate is rapidly and completely hydrolyzed to methylprednisolone with a half-life of 10 min. Dosing with the free alcohol or ester produces identical disposition curves for methylprednisolone. Methylprednisolone was found to undergo rapid and reversible metabolism with methylprednisone, a phenomenon also seen in man. Plasma concentrations of methylprednisolone are appreciably greater than the metabolite regardless of the form of steroid given. Administration of the metabolite yields 67% availability of methylprednisolone. The occurrence of reversible metabolism produces an apparent clearance which is about 71% of the value of the "real" elimination clearance for both steroids. Man and rabbit show identical plasma protein binding of methylprednisolone (77%). Small differences in apparent clearance (man, 5.74 ml/min/kg; rabbit, 7.93 ml/min/kg) can be accounted for by the animal scale-up principle (body weight0.89). The rabbit is thus a useful animal model for further assessing mechanisms of drug- or disease-steroid interactions which occur in man.


Hospitalization rates and utilization among patients with rheumatoid arthritis: a population-based study from 1987 to 2012 in Olmsted County, Minnesota.
To examine whether all-cause hospitalization rates for patients with rheumatoid arthritis (RA) differ from those for patients without RA. This was a retrospective population-based cohort study focused on Olmsted County, Minnesota. The RA cohort consisted of patients 18 years and older who first fulfilled 1987 American College of Rheumatology criteria for RA in the 1980 to 2007 period, and was compared with a cohort of similar age, sex, and calendar year without RA. Data on all hospitalizations were retrieved electronically for the 1987 to 2012 period. Analyses used person-year methods and rate ratios (RRs) comparing patients with and without RA. The 799 patients with RA experienced 2968 hospitalizations, and the 797 patients without RA experienced 2069 hospitalizations. Patients with RA were hospitalized at a greater rate than were patients without RA (RR, 1.51; 95% CI, 1.42-1.59). This increased rate of hospitalization was found in both sexes, all age groups, all calendar years studied, and throughout disease duration. Men with RA were hospitalized for depression at a greater rate than were men without RA (RR, 7.16; 95% CI, 2.78-30.67). Patients with RA were hospitalized at a greater rate for diabetes mellitus than were subjects without RA (RR, 2.45; 95% CI, 1.34-4.89). In patients with RA, the indicators of disease severity (eg, seropositivity, erosions, and nodules) in the first year after RA incidence were associated with higher rates of hospitalization. Patients with RA were hospitalized for all causes at a greater rate than were patients without RA. Increased rates of hospitalization were true for several disease categories and patient subgroups.


C-reactive protein levels and the expansion of screen-detected abdominal aortic aneurysms in men.
C-reactive protein (CRP) levels have been shown to predict a number of cardiovascular outcomes. CRP levels have also been found to be elevated in patients with abdominal aortic aneurysms (AAAs). The aim of this study was to assess the relation between CRP levels and rates of expansion of small AAAs. A cohort of men with small aneurysms was identified in a trial of screening with ultrasound scanning. After initial screening, men were rescanned at 6- to 12-month intervals. CRP levels were measured at the first follow-up visit. Rates of expansion and risk factors for expansion were assessed with the use of data from 545 men who attended for at least 1 scan after CRP levels were measured. These men were followed for a median of 48 (range, 5 to 69) months. The mean annual rate of expansion was 1.6 mm. The median CRP level was 2.6 mg/L in men with the smaller AAAs (30 to 39 mm, n=433) compared with 3.5 mg/L in men with larger AAAs (40 to 54 mm, n=112) (P=0.007). The multivariate age-adjusted logistic model confirmed initial aortic diameter to be the only factor associated with rapid expansion with an odds ratio of 7.2 (95% CI, 4.3,12.2) for an initial diameter of 40 to 54 mm relative to one of 30 to 39 mm. Most small aneurysms expand slowly. CRP levels are elevated in larger aneurysms but do not appear to be associated with rapid expansion. The most useful predictor of aneurysmal expansion in men is aortic diameter.


Fine mapping of genetic susceptibility loci for melanoma reveals a mixture of single variant and multiple variant regions.
At least 17 genomic regions are established as harboring melanoma susceptibility variants, in most instances with genome-wide levels of significance and replication in independent samples. Based on genome-wide single nucleotide polymorphism (SNP) data augmented by imputation to the 1,000 Genomes reference panel, we have fine mapped these regions in over 5,000 individuals with melanoma (mainly from the GenoMEL consortium) and over 7,000 ethnically matched controls. A penalized regression approach was used to discover those SNP markers that most parsimoniously explain the observed association in each genomic region. For the majority of the regions, the signal is best explained by a single SNP, which sometimes, as in the tyrosinase region, is a known functional variant. However in five regions the explanation is more complex. At the CDKN2A locus, for example, there is strong evidence that not only multiple SNPs but also multiple genes are involved. Our results illustrate the variability in the biology underlying genome-wide susceptibility loci and make steps toward accounting for some of the "missing heritability."


Direct electro-deposition of graphene from aqueous suspensions.
We describe the direct electro-chemical reduction of graphene oxide to graphene from aqueous suspension by applying reduction voltages exceeding -1.0 to -1.2 V. The conductivity of the deposition medium is of crucial importance and only values between 4-25 mS cm(-1) result in deposition. Above 25 mS cm(-1) the suspension de-stabilises while conductivities below 4 mS cm(-1) do not show a measurable deposition rate. Furthermore, we show that deposition can be carried out over a wide pH region ranging from 1.5 to 12.5. The electro-deposition process is characterised in terms of electro-chemical methods including cyclic voltammetry, quartz crystal microbalance, impedance spectroscopy, constant amperometry and potentiometric titrations, while the deposits are analysed via Raman spectroscopy, infra-red spectroscopy, X-ray photoelectron spectroscopy and X-ray diffractometry. The determined oxygen contents are similar to those of chemically reduced graphene oxide, and the conductivity of the deposits was found to be ∼20 S cm(-1).


RN as gatekeeper: gatekeeping as monitoring and supervision.
To understand the variation of ways that students understand the informal or buddy registered nurse role during facilitated clinical experience, and to identify the relationship between student learning and student understanding and experience of the registered nurse role during clinical experience. Student clinical experience is an essential aspect of all undergraduate nursing programs. Students expect registered nurses to supervise and support them and to provide learning experiences during clinical placement. Both positive and negative experiences have been reported in the research literature. The quality of the relationship between the registered nurse and the student directly affects the learning outcome for students. Qualitative research using a phenomenographic approach. Semi-structured individual interviews with 24 students from all three years of an undergraduate nursing program at a metropolitan university in Brisbane, Queensland, Australia, who voluntarily participated in this study. Interviews were conducted at the completion of a recent clinical experience. While adequate monitoring and supervision is an expectation of students, there is a wide variation in the way registered nurses appear to understand this aspect of student learning. In the category of description, 'registered nurse as gatekeeper: gatekeeping as monitoring and supervision', student conceptions were identified as: registered nurse awareness, registered nurse vigilance, promoting learning/developing learning and growing (as) students. Students identified their experiences and the strategies they used when monitoring and supervision were lacking or limited. The findings of this study illuminate the need for recognition of the complexity of the informal registered nurse role with students and highlight the areas that should be addressed to promote quality student learning experiences. Registered nurses need adequate preparation for their informal role to support and supervise undergraduate students in clinical placement to ensure the safe development of student competence and confidence for their graduate registered nurse role.


Income development of General Practitioners in eight European countries from 1975 to 2005.
This study aims to gain insight into the international development of GP incomes over time through a comparative approach. The study is an extension of an earlier work (1975-1990, conducted in five yearly intervals). The research questions to be addressed in this paper are: 1) How can the remuneration system of GPs in a country be characterized? 2) How has the annual GP income developed over time in selected European countries? 3) What are the differences in GP incomes when differences in workload are taken into account? And 4) to what extent do remuneration systems, supply of GPs and gate-keeping contribute to the income position of GPs? Data were collected for Belgium, Denmark, Germany, Finland, France, the Netherlands, Sweden and the United Kingdom. Written sources, websites and country experts were consulted. The data for the years 1995 and 2000 were collected in 2004-2005. The data for 2005 were collected in 2006-2007. During the period 1975-1990, the income of GPs, corrected for inflation, declined in all the countries under review. During the period 1995-2005, the situation changed significantly: The income of UK GPs rose to the very top position. Besides this, the gap between the top end (UK) and bottom end (Belgium) widened considerably. Practice costs form about 50% of total revenues, regardless of the absolute level of revenues. Analysis based on income per patient leads to a different ranking of countries compared to the ranking based on annual income. In countries with a relatively large supply of GPs, income per hour is lower. The type of remuneration appeared to have no effect on the financial position of the GPs in the countries in this study. In countries with a gate-keeping system the average GP income was systematically higher compared to countries with a direct-access system. There are substantial differences in the income of GPs among the countries included in this study. The discrepancy between countries has increased over time. The income of British GPs showed a marked increase from 2000 to 2005, due to the introduction of a new contract between the NHS and GPs.


Cervical spine and muscle adaptation after spaceflight and relationship to herniation risk: protocol from 'Cervical in Space' trial.
Astronauts have a higher risk of cervical intervertebral disc herniation. Several mechanisms have been attributed as causative factors for this increased risk. However, most of the previous studies have examined potential causal factors for lumbar intervertebral disc herniation only. Hence, we aim to conduct a study to identify the various changes in the cervical spine that lead to an increased risk of cervical disc herniation after spaceflight. A cohort study with astronauts will be conducted. The data collection will involve four main components: a) Magnetic resonance imaging (MRI); b) cervical 3D kinematics; c) an Integrated Protocol consisting of maximal and submaximal voluntary contractions of the neck muscles, endurance testing of the neck muscles, neck muscle fatigue testing and questionnaires; and d) dual energy X-ray absorptiometry (DXA) examination. Measurements will be conducted at several time points before and after astronauts visit the International Space Station. The main outcomes of interest are adaptations in the cervical discs, muscles and bones. Astronauts are at higher risk of cervical disc herniation, but contributing factors remain unclear. The results of this study will inform future preventive measures for astronauts and will also contribute to the understanding of intervertebral disc herniation risk in the cervical spine for people on Earth. In addition, we anticipate deeper insight into the aetiology of neck pain with this research project. German Clinical Trials Register, DRKS00026777. Registered on 08 October 2021.


Larval Red Drum (Sciaenops ocellatus) Sublethal Exposure to Weathered Deepwater Horizon Crude Oil: Developmental and Transcriptomic Consequences.
The Deepwater Horizon (DWH) incident resulted in extensive oiling of the pelagic zone and shoreline habitats of many commercially important fish species. Exposure to the water-accommodated fraction (WAF) of oil from the spill causes developmental toxicity through cardiac defects in pelagic fish species. However, few studies have evaluated the effects of the oil on near-shore estuarine fish species such as red drum (Sciaenops ocellatus). Following exposure to a certified weathered slick oil (4.74 μg/L ∑PAH50) from the DWH event, significant sublethal impacts were observed ranging from impaired nervous system development [average 17 and 22% reductions in brain and eye area at 48 h postfertilization (hpf), respectively] to abnormal cardiac morphology (100% incidence at 24, 48, and 72 hpf) in red drum larvae. Consistent with the phenotypic responses, significantly differentially expressed transcripts, enriched gene ontology, and altered functions and canonical pathways predicted adverse outcomes in nervous and cardiovascular systems, with more pronounced changes at later larval stages. Our study demonstrated that the WAF of weathered slick oil of DWH caused morphological abnormalities predicted by a suite of advanced bioinformatic tools in early developing red drum and also provided the basis for a better understanding of molecular mechanisms of crude oil toxicity in fish.


Regulation of lens aldose reductase activity by nitric oxide.
To examine the regulation of aldose reductase (AR) activity by nitric oxide (NO) in human lens epithelial cells (HLEC), cultured rat lens, and normal and diabetic rat lens, we have incubated HLEC or cultured rat lenses with 1 mm of the NO donors S-nitroso-N-acetylpenicillamine (SNAP) or S-nitrosoglutathione (GSNO), and the AR activity and sorbitol content were measured. Non-diabetic and diabetic (treated with streptozotocin 65 mg kg(-1) body wt, i.p.) rats were injected with the nitric oxide synthase (NOS) inhibitor, L-NAME (50 mg kg(-1) body wt day(-1), x 10 days i.p.) or NOS substrate, L-arginine (200 mg kg(-1) body wt day(-1), x 10 days i.p.). In a separate group of rats, a nitroglycerin (NG)-patch that releases 200 ng min(-1) NO was applied to the dorsal neck region. After 10 days of treatment, the lenses were removed and their AR activity and sorbitol content were measured. Incubation of HLEC with SNAP or GSNO reduced AR activity. A similar reduction in AR activity and sorbitol accumulation was observed when diabetic and non-diabetic rat lenses were cultured in the presence of SNAP and GSNO. Total protein-SSG in diabetic lens was lower compared to normal lens. Treatment of diabetic and non-diabetic rats with L-NAME enhanced AR activity and sorbitol accumulation, whereas NG patch and L-arginine significantly decreased AR activity and sorbitol accumulation in diabetic lenses compared to non-diabetic. Increased S-glutathiolation of AR was observed in the presence of SNAP. These results suggest that decreased glutathiolation of cellular proteins in diabetic rat lens compared to non-diabetic lens is related to decreased NO availability in diabetic rats which would decrease GSNO. Restoring the NO levels in diabetic animals increases glutathiolation of cellular proteins, inhibits AR activity and prevents sorbitol accumulation. Exogenous delivery of NO may represent a potentially useful strategy for preventing or delaying diabetic cataractogenesis and the development of other diabetic complications.


[Post-graduation in Public Health from 1997 to 2007: challenges, advances and tendencies].
This article debates the performance of the Collective Health Post-Graduation in the last 12 years. It is based on a wide evaluative research performed by a group of researches of the area, through a project financed by CNPq, during the years of 2008-2009. This proposal is a sequence of another study with the same importance that occurred among the years of 1994-1997 taking it in comparison. The investigation realized in 2008-2009 analyzed the field construction, the demand, and the alumnus, the teaching staff profile, the scientific production and the internationalization of the area. There was field work and the utilization of secondary sources, mainly from Cadernos CAPES. The study showed a field that is in growing organization and powerful on the point of view of the demand, the number of masters and PhDs being titled, the content adequacy and the teaching staff as well as the scientific production. Among the persistent problems are: the high concentration of programs in the southeast region, the difference in quality among them, the difficult to absorption of the number of titled and the erratic investment in international cooperation. The Collective Health Post-Graduation is increasingly more oriented to the improvement of SUS.


In vitro and in vivo correlation for lipid-based formulations: Current status and future perspectives.
Lipid-based formulations (LBFs) have demonstrated a great potential in enhancing the oral absorption of poorly water-soluble drugs. However, construction of in vitro and in vivo correlations (IVIVCs) for LBFs is quite challenging, owing to a complex in vivo processing of these formulations. In this paper, we start with a brief introduction on the gastrointestinal digestion of lipid/LBFs and its relation to enhanced oral drug absorption; based on the concept of IVIVCs, the current status of in vitro models to establish IVIVCs for LBFs is reviewed, while future perspectives in this field are discussed. In vitro tests, which facilitate the understanding and prediction of the in vivo performance of solid dosage forms, frequently fail to mimic the in vivo processing of LBFs, leading to inconsistent results. In vitro digestion models, which more closely simulate gastrointestinal physiology, are a more promising option. Despite some successes in IVIVC modeling, the accuracy and consistency of these models are yet to be validated, particularly for human data. A reliable IVIVC model can not only reduce the risk, time, and cost of formulation development but can also contribute to the formulation design and optimization, thus promoting the clinical translation of LBFs.


[Prevalence of metabolic syndrome in health employees].
To determine the prevalence of metabolic syndrome in health employees of a general hospital in Celaya, Guanajuato. Cross-sectional survey to 200 healthy employees who were selected by labor category: nurses 71 (35 %), general services 66 (33 %), administrative 39 (19.5 %), physicians 12 (6 %) and chiefs of clinical department 12 (6 %). The instrument was used to detect risk factors, evaluate clinically and through laboratory tests. The diagnosis of metabolic syndrome was done by following the NCEP-ATPIII criteria. A descriptive analysis was carried out. The study included 142 women (71 %) and 58 men (29 %) with an average age of 41 years (range 19 to 59). The global prevalence of MS was 29.5 % (59 events). Six new cases of type 2 diabetes mellitus (3 %), 38 with abnormal fasting glucose (19 %) and 33 with abnormal blood pressure (16.5 %): 23 participants with pre-hypertension, 7 in stage 1 and 3 in stage 2 were detected. Ten employees with MS (21%) tested positive for C-reactive protein. The prevalence of MS of health employees is above figures reported in the literature for the general population.


Correlation of technetium-99m MIBI and thallium-201 retention in solitary cold thyroid nodules with postoperative histopathology.
A comparative prospective study of technetium-99m methoxyisobutylisonitrile (MIBI) and thallium-201 with early (15 min) and delayed (90 min for MIBI, 3 h for 201Tl) imaging in the differentiation of thyroid lesions is presented. Forty patients with cold thyroid nodules visualised on 99mTc-pertechnetate scan and with dyskaryotic or atypical epithelial cells verified by fine needle aspiration biopsy underwent MIBI and 201Tl scintigraphy at 3-day intervals. Subsequent thyroidectomies were carried out in all patients. Semiquantitative analysis was performed using a lesion to non-lesion ratio on early (ER) and delayed images (DR). Additionally, a retention index (RI) was calculated using the formula RI=(DR-ER) x 100/ER. The reproducibility of the method for the early and delayed measurements was tested by analysing intra- and inter-observer variability and repeatability coefficients. Histopathologically, the nodules were found to be well-differentiated thyroid cancer in 21 patients and benign in 19 patients. There was no significant difference in the ER between malignant and benign lesions for either 201Tl or MIBI (P>0.05). However, for both agents significant differences were found between malignant and benign lesions with regard to DR (P<0.01 for 201Tl and P<0.001 for MIBI) and RI (P<0.001 for both agents). Statistical comparison of the two agents showed no significant differences (P>0.05) except with regard to DR and RI in malignant nodules (P<0.05). A receiver operating characteristic analysis was performed to determine threshold levels for the differentiation of malignant from benign nodules. Following this analysis, ER, DR and RI levels of 1.03, 1.54 and 2 for MIBI and < or =1.42, 1.24 and 5 for 201Tl were selected. Using these threshold levels, the sensitivity, specificity and accuracy of the study were 90.5%, 36.8% and 65% for ER MIBI, 61.9%, 94.7% and 77.5% for DR MIBI, 95.2%, 89.4% and 92.5% for RI MIBI, 85.7%, 47.3% and 67.5% for ER 201Tl, 80.9%, 73.6% and 77.5% for DR 201Tl, and 90.5%, 94.7% and 92.5% for RI 201Tl. In conclusion, the DR for MIBI and 201Tl is superior to the ER in detecting malignant nodules, and the RI for both MIBI and 201Tl is more valuable than the DR in differentiating malignant from benign thyroid nodules.


A role for caveolin 1 in assembly and budding of the paramyxovirus parainfluenza virus 5.
Caveolin 1 (Cav-1) is an integral membrane protein that forms the coat structure of plasma membrane caveolae and regulates caveola-dependent functions. Caveolae are enriched in cholesterol and sphingolipids and are related to lipid rafts. Many studies implicate rafts as sites of assembly and budding of enveloped virus. We show that Cav-1 colocalizes with the paramyxovirus parainfluenza virus 5 (PIV-5) nucleocapsid (NP), matrix (M), and hemagglutinin-neuraminidase (HN) proteins. Moreover, electron microscopy shows that Cav-1 is clustered at sites of viral budding. HN, M, and F(1)/F(2) are associated with detergent-resistant membranes, and these proteins float on sucrose gradients with Cav-1-rich fractions. A complex containing Cav-1 with M, NP, and HN from virus-infected cells and a complex containing Cav-1 and M from M-transfected cells were found on coimmunoprecipitation. A role of Cav-1 in the PIV-5 life cycle was investigated by utilizing MCF-7 human breast cancer cells that stably express Cav-1 (MCF-7/Cav-1). PIV-5 entry into MCF-7 and MCF-7/Cav-1 was found to be Cav-1 independent. However, the interaction between HN and M proteins was dramatically reduced in the Cav-1 null MCF-7 cells, and PIV-5 grown in MCF-7 cells had a reduced infectivity. Similarly, when PIV-5 was grown in MDCK cells that stably expressed dominant negative Cav-1 (MDCK/P132LCav-1), the virus showed a reduced infectivity. Virions lacking Cav-1 were defective and contained high levels of host cellular proteins and reduced levels of HN and M. These data suggest that Cav-1 affects assembly and/or budding, and this is supported by the finding that Cav-1 is incorporated into mature viral particles.


Inhibition of lipoprotein oxidation by prenylated xanthones derived from mangostin.
Oxidative damage is thought to play a critical role in cardiovascular and other chronic diseases. This has led to considerable interest in the antioxidant activity of dietary compounds. Flavonoids have received the most attention and much is known about the structural requirements for antioxidant activity. However, little is known about the antioxidant activity of other plant derived phenolic compounds such as the xanthones. We have previously shown that the prenylated xanthone, mangostin, can inhibit the oxidation of low density lipoprotein. In order to examine the effects of structure modification on antioxidant activity of this class of compound we have prepared a number of derivatives of mangostin and tested antioxidant activity in an isolated LDL and plasma assay. The results of this study show that structural modification of mangostin can have a profound effect on antioxidant activity. Derivatisation of the C-3 and C-6 hydroxyl groups with either methyl, acetate, propane diol or nitrile substantially reduces antioxidant activity. In contrast, derivatisation of C-3 and C-6 with aminoethyl derivatives enhanced antioxidant activity, which may be related to changes in solubility. Cyclisation of the prenyl chains had little influence on antioxidant activity.


Do personality traits moderate the effect of late-life spousal loss on psychological distress?
We use data from the Changing Lives of Older Couples (CLOC) study to investigate the extent to which: (1) five personality traits (agreeableness, conscientiousness, emotional stability/neuroticism, extraversion, and openness) moderate the effect of late-life spousal loss on depressive symptoms; (2) these patterns vary based on the expectedness of the death; and (3) the patterns documented in (1) and (2) are explained by secondary stressors and social support. Widowed persons report significantly more depressive symptoms than married persons, yet the deleterious effects of loss are significantly smaller for highly extraverted and conscientious individuals. The protective effects of personality traits, however, vary based on the expectedness of the death. Extraversion is protective against depression only for persons who had forewarning of the death. Extraverts may be particularly good at marshalling social support during prolonged periods of spousal illness. We discuss the ways that extraversion and conscientiousness may buffer against bereavement-related stressors.


Atmospheric heat transport is governed by meridional gradients in surface evaporation in modern-day earth-like climates.
Evaporation adds moisture to the atmosphere, while condensation removes it. Condensation also adds thermal energy to the atmosphere, which must be removed from the atmosphere by radiative cooling. As a result of these two processes, there is a net flow of energy driven by surface evaporation adding energy and radiative cooling removing energy from the atmosphere. Here, we calculate the implied heat transport of this process to find the atmospheric heat transport in balance with the surface evaporation. In modern-day Earth-like climates, evaporation varies strongly between the equator and the poles, while the net radiative cooling in the atmosphere is nearly meridionally uniform, and as a consequence, the heat transport governed by evaporation is similar to the total poleward heat transport of the atmosphere. This analysis is free from cancellations between moist and dry static energy transports, which greatly simplifies the interpretation of atmospheric heat transport and its relationship to the diabatic heating and cooling that governs the atmospheric heat transport. We further demonstrate, using a hierarchy of models, that much of the response of atmospheric heat transport to perturbations, including increasing CO2 concentrations, can be understood from the distribution of evaporation changes. These findings suggest that meridional gradients in surface evaporation govern atmospheric heat transport and its changes.


Comparison of kriging and cokriging for the geostatistical estimation of specific capacity in the Newark Basin (NJ) aquifer system.
Groundwater is a major water source in New Jersey; hence, accurate hydrogeologic data are extremely important. However, most measured data have inadequate spatial density and their locations are often clustered. Our study focuses on implementing geostatistical methods to generate the spatial distribution of specific capacity over the Newark Basin in New Jersey. Two geostatistical methods, ordinary kriging and cokriging, were employed and compared. Ordinary kriging was employed to estimate the spatial distribution of specific capacity by using measured values. Cokriging incorporated the spatial variability of fracture density into the estimation with the spatial variability of specific capacity, as groundwater flow in fractured rock aquifers depends on the fracture characteristics in the Newark Basin. Results indicate that cokriging manifested substantial improvements over ordinary kriging including a larger areal coverage, a more detailed variation of specific capacity, and reduction in the variance of its estimates.