Impact of Angiotensin Converting Enzyme Inhibitor versus Angiotensin Receptor Blocker on Incidence of New-Onset Diabetes Mellitus in Asians.
Angiotensin converting enzyme inhibitor (ACEI) and angiotensin receptor blocker (ARB) are associated with a decreased incidence of new-onset diabetes mellitus (NODM). The aim of this study was to compare the protective effect of ACEI versus ARBs on NODM in an Asian population. We investigated a total of 2817 patients who did not have diabetes mellitus from January 2004 to September 2009. To adjust for potential confounders, a propensity score matched (PSM) analysis was performed using a logistic regression model. The primary end-point was the cumulative incidence of NODM, which was defined as having a fasting blood glucose ≥126 mg/dL or HbA1c ≥6.5%. Multivariable cox-regression analysis was performed to determine the impact of ACEI versus ARB on the incidence of NODM. Mean follow-up duration was 1839±1019 days in all groups before baseline adjustment and 1864±1034 days in the PSM group. After PSM (C-statistics=0.731), a total 1024 patients (ACEI group, n=512 and ARB group, n=512) were enrolled for analysis and baseline characteristics were well balanced. After PSM, the cumulative incidence of NODM at 3 years was lower in the ACEI group than the ARB group (2.1% vs. 5.0%, p=0.012). In multivariate analysis, ACEI vs. ARB was an independent predictor of the lower incidence for NODM (odd ratio 0.37, confidence interval 0.17-0.79, p=0.010). In the present study, compared with ARB, chronic ACEI administration appeared to be associated with a lower incidence of NODM in a series of Asian cardiovascular patients.


Using Gene Expression Analysis to Examine Changes in Loneliness, Depression and Systemic Inflammation in Lonely Chronically Ill Older Adults.
The purpose of this study was to evaluate the effectiveness of LISTEN (Loneliness Intervention) on loneliness, depression, physical health, systemic inflammation, and genomic expression in a sample of lonely, chronically ill, older adults. This was a prospective, longitudinal randomized trial of LISTEN, a novel intervention based on theories of narrative and cognitive restructuring to target specific aspects of loneliness. Twenty-three older, lonely, chronically ill adults were recruited from a family medicine clinic in West Virginia. Participants were randomized to two groups, 13 in LISTEN group (Loneliness Intervention) and 10 in attention control (healthy aging education). Participants attended an enrollment session where they completed consent, survey data (including sociodemographics and chronic illness diagnoses), baseline physical measures, and blood sampling for gene expression analysis. After completing the 5 weekly sessions, all participants attended a 12 week post data collection meeting (17 weeks post-baseline) for survey completion, physical measures and blood sampling. The results of this study show that the LISTEN intervention improves measures of physical and psychosocial health. Specifically, subjects enrolled in LISTEN showed reductions in systolic blood pressure, as well as decreased feelings of loneliness and depression. These changes may be due, in part, to a reduction in systemic inflammation, as measured by interleukin-2. This study provides support for the use of LISTEN in reducing loneliness in chronically ill, older adults. Further, while some of our results are inconclusive, it provides rationale to expand our study population to evaluate the relationship between loneliness and systemic inflammation. In the future, enhancing knowledge about the relationships among loneliness, chronic illness, systemic inflammation, and gene expression of these particular targets, and how these relationships may change over time with intervention will inform translation of findings to clinical settings.


Increased Cardiac Sympathetic Activity and Oxidative Stress in Habitual Electronic Cigarette Users: Implications for Cardiovascular Risk.
Electronic cigarettes (e-cigarettes) have gained unprecedented popularity, but virtually nothing is known about their cardiovascular risks. To test the hypothesis that an imbalance of cardiac autonomic tone and increased systemic oxidative stress and inflammation are detectable in otherwise healthy humans who habitually use e-cigarettes. Cross-sectional case-control study of habitual e-cigarette users and nonuser control individuals from 2015 to 2016 at the University of California, Los Angeles. Otherwise healthy habitual e-cigarette users between the ages of 21 and 45 years meeting study criteria, including no current tobacco cigarette smoking and no known health problems or prescription medications, were eligible for enrollment. Healthy volunteers meeting these inclusion criteria who were not e-cigarette users were eligible to be enrolled as control individuals. A total of 42 participants meeting these criteria were enrolled in the study including 23 self-identified habitual e-cigarette users and 19 self-identified non-tobacco cigarette, non-e-cigarette user control participants. Heart rate variability components were analyzed for the high-frequency component (0.15-0.4 Hz), an indicator of vagal activity, the low-frequency component (0.04-0.15 Hz), a mixture of both vagal and sympathetic activity, and the ratio of the low frequency to high frequency, reflecting the cardiac sympathovagal balance. Three parameters of oxidative stress were measured in plasma: (1) low-density lipoprotein oxidizability, (2) high-density lipoprotein antioxidant/anti-inflammatory capacity, and (3) paraoxonase-1 activity. Of the 42 participants, 35% were women, 35% were white, and the mean age was 27.6 years. The high-frequency component was significantly decreased in the e-cigarette users compared with nonuser control participants (mean [SEM], 46.5 [3.7] nu vs 57.8 [3.6] nu; P = .04). The low-frequency component (mean [SEM], 52.7 [4.0] nu vs 39.9 [3.8] nu; P = .03) and the low frequency to high frequency ratio (mean [SEM], 1.37 [0.19] vs 0.85 [0.18]; P = .05) were significantly increased in the e-cigarette users compared with nonuser control participants, consistent with sympathetic predominance. Low-density lipoprotein oxidizability, indicative of the susceptibility of apolipoprotein B-containing lipoproteins to oxidation, was significantly increased in e-cigarette users compared with nonuser control individuals (mean [SEM], 3801.0 [415.7] U vs 2413.3 [325.0] U; P = .01) consistent with increased oxidative stress, but differences in high-density antioxidant/anti-inflammatory capacity and paraoxonase-1 activity were not significant. In this study, habitual e-cigarette use was associated with a shift in cardiac autonomic balance toward sympathetic predominance and increased oxidative stress, both associated with increased cardiovascular risk.


Acute Agitation and Self-Injury in a 5-Year Old with Autism.
A 5-year-old nonverbal child with autism spectrum disorder (ASD) was admitted to inpatient pediatrics with new onset agitation and self-injurious behavior. His parents described him as a pleasant child without previous episodes of self-injury. Four days before admission, the parents noted new irritability followed by 2 days of self-injury to the face without clear precipitant. His hitting intensified with closed fist to face, and he required parental physical restraint to prevent further injury. Car rides and ibuprofen provided only temporary relief. He consumed minimal liquid and ate no solid food for 2 days. The parents denied any changes to the environment or routine and denied recent travel, sick contacts, fevers, cough, otalgia, vomiting, diarrhea, and constipation. The patient had been diagnosed with ASD at age 18 months old but had no other significant medical history.On examination, the child was alert but distressed and restless, wearing padded mitts as his parents attempted to calm him by pushing him in a stroller. He had multiple areas of severe bruising and facial swelling in the right periorbital area, cheek, and jaw. The rest of the physical examination was unremarkable. Laboratory results included a leukocytosis with left shift, a normal metabolic panel, and an elevated creatine kinase. Other investigations included a normal lumber puncture, chest radiograph, head and face computerized tomography without contrast, and brain magnetic resonance imaging. A dentist consultant examined him and noted an erupting molar but no decay or abscesses. A psychiatric evaluation was requested as there was no clear medical source for the patient's distress.


Anti-EphA2 Antibodies with Distinct In Vitro Properties Have Equal In Vivo Efficacy in Pancreatic Cancer.
The EphA2 receptor tyrosine kinase is overexpressed in a variety of human epithelial cancers and is a determinant of malignant cellular behavior in pancreatic adenocarcinoma cells. Moreover, it is expressed in tumor endothelium and its activation promotes angiogenesis. To better clarify the therapeutic potential of monoclonal antibodies (mAbs) directed to the EphA2 receptor, we generated a large number of mAbs by differential screening of phage-Ab libraries by oligonucleotide microarray technology and implemented a strategy for the rapid identification of antibodies with the desired properties. We selected two high-affinity and highly specific EphA2 monoclonal antibodies with different in vitro properties on the human pancreatic tumor cell line MiaPaCa2. One is a potent EphA2-agonistic antibody, IgG25, that promotes receptor endocytosis and subsequent degradation, and the second is a ligand antagonist, IgG28, that blocks the binding to ephrin A1 and is cross-reactive with the mouse EphA2 receptor. We measured the effect of antibody treatment on the growth of MiaPaCa2 cells orthotopically transplanted in nude mice. Both IgG25 and IgG28 had strong antitumor and antimetastatic efficacy. In vivo treatment with IgG25 determined the reduction of the EphA2 protein levels in the tumor and the phosphorylation of FAK on Tyr576 while administration of IgG28 caused a decrease in tumor vascularization as measured by immunohistochemical analysis of CD31 in tumor sections. These data show that in a pancreatic cancer model comparable therapeutic efficacy is obtained either by promoting receptor degradation or by blocking receptor activation.


A quantitative study of adipokinetic hormone of the firebug, Pyrrhocoris apterus.
The development of an enzyme-linked immunoassay (ELISA) for the adipokinetic neuropeptide hormone, Pya-AKH, from the firebug Pyrrhocoris apterus L. is described. The ELISA measures as little as 20 fmol of Pya-AKH. Tested against a range of synthetic peptides, the assay has a high sensitivity for peptides containing the C-terminal motif FTPNWamide. The amounts of Pya-AKH in the brain, corpora cardiaca, suboesophageal ganglia, and fused thoracic and abdominal ganglionic mass are very small, with only the corpora cardiaca containing appreciable levels of the hormone (ca. 4 pmol per bug). Preliminary estimates of the persistence of the hormone in the haemolymph are consistent with values determined for AKHs in other insects, and suggest that Pya-AKH has a rapid turnover with a half-life of ca. 18 min. Measurements of circulating titres of AKH in Pyrrhocoris are only possible in the ELISA described here by using pooled samples of haemolymph, and after preliminary clean-up of the haemolymph samples. The titre of Pya-AKH in resting reproductive female Pyrrhocoris is ca. 1 fmol/&mgr;l.


[Radiofrequency electromagnetic fields, mobile phones, and health effects: where are we now?]
This paper aims to present useful elements for framing the issue of exposure to radio frequencies (RFs), in particular those related to telecommunications, and the possible effects on health also in the light of the rapid evolution of technologies (the advent of 5G). New developments in the field oblige us to reflect on the possible implications in terms of public health. Here, we have preferred to take stock and not to demand a systematic review. The development of telecommunications is creating great interest in all sectors for the possibility of new applications, but is also increasing concern for the effects on health not yet fully known, to the point that there is a growing mobilization against the introduction of 5G both at national and at international level. Epidemiological studies and metanalyses on the relationship between cancer and RFs, particularly those on mobile phones, still identify areas of uncertainty that need to be investigated, and studies on non-cancer effects are growing in number, suggesting the possibility of new risks. The relative scenarios that will open with the 5G trial are likely to change the overall exposure level of the population as a result of major changes in the network architecture. Therefore, it is important to adopt a strongly precautionary approach. Given the strong concerns of the population, the competent institutions should implement information and awareness programmes through adequate risk communication.


To what extent can zero tillage lead to a reduction in greenhouse gas emissions from temperate soils?
Soil tillage practices have a profound influence on the physical properties of soil and the greenhouse gas (GHG) balance. However there have been very few integrated studies on the emission of carbon dioxide (CO2), methane (CH4) and nitrous oxide (N2O) and soil biophysical and chemical characteristics under different soil management systems. We recorded a significantly higher net global warming potential under conventional tillage systems (26-31% higher than zero tillage systems). Crucially the 3-D soil pore network, imaged using X-ray Computed Tomography, modified by tillage played a significant role in the flux of CO2 and CH4. In contrast, N2O flux was determined mainly by microbial biomass carbon and soil moisture content. Our work indicates that zero tillage could play a significant role in minimising emissions of GHGs from soils and contribute to efforts to mitigate against climate change.


Neurochemical and behavioral effects of Nigella sativa and Olea europaea oil in rats.
In the last few decades, therapeutic uses of medicinal compounds present in food as a normal constituent has risen substantially, largely because of their fewer side effects and adequate efficacy. This study is designed to investigate a role of brain serotonin (5-HT) and dopamine (DA) in the potential nootropic, anxiolytic, and other beneficial effects of Nigella sativa (NS) and Olea europaea (OE) oil in rat models. Animals were treated with NS and OE oil orally at doses of 0.1 ml/kg and 0.25 ml/kg for 5 weeks. Food intake and body weight change, anxiety-like effects in elevated plus maze and activity in a novel and familiar environment were monitored weekly. Effects on learning and memory after 5 weeks treatment were monitored using Morris water maze test. Neurochemical analysis was carried using HPLC-ECD method. NS and OE oil administration enhanced learning and memory in Morris water maze test and the effects were greater in NS than OE oil-treated animals. Low dose of OE oil increased exploration in an open field, higher dose of OE oil and both doses of NS oil produced no consistent effect on open field exploration. Effects of both oils on anxiety-like behavior, food and water intake, and activity in activity box were either not consistent or did not occur. The treatment increased homovanillic acid (HVA). 5-HT levels increased in high dose of NS oil and low dose of OE oil-treated groups. Low dose NS oil decreased 5-HT. The present study suggests that active components in NS and OE oil may prove useful in treating impaired cognition. OE oil may produce psychostimulant-like effect. Modulation of DA and serotonin neurotransmission seems important in the pharmacological effect of these oils.


Alterations in Cardiac Deformation, Timing of Contraction and Relaxation, and Early Myocardial Fibrosis Accompany the Apparent Recovery of Acute Stress-Induced (Takotsubo) Cardiomyopathy: An End to the Concept of Transience.
Takotsubo syndrome is an increasingly recognized cause of chest pain and occasionally of cardiogenic shock. Despite rapid improvement of the left ventricular (LV) ejection fraction, recent registry data raise concerns about long-term prognosis. The aim of this study was to test the hypothesis that restoration of normal ejection fraction after acute takotsubo syndrome is not equivalent to full functional recovery. Fifty-two patients with takotsubo syndrome (according to the Mayo Clinic criteria plus cardiac magnetic resonance imaging to exclude myocardial infarction) and 44 healthy control subjects of the same age, gender, and cardiovascular comorbidity distribution were prospectively recruited. The focus of the investigation was on patients with takotsubo syndrome presenting with ST-segment elevation-type electrocardiographic findings or malignant arrhythmias and with LV apical ballooning variant, and a 4-month recovery endpoint was assessed. Patients underwent echocardiographic assessment of LV myocardial deformation (global longitudinal, radial, and circumferential strain; LV twist, torsion, and untwist; and time to peak twist and untwist) and assessment of LV myocardial structure by pre- and post-contrast-enhanced cardiac magnetic resonance by T1 mapping acutely and at 4-month follow-up. Control subjects underwent a single-time-point investigation. Data were analyzed using paired or unpaired tests, as appropriate for their distribution, and corrected for multiple comparisons. The patients' mean age was 66 years (range, 28-87 years), and 92% were women. All abnormal echocardiographic indices observed acutely in patients with takotsubo syndrome improved (but did not necessarily normalize) at follow-up. Significant mechanotemporal alterations characterizing both systole (global longitudinal strain and apical circumferential strain, P < .01 for both; LV twist, twist rate, and torsion, P < .0001 for all) and diastole (untwist rate and time to peak untwisting, P < .001 for both) persisted at 4-month follow-up compared with control subjects, despite normalization of LV ejection fraction and volumes. Although native T1 (which demonstrates edema) normalized at 4-months follow-up only in segments contracting normally during the acute phase (T1 = 1,180 ± 40.6 msec [normally contracting segments, P = .20 vs control value of 1,189 ± 16 msec] and T1 = 1,208 ± 60.3 msec [dysfunctional segments, P < .05 vs control]), the extracellular volume fraction (which demonstrates diffuse fibrosis) remained significantly abnormal in all LV segments (whether normally contracting [0.328 ± 0.043, P < .001] or ballooning during acute presentation [0.320 ± 0.044, P < .001], both vs control value of 0.273 ± 0.045). In patients with the most clinically severe spectrum of takotsubo cardiomyopathy, regional LV systolic and diastolic deformation abnormalities persist beyond the acute event, despite normalization of global LV ejection fraction and size. In addition, although myocardial edema partly subsides, a process of global microscopic fibrosis develops in its place, detected as early as 4 months.


First results from the XENON10 dark matter experiment at the Gran Sasso National Laboratory.
The XENON10 experiment at the Gran Sasso National Laboratory uses a 15 kg xenon dual phase time projection chamber to search for dark matter weakly interacting massive particles (WIMPs). The detector measures simultaneously the scintillation and the ionization produced by radiation in pure liquid xenon to discriminate signal from background down to 4.5 keV nuclear-recoil energy. A blind analysis of 58.6 live days of data, acquired between October 6, 2006, and February 14, 2007, and using a fiducial mass of 5.4 kg, excludes previously unexplored parameter space, setting a new 90% C.L. upper limit for the WIMP-nucleon spin-independent cross section of 8.8x10(-44) cm2 for a WIMP mass of 100 GeV/c2, and 4.5x10(-44) cm2 for a WIMP mass of 30 GeV/c2. This result further constrains predictions of supersymmetric models.


[Seroprevalence of HIV infection in pregnant women in the Annaba region (Algeria)].
The goal of the study is to assess the prevalence and the risk factors of the infection by the human immunodeficiency virus (HIV) among pregnant women in the area of Annaba (Algeria). We performed a cross-sectional study with analytical purposes. The study included 3044 pregnant women admitted to two regional hospitals within a period of time of five months. Two Elisa tests were used to determine the prevalence of HIV infection. An analysis of medical history and serum tests for biomarkers hepatitis virus B infection, hepatitis virus C infection and syphilis to determine the possible mode of contamination, by blood or sexual transmission. HIV prevalence was 5.3/1000 (CI 95%; 3.12-8.37), HBV prevalence 24.7/1000 (CI 95%; 19.6-30.7), HCV prevalence 6.3/1000 (CI 95%; 3.8-9.5) and syphilis prevalence 2.6/1000 (CI 95%; 1.2-5). On average, pregnant women infected by HIV were 33+/-5 years old, married, and had three children. The analysis of the markers of exposure risk investigated in our study showed that the pregnant women infected with HIV do not compose a specific risk group. Overall our results suggest that the more probable route of HIV transmission for women of the Annaba region is via heterosexual intercourse with spouse. The prevalence of HIV infection in Annaba remains high 5.3/1000, compared with the national average of 1/1000. In this region, pregnant women infected with HIV are not part of a group at particular risk. The HIV monitoring should be further strengthened in our country.


Novel Therapeutics Identification for Fibrosis in Renal Allograft Using Integrative Informatics Approach.
Chronic allograft damage, defined by interstitial fibrosis and tubular atrophy (IF/TA), is a leading cause of allograft failure. Few effective therapeutic options are available to prevent the progression of IF/TA. We applied a meta-analysis approach on IF/TA molecular datasets in Gene Expression Omnibus to identify a robust 85-gene signature, which was used for computational drug repurposing analysis. Among the top ranked compounds predicted to be therapeutic for IF/TA were azathioprine, a drug to prevent acute rejection in renal transplantation, and kaempferol and esculetin, two drugs not previously described to have efficacy for IF/TA. We experimentally validated the anti-fibrosis effects of kaempferol and esculetin using renal tubular cells in vitro and in vivo in a mouse Unilateral Ureteric Obstruction (UUO) model. Kaempferol significantly attenuated TGF-β1-mediated profibrotic pathways in vitro and in vivo, while esculetin significantly inhibited Wnt/β-catenin pathway in vitro and in vivo. Histology confirmed significantly abrogated fibrosis by kaempferol and esculetin in vivo. We developed an integrative computational framework to identify kaempferol and esculetin as putatively novel therapies for IF/TA and provided experimental evidence for their therapeutic activities in vitro and in vivo using preclinical models. The findings suggest that both drugs might serve as therapeutic options for IF/TA.


Sugar-induced increase in cytosolic Ca(2+) in Arabidopsis thaliana whole plants.
Using Ca(2+)-dependent photoprotein aequorin-transformed Arabidopsis thaliana, sugar-induced increase in cytosolic free Ca(2+ )concentration ([Ca(2+)](cyt))( )was investigated by luminescence imaging technique. When 0.1 M sucrose was fed to roots of autotrophically grown intact whole plants whose roots had been incubated overnight with coelenterazine to reconstitute aequorin systemically, strong and transient (within 20 s) luminescence was observed in the roots; that luminescence was followed by weak luminescence moving from the lower leaves to the upper leaves. The moving rate of luminescence was roughly comparable to that of [(14)C]sucrose. Application of 0.1 M glucose or fructose induced transient luminescence in excised leaves. No such luminescence was observed in heterotrophically grown (with sucrose) whole plants or in excised tissues. mRNA levels of sucrose-H(+) symporter genes AtSUC1 and AtSUC2 were higher in autotrophic plants than in heterotrophic plants. These results indicate that influx of transported sucrose together with H(+) into the mesophyll cells of autotrophic plants may depolarize the membrane potential, and subsequently activate a voltage-gated Ca(2+) channel on the plasma membrane, resulting in a [Ca(2+)](cyt) increase. The [Ca(2+)](cyt) increase might initiate Ca(2+ )signaling leading to the expression of genes related to biosynthesis of storage carbohydrates. Hexoses, when applied, might also be involved in the [Ca(2+)](cyt) increase mediated by monosaccharide-H(+) co-transporters.


Predominant role of host genetics in controlling the composition of gut microbiota.
The human gastrointestinal tract is inhabited by a very diverse symbiotic microbiota, the composition of which depends on host genetics and the environment. Several studies suggested that the host genetics may influence the composition of gut microbiota but no genes involved in host control were proposed. We investigated the effects of the wild type and mutated alleles of the gene, which encodes the protein called pyrin, one of the regulators of innate immunity, on the composition of gut commensal bacteria. Mutations in MEFV lead to the autoinflammatory disorder, familial Mediterranean fever (FMF, MIM249100), which is characterized by recurrent self-resolving attacks of fever and polyserositis, with no clinical signs of disease in remission. A total of 19 FMF patients and eight healthy individuals were genotyped for mutations in the MEFV gene and gut bacterial diversity was assessed by sequencing 16S rRNA gene libraries and FISH analysis. These analyses demonstrated significant changes in bacterial community structure in FMF characterized by depletion of total numbers of bacteria, loss of diversity, and major shifts in bacterial populations within the Bacteroidetes, Firmicutes and Proteobacteria phyla in attack. In remission with no clinical signs of disease, bacterial diversity values were comparable with control but still, the bacterial composition was substantially deviant from the norm. Discriminant function analyses of gut bacterial diversity revealed highly specific, well-separated and distinct grouping, which depended on the allele carrier status of the host. This is the first report that clearly establishes the link between the host genotype and the corresponding shifts in the gut microbiota (the latter confirmed by two independent techniques). It suggests that the host genetics is a key factor in host-microbe interaction determining a specific profile of commensal microbiota in the human gut.


Real-time gating of IVUS sequences based on motion blur analysis: method and quantitative validation.
Intravascular Ultrasound (IVUS) is an image-guiding technique for cardiovascular diagnostic, providing cross-sectional images of vessels. During the acquisition, the catheter is pulled back (pullback) at a constant speed in order to acquire spatially subsequent images of the artery. However, during this procedure, the heart twist produces a swinging fluctuation of the probe position along the vessel axis. In this paper we propose a real-time gating algorithm based on the analysis of motion blur variations during the IVUS sequence. Quantitative tests performed on an in-vitro ground truth data base shown that our method is superior to state of the art algorithms both in computational speed and accuracy.


Moderate aerobic exercise training decreases middle-aged induced pathologic cardiac hypertrophy by improving Klotho expression, MAPK signaling pathway, and oxidative stress status in Wistar rats.
This study aimed to investigate the effect of aerobic training on serum levels of Klotho, cardiac tissue levels of H2O2 and phosphorylation of ERK1/2 and P38 as well as left ventricular internal diameter (LVID), the left ventricle wall thickness (LVWT) and fibrosis in middle-aged rats. Forty wistar rats, including young rats (n=10, 4 month-old) and middle-aged rats (n=30, 13-15 months-old) were enrolled in this experimental study. The all young and 10 middle-aged rats were sacrificed (randomly) under deep anesthesia without any exercise training as normal young control and normal middle-aged control respectively. The remaining 20 middle-aged rats participated in 4 (n=10) or 8-week (n=10) aerobic exercise training. There were significant differences in the plasmatic Klotho levels and the heart tissue levels of phosphorylated-ERK1/2 (p-ERK1/2), P-P38 and H2O2, LVWT, LVID and fibrosis between young and middle-aged rats (P=0.01). Plasmatic Klotho level was significantly increased after eight weeks training (P=0.011). Also, p-ERK1/2 was significantly decreased after eight weeks and p-P38 was significantly decreased in the fourth (P=0.01) and eight weeks of training (P=0.01). A similar decrease was reported for aging-induced H2O2 in the fourth (P=0.016) and eighth weeks (P=0.001). LVID was significantly increased in eight weeks, but LVWT and fibrosis was significantly reduced in the eighth week (P=0.011, P=0.028, P=0.001 respectively). Moderate aerobic training attenuates aging-induced pathological cardiac hypertrophy at least partially by restoring the Klotho levels, attenuating oxidative stress, and reduction in the phosphorylation of ERK1/2, P38 and fibrosis.


High frequency of antiviral drug resistance and non-b subtypes in HIV-1 patients failing antiviral therapy in Cuba.
Emergence of HIV-1 drug resistance may limit the sustained benefits of antiretroviral therapy (ART) in settings with limited laboratory monitoring and drug options. The objective is to implement the surveillance of drug resistance and subtypes in HIV-1 patients failing ART in Cuba. This study compiled clinical and genotypic drug resistance data 588 ART-experienced HIV-1 patients attending a clinical center in Havana in 2009-2013. Drug resistance testing was performed as part of routine clinical care. Drug resistance mutations and levels were determined using Rega version 8.0.2. Eighty-three percent received solely ART containing at least three drugs. Patients from 2009 to 2010 were longer treated (median: 4.9 vs 2.7 years) and exposed to more ART regimens (median: 4 vs 2 regimens) compared to patients from 2011-2013. Nucleoside reverse transcriptase inhibitor (NRTI), non-nucleoside RTI (NNRTI) and PI mutations were present in 83.5, 77.4 and 52.0%. Full-class resistance (FCR) to NRTI, NNRTI, PI and multidrug resistance (MDR) were detected in 25.0, 33.7, 11.4 and 6.3%. FCR to NRTI, NNRTI, PI and MDR were present in 12.8, 28.7, 0 and 0% after first-line failure (164 patients) and in 23.1, 34.6, 3.8 and 3.1% after second-line failure (130 patients). Subtype B (32.5%), BG recombinants (19.6%) and CRF19_cpx (16.2%) were the most prevalent genetic forms. Subtype distribution did not change significantly between 2009-2010 and 2011-2013, except for BG recombinants that increased from 12.2 to 21.3% (p=0.002). Our study found a high prevalence of drug resistance and supports the need for appropriate laboratory monitoring in clinical practice and access to drug options in case of virological failure.


Combination therapy of hyaluronic acid mesotherapic injections and sclerotherapy for treatment of lower leg telangiectasia without major venous insufficiency: a preliminary clinical study.
Telangiectasia is the dilation of dermal capillaries mainly due to hypertension and vein insufficiency. Treatments of choice for this condition are sclerotherapy with foam liquid or intradermal fiber optic laser energy delivery. The aim of this study was to assess the efficacy of a new therapeutic approach consisting in the use of polymerized hyaluronic acid mesotherapic injections following sclerotherapy in the areas of the skin affected by telangiectasia in patients without major vein insufficiency. A total of 20 women, aged between 19 and 64 years, affected by recurrent lower leg telangiectasia, were included in this study. Patients were preliminarily submitted to echo color Doppler sonography to rule out severe saphenofemoral valve and lower limb major vein insufficiency. All patients underwent 3 sessions a month of polidocanol 1% capillary injections for 2 months. This was followed by 0.1 ml cross-linked hyaluronic acid introduction in the polidocanol 1% needle track. A total of 50 mesotherapic injections (0.05 ml each) were performed on the skin surface where an ice pack was previously applied for 4 to 5 minutes. A follow-up visit was performed at 3 months. The results, based on photographic examination, were rated as follows: poor improvement (0%-50%), good improvement (51%-75%), and very good improvement (76%-100%). The side effects of the clinical procedure, in terms of pain, itching, paresthesia, ecchymosis, and relapse of telangiectasia over the treated skin surface, as well as a persisting pigmentation in the injection spots and induced benefits related to leg heaviness and comfort, were recorded. In total, 6 patients displayed a slight venous insufficiency, 3 patients displayed patent venous insufficiency, and 11 patients did not show any venous insufficiency. Before treatment, itching was present in 18 out of 20 patients, paresthesia in 15 out of 20 patients, ecchymosis in 16 out of 20 patients, and leg heaviness in 15 out of 20 patients. At the 3-month follow-up, an improvement of 0% to 50% was observed in 4 patients who had a relapse in telangiectasia. A 51% to 75% improvement was observed in 3 patients and a 76% to 100% improvement occurred in 13 patients. At the 3-month follow-up, itching persisted only in 4 patients; paresthesia was absent in 12 patients, while 3 patients still presented this symptom; ecchymosis was absent in 16 patients; 15 patients reported a feeling of lightweight legs. Among the patients with relapsing telangiectasia, 2 patients reported pigmentation due to hemosiderin deposit in the skin at the 3-month follow-up. The slight venous insufficiency, observed at the beginning of the study, improved in 5 out of 6 patients. The patients' compliance with the procedure was high and 16 out of 20 patients declared their willingness to repeat the whole clinical procedure, if necessary. This pilot clinical study supports the use of hyaluronic acid mesotherapic injections following sclerotherapy for treatment of lower leg telangiectasia without major venous insufficiency. We propose that the prolonged persistence of cross-linked hyaluronic acid, across the microvascular venous areas, is able to induce a stronger stromal tissue, thus preventing relapse. Further clinical studies, comparing this new approach with existing clinical procedures, are needed in a larger number of patients.


Targeting chelatable iron as a therapeutic modality in Parkinson's disease.
The pathophysiological role of iron in Parkinson's disease (PD) was assessed by a chelation strategy aimed at reducing oxidative damage associated with regional iron deposition without affecting circulating metals. Translational cell and animal models provided concept proofs and a delayed-start (DS) treatment paradigm, the basis for preliminary clinical assessments. For translational studies, we assessed the effect of oxidative insults in mice systemically prechelated with deferiprone (DFP) by following motor functions, striatal dopamine (HPLC and MRI-PET), and brain iron deposition (relaxation-R2*-MRI) aided by spectroscopic measurements of neuronal labile iron (with fluorescence-sensitive iron sensors) and oxidative damage by markers of protein, lipid, and DNA modification. DFP significantly reduced labile iron and biological damage in oxidation-stressed cells and animals, improving motor functions while raising striatal dopamine. For a pilot, double-blind, placebo-controlled randomized clinical trial, early-stage Parkinson's patients on stabilized dopamine regimens enrolled in a 12-month single-center study with DFP (30 mg/kg/day). Based on a 6-month DS paradigm, early-start patients (n=19) compared to DS patients (n=18) (37/40 completed) responded significantly earlier and sustainably to treatment in both substantia nigra iron deposits (R2* MRI) and Unified Parkinson's Disease Rating Scale motor indicators of disease progression (p<0.03 and p<0.04, respectively). Apart from three rapidly resolved neutropenia cases, safety was maintained throughout the trial. A moderate iron chelation regimen that avoids changes in systemic iron levels may constitute a novel therapeutic modality for PD. The therapeutic features of a chelation modality established in translational models and in pilot clinical trials warrant comprehensive evaluation of symptomatic and/or disease-modifying potential of chelation in PD.


Surface related intrinsic luminescence from carbon nanodots: solvent dependent piezochromism.
There has been a long standing debate on the luminescence origination from carbon nanodots (CDs). Herein, we report the solvent dependent piezochromism of CDs by diamond anvil cells experiment. Red- and blue-shift piezochromism were observed in CDs with N,N-dimethylformamide and water as pressure transmitting medium (PTM) with increasing pressure from atmospheric pressure to 25 GPa, which were related to increased π-π stacking and protic-solvent-induced surface chemical structural changes, respectively. Based on theoretical modeling and structural analysis of hydrothermally treated CDs (h-CDs), the reversible and irreversible piezochromism from green emission to blue emission with water as PTM was attributed to pressure induced enhanced intermolecular hydrogen bonding and addition reaction between water molecules and surface electron withdrawing groups on the CDs, respectively. The decreased electron withdrawing ability of the surface chemical structures of CDs further affects their intrinsic luminescence. This work provides a new understanding of the piezochromic luminescence origination from CDs, which is related to the surface related intrinsic luminescence.


Sub-Nanowatt Ultrasonic Bio-Telemetry Using B-Scan Imaging.
The objective of this paper is to investigate if the use of a B-scan ultrasound imaging system can reduce the energy requirements, and hence the power-dissipation requirements to support wireless bio-telemetry at an implantable device. B-scan imaging data were acquired using a commercial 256-element linear ultrasound transducer array which was driven by a commercial echoscope. As a transmission medium, we used a water-bath and the operation of the implantable device was emulated using a commercial-off-the-shelf micro-controller board. The telemetry parameters (e.g. transmission rate and transmission power) were wirelessly controlled using a two-way radio-frequency transceiver. B-scan imaging data were post-processed using a maximum-threshold decoder and the quality of the ultrasonic telemetry link was quantified in terms of its bit-error-rate (BER). Measured results show that a reliable B-scan communication link with an implantable device can be achieved at transmission power levels of 100 pW and for implantation depths greater than 10 cm. In this paper we demonstrated that a combination of B-scan imaging and a simple decoding algorithm can significantly reduce the energy-budget requirements for reliable ultrasonic telemetry.


Effect of patient comorbidities on filling of antihypertensive prescriptions.
To evaluate the extent of patient failure to fill antihypertensive prescriptions and to test the hypothesis that the presence of noncardiovascular disease is negatively associated with filling an antihypertensive prescription, and, conversely, that the presence of cardiovascular disease is positively associated with filling an antihypertensive prescription. Cross-sectional. We sampled prescriptions written for 327 African Americans aged >or=18 years. Patients were enrolled in a Medicaid managed care plan and treated in 6 primary care practices between January 1, 2003, and February 8, 2005. Prescription filling was defined as a match between a new or renewed electronic prescription and an insurance claim within the next 30 days. We assessed the association of comorbidity type with filling an antihypertensive prescription by using an adjusted logistic regression model that accounted for clustering of prescriptions within patients. Of 1742 antihypertensive prescriptions, 1309 (75.1%) were filled. Prescriptions written for persons with 5 or more noncardiovascular comorbidities were significantly more likely to be filled (adjusted odds ratio [OR], 1.59; 95% confidence interval [CI], 1.07 +/- 2.36) versus those for persons with fewer noncardiovascular comorbidities. The presence of cardiovascular comorbidities was not associated with filling of an antihypertensive prescription (adjusted OR, 0.72; 95% CI, 0.45-1.14). Many antihypertensive prescriptions were not filled. Different types of patient comorbidity may differentially impact prescription filling. Further studies should examine whether these results generalize to other populations.


Proteomic analysis of lysine acetylation sites in rat tissues reveals organ specificity and subcellular patterns.
Lysine acetylation is a major posttranslational modification involved in a broad array of physiological functions. Here, we provide an organ-wide map of lysine acetylation sites from 16 rat tissues analyzed by high-resolution tandem mass spectrometry. We quantify 15,474 modification sites on 4,541 proteins and provide the data set as a web-based database. We demonstrate that lysine acetylation displays site-specific sequence motifs that diverge between cellular compartments, with a significant fraction of nuclear sites conforming to the consensus motifs G-AcK and AcK-P. Our data set reveals that the subcellular acetylation distribution is tissue-type dependent and that acetylation targets tissue-specific pathways involved in fundamental physiological processes. We compare lysine acetylation patterns for rat as well as human skeletal muscle biopsies and demonstrate its general involvement in muscle contraction. Furthermore, we illustrate that acetylation of fructose-bisphosphate aldolase and glycerol-3-phosphate dehydrogenase serves as a cellular mechanism to switch off enzymatic activity.


The Effect of Anonymous Computer-Mediated Communication on State Anxiety: An Experimental Study.
This study examined the effect of anonymous computer-mediated communication (CMC) on state anxiety, specifically focusing on whether the valence of the interaction affected state anxiety before completing an anxiety-inducing task. Sixty-two female participants aged 18-25 were randomly assigned to one of three conditions: positive CMC, negative CMC, and blog. Self-report measures of state anxiety were taken at baseline; after participants had been given instructions about the anxiety-inducing task; after 10 minutes of CMC/blog writing; and after the anxiety-inducing task had been completed. Results showed that participants in the positive CMC condition showed a significant and moderate decrease in anxiety following the CMC, whereas those in the negative CMC condition showed a nonsignificant but moderate increase in anxiety following the CMC. Anxiety remained relatively unaffected by the blog condition. After completing the anxiety-inducing task, there were no differences in anxiety scores between groups. The findings show that CMC can be beneficial for relieving state anxiety, but the valence of the communication is crucial. This has implications for advice and training given to those participating in and supporting CMC where mental health issues might be discussed.


On the evolutionary origins of equity.
Equity, defined as reward according to contribution, is considered a central aspect of human fairness in both philosophical debates and scientific research. Despite large amounts of research on the evolutionary origins of fairness, the evolutionary rationale behind equity is still unknown. Here, we investigate how equity can be understood in the context of the cooperative environment in which humans evolved. We model a population of individuals who cooperate to produce and divide a resource, and choose their cooperative partners based on how they are willing to divide the resource. Agent-based simulations, an analytical model, and extended simulations using neural networks provide converging evidence that equity is the best evolutionary strategy in such an environment: individuals maximize their fitness by dividing benefits in proportion to their own and their partners' relative contribution. The need to be chosen as a cooperative partner thus creates a selection pressure strong enough to explain the evolution of preferences for equity. We discuss the limitations of our model, the discrepancies between its predictions and empirical data, and how interindividual and intercultural variability fit within this framework.


An l ∞ Eigenvector Perturbation Bound and Its Application to Robust Covariance Estimation.
In statistics and machine learning, we are interested in the eigenvectors (or singular vectors) of certain matrices (e.g. covariance matrices, data matrices, etc). However, those matrices are usually perturbed by noises or statistical errors, either from random sampling or structural patterns. The Davis-Kahan sin θ theorem is often used to bound the difference between the eigenvectors of a matrix A and those of a perturbed matrix A ˜ = A + E , in terms of l 2 norm. In this paper, we prove that when A is a low-rank and incoherent matrix, the l ∞ norm perturbation bound of singular vectors (or eigenvectors in the symmetric case) is smaller by a factor of d 1 or d 2 for left and right vectors, where d 1 and d 2 are the matrix dimensions. The power of this new perturbation result is shown in robust covariance estimation, particularly when random variables have heavy tails. There, we propose new robust covariance estimators and establish their asymptotic properties using the newly developed perturbation bound. Our theoretical results are verified through extensive numerical experiments.


Aberrant resting-state functional connectivity of the dorsolateral prefrontal cortex to the anterior insula and its association with fear avoidance belief in chronic neck pain patients.
Chronic neck pain (CNP), a global health problem, involves a large amount of psychological and socioeconomic burdens. Not only physical causes but also behavioral disorders such as a fear-avoidance belief (FAB) can associate with the chronicity of neck pain. However, functional brain mechanisms underlying CNP and its related behavioral disorders remain unknown. The aim of the current resting-state functional magnetic resonance imaging (fMRI) study was to explore how the functional brain networks differed between CNP patients and age- and sex-matched healthy, pain-free controls (HCs). We also investigated whether these possible brain network changes in CNP patients were associated with fear avoidance belief (FAB) and the intensity of pain. We analyzed the resting-state fMRI data of 20 CNP patients and 20 HCs. FAB and the intensity of pain were assessed by Tampa Scale for Kinesiophobia (TSK) and Visual Analog Scale (VAS) of pain. The whole brain analysis showed that CNP patients had significant different functional connectivity (FC) compared with HCs, and the right dorsolateral prefrontal cortex (DLPFC) was a core hub of these altered functional networks. Furthermore, general linear model analyses showed that, in CNP patients, the increased FC between the right DLPFC and the right anterior insular cortex (aIC) significantly associated with increased TSK (p = 0.01, statistical significance after Bonferroni correction: p<0.025), and the FC between the right DLPFC and dorsal posterior cingulate cortex had a trend of inverse association with VAS (p = 0.04). Our findings suggest that aberrant FCs between the right DLPFC and aIC associated with CNP and its related FAB.


Cellular and molecular biology of aging endothelial cells.
Cardiovascular disease (CVD) is the leading cause of death in the United States and aging is a major risk factor for CVD development. One of the major age-related arterial phenotypes thought to be responsible for the development of CVD in older adults is endothelial dysfunction. Endothelial function is modulated by traditional CVD risk factors in young adults, but advancing age is independently associated with the development of vascular endothelial dysfunction. This endothelial dysfunction results from a reduction in nitric oxide bioavailability downstream of endothelial oxidative stress and inflammation that can be further modulated by traditional CVD risk factors in older adults. Greater endothelial oxidative stress with aging is a result of augmented production from the intracellular enzymes NADPH oxidase and uncoupled eNOS, as well as from mitochondrial respiration in the absence of appropriate increases in antioxidant defenses as regulated by relevant transcription factors, such as FOXO. Interestingly, it appears that NFkB, a critical inflammatory transcription factor, is sensitive to this age-related endothelial redox change and its activation induces transcription of pro-inflammatory cytokines that can further suppress endothelial function, thus creating a vicious feed-forward cycle. This review will discuss the two macro-mechanistic processes, oxidative stress and inflammation, that contribute to endothelial dysfunction with advancing age as well as the cellular and molecular events that lead to the vicious cycle of inflammation and oxidative stress in the aged endothelium. Other potential mediators of this pro-inflammatory endothelial phenotype are increases in immune or senescent cells in the vasculature. Of note, genomic instability, telomere dysfunction or DNA damage has been shown to trigger cell senescence via the p53/p21 pathway and result in increased inflammatory signaling in arteries from older adults. This review will discuss the current state of knowledge regarding the emerging concepts of senescence and genomic instability as mechanisms underlying oxidative stress and inflammation in the aged endothelium. Lastly, energy sensitive/stress resistance pathways (SIRT-1, AMPK, mTOR) are altered in endothelial cells and/or arteries with aging and these pathways may modulate endothelial function via key oxidative stress and inflammation-related transcription factors. This review will also discuss what is known about the role of "energy sensing" longevity pathways in modulating endothelial function with advancing age. With the growing population of older adults, elucidating the cellular and molecular mechanisms of endothelial dysfunction with age is critical to establishing appropriate and measured strategies to utilize pharmacological and lifestyle interventions aimed at alleviating CVD risk. This article is part of a Special Issue entitled "SI: CV Aging".


Return-to-Sport Outcomes After Revision Anterior Cruciate Ligament Reconstruction Surgery.
There are limited and inconsistent data regarding return-to-sport outcomes after revision anterior cruciate ligament reconstruction (ACLR). Return-to-sport rates will be lower after revision ACLR when compared with primary ACLR. Case series; Level of evidence, 4. The study cohort consisted of 136 eligible patients who had undergone their first revision ACLR between March 2006 and March 2010. Of these, 109 patients (80%) completed a sports activity survey at a mean 5-year follow-up (range, 3-7 years). Follow-up also included the International Knee Documentation Committee (IKDC) subjective form, Marx Activity Scale, and Knee injury and Osteoarthritis Outcome Score-quality of life (KOOS-QOL) form. Operative details were obtained from the clinical record. After revision ACLR, 46% (95% CI, 37%-55%) of patients returned to their preinjury level of sport, compared with 50% (95% CI, 41%-59%) after the primary reconstruction in the same patients. Of the patients who were not able to return to their preinjury level of sport after primary reconstruction, 33% improved to the point that they were able to do so after revision. Younger patients were more likely to have returned to their same level of sport (58% vs 38%, P < .05), while the rate of return was the same between male and female patients. Those who returned to their preinjury level of sport scored higher Marx (P < .01), KOOS-QOL (P < .001), and IKDC scores (P < .01) than those who did not. Patients with <50% thickness articular cartilage lesions at revision surgery were more likely to have returned to their preinjury level (52% vs 31%, P < .05) and had significantly better Marx (P < .01), KOOS-QOL (P < .01), and IKDC scores (P < .01) at follow-up. The status of the menisci at the time of revision surgery was not associated with rates of return to sport, but patients with an intact medial meniscus had significantly higher KOOS-QOL (P < .05) scores at follow-up. Return-to-sport rates of patients after revision ACLR were similar to those after their primary surgery but were still lower than the reported rates of ACLR patients who did not need revision surgery. Greater chondral pathologic abnormalities at revision surgery were associated with reduced function at follow-up.


Rapid turnover of phosphatidylinositol 3-phosphate in the green alga Chlamydomonas eugametos: signs of a phosphatidylinositide 3-kinase signalling pathway in lower plants?
When Chlamydomonas eugametos gametes were incubated in carrier-free [32P]P1, the label was rapidly incorporated into PtdInsP and PtdInsP2 and, after reaching a maximum within minutes, was chased out by recirculating unlabelled P1 in the cell. This pulse-chase labelling pattern reflects their rapid turnover. In contrast, 32P incorporation into the structural lipids was slow and continued for hours. Of the radioactivity in the PtdInsP spot, 15% was in PtdIns3P and the rest in PtdIns4P, and of that in the PtdInsP2 spot, 1% was in PtdIns(3,4)P2 and the rest in PtdIns(4,5)P2, confirming the findings by Irvine, Letcher, Stephens and Musgrave [(1992) Biochem. J. 281, 269-266]. When cells were labelled with carrier-free [32P]P1, both PtdInsP isomers incorporated label in a pulse-chase-type pattern, demonstrating for the first time in a plant or animal system that D-3 poly-phosphoinositides turn over rapidly in non-stimulated cells, with kinetics similar to those shown by the D-4 isomers. In animal systems such lipids are already established as signalling molecules, and the data suggest that a similar role must be sought for them in lower plants such as Chlamydomonas.


Forgiveness and collective guilt assignment to historical perpetrator groups depend on level of social category inclusiveness.
The authors examined how categorization influences victimized group members' responses to contemporary members of a historical perpetrator group. Specifically, the authors tested whether increasing category inclusiveness--from the intergroup level to the maximally inclusive human level--leads to greater forgiveness of a historical perpetrator group and decreased collective guilt assignment for its harmdoing. Among Jewish North Americans (Experiments 1, 2, and 4) and Native Canadians (Experiment 3) human-level categorization resulted in more positive responses toward Germans and White Canadians, respectively, by decreasing the uniqueness of their past harmful actions toward the in-group. Increasing the inclusiveness of categorization led to greater forgiveness and lessened expectations that former out-group members should experience collective guilt compared with when categorization was at the intergroup level. Discussion focuses on obstacles that are likely to be encountered on the road to reconciliation between groups that have a history of conflictual relations.


Application of an LC-MS/MS method for the simultaneous quantification of human intestinal transporter proteins absolute abundance using a QconCAT technique.
Transporter proteins expressed in the gastrointestinal tract play a major role in the oral absorption of some drugs, and their involvement may lead to drug-drug interaction (DDI) susceptibility when given in combination with drugs known to inhibit gut wall transporters. Anticipating such liabilities and predicting the magnitude of the impact of transporter proteins on oral drug absorption and DDIs requires quantification of their expression in human intestine, and linking these to data obtained through in vitro experiments. A quantitative targeted absolute proteomic method employing liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) together with a quantitative concatenation (QconCAT) strategy to provide proteotypic peptide standards has been applied to quantify ATP1A1 (sodium/potassium-ATPase; Na/K-ATPase), CDH17 (human peptide transporter 1; HPT1), ABCB1 (P-glycoprotein; P-gp), ABCG2 (breast cancer resistance protein; BCRP), ABCC2 (multidrug resistance-associated protein 2; MRP2) and SLC51A (Organic Solute Transporter subunit alpha; OST-α), in human distal jejunum (n=3) and distal ileum (n=1) enterocyte membranes. Previously developed selected reaction monitoring (SRM) schedules were optimised to enable quantification of the proteotypic peptides for each transporter. After harvesting enterocytes by calcium chelation elution and generating a total membrane fraction, the proteins were subjected to proteolytic digestion. To account for losses of peptides during the digestion procedure, a gravimetric method is also presented. The linearity of quantifying the QconCAT from an internal standard (correlation coefficient, R(2)=0.998) and quantification of all target peptides in a pooled intestinal quality control sample (R(2)≥ 0.980) was established. The assay was also assessed for within and between-day precision, demonstrating a <15% coefficient of variation for all peptides across 3 separate analytical runs, over 2 days. The methods were applied to obtain the absolute abundances for all targeted proteins. In all samples, Na/K-ATPase, HPT1, P-gp and BCRP were detected above the lower limit of quantitation (i.e., >0.2 fmol/μg membrane protein). MRP2 abundance could be quantified in distal jejunum but not in the distal ileum sample. OST-α was not detected in 2 out of 3 jejunum samples. This study highlights the utility of a QconCAT strategy to quantify absolute transporter abundances in human intestinal tissues.


Plutonium and Americium Alpha Radiolysis of Nitric Acid Solutions.
The yield of HNO2, as a function of absorbed dose and HNO3 concentration, from the α-radiolysis of aerated HNO3 solutions containing plutonium or americium has been investigated. There are significant differences in the yields measured from solutions of the two different radionuclides. For 0.1 mol dm-3 HNO3 solutions, the radiolytic yield of HNO2 produced by americium α-decay is below the detection limit, whereas for plutonium α-decay the yield is considerably greater than that found previously for γ-radiolysis. The differences between the solutions of the two radionuclides are a consequence of redox reactions involving plutonium and the products of aqueous HNO3 radiolysis, in particular H2O2 and HNO2 and its precursors. This radiation chemical behavior is HNO3 concentration dependent with the differences between plutonium and americium α-radiolysis decreasing with increasing HNO3 concentration. This change may be interpreted as a combination of α-radiolysis direct effects and acidity influencing the plutonium oxidation state distribution, which in turn affects the radiation chemistry of the system.


A Genome-wide Association Study Identifying RAP1A as a Novel Susceptibility Gene for Crohn's Disease in Japanese Individuals.
Genome-wide association studies [GWASs] of European populations have identified numerous susceptibility loci for Crohn's disease [CD]. Susceptibility genes differ by ethnicity, however, so GWASs specific for Asian populations are required. This study aimed to clarify the Japanese-specific genetic background for CD by a GWAS using the Japonica array [JPA] and subsequent imputation with the 1KJPN reference panel. Two independent Japanese case/control sets (Tohoku region [379 CD patients, 1621 controls] and Kyushu region [334 CD patients, 462 controls]) were included. GWASs were performed separately for each population, followed by a meta-analysis. Two additional replication sets [254 + 516 CD patients and 287 + 565 controls] were analysed for top hit single nucleotide polymorphisms [SNPs] from novel genomic regions. Genotype data of 4 335 144 SNPs from 713 Japanese CD patients and 2083 controls were analysed. SNPs located in TNFSF15 (rs78898421, Pmeta = 2.59 × 10-26, odds ratio [OR] = 2.10), HLA-DQB1 [rs184950714, pmeta = 3.56 × 10-19, OR = 2.05], ZNF365, and 4p14 loci were significantly associated with CD in Japanese individuals. Replication analyses were performed for four novel candidate loci [p <1 × 10-6], and rs488200 located upstream of RAP1A was significantly associated with CD [pcombined = 4.36 × 10-8, OR = 1.31]. Transcriptome analysis of CD4+ effector memory T cells from lamina propria mononuclear cells of CD patients revealed a significant association of rs488200 with RAP1A expression. RAP1A is a novel susceptibility locus for CD in the Japanese population.


Candida species and selected behavioral factors co-associated with severe early childhood caries: Case-control study.
Severe Early Childhood Caries (sECC) is a multifactorial disease associated with the occurrence of specific oral microorganisms and other environmental, behavioral, and genetic factors. This study aimed to construct a multivariable model including the occurrence of Candida spp. and selected behavioral factors (length of breastfeeding, serving sweet beverages and beginning of brushing child's teeth) to determine their relationships to the occurrence of sECC. In this case-control study 164 children with sECC and 147 children without dental caries were included. MALDI-TOF MS and multiplex qPCR were used to identify Candida spp. and selected bacteria in dental plaque samples, respectively. A questionnaire on oral hygiene, diet, and children's health was filled in by the parents. The constructed multivariable logistic regression model showed an independent influence of the microbial and behavioral factors in sECC etiopathogenesis. The occurrence of C. albicans and C. dubliniensis was associated with higher odds of sECC development (odds ratio, OR: 9.62 and 16.93, respectively), together with breastfeeding of 6 months or less (OR: 2.71), exposure to sweet beverages (OR: 3.77), and starting to brush child's teeth after the 12th month of age (OR: 4.10), all statistically significant (p < 0.01). Considering the high occurrence of C. albicans and C. dubliniensis in dental plaque in children with sECC, we propose them as "keystone pathogens" and risk factors for sECC. The models showed that presence of specific species of Candida in dental plaque may be a better descriptor of sECC than the mentioned behavioral factors.


A modified corporoplasty for treating congenital penile curvature and reducing the incidence of palpable indurations.
To reduce the incidence of postoperative palpable induration after treating congenital penile curvature, using a modified corporoplasty technique. In a retrospective unrandomized clinical trial, 105 patients with a congenital penile angulation of >30 degrees and for whom coitus was therefore difficult or impossible, underwent surgical correction. Of the 105 patients, 55 underwent the Nesbit-Kelâmi technique, whereby a diamond-shaped section of the tunica albuginea is excised and the defect closed with an interrupted suture. The remaining 50 patients underwent the modified corporoplasty, the edges of the tunica albuginea being brought together with a continuous, blood-tight, intratunical suture, and the end knots buried. The early results (<6 months) were comparable in both groups, with correction of the curvature in 94% and 95%, and postoperative complications in 14% and 15%. There were fewer postoperative haematomas in those undergoing modified corporoplasty (6% vs 18%). The late results (>6 months) also showed that these patients developed fewer palpable indurations (16% vs 44%). The modified corporoplasty reduced the incidence of postoperative haematoma and late complications (e.g. palpable indurations) after the surgical correction of congenital penile curvature.


Sulphur management in onion (Allium cepa) cultivation in hills of Himachal Pradesh.
Field experiment were conducted at CSK HPKV Research Farm, Palampur during Rabi seasons of 2000-01 and 2001-02, to study the response of onion (Allium cepa var Patna red) at four sulphur levels (0, 15, 30 and 60 kg ha(-1)) applied through Gypsum and S95. The analysis was done to allocate the limited availability of sulphur for maximizing net profit over fertilizer cost. The results show that the dose of sulphur under its full availability is 43.02 kg ha(-1). But under its scarce availability the maximum benefit would occur when it is applied up to 32.11 kg ha(-1) followed by even distribution of fertilizer i.e. 20 kg ha(-1). The returns following sulphur application at these rates, would be Rs 69340, 73092 and 68700 ha(-1) respectively.


Binding of an antimicrobial peptide to bacterial cells: Interaction with different species, strains and cellular components.
Antimicrobial peptides (AMPs) selectively kill bacteria by disrupting their cell membranes, and are promising compounds to fight drug-resistant microbes. Biophysical studies on model membranes have characterized AMP/membrane interactions and the mechanism of bilayer perturbation, showing that accumulation of cationic peptide molecules in the external leaflet leads to the formation of pores ("carpet" mechanism). However, similar quantitative studies on real cells are extremely limited. Here, we investigated the interaction of the dansylated PMAP23 peptide (DNS-PMAP23) with a Gram-positive bacterium, showing that 107 bound peptide molecules per cell are needed to kill it. This result is consistent with our previous finding for Gram-negative strains, where a similar high threshold for killing was determined, demonstrating the general relevance of the carpet model for real bacteria. However, in the case of the Gram-positive strain, this number of molecules even exceeds the total surface available on the bacterial membrane. The high affinity of DNS-PMAP23 for the anionic teichoic acids of the Gram-positive cell wall, but not for the lipopolysaccharides of Gram-negative bacteria, provides a rationale for this finding. To better define the role of anionic lipids in peptide/cell association, we studied DNS-PMAP23 interaction with E. coli mutant strains lacking phosphatidylglycerol and/or cardiolipin. Surprisingly, these strains showed a peptide affinity similar to that of the wild type. This finding was rationalized by observing that these bacteria have an increased content of other anionic lipids, thus maintaining the total membrane charge essentially constant. Finally, studies of DNS-PMAP23 association to dead bacteria showed an affinity an order of magnitude higher compared to that of live cells, suggesting strong peptide binding to intracellular components that become accessible after membrane perturbation. This effect could play a role in population resistance to AMP action, since dead bacteria could protect the surviving cells by sequestering significant amounts of peptide molecules. Overall, our data indicate that quantitative studies of peptide association to bacteria can lead to a better understanding of the mechanism of action of AMPs.


Mobile technology use in medical education.
This study was undertaken to determine the PDA functionalities for a problem-based learning (PBL) medical curriculum at the Graduate School of Medicine (GSM), the University of Wollongong (UOW). The study determines the factors/aspects of incorporating PDAs, and the attitudes of stakeholders regarding the use of PDAs in such a PBL-based medical curriculum. In-depth interviews were designed and conducted with medical faculty, the medical education technology team and honorary medical academics. Four major PDA functionalities were identified, these being: clinical-log, reference, communication, and general functions. Two major aspects for the incorporation of PDAs into the PBL-medical curriculum at the UOW were determined from the interviews, these being technical and practical aspects. There is a potential for PDAs to be incorporated into the PBL-medical curricula at the UOW. However, a clear strategy needs to be defined as to how best to incorporate PDAs into PBL-medical curricula with minimal impact on students, as well as financial and resource implications for the GSM.


Expression and localisation of insulin receptor substrate 2 in normal intestine and colorectal tumours. Regulation by intestine-specific transcription factor CDX2.
Self-renewal and differentiation of intestinal epithelium is a tightly regulated process, whose perturbations are implicated in human colorectal tumourigenesis. The insulin/insulin-like growth factor (IGF) signalling pathway may play an important role in intestinal epithelium homeostasis. Insulin receptor substrate 2 (IRS2) is a poorly characterised component in this pathway. Using complementary in vitro and in vivo human and murine models, expression (mRNA and protein levels), localisation (immunohistochemistry) and regulation of IRS2 were investigated in the normal intestine and colorectal tumours. In silico analysis of the human IRS2 promoter was performed together with reporter and chromatin immunoprecipitation assays. Significant IRS2 expression was detected in the intestine, with specific protein localisation in the villus region of the ileum and in the surface epithelium of the colon. In human HT29 and Caco2 cells, IRS2 mRNA levels increased with spontaneous and induced differentiation, together with CDX2 (caudal-related homeobox protein 2), P21 and KLF4 (Krüppel-like factor 4). Adenoviral infection with human CDX2 induced IRS2 expression in APC- (adenomatous polyposis coli) and beta-catenin-mutated cells. On the other hand, IRS2 downregulation was observed in differentiated enterocytes after adenoviral infection with short hairpin CDX2 (shCDX2), in the intestine of CDX2 heterozygous mice and in colorectal tumours of Apc(Min/+) and patients with familial adenomatous polyposis (FAP). The human IRS2 promoter region presents several CDX2-binding sites where CDX2 immunoprecipitated in vivo. IRS2 reporters were functionally activated via CDX2 and blocked via a dominant-negative CDX2 protein. Combining gain- and loss-of-function approaches, an intriguing scenario is presented whereby IRS2 is significantly expressed in the apical intestinal compartment and is directly controlled by CDX2 in normal intestine and tumours.


Astragalin Suppresses Inflammatory Responses and Bone Destruction in Mice With Collagen-Induced Arthritis and in Human Fibroblast-Like Synoviocytes.
Astragalin, as a bioactive flavonoid with anti-inflammatory, antioxidant, and protective properties, provides a potential agent for rheumatoid arthritis (RA). In this study, its therapeutic efficacy and the underlying mechanisms were explored using DBA/1J mice with collagen-induced arthritis (CIA). It was demonstrated that astragalin could significantly attenuate inflammation of CIA mice. The effects were associated with decreased severity of arthritis (based on the arthritis index), joint swelling and reduced bone erosion and destruction. Furthermore, astragalin treatment suppressed the production of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6, and IL-8), and inhibited the expression of matrix metalloproteinases (MMP-1, MMP-3, and MMP-13) in chondrocytes and synovial cells of CIA mice. Fibroblast-like synoviocytes derived from RA patients (MH7A cells) were applied to verify these effects. In vitro, astragalin inhibited the expression of matrix metalloproteinases (MMP-1, MMP-3, and MMP-13) dose-dependently in TNF-α-induced MH7A cells, with no apparent cytotoxicity. Furthermore, astragalin suppressed the phosphorylation of p38, JNK, and the activation of c-Jun/AP-1 in TNF-α-induced MH7A cells. In conclusion, it has proven that astragalin could attenuate synovial inflammation and joint destruction in RA at least partially by restraining the phosphorylation of MAPKs and the activating of c-Jun/AP-1. Therefore, astragalin can be a potential therapeutic agent for RA.


Making friends in the rainforest: "negrito" adaptation to risk and uncertainty.
The so-called negritos adapt not just to a tropical forest environment but also to an environment characterized by perturbations and fluctuations. As with other hunter-gatherers in the region and, indeed, throughout the world, they use both social and ecological methods to enhance their chances of survival in this changing environment: socially, they have developed networks of trading and marriage partners; ecologically, they maintain patches of key resources that are available for future harvesting. As evidenced in the case of the Batek (Orang Asli), patterns of forest structure and composition are sometimes direct outcomes of intentional resource concentration and enrichment strategies. While little of the above is controversial anthropologically, what has drawn some debate is the nature of the relationship with partner societies. Conventional wisdom posits relations of inequality between foragers and "others": foragers and farmers are often construed as hierarchical dyads where foragers supply products or labor to farmers in exchange for agricultural harvests and other trade goods. This kind of adaptation appears to be one of divergent specialization. However, there are cases, such as in the relationship between Batek and Semaq Beri, where both societies follow a roughly similar mode of adaptation, and specialization has not materialized. In sum, while not denying that hierarchy and inequality exist, I suggest that they have to be contextualized within a larger strand of relationships that includes both hierarchy and egality. Further, such relationships are part of the general portfolio of risk reduction strategies, following which access to widely scattered environmental resources, and passage from one location to another, is enhanced not by competing with and displacing neighbors but by maintaining a flexible regime of friendly exchange partners.


Late extended adjuvant treatment with letrozole improves outcome in women with early-stage breast cancer who complete 5 years of tamoxifen.
The National Cancer Institute of Canada Clinical Trials Group MA.17 trial examined the efficacy of letrozole (LET) started within 3 months of 5 years of adjuvant tamoxifen in postmenopausal hormone receptor-positive early-stage breast cancer. When the trial was unblinded, patients who received placebo (PLAC) were offered LET. This cohort analysis describes the outcomes of women assigned PLAC at the initial random assignment after unblinding. Efficacy outcomes of women who chose LET (PLAC-LET group) were compared with those who did not (PLAC-PLAC group) by the hazard ratios and by P values calculated from Cox models that adjusted for imbalances between the groups. Toxicity analyses included only events that occurred after unblinding. There were 1,579 women in the PLAC-LET group (median time from tamoxifen, 2.8 years) and 804 in the PLAC-PLAC group. Patients in the PLAC-LET group were younger; had a better performance status; and were more likely to have had node-positive disease, axillary dissection, and adjuvant chemotherapy than those in the PLAC-PLAC group. At a median follow-up of 5.3 years, disease-free survival (DFS; adjusted hazard ratio [HR], 0.37; 95% CI, 0.23 to 0.61; P < .0001) and distant DFS (HR, 0.39; 95% CI, 0.20 to 0.74; P = .004) were superior in the PLAC-LET group. More self-reported new diagnoses of osteoporosis and significantly more clinical fractures occurred in the women who took LET (5.2% v 3.1%, P = .02). Interpretation of this cohort analysis suggests that LET improves DFS and distant DFS even when there has been a substantial period of time since the discontinuation of prior adjuvant tamoxifen.


Electric power from offshore wind via synoptic-scale interconnection.
World wind power resources are abundant, but their utilization could be limited because wind fluctuates rather than providing steady power. We hypothesize that wind power output could be stabilized if wind generators were located in a meteorologically designed configuration and electrically connected. Based on 5 yr of wind data from 11 meteorological stations, distributed over a 2,500 km extent along the U.S. East Coast, power output for each hour at each site is calculated. Each individual wind power generation site exhibits the expected power ups and downs. But when we simulate a power line connecting them, called here the Atlantic Transmission Grid, the output from the entire set of generators rarely reaches either low or full power, and power changes slowly. Notably, during the 5-yr study period, the amount of power shifted up and down but never stopped. This finding is explained by examining in detail the high and low output periods, using reanalysis data to show the weather phenomena responsible for steady production and for the occasional periods of low power. We conclude with suggested institutions appropriate to create and manage the power system analyzed here.


Investigation of field and diffusion time dependence of the diffusion-weighted signal at ultrahigh magnetic fields.
Over the last decade, there has been a significant increase in the number of high-magnetic-field MRI magnets. However, the exact effect of a high magnetic field strength (B0 ) on diffusion-weighted MR signals is not yet fully understood. The goal of this study was to investigate the influence of different high magnetic field strengths (9.4 T and 14.1 T) and diffusion times (9, 11, 13, 15, 17 and 24 ms) on the diffusion-weighted signal in rat brain white matter. At a short diffusion time (9 ms), fractional anisotropy values were found to be lower at 14.1 T than at 9.4 T, but this difference disappeared at longer diffusion times. A simple two-pool model was used to explain these findings. The model describes the white matter as a first hindered compartment (often associated with the extra-axonal space), characterized by a faster orthogonal diffusion and a lower fractional anisotropy, and a second restricted compartment (often associated with the intra-axonal space), characterized by a slower orthogonal diffusion (i.e. orthogonal to the axon direction) and a higher fractional anisotropy. Apparent T2 relaxation time measurements of the hindered and restricted pools were performed. The shortening of the pseudo-T2 value from the restricted compartment with B0 is likely to be more pronounced than the apparent T2 changes in the hindered compartment. This study suggests that the observed differences in diffusion tensor imaging parameters between the two magnetic field strengths at short diffusion time may be related to differences in the apparent T2 values between the pools.


In search of salience: phenomenological analysis of moral distress.
The nurse's moral competences in the management of situations which present ethical implications are less investigated in literature than other ethical problems related to clinical nursing. Phenomenology affirms that emotional warmth is the first fundamental attitude as well as the premise of any ethical reasoning. Nevertheless, it is not clear how and when this could be confirmed in situations where the effect of emotions on the nurse's decisional process is undiscovered. To explore the processes through which situations of moral distress are determined for the nurses involved in nursing situations, a phenomenological-hermeneutic analysis of a nurse's report of an experience lived by her as a moral distress situation has been conducted. Nursing emerges as a relational doctrine that requires the nurse to have different degrees of personal involvement, the integration between logical-formal thinking and narrative thinking, the perception of the salience of the given situation also through the interpretation and management of one's own emotions, and the capacity to undergo a process of co-construction of shared meanings that the others might consider adequate for the resolution of her problem. Moral action requires the nurse to think constantly about the important things that are happening in a nursing situation. Commitment towards practical situations is directed to training in order to promote the nurse's reflective ability towards finding salience in nursing situations, but it is also directed to the management of nursing assistance and human resources for the initial impact that this reflexive ability has on patients' and their families' lives and on their need to be heard and assisted. The only case analysed does not allow generalizations. Further research is needed to investigate how feelings generated by emotional acceptance influence ethical decision making and moral distress in nursing situations.


Effect of chlorogenic acids on fatigue and sleep in healthy males: A randomized, double-blind, placebo-controlled, crossover study.
Chlorogenic acids (CGAs) are found in abundance in coffee beans and have numerous health benefits. This study investigated the effect of CGAs extracted from coffee beans on fatigue and sleep in healthy participants. This crossover study involved 16 men (aged 30-54 years) who were daytime workers with weekends off work. The participants were randomized into two groups: One group was given a placebo beverage, and the other was given an active beverage containing 300 mg of CGAs. The test beverages were consumed for 13 days starting on a Sunday. The evaluation criteria were feelings of fatigue and sleep quality, sleep-related indices recorded by an activity meter, and biomarkers. Feelings of fatigue and sleep-related indices during the first (first half of week 1) and second (second half of week 2) halves of the consumption periods were compared. Within the first half of week 1, no differences in feelings of fatigue were observed between the groups. However, during the second half of week 2, fatigue upon awakening and sleep quality in the active group were significantly improved compared with those in the placebo group. Sleep efficiency and total nocturnal awakening time were significantly deteriorated in the second half of week 2 compared with the first half of week 1 in the placebo group. Furthermore, significant differences in these indices were observed between the two groups in the second half of week 2. These results suggest that the daily consumption of CGA-containing beverages may improve fatigue upon awakening and sleep quality.


Highly Sensitive SERS Detection of Neonicotinoid Pesticides. Complete Raman Spectral Assignment of Clothianidin and Imidacloprid.
The use of surface enhanced Raman spectroscopy in the development of low cost, portable sensor devices that can be used in the field for nitroguanidine neonicotinoid insecticide detection is appealing. However, a key challenge to achieving this goal is the lack of detailed analysis and vibrational assignment for the most popular neonicotinoids. To make progress toward this goal, this paper presents an analysis of the bulk Raman and SERS spectra of two neonicotinoids, namely clothianidin and imidacloprid. Combined with first-principles simulations, this allowed assignment of all Raman spectral modes for both molecules. To our knowledge, this is the first report of SERS analysis and vibrational assignment of clothianidin, and a comprehensive assignment and analysis is provided for imidacloprid. Silver nanostructured surfaces were fabricated for qualitative SERS analysis, which provides the characteristic spectra of the target molecules and demonstrates the ability of SERS to sense these molecules at concentrations of 1 ng/mL. These concentrations are on par with high-end chromatographic-mass spectroscopy laboratory methods. These SERS sensors thus allow for the selective and sensitive detection of neonicotinoids and provide complementary qualitative data for the molecules. Furthermore, this technique can be adapted to portable devices for remote sensing applications. Further work focuses on integrating our device with an electronics platform for truly portable residue detection.


Unawareness of the effects of soy intake on the management of congenital hypothyroidism.
It has been established that soy products can interfere with thyroid hormone absorption resulting in continued hypothyroidism in individuals receiving recommended levothyroxine replacement. It has also been reported that achievement of euthyroidism in hypothyroid patients using soy products requires increased doses of levothyroxine. We have observed 2 patients with congenital hypothyroidism who continued to manifest clinical hypothyroidism while receiving recommended doses of hormone and ingesting soy products. The first patient was diagnosed by newborn screening (thyroid-stimulating hormone [TSH] =169 µIU/mL) and treated with 50 µg of levothyroxine since 6 days of age while simultaneously starting soy formula. At 3 weeks of age, she was clinically and biochemically hypothyroid (thyroxine = 4.0 µg/dL, TSH = 216 µIU/mL). We stopped her soy formula and decreased her levothyroxine dose. Three weeks later signs of hypothyroidism were resolving, and, by 10 weeks of age, she was clinically and biochemically euthyroid. Another patient was diagnosed by newborn screening, received levothyroxine, and did well. She was lost to us for 2 years. During this interval she began consuming soy milk and became profoundly hypothyroid (free thyroxine <0.4 ng/dL, TSH = 248 µIU/mL), even though the primary care physician had increased her levothyroxine dose to 112 µg/day. She was switched to cow milk, and her thyroid function slowly normalized with decreasing doses of levothyroxine. These 2 patients reinforce the importance of remembering that soy products interfere with levothyroxine absorption and can endanger infants and young children with congenital hypothyroidism who are at risk for developmental and growth delay.


Investigation of the koala (Phascolarctos cinereus) hindgut microbiome via 16S pyrosequencing.
As a dietary source, the foliage of Eucalyptus spp. is low in available protein and carbohydrate while containing polyphenolic compounds that interfere with enzymatic digestion. To overcome this, the koala (Phascolarctos cinereus) has evolved a range of anatomical and physiological adaptations to assist with digestion and absorption of nutrients from this food source. Microbial fermentation of partially digested eucalyptus leaves is thought to be critical in this process, however, little is known about the composition and diversity of microorganisms that are associated with digestive health in this native species. In this study, we performed 16S rRNA gene pyrosequencing of caecum, colon and faecal pellet samples from two wild, free ranging, Queensland koalas. Our results reveal a highly complex and diverse ecosystem with considerable intra-individual variation. Although samples were dominated by sequences from the Bacteroidetes and Firmicutes phyla there was considerable variation at the genus level. This study is the first non-culture based microbiota analysis, using 454-amplicon pyrosequencing, and provides preliminary data to expand our understanding of the koala hindgut.


Adverse health consequences that co-occur with depression: a longitudinal study of black adolescent females.
The purpose of this study was to identify adverse health consequences that may co-occur with depression among black female adolescents. Adolescents were recruited from high-risk neighborhoods in Birmingham, Alabama. The sample comprised 460 black female adolescents (aged 14-18 years) who completed assessments at baseline and at 6 and 12 months. Only adolescents who consistently scored above the threshold for depression at all 3 assessments (n = 76) or below the threshold at all 3 assessments (n = 174) were included (N = 250) in the data analysis. Within this sample, adolescents who were depressed were compared with those who were not depressed with respect to the following health consequences: low self-esteem, emotional abuse, physical abuse, verbal abuse, poor body image, and antisocial behavior. Using generalized estimating equations and controlling for covariates, depressed adolescents were 5.3 times more likely to report low self-esteem, 4.3 times more likely to report emotional abuse, 3.7 times more likely to report being physically abused, and almost 3 times as likely to report being verbally abused. Furthermore, depressed adolescents were more than twice as likely to report poor body image and nearly twice as likely to report engaging in antisocial behaviors. The findings suggest that a broad range of adverse health consequences may accompany depression among black female adolescents. Physicians need to be alert to the co-occurrence of depression and low self-esteem; emotional, physical, and verbal abuse; poor body image; and antisocial behaviors among this population.


Understanding adaptive capacity and capacity to innovate in social-ecological systems: Applying a gender lens.
Development policy increasingly focuses on building capacities to respond to change (adaptation), and to drive change (innovation). Few studies, however, focus specifically on the social and gender differentiation of capacities to adapt and innovate. We address this gap using a qualitative study in three communities in Solomon Islands; a developing country, where rural livelihoods and well-being are tightly tied to agriculture and fisheries. We find the five dimensions of capacity to adapt and to innovate (i.e. assets, flexibility, learning, social organisation, agency) to be mutually dependant. For example, limits to education, physical mobility and agency meant that women and youth, particularly, felt it was difficult to establish relations with external agencies to access technical support or new information important for innovating or adapting. Willingness to bear risk and to challenge social norms hindered both women's and men's capacity to innovate, albeit to differing degrees. Our findings are of value to those aspiring for equitable improvements to well-being within dynamic and diverse social-ecological systems.


Outcome of modified St Jude total therapy 13A for childhood acute lymphoblastic leukemia in the southeast region of Turkey.
To fill the gap in the current data on childhood acute lymphoblastic leukemia (ALL) in low-income and middle-income countries. This study included 106 children between the ages of 1 and 17 years with newly diagnosed ALL monitored between 1999 and 2010. All the patients were treated with the modified St Jude Total 13A treatment plan at the Pediatric Hematology Clinic at Harran University. Sixty-eight (64.2%) patients were boys and 38 (35.8%) were girls. The median age at diagnosis was 5.9 ± 3.7 years. Thirty-eight (35.8%) children were classified as standard risk, 53 (39.3%) were intermediate risk, and 15 (14.2%) were high risk. Thirteen (12.3%) children died in induction before the remission date (43 d of remission induction). Of all the 93 (100%) patients who completed remission induction therapy and whose bone marrow were in remission, 5 (4.7%) had a bone marrow relapse, 1 (0.9%) had a retinal relapse, and 5 (4.7%) had secondary acute myeloid leukemia. At a median follow-up of 44 months (range, 0.36 to 135.5 mo), the estimated 5-year overall survival and event-free survival were 77.4 ± 5% and 68.9 ± 6.5%, respectively. The estimated 5-year overall survival for boys and girls was 76.5 ± 6% and 65.8 ± 8%, respectively (P = 0.182). St Jude Total 13A treatment protocols to treat childhood ALL can be successfully adapted, which suggests that such an approach may be useful in low socioeconomic regions; however, it should be noted that secondary leukemia can occur at a high rate.


Fluvial network organization imprints on microbial co-occurrence networks.
Recent studies highlight linkages among the architecture of ecological networks, their persistence facing environmental disturbance, and the related patterns of biodiversity. A hitherto unresolved question is whether the structure of the landscape inhabited by organisms leaves an imprint on their ecological networks. We analyzed, based on pyrosequencing profiling of the biofilm communities in 114 streams, how features inherent to fluvial networks affect the co-occurrence networks that the microorganisms form in these biofilms. Our findings suggest that hydrology and metacommunity dynamics, both changing predictably across fluvial networks, affect the fragmentation of the microbial co-occurrence networks throughout the fluvial network. The loss of taxa from co-occurrence networks demonstrates that the removal of gatekeepers disproportionately contributed to network fragmentation, which has potential implications for the functions biofilms fulfill in stream ecosystems. Our findings are critical because of increased anthropogenic pressures deteriorating stream ecosystem integrity and biodiversity.


Characterization of antibodies as probes for structural and biochemical studies of tektins from ciliary and flagellar microtubules.
Rabbit antibodies raised and purified against three tektins, proteins of flagellar doublet microtubules from sea-urchin sperm (Lytechinus pictus and Strongylocentrotus purpuratus), were used to study tektin biochemistry and their structural localization. Doublet microtubules were fractionated into tektin filaments and separated by SDS-PAGE into three major tektin polypeptide bands (Mr = 47, 51 and 55 (X 10(3)), which were used to immunize rabbits. Antibodies against each tektin (anti-tektins) were affinity-purified and then characterized by two-dimensional isoelectric focusing/SDS-PAGE immunoblotting and by immunofluorescence microscopy. In two-dimensional immunoblots of 0.5% Sarkosyl-resistant fractions of flagellar microtubules, the antibody against the 55 X 10(3) Mr tektin (anti-55) stained one major polypeptide of 55 X 10(3) Mr and pI 6.9, anti-51 stained two polypeptides of 51 X 10(3) Mr and pI approximately 6.15, and anti-47 stained one major polypeptide of 47 X 10(3) Mr and pI 6.15. The anti-tektins also stained several minor neighbouring polypeptides, which may be isoelectric variants, novel tektins or unrelated proteins. Furthermore, anti-47 crossreacted with the major 55 X 10(3) Mr polypeptide. By immunofluorescence microscopy all three anti-tektins stained methanol-fixed echinoderm sperm flagella and embryonic cilia. In addition, anti-47 and anti-55 stained unfixed, demembranated axonemes. Besides staining axonemes, all anti-tektins labelled the basal body region, and anti-51 labelled the sperm head envelope. These results indicate that the tektins are a complex family of proteins that are components of axonemal microtubules and possibly other cytoplasmic and nuclear structures.


SUZUKI-MIYAURA COUPLING REACTIONS OF 3,5-DICHLORO-1,2,4-THIADIAZOLE.
3,5-Dichloro-1,2,4-thiadiazole was allowed to react with different arylboronic acids under different Suzuki-Miyaura coupling conditions: at room temperature 5-aryl-3-chloro-1,2,4-thiadiazoles were obtained and at toluene reflux temperature the products were 3,5-diaryl-1,2,4-thiadiazoles. Sequential coupling reactions lead to 3,5-diaryl-1,2,4-thiadiazoles with non-identical aryl groups. The structure of 3-methoxy-5-(4-methoxyphenyl)-1,2,4-thiadiazole was established from X-ray crystallographic data.


A novel in vitro assay of tumor-initiating cells in xenograft prostate tumors.
The field of prostate cancer has been stymied by the difficulty of cultivating patient-derived samples in the laboratory. In order to help circumvent this challenge, we sought to develop an in vitro assay of human prostate cancer initiation employing a prostate-associated mesenchymal feeder layer. Rat seminal vesicle mesenchyme (rSVM) harvested from male neonatal rats was plated in 12-well plates and then irradiated with 30 Gy after approximately 75% confluence. Single-cell suspensions of two human non-adherent prostate cancer xenograft lines (TRPC and LAPC9) were then plated on irradiated rSVM. At 3-4 weeks, three-dimensional solid structures, termed glandoids, were harvested and analyzed or transplanted singly into the renal capsule of immunodeficient mice. Animals were assessed for tumor formation 8-12 weeks after engraftment. Finally, clonality assays were performed to determine whether glandoids usually arise from a single cell and are therefore clonal in origin. Glandoids form with reliable frequency (1/ approximately 300 plated cells), are constituted by relevant cell types (CK8+, CK5-, PSA+) and after implantation into immunocompromised mice, give rise to tumors that recapitulate original xenograft histology and cell composition; defining a glandoid as a tumor-initiating unit. In addition, assessment of red fluorescent protein (RFP)-labeled glandoids revealed either all red or non-red structures, with few areas of fusion, suggesting glandoids are clonal in origin. The above assay describes an adjunct technique to readily cultivate cells from prostate cancer xenografts in vitro and as such provides a platform on which tumor-initiating cell studies and high-throughput drug discovery may be performed.


Impact of a Social Work Care Coordination Intervention on Hospital Readmission: A Randomized Controlled Trial.
This study assessed how a social work-led care coordination intervention would reduce the within-30-day hospital readmission rate among moderate- and high-risk patients age 50 years or older. Authors ran a randomized controlled trial to determine whether there was a significant difference in within-30-day readmission rates between patients receiving usual care post-discharge and those receiving intervention from an MSW intern (one home visit and one to two phone calls). Results were obtained using a sample of hospitalized patients with a LACE index score of 7 or higher (N = 89). Analysis suggests that the intervention improved the likelihood of not being readmitted by some 22 percent (RR = 1.222; 95% CI = 1.063-1.405). The risk improvement with the intervention was highly statistically significant (p = .003). This study shows that a time-efficient care coordination intervention by MSW interns may decrease hospital readmission rates. Replications of this study in other communities, with more diverse populations, and with larger numbers of patients will indicate whether results are generalizable.