Tumor microenvironment responsive hollow mesoporous Co9S8@MnO2-ICG/DOX intelligent nanoplatform for synergistically enhanced tumor multimodal therapy.
The development of multifunctional nanoplatform with combination of tumor microenvironment (TME)-responsive dual T1/T2 magnetic resonance (MR) imaging and synergistically self-enhanced photothermal/photodynamic/chemo-therapy is of significant importance for tumor theranostic, which still remains a great challenge. Herein, a novel hollow mesoporous double-shell Co9S8@MnO2 nanoplatform loaded with photodynamic agent of indocyanine green molecules (ICG) and chemotherapy drug of doxorubicin (DOX) was designed for TME responsive dual T1/T2 enhanced MR imaging and synergistically enhanced anti-tumor therapy. The designed nanoplatform with MnO2 shell can act as a TME-responsive oxygen self-supplied producer to alleviate tumor hypoxia and simultaneously improve photodynamic therapy (PDT) efficiency. Moreover, the TME-induced MnO2 dissolving and near-infrared (NIR) triggered photothermal nature from Co9S8 shell can further promote the tumor-targeted DOX release, leading to the synergistically improved anti-tumor efficacy. And the simultaneous enhancement in dual T1/T2 MR signal was achieved for highly specific tumor diagnosis. The in vivo and in vitro results confirmed that the designed TME-triggered nanoplatform with synergistic combination therapy presented good biocompatibility, and superior inhibition of tumor growth than monotherapy. This study provides the opportunities of designing intelligent TME-activated nanoplatform for highly specific tumor MR imaging and collaborative self-enhanced tumor therapy.


Role of estradiol in intrinsic hindbrain AMPK regulation of hypothalamic AMPK, metabolic neuropeptide, and norepinephrine activity and food intake in the female rat.
This study addressed the hypothesis that dorsomedial hindbrain adenosine 5'-monophosphate-activated protein kinase (AMPK) imposes inherent estradiol-dependent control of hypothalamic AMPK, neuropeptide, and norepinephrine (NE) activity and feeding in the female rat. Estradiol (E)- or oil (O)-implanted ovariectomized rats were injected with the AMPK inhibitor compound c (Cc) or vehicle into the caudal fourth ventricle (CV4) prior to micropunch-dissection of individual hypothalamic metabolic loci or assessment of food intake. Cc decreased hindbrain dorsal vagal complex phosphoAMPK (pAMPK) in both E and O; tissue ATP levels were reduced by this treatment in O only. In E/Cc, pAMPK expression was diminished in the lateral hypothalamic area (LHA) and ventromedial (VMH) and paraventricular (PVH) nuclei; only PVH pAMPK was suppressed by this treatment in O/Cc. Cc decreased PVH corticotropin-releasing hormone and arcuate (ARH) proopiomelanocortin (POMC) and neuropeptide Y in O, but suppressed only POMC in E. O/Cc exhibited both augmented (PVH, VMH) and decreased (LHA, ARH) hypothalamic NE content, whereas Cc treatment of E elevated preoptic and dorsomedial hypothalamic nucleus NE. Cc completely or incompletely repressed feeding in E versus O, respectively. Results implicate dorsomedial hindbrain AMPK in physiological stimulus-induced feeding in females. Excepting POMC, hypothalamic neuropeptide responses to this sensor may be contingent on estrogen. Estradiol likely designates hypothalamic targets of altered NE signaling due to hindbrain AMPK activation. Divergent changes in NE content of hypothalamic loci in O/Cc uniquely demonstrate sensor-induced bimodal catecholamine signaling to those sites.


Clinical practice guidelines for feeding behaviors and weight-for-age at 12 months: a secondary analysis of the Infant Feeding Practices Study II.
The World Health Organization has identified childhood obesity as a major threat to global health. Accumulating evidence indicates that excess weight early in life is predictive of later childhood and adolescent obesity. Clinical practice guidelines for infant feeding behaviors have been developed by national and international health organizations. The relationship between these guidelines and infant weight status has not been established. To examine the relationship between weight-for-age at 1 year and adherence to four clinical practice guidelines for feeding behaviors: no bottle-to-bed, minimal juice consumption, breastfeeding throughout the first year of life, and introduction to solid food no earlier than age 4-6 months. Data were obtained from the Infant Feeding Practices Study II, a longitudinal, national survey administered by the U.S. Food and Drug Administration and Centers for Disease Control and Prevention that followed mother-infant dyads from pregnancy through 1 year postpartum. The sample was comprised of 691 infants for whom 12-month survey data were available. Significant associations with weight-for-age were found for juice consumption (p= 0.003), breastfeeding during the second half of infancy (p < 0.001), and introduction to solid foods prior to age 4 months (p < 0.001). A regression model that controlled for infant and maternal characteristics demonstrated that these feeding behaviors remained significant predictors of weight-for-age at 12 months. Modifiable infant feeding behaviors contributed to weight-for-age at 1 year. Replication studies with economically and culturally diverse samples are needed. Further, testing longitudinal interventions that address infant feeding practices is likely to yield the evidence needed for shaping future clinical practice guidelines that reduce the risk for childhood obesity and related pediatric comorbidities.


Correction: Y2O3:Yb,Er@mSiO2-CuxS double-shelled hollow spheres for enhanced chemo-/photothermal anti-cancer therapy and dual-modal imaging.
Correction for 'Y2O3:Yb,Er@mSiO2-CuxS double-shelled hollow spheres for enhanced chemo-/photothermal anti-cancer therapy and dual-modal imaging' by Dan Yang et al., Nanoscale, 2015, 7, 12180-12191, DOI: 10.1039/C5NR02269J.


Genome-wide scan with nearly 700,000 SNPs in two Sardinian sub-populations suggests some regions as candidate targets for positive selection.
This paper explores the genetic structure and signatures of natural selection in different sub-populations from the Island of Sardinia, exploiting information from nearly 700,000 autosomal SNPs genotyped with the Affymetrix Genome-Wide Human SNP 6.0 Array. The genetic structure of the Sardinian population and its position within the context of other Mediterranean and European human groups were investigated in depth by comparing our data with publicly available data sets. Principal components and admixture analyses suggest a clustering of the examined samples in two significantly differentiated sub-populations (Ogliastra and Southern Sardinia), as confirmed by AMOVA (F(ST)=0.011; P<0.001). Differentiation of these sub-populations was still evident when they were pooled together with supplementary Sardinian samples from HGDP and compared with several other European, North-African and Near Eastern populations, confirming the uniqueness of the Sardinian genetic background. Moreover, by applying several statistical approaches aimed at assessing differences at the SNP level, the highest differentiated genomic regions between Ogliastra and Southern Sardinia were thus investigated via an extended haplotype homozygosity (EHH)-based test to point out potential selective sweeps. Using this approach, 40 genomic regions were detected, with significant differences between Ogliastra and Southern Sardinia. These regions were subsequently investigated using a long-range haplotype test, which found significant REHH values for SNPs rs11070188 and rs11070192 in the Ogliastra sub-population. In the light of these results and the overlap of the different computed statistics, the region encompassing these loci can be considered a strong candidate to have undergone selective pressure in Ogliastra.


Microfluidic based single cell or droplet manipulation: Methods and applications.
The isolation of single cell or droplet is first and crucial step to single-cell analysis, which is important for cancer research and diagnostic methods. This review provides an overview of technologies that are currently used or in development to realize the isolation. Microfluidic based manipulation is an emerging technology with the distinct advantages of miniaturization and low cost. Therefore, recent developments in microfluidic isolated methods have attracted extensive attention. We introduced herein five strategies based on microfluid: trap, microfluidic discrete manipulation, bioprinter, capillary and inertial force. For every technology, their basic principles and features were discussed firstly. Then some modified approaches and applications were listed as the extension. Finally, we compared the advantages and drawbacks of these methods, and analyzed the trend of the manipulation based on microfluidics.


Long-Term Electrocardiographic Changes and Clinical Outcomes of Transcatheter Aortic Valve Implantation Recipients Without New Postprocedural Conduction Disturbances.
The objective of this study was to determine the long-term (>1 year) electrocardiographic (ECG) and clinical outcomes of patients without significant changes in their electrocardiogram after transcatheter aortic valve implantation (TAVI; including patients with pre-existing ECG abnormalities). Among 772 consecutive patients who underwent TAVI in our institution, 397 patients (51%) without new ECG changes were included. TAVI patients were divided into 2 groups according to the presence of pre-existing ECG-conduction disturbances (ECG-CD: 140 patients, non-ECG-CD: 257 patients). Clinical follow-up (median: 35 [22 to 57] months) was complete in all patients but 5 (1.2%), and ECG data were available in 291 patients (84.3% of patients at risk) at a median of 29 (20 to 50) months. In the non-ECG-CD group, most patients (79.8%) remained without significant ECG changes at follow-up, and 16.9% developed first-degree atrioventricular block and/or bundle branch block over time. The rate of permanent pacemaker (PPM) implantation at follow-up was 3.5% (1.1%/year) in the non-ECG-CD group versus 15.7% (5.5%/year) in the ECG-CD group (p <0.001). The presence of pre-existing CD was an independent predictor of PPM at follow-up (hazard ratio [HR] 4.67, 95% confidence interval [CI] 2.15 to 10.16, p <0.001). The ECG-CD group exhibited a higher risk of heart failure hospitalization (non-ECG-CD: 25%, ECG-CD: 29%, log-rank p = 0.01), but not mortality (non-ECG-CD: 50%, ECG-CD: 46%, log-rank p = 0.60) at 5-year follow-up. In conclusion, the ECG remained unchanged in most TAVI recipients without new postprocedural CD. Pre-existing ECG-CD was associated with an increased risk of PPM and heart failure hospitalization at long-term follow-up. These results provide reassuring data in the era of TAVI expanding toward candidates with a longer life expectancy, and highlight the importance of a closer follow-up of those patients with pre-existing ECG-CDs.


Intrahepatic cholestasis of pregnancy: Recent advances.
Intrahepatic cholestasis of pregnancy, also known as obstetric cholestasis, is a pruritic condition of pregnancy characterized by an underlying elevation in circulating bile acids and liver derangement, and associated with adverse fetal outcomes, such as preterm labor and stillbirth. Limited understanding of the underlying pathophysiology and mechanisms involved in adverse outcomes has previously restricted treatment options and pregnancy management. Recent advances in these research fields provide tantalizing targets to improve the care of pregnant women affected by this condition.


Potential hazard of East-Radcliffe ventilator. Failure to entrain adequate oxygen.
Reports of two hypoxic episodes which occurred during the use of the East Radcliffe PNA 1 ventilator in the 'complete rebreathing' mode led to the study of the efficiency of the emergency air entrainment system. The inability of this system to maintain adequate oxygen concentrations during interruption of the fresh gas supply results in the development of a hypoxic gas mixture despite patency of the entrainment valve. The reasons for this, and their clinical implications during intermittent positive pressure ventilation in the 'complete rebreathing' mode, are discussed.


Myeloperoxidase -463G>A polymorphism and risk of primary lung cancer in a Korean population.
Myeloperoxidase (MPO) contributes to pulmonary carcinogenesis through activation of a wide range of tobacco smoke procarcinogens, including benzo[a]pyrene and aromatic amines. A -463G>A polymorphism in the promoter region of the MPO gene has been shown to reduce MPO expression and activity. It is therefore possible that carriers of the -463A allele may be at decreased risk of lung cancer. To test this hypothesis we have investigated the association between the -463G>A polymorphism of MPO gene and the risk of lung cancer in a Korean population. The MPO genotype was determined in 432 lung cancer patients and 432 healthy controls that were frequency-matched for age and gender. In the current study, the risk estimate for lung cancer of the combined -463 AA+GA genotype was not significantly different from that of the -463GG genotype (adjusted OR=1.03, 95% CI=0.72-1.47). In addition, we observed no evidence of effect modification by age, gender, smoking history or tumor histology. These results suggest that the MPO -463G>A polymorphism does not significantly affect the susceptibility to lung cancer in Koreans.


Plasma exudation. Correlation between Evans blue dye and radiolabeled albumin in guinea pig airways in vivo.
We quantified the tissue exudation and luminal transudation of two plasma markers, Evans blue (EB) dye and [125I]-human serum albumin (HSA), into the airways of the anesthetized guinea pig in response to platelet activating factor (PAF). There was a highly significant correlation between the tissue content of EB and [125I]-HSA in all airways studied. Significant correlation for transudation of the two markers was limited to high rates of plasma leakage. [125I]-HSA was the more sensitive marker for the association between exudation and transudation and the effect of PAF on transudation. EB was the better marker for assessing the relationship between the dose of PAF and plasma exudation.


Quantum dots based in-vitro co-culture cancer model for identification of rare cancer cell heterogeneity.
Cancer cell heterogeneity (CCH) is crucial in understanding cancer progression and metastasis. The CCH is one of the stumbling blocks in modern medicine's therapeutics and diagnostics . An in-vitro model of co-culture systems of MCF-7, HeLa, HEK-293, with THP-1 cells showed the occurrence of EpCAM positive (EpCAM+) and EpCAM negative (EpCAM-) heterogenetic cancer cell types labeled with the Quantum Dot antibody conjugates (QDAb). This in-vitro model study could provide insights into the role of rare cancer cells manifestation and their heterogeneity in metastatic progression and risk for severe infections in these patients. We successfully report the presence of CCH based on the fluorescence ratios of the co-cultured cancer cells when treated with the QDAb. These short-term mimic co-cultures give a compelling and quite associated model for assessing early treatment responses in various cancers.


[Mapping the genes for ribosomal proteins S14 and S17 on human chromosomes using cDNA from a panel of hybrid cells].
A new method of mapping transcriptionally active genes of ribosomal proteins onto human chromosomes is proposed. The method is based on the detection of the expression of human ribosomal protein mRNA in rodent-human hybrid cells carrying different human chromosomes. Using this method, the functional gene of the human ribosomal protein S17 was mapped and the location of the S14 ribosomal protein gene on chromosome 5 was confirmed.


Local application of n-3 or n-6 polyunsaturated fatty acids in the treatment of human experimental gingivitis.
Polyunsaturated fatty acids have the potential to attenuate inflammation by the synthesis of mediators of the 15-lipoxygenase pathways, which show opposite effects to the pro-inflammatory arachidonic acid metabolites such as leukotriene B4 (LTB4). The aim of this clinical study was to evaluate the effects of topical application of n-6 or n-6 polyunsaturated fatty acids in patients with experimental gingivitis. In each subject, similar teeth served as experimental and control over a 21-day non-hygiene phase and a 9-day resolving phase. Efficacy assessment was based on the bleeding on probing frequency (BOP) and the gingivocrevicular fluid volume (GCF). GCF was determined by inserting a filter paper strip for 30 s and measurements were performed on a Periotron 8000. The LTB4 concentration was analyzed by reversed-phase high-pressure liquid chromatography. After 21 days of plaque growth, the BOP, GCF and LTB4 levels were significantly increased in all groups, with no differences between the control and experimental side. Rinsing of an area with established gingivitis for a 9-day period significantly reduced the GCF in the n-6 group (71.9 (18.7) versus 47.4 (11.4) Periotron Units, median (inter quartile range)). The topical application of n-6 or n-6 fatty acids failed to inhibit the development of experimental gingivitis. Rinsing with n-6 fatty acids could reduce the level of GCF in established experimental gingivitis.


Application of mesenchymal stem cells for the regeneration of cardiomyocyte and its use for cell transplantation therapy.
We have isolated a cardiomyogenic cell line (CMG cell) from murine bone marrow mesenchymal stem cells. The cells showed a fibroblast-like morphology, but the morphology changed after 5-azacytidine exposure. They began spontaneous beating after 2 weeks, and expressed ANP and BNP. Electron microscopy revealed a cardiomyocyte-like ultrastructure. These cells had several types of action potentials; sinus node-like and ventricular cell-like action potentials. The isoform of contractile protein genes indicated that their muscle phenotype was similar to fetal ventricular cardiomyocytes. They expressed alpha1A, alpha1B, alpha1D, beta1, and beta2 adrenergic and M1 and M2 muscarinic receptors. Stimulation with phenylephrine, isoproterenol and carbachol increased ERK phosphorylation and second messengers. Isoproterenol increased the beating rate, which was blocked with CGP20712A (beta1-selective blocker). These findings indicated that cell transplantation therapy for the patients with heart failure might possibly be achieved using the regenerated cardiomyocytes from autologous bone marrow cells in the near future.


Analysis of upstream region of nicotianamine synthase gene from Arabidopsis thaliana: presence of putative ERE-like sequence.
Nicotianamine (NA) is present in all plants so far examined, and is thought to chelate transition metal ions. Previously, we isolated three nicotianamine synthase (NAS) genes of Arabidopsis thaliana (AtNAS1, 2, and 3) and showed that each NAS gene is differentially expressed. Deletion analysis of the 5' flanking region of AtNAS3 found a putative ethylene-responsive sequence, ATTTTCAAA.


[Internet, SMS or voice portals tools. New technologies for an old problem].
To analyse the frequency of use, effectiveness and usability of automated systems for obtaining appointments in primary care from a user point of view. A cross-sectional study was conducted using a telephone survey of a random sample of 6193 patients (or parents or guardians of paediatric patients) treated in primary care in the Valencian Autonomous Community. A total of 397 (13.4%) adult patients and 1000 (31%) of parents or guardians of the paediatric patients used the Internet. The Voice Portal (225, 3.6%) and SMS (57, 0.9%) was the least used. The Internet was mostly used by men (χ(2) 15.1, P<.004) and among adult patients aged between 51 and 70 years (χ(2) 40.5, P<.001). The traditional channels (telephone call or asking for an appointment personally) were used by chronic patients (χ(2) 28.7, P<.001) and those with who used the health sytem less (χ(2) 52, P<.001). The use of ICT is not responsible for delays in the date of appointment. Usability was very high (above 90%), except in the case of the system based on SMS (80.7%). The Internet is the preferred channel among ICT to obtain an appointment. Its use is expected to increase. The effectiveness of ICT to get an appointment is somewhat higher than traditional channels. The usability of ICT to get an appointment is similar or superior to the traditional channels. The exception is the messages from a mobile.


An evaluation of Midwifery Group Practice. Part II: women's satisfaction.
Midwifery Group Practice (MGP) is a continuity of midwifery care model for women of all levels of pregnancy risk available at a tertiary metropolitan hospital in Australia. This paper presents Part II of the demonstration study exploring the effectiveness of MGP, and reports on women's satisfaction with the model of care. A Maternal Satisfaction Questionnaire was developed and sent to all women (n=120) enrolled in MGP over a three-month period. The questionnaire comprised two open-ended questions asking women to list up to three things they liked and did not like about MGP, and a structured section exploring levels of satisfaction through a five-point Likert response format. The open-ended questions were analysed using qualitative content analysis, and analysis of the structured part of the questionnaire was undertaken by comparing mean scores of satisfaction ranging from -2 (very negative attitudes) to +2 (very positive attitudes). Of the 120 women who were sent a Maternal Satisfaction Questionnaire, 84 returned their questionnaire (70% response rate). Three overarching themes were identified in the content analysis of open-ended questions, namely: Continuity of care; Accessibility; and Personal and professional attributes of the midwife. Analysis of the structured part of the questionnaire showed that women were satisfied with the care they received in MGP, as indicated by positive scores on all questions. Women being cared for in MGP are satisfied with their care.


Analysis of two translocation breakpoints and identification of a negative regulatory element in patients with Rieger's syndrome.
Rieger's syndrome is an autosomal dominant disorder characterized by eye, tooth, and umbilical anomalies. A gene responsible for Rieger's syndrome, PITX2, has previously been cloned using two patients with balanced translocations, t(4;16) and t(4;11), with breakpoints that lie near the gene, but which do not interrupt it. We sequenced both breakpoint regions on chromosome 4 and screened this area for novel genes. Fluorescence in situ hybridization (FISH) was used to determine if PITX2 was still present on the 4:16 chromosome. Both the chromosome 16 and chromosome 11 breakpoints were cloned and sequenced using panhandle polymerase chain reaction (PHPCR). Transient transfection studies were performed to compare effects on a reporter gene between native chromosome 4 sequence and chromosome 11 sequence. The region surrounding PITX2 on chromosome 4 is rich in repetitive elements, but no novel genes were identified. FISH demonstrated that PITX2 was intact on the 4:16 translocation chromosome. The PHPCR experiments demonstrated that the translocated regions of chromosomes 16 and 11 were repeat-rich, and transfection studies revealed a slight enhancer effect with the chromosome 4 sequence, and a strong silencer effect when the chromosome 11 sequence was present. Given the lack of any novel genes near either breakpoint, changes in potential regulatory elements may be the best model to explain the loss of PITX2 expression in these patients and hence the Rieger's syndrome phenotype.


Use of simulation models when developing and testing hospital evacuation plans: a tool for improving emergency preparedness.
In recent decades, analyses of hospitals evacuations have generated valuable knowledge. Unfortunately, these evacuation case studies often lack crucial details and policies that would be helpful in evacuation preparedness. The aim of this study was to use a simulation model to illustrate how it can aid emergency planners in the development, testing, and revising of hospitals evacuation plans. This study includes evacuation exercises at two emergency hospitals in Region Stockholm, Sweden. A scientifically validated simulation system for "table top" exercises was used for interactive training of hospital medical staff, prehospital staff and collaborating agencies. All participants acted in their usual professionals' roles. The exercises were run in real-time and mirrored actual hospital resources with the aid of moveable magnetic symbols illustrating patients, staff and transport, presented on whiteboards. During the exercises, observers and independent instructors documented actions taken and post-exercise surveys were conducted to obtain reactions and compare results. The simulation system allowed the emergency planner to test the whole evacuation process, making it possible to train and evaluate the important functions of management, coordination, and communication. Post-exercise surveys explored participants perception of the exercises. Analysis of open-ended questions included areas for improvement and resulted in five main categories: (1) management and liaison; (2) communication; (3) logistics; (4) medical care and patient prioritisation; and (5) resource utilisation. This study has shown that "table top" exercises using a validated simulation system can serve to guide emergency planners when developing evacuation plans, procedures, and protocols as well in training of all medical staff. The system also served to train adaptive thinking, leadership, communication, and clarification of critical functions.


Bioaccumulation of Silver and Impairment of Vital Organs in Clarias gariepinus from Co-Exposure to Silver Nanoparticles and Cow Dung Contamination.
This study reports the implications of silver nanoparticles (AgNPs) and cow-dung contamination on water quality and oxidative perturbations in antioxidant biomarkers in the exposed Clarias gariepinus. Sixteen samples of C. gariepinus were exposed to fresh-water, 0.75 mg/mL each of AgNPs, cow-dung and a mixture of AgNPs-cow dung dosed water for 10 days. Cow-dung significantly (p < 0.05) depleted dissolved oxygen (DO) and increased biochemical oxygen demand (BOD) by 14% and 75% respectively. The trends of abundance and bioaccumulation of Ag in C. gariepinus exposed to different treatments followed kidney > muscle > gill > liver, implying the kidney was the worst affected organ. The AgNPs significantly (p < 0.05) perturbed vital organs in C. gariepinus by altering activities of antioxidant biomarkers, whereas AgNPs-cow dung had reduced perturbations implying organic matter bound Ag+ to reduce toxicity. These results conclude that AgNPs posed a challenging environment for C. gariepinus to thrive.


Using machine learning to assess the livelihood impact of electricity access.
In many regions of the world, sparse data on key economic outcomes inhibit the development, targeting and evaluation of public policy1,2. We demonstrate how advancements in satellite imagery and machine learning (ML) can help ameliorate these data and inference challenges. In the context of an expansion of the electrical grid across Uganda, we show how a combination of satellite imagery and computer vision can be used to develop local-level livelihood measurements appropriate for inferring the causal impact of electricity access on livelihoods. We then show how ML-based inference techniques deliver more reliable estimates of the causal impact of electrification than traditional alternatives when applied to these data. We estimate that grid access improves village-level asset wealth in rural Uganda by up to 0.15 standard deviations, more than doubling the growth rate during our study period relative to untreated areas. Our results provide country-scale evidence on the impact of grid-based infrastructure investment and our methods provide a low-cost, generalizable approach to future policy evaluation in data-sparse environments.


Synthesis and mechanical properties of double cross-linked gelatin-graphene oxide hydrogels.
Gelatin is an interesting biological macromolecule for biomedical applications. Here, double cross-linked gelatin nanocomposite hydrogels with incorporation of graphene oxide (GO) were synthesized in one pot using glutaraldehyde (GTA) and GTA-grafted GO as double chemical cross-linkers. The nanocomposite hydrogels, in contrast to the neat gelatin hydrogel, exhibited significant increases in mechanical properties by up to 288% in compressive strength, 195% in compressive modulus, 267% in compressive fracture energy and 160% shear storage modulus with the optimal GO concentration. Fourier transform infrared spectroscopy, scanning electron microscopy and swelling tests were implemented to characterize the nanocomposite hydrogels.


Factors impacting attrition of vulnerable women from a longitudinal mental health intervention study.
This study explored factors associated with attrition of vulnerable women from a community-based, longitudinal mental health intervention study. The study employed a quasi-experimental, nonequivalent comparison group pretest-posttest design. The intervention consisted of six, 90-min meetings featuring education and support. One hundred and eighteen women aged 18-88 years enrolled from four urban neighborhoods. The team used the Generalized Anxiety Disorder-7, the Primary Health Questionnaire-9, a self-care knowledge for anxiety and depression instrument, and demographics to measure variables. Sessions occurred at trusted neighborhood sites. The team provided transportation, child care, and reminder calls or texts. Community health workers actively encouraged participants to continue in the study. The researchers did not offer financial incentives. Completion of the intervention involved attending four of six sessions. The study had a 39% attrition rate. Results, using a Chi-square test for independence, indicated significant associations between attrition, neighborhood/homelessness, and family income. Additionally, there were significant associations between attrition, a past diagnosis of anxiety, and a lack of concurrent therapy for anxiety/depression. This study identified social determinants and mental health factors linked to the attrition of urban, ethnically diverse, and impoverished women from longitudinal intervention studies.


Liver nonparenchymal cells involved in hyporesponsiveness induced by portal vein injection of alloantigen.
Intrahepatic injection of alloantigen prolongs allograft survival and inhibits T-lymphocyte release of both IL-2 and IFN-gamma but not IL-4. This suggests that intrahepatic processing of antigen lead to a predominance of Th2 cell population with inhibition of Th1 cell type. This study examines the effects of hepatic nonparenchymal cells (NPCs) on T cell function and cytokine mRNA expression profiles. Following portal vein (p.v.) injection of allogeneic splenic mononuclear cells (SMNC) in mice, heterotopic cardiac allograft survival and donor-specific immune responses were assessed. The cytokine profiles were evaluated in heart grafts and spleens from transplanted mice, or in recipient lymphocytes stimulated in vitro with alloantigen. The immunoregulatory role of NPCs from p.v. injected mice was evaluated. Transplanted mice with prolonged graft survival demonstrated increased IL-4, TGF-beta and IL-10 and/or decreased IFN-gamma and IL-2 mRNA expression within the spleen and the transplanted graft. This correlated with increased antigen-specific IL-4, IL-10 and TGF-beta expression in lymphocytes isolated from the p.v. injected mice. In mixed lymphocyte cultures using NPC from p.v. injected mice as regulatory cells, there was decreased proliferation of lymphocytes from the p.v. injected mice in response to allogeneic stimulation, associated with increased IL-4, TGF-beta and IL-10 production and decreased IFN-gamma and IL-2 production. The regulatory effects of the NPC was reversed by prostaglandin E inhibitor. Interactions between allogeneic lymphocytes and NPCs results in an impaired Th1 response and preferential shift towards a Th2 cytokine response which may regulate allograft rejection.


Improving access to health care for malaria in Africa: a review of literature on what attracts patients.
Increasing access to health care services is considered central to improving the health of populations. Existing reviews to understand factors affecting access to health care have focused on attributes of patients and their communities that act as 'barriers' to access, such as education level, financial and cultural factors. This review addresses the need to learn about provider characteristics that encourage patients to attend their health services. This literature review aims to describe research that has identified characteristics that clients are looking for in the providers they approach for their health care needs, specifically for malaria in Africa. Keywords of 'malaria' and 'treatment seek*' or 'health seek*' and 'Africa' were searched for in the following databases: Web of Science, IBSS and Medline. Reviews of each paper were undertaken by two members of the team. Factors attracting patients according to each paper were listed and the strength of evidence was assessed by evaluating the methods used and the richness of descriptions of findings. A total of 97 papers fulfilled the inclusion criteria and were included in the review. The review of these papers identified several characteristics that were reported to attract patients to providers of all types, including lower cost of services, close proximity to patients, positive manner of providers, medicines that patients believe will cure them, and timeliness of services. Additional categories of factors were noted to attract patients to either higher or lower-level providers. The strength of evidence reviewed varied, with limitations observed in the use of methods utilizing pre-defined questions and the uncritical use of concepts such as 'quality', 'costs' and 'access'. Although most papers (90%) were published since the year 2000, most categories of attributes had been described in earlier papers. This paper argues that improving access to services requires attention to factors that will attract patients, and recommends that public services are improved in the specific aspects identified in this review. It also argues that research into access should expand its lens to consider provider characteristics more broadly, especially using methods that enable open responses. Access must be reconceptualized beyond the notion of barriers to consider attributes of attraction if patients are to receive quality care quickly.


Lactation-associated macrophages exist in murine mammary tissue and human milk.
Macrophages are involved in immune defense, organogenesis and tissue homeostasis. Macrophages contribute to the different phases of mammary gland remodeling during development, pregnancy and involution postlactation. Less is known about the dynamics of mammary gland macrophages in the lactation stage. Here, we describe a macrophage population present during lactation in mice. By multiparameter flow cytometry and single-cell RNA sequencing, we identified a lactation-induced CD11c+CX3CR1+Dectin-1+ macrophage population (liMac) that was distinct from the two resident F4/80hi and F4/80lo macrophage subsets present pregestationally. LiMacs were predominantly monocyte-derived and expanded by proliferation in situ concomitant with nursing. LiMacs developed independently of IL-34, but required CSF-1 signaling and were partly microbiota-dependent. Locally, they resided adjacent to the basal cells of the alveoli and extravasated into the milk. We found several macrophage subsets in human milk that resembled liMacs. Collectively, these findings reveal the emergence of unique macrophages in the mammary gland and milk during lactation.


HIF1α-AS1 is a DNA:DNA:RNA triplex-forming lncRNA interacting with the HUSH complex.
DNA:DNA:RNA triplexes that are formed through Hoogsteen base-pairing of the RNA in the major groove of the DNA duplex have been observed in vitro, but the extent to which these interactions occur in cells and how they impact cellular functions remains elusive. Using a combination of bioinformatic techniques, RNA/DNA pulldown and biophysical studies, we set out to identify functionally important DNA:DNA:RNA triplex-forming long non-coding RNAs (lncRNA) in human endothelial cells. The lncRNA HIF1α-AS1 was retrieved as a top hit. Endogenous HIF1α-AS1 reduces the expression of numerous genes, including EPH Receptor A2 and Adrenomedullin through DNA:DNA:RNA triplex formation by acting as an adapter for the repressive human silencing hub complex (HUSH). Moreover, the oxygen-sensitive HIF1α-AS1 is down-regulated in pulmonary hypertension and loss-of-function approaches not only result in gene de-repression but also enhance angiogenic capacity. As exemplified here with HIF1α-AS1, DNA:DNA:RNA triplex formation is a functionally important mechanism of trans-acting gene expression control.


Assessment of candidate biomarkers in paired saliva and plasma samples from oral cancer patients by targeted mass spectrometry.
For oral cancer, numerous saliva- and plasma-derived protein biomarker candidates have been discovered and/or verified; however, it is unclear about the behavior of these candidates as saliva or plasma biomarkers. In this study, we developed two targeted assays, MRM and SISCAPA-MRM, to quantify 30 potential biomarkers in both plasma and saliva samples collected from 30 healthy controls and 30 oral cancer patients. Single point measurements were used for target quantification while response curves for assay metric determination. In comparison with MRM assay, SISCAPA-MRM effectively improved (>1.5 fold) the detection sensitivity of 11 and 21 targets in measurement of saliva and plasma samples, respectively. The integrated results revealed that the salivary levels of these 30 selected biomarkers weakly correlated (r < 0.2) to their plasma levels. Five candidate biomarkers (MMP1, PADI1, TNC, CSTA and MMP3) exhibited significant alterations and disease-discriminating powers (AUC = 0.914, 0.827, 0.813, 0.77, and 0.753) in saliva sample; nevertheless, no such targets could be found in plasma samples. Our data support the notion that saliva may be more suitable for the protein biomarker-based detection of oral cancer, and the newly developed SISCAPA-MRM assay could be applied to verify multiple oral cancer biomarker candidates in saliva samples. SIGNIFICANCE: In this work we systematically determined the abundance of 30 selected targets in the paired saliva and plasma samples to evaluate the utility of saliva and plasma samples for protein biomarker-based detection of oral cancer. Our study provides significant evidence to support the use of saliva, but not blood samples, offer more opportunity to achieve the success of protein biomarker discovery for oral cancer detection.


Autonomic nervous system function in Baltic myoclonus epilepsy.
Baltic myoclonus epilepsy (BME) is a neurodegenerative disease characterized by tonic-clonic seizures, myoclonus and a progressive course. The aim of the present study was to assess the clinical symptoms and signs of possible involvement of the autonomic nervous system (ANS) and objectively evaluate autonomically mediated cardiovascular reflexes in this syndrome. Fifteen patients with BME and 14 healthy control subjects were studied. Thirteen (87%) of the patients had symptoms suggesting ANS dysfunction. The most common symptoms were postural dizziness and sweating disturbances. The heart rate variation during deep breathing was lower in patients than in controls. The heart rate response and systolic blood pressure response during tilting were similar in both groups. Our results suggest a mild parasympathetic hypofunction and an intact sympathetic function in ambulatory patients with BME.


Regulation and function of adiponectin in the intestinal epithelial cells in response to Trichinella spiralis infection.
Besides metabolic homeostasis regulation, adipokines are recently emerged as important players in regulating immunity and inflammation. Helminth infection has known to modulate circulating adipokine secretion; however, the regulation and function of adipokines in response to helminth infection is still unclear. Here, we investigated the regulation and function of adiponectin during T. spiralis infection. While there was no change in circulating level of adiponectin, we found an increased adiponectin, but not leptin expression in the small intestine. Interestingly, the intestinal adiponectin expression was strongly associated with the expression of epithelial cell-derived cytokines IL-25, IL-33, and TSLP following infection. Indeed, mice deficiency of IL-25 receptor exhibited no intestinal adiponectin induction upon helminth infection. Interestingly, IL-25-induced adiponectin modulated intestinal epithelial cell responses by enhancing occludin and CCL17 expression. Using LPS-induced intestinal epithelial barrier dysfunctions in a Caco-2 cell monolayer model, adiponectin pretreatment enhanced a Transepithelial electrical resistance (TEER) and occludin expression. More importantly, adiponectin pretreatment of Caco2 cells prevented T. spiralis larval invasion in vitro and its administration during infection enhanced intestinal IL-13 secretion and worm expulsion in vivo. Altogether, our data suggest that intestinal adiponectin expression induced by helminth infection through the regulation of IL-25 promotes worm clearance and intestinal barrier function.


Hepatic Sdf2l1 controls feeding-induced ER stress and regulates metabolism.
Dynamic metabolic changes occur in the liver during the transition between fasting and feeding. Here we show that transient ER stress responses in the liver following feeding terminated by Sdf2l1 are essential for normal glucose and lipid homeostasis. Sdf2l1 regulates ERAD through interaction with a trafficking protein, TMED10. Suppression of Sdf2l1 expression in the liver results in insulin resistance and increases triglyceride content with sustained ER stress. In obese and diabetic mice, Sdf2l1 is downregulated due to decreased levels of nuclear XBP-1s, whereas restoration of Sdf2l1 expression ameliorates glucose intolerance and fatty liver with decreased ER stress. In diabetic patients, insufficient induction of Sdf2l1 correlates with progression of insulin resistance and steatohepatitis. Therefore, failure to build an ER stress response in the liver may be a causal factor in obesity-related diabetes and nonalcoholic steatohepatitis, for which Sdf2l1 could serve as a therapeutic target and sensitive biomarker.


[Idiopathic pulmonary fibrosis].
Idiopathic pulmonary fibrosis (IPF) is currently defined by a set of histopathological-radiological-clinical criteria including an histopathological pattern of usual interstitial pneumonia, reticular opacities with honeycombing at tomodensitometry, progressive exercise dyspnea in a patient older than 60 years with fine crackles at lung bases at auscultation. The incidence of IPF is increasing. Risk factors for the disease have been identified (smoking, exposure to various dusts, genetic polymorphism) but the true cause of FPI remains unknown. Progression to death within 2-4 years may be accelerated by acute exacerbation which may cause death. There is no efficient treatment for IPF. Corticosteroids and immunosuppressors are of no benefit. Therapeutic trials are on the way.


Safety of irinotecan and infusional fluorouracil/leucovorin (FOLFIRI) in Japan: a retrospective review of 48 patients with metastatic colorectal cancer.
A combination of irinotecan and infusional fluorouracil/leucovorin (FOLFIRI) has become one of the global standard chemotherapy regimens for metastatic colorectal cancer. The aim of this study was to evaluate the feasibility of FOLFIRI in a Japanese population with metastatic colorectal cancer. This retrospective analysis included 48 patients with unresectable metastatic colorectal cancer who received FOLFIRI between May 2004 and June 2005. Evaluation points included adverse events, dose intensity, response rate, progression-free survival, and overall survival. Thirty-eight (79%) patients received FOLFIRI as first-line chemotherapy. Eighteen patients received original full-dose FOLFIRI and 30 patients received reduced FOLFIRI with irinotecan at 150 mg/m(2). Eighteen (38%) of the 48 patients experienced grade 3 or 4 neutropenia, 5 (10%) had grade 3 vomiting and 5 (10%) had grade 3 diarrhea. Toxicity was tolerable, with appropriate dose reduction if necessary. There were no treatment-related deaths or early deaths within the first 60 days of treatment. Median dose intensities (with relative dose intensities in parentheses) in all patients and in patients who received full-dose FOLFIRI were 129 mg/m(2) per 2 weeks (71%) and 144 mg/m(2) per 2 weeks (80%) for irinotecan and 2349 mg/m(2) per 2 weeks (84%) and 2376 mg/m(2) per 2 weeks (85%) for fluorouracil, respectively. The response rate in patients with measurable lesions was 37% (13/35; 95% confidence interval [CI], 21.1%-53.2%), and median progression-free survival was 8.4 months (95% CI, 6.4-10.3). The dose intensity of irinotecan was relatively low, and toxicity was tolerable with appropriate dose reduction; efficacy was comparable to that previously reported. FOLFIRI is feasible and can be one of the standard treatment options for Japanese patients with metastatic colorectal cancer.


Evaluate the heavy metal toxicity to Pseudomonas fluorescens in a low levels of metal-chelates minimal medium.
A 2-(n-morpholino)ethane sulfonic acid (MES)-buffered minimal medium with low levels of metal chelates was used to evaluate the heavy metal (Co+2, Pb+2, Zn+2, Fe+2, Fe+3, Cd+2, Cu+2, and Cr+6) toxicity to Pseudomonas fluorescens through minimizing the limitation of the existing medium. The interaction between bacteria and heavy metals was real-time monitored by microcalorimetry and reflected by thermogenic curves. Compared with the main parameters, microbial growth rate constant k and total heat evolution Q total, a general order of toxicity was found to be Fe+3<Co+2<Fe+2<Cu+2<Cr+6<Zn+2<Pb+2<Cd+2. The main metal speciation was Co+2, Zn+2, Fe+2, Cd+2, PbOH+, Fe(OH)+2, CuOH+, HCrO4-, and CrO4(-2) at pH 6.4. These metal speciations are main factors to exhibit the metal toxicity to bacteria. To validate their interaction, the surface chemical functional groups of P. fluorescens biomass identified by Fourier transform infrared (FTIR) were amino, carboxyl, hydroxyl, and phosphoryl groups, which maybe involved in the biosorption of metal ions.


C-X-C motif chemokine ligand 1 induced by Hedgehog signaling promotes mouse extrahepatic bile duct repair after acute injury.
In extrahepatic bile duct (EHBD) cholangiopathies, including primary sclerosing cholangitis, a reactive cholangiocyte phenotype is associated with inflammation and epithelial hyperproliferation. The signaling pathways involved in EHBD injury response are poorly understood. In this study, we investigated the role of Hedgehog (HH) signaling and its downstream effectors in controlling biliary proliferation and inflammation after EHBD injury. Using mouse bile duct ligation as an acute EHBD injury model, we used inhibitory paradigms to uncover mechanisms promoting the proliferative response. HH signaling was inhibited genetically in Gli1-/- mice or by treating wild-type mice with LDE225. The role of neutrophils was tested using chemical (SB225002) and biological (lymphocyte antigen 6 complex locus G6D [Ly6G] antibodies) inhibitors of neutrophil recruitment. The cellular response was defined through morphometric quantification of proliferating cells and CD45+ and Ly6G+ immune cell populations. Key signaling component expression was measured and localized to specific EHBD cellular compartments by in situ hybridization, reporter strain analysis, and immunohistochemistry. Epithelial cell proliferation peaked 24 h after EHBD injury, preceded stromal cell proliferation, and was associated with neutrophil influx. Indian HH ligand expression in the biliary epithelium rapidly increased after injury. HH-responding cells and neutrophil chemoattractant C-X-C motif chemokine ligand 1 (CXCL1) expression mapped to EHBD stromal cells. Inhibition of HH signaling blocked CXCL1 induction, diminishing neutrophil recruitment and the biliary proliferative response to injury. Directly targeting neutrophils by inhibition of the CXCL1/C-X-C motif chemokine receptor 2/Ly6G signaling axis also decreased biliary proliferation. HH-regulated CXCL1 orchestrates the early inflammatory response and biliary proliferation after EHBD injury through complex cellular crosstalk.


Trans fat and cardiovascular disease mortality: Evidence from bans in restaurants in New York.
This paper analyzes the impact of trans fat bans on cardiovascular disease (CVD) mortality rates. Several New York State jurisdictions have restricted the use of ingredients containing artificial trans fat in food service establishments. The resulting within-county variation over time and the differential timing of the policy's rollout is used in estimation. The results indicate that the policy caused a 4.5% reduction in CVD mortality rates, or 13 fewer CVD deaths per 100,000 persons per year. The averted deaths can be valued at about $3.9 million per 100,000 persons annually.


Cytomegaloviruria in older infants in intensive care nurseries.
Over a four-month period, urine specimens for viral isolation were obtained weekly from all infants older than three weeks in two intensive care nurseries. These babies comprised 43% of the patients in the nurseries surveyed. Cytomegalovirus was cultured from 13 of 93 (14%) of these infants. Eleven of 13 infants who developed cytomegaloviruria were born prematurely, and nine of these 11 were found to be excreting CMV before they reached 40 weeks postconception. Infants excreting CMV received blood transfusions from a mean of 10.45 (+/- 1.80 SE) different donors versus 5.10 (+/- 0.55 SE) for infants without viruria (P less than 0.002) and five of 14 infants undergoing one or more exchange transfusions developed cytomegaloviruria (P less than 0.05). The possible role of other CMV reservoirs and the importance of these findings are discussed.


Long-term efficacy of antipsychotic drugs in initially acutely ill adults with schizophrenia: systematic review and network meta-analysis.
Most acute phase antipsychotic drug trials in schizophrenia last only a few weeks, but patients must usually take these drugs much longer. We examined the long-term efficacy of antipsychotic drugs in acutely ill patients using network meta-analysis. We searched the Cochrane Schizophrenia Group register up to March 6, 2022 for randomized, blinded trials of at least 6-month duration on all second-generation and 18 first-generation antipsychotics. The primary outcome was change in overall symptoms of schizophrenia; secondary outcomes were all-cause discontinuation; change in positive, negative and depressive symptoms; quality of life, social functioning, weight gain, antiparkinson medication use, akathisia, serum prolactin level, QTc prolongation, and sedation. Confidence in the results was assessed by the CINeMA (Confidence in Network Meta-Analysis) framework. We included 45 studies with 11,238 participants. In terms of overall symptoms, olanzapine was on average more efficacious than ziprasidone (standardized mean difference, SMD=0.37, 95% CI: 0.26-0.49), asenapine (SMD=0.33, 95% CI: 0.21-0.45), iloperidone (SMD=0.32, 95% CI: 0.15-0.49), paliperidone (SMD=0.28, 95% CI: 0.11-0.44), haloperidol (SMD=0.27, 95% CI: 0.14-0.39), quetiapine (SMD=0.25, 95% CI: 0.12-0.38), aripiprazole (SMD=0.16, 95% CI: 0.04-0.28) and risperidone (SMD=0.12, 95% CI: 0.03-0.21). The 95% CIs for olanzapine versus aripiprazole and risperidone included the possibility of trivial effects. The differences between olanzapine and lurasidone, amisulpride, perphenazine, clozapine and zotepine were either small or uncertain. These results were robust in sensitivity analyses and in line with other efficacy outcomes and all-cause discontinuation. Concerning weight gain, the impact of olanzapine was higher than all other antipsychotics, with a mean difference ranging from -4.58 kg (95% CI: -5.33 to -3.83) compared to ziprasidone to -2.30 kg (95% CI: -3.35 to -1.25) compared to amisulpride. Our data suggest that olanzapine is more efficacious than a number of other antipsychotic drugs in the longer term, but its efficacy must be weighed against its side effect profile.


Superiority of manual disinfection using pre-soaked wipes over automatic UV-C radiation without prior cleaning.
The efficacy of ultraviolet C (UV-C) radiation against a broad spectrum of micro-organisms has been demonstrated in several studies, but differences in the specific doses and the extent of microbial reduction were found. Furthermore, the conditions of laboratory tests differ greatly from reality, such that efficacy achieved in tests may not necessarily be assumed in reality. Consequently, it is important to investigate the effectiveness of UV-C in representative field trials. The aim was therefore to develop and establish a field test to evaluate automatic UV-C in comparison to manual disinfection. Before and after disinfection, samples were repeatedly collected from naturally highly contaminated surfaces using the swab technique to obtain representative data sets for disinfected and non-disinfected surfaces. Subsequently, the log reduction values (LRV) and the disinfection success were evaluated for UV-C radiation and full compliant manual disinfection using alcohol-based wipes. Surfaces that are naturally contaminated with bacteria on a regular and nearly uniform basis have been identified as particularly suitable for field testing. Mean contamination was reduced from 23.3 to 1.98 cfu/cm2 (LRV 0.9) and 29.7 to 0.26 cfu/cm2 (LRV 1.2) for UV-C and manual disinfection, respectively. UV-C disinfection achieved 75.5% successful disinfected surfaces, whereas manual disinfection showed 98.1%. Full compliant manual disinfection showed slightly higher LRVs and disinfection success than automatic UV-C disinfection. Successful, operator-independent UV-C disinfection still has the potential to improve disinfection performance in addition to manual disinfection.


Bilateral mechanical rotational vertebral artery occlusion.
Rotational vertebral artery occlusion, or bow hunter's stroke, is reversible, positional symptomatic vertebrobasilar ischemia. The typical mechanism of action is obstruction of a dominant vertebral artery with contralateral head rotation in the setting of baseline ipsilateral vertebral artery stenosis or occlusion. Here we present a rare case of mechanical occlusion of bilateral patent vertebral arteries manifesting as near syncope with rightward head rotation. Diagnostic cerebral angiography showed dynamic right C5 vertebral occlusion and left C2 vertebral occlusion. The patient underwent right C4/5 transverse process decompression. Postoperative angiogram showed patent flow through the right vertebral artery in neutral position and with head turn with resultant resolution of symptoms.


Affinity methods with lectins: a tool to identify canine alkaline phosphatase isoenzymes.
Affinity methods were used to characterize selective interactions of alkaline phosphatase (ALP) isoenzymes from different dog tissues with lectins. Specific lectins were used to identify liver, intestinal and steroid-induced ALP isoenzymes in serum from dogs with Cushing syndrome or steroid-treated dogs. For the first approach, 12 lectins were assayed by affinity dots. Selective interactions were found among wheat germ agglutinin (WGA), jacalin, con A (concanavalin A) and Helix pomatia agglutinin (HPA) and several ALP-containing samples. These four reactive lectins were assayed by line electrophoresis with lectins in holes. A strong reactivity of con A with all isoenzymes was found, although the patterns were different. WGA interacted with intestinal, bone marrow extracts and Cushing syndrome serum. Jacalin changed the electrophoretic patterns of intestinal and liver ALP, and Cushing serum. Finally, by crossed electrophoresis with lectins in gels, it was possible to distinguish among hepatic or intestinal ALPs and the steroid-induced isoenzyme in serum. Affinity electrophoresis with lectins provided a clear separation and identification of the different dog ALP isoenzymes.


Enhancement patterns and pseudo-washout of hepatic haemangiomas on gadoxetate disodium-enhanced liver MRI.
To compare the enhancement patterns and prevalence of pseudo-washout between rapidly and slowly enhancing hepatic haemangiomas on gadoxetate disodium-enhanced MRI in patients with chronic liver disease (CLD) and healthy liver (HL). On gadoxetate disodium-enhanced MRI, the extent of intralesional arterial enhancement >50 % and ≤ 50 % of lesions was defined as rapid and slow enhancement, respectively. The enhancement patterns and presence of pseudo-washout during the portal venous phase (PVP) and transitional phase (TP) of 74 hepatic haemangiomas were retrospectively evaluated in the CLD and HL groups. Sequential changes of signal-to-noise ratio (SNR) were measured in unenhanced phase, PVP and TP. Irrespective of hepatic health status, pseudo-washout in TP was significantly more common in the rapidly enhancing haemangiomas (p ≤ 0.026). In both groups, rapidly enhancing haemangiomas showed complete or progressive incomplete enhancement in PVP, which either lasted or transformed to pseudo-washout in TP, whereas slowly enhancing haemangiomas showed progressive incomplete enhancement in PVP and TP. SNR of hepatic parenchyma continued to rise until TP, whereas that of portal vein and haemangioma falls in TP. Regardless of CLD, pseudo-washout in TP was more common in rapidly than in slowly enhancing haemangiomas, with enhancement patterns differing in the two subgroups. On gadoxetate disodium-enhanced MRI, some hepatic haemangiomas show pseudo-washout in transitional phase. Regardless of chronic liver disease, pseudo-washout is significantly more common in rapidly enhancing haemangiomas. Rapidly enhancing haemangiomas show complete or progressive incomplete enhancement or pseudo-washout in TP. Slowly enhancing haemangiomas show progressive incomplete enhancement in portal venous phase and TP.


Structure-activity relationship homology (SARAH): a conceptual framework for drug discovery in the genomic era.
Extension of the traditional pharmacological approach of protein target classification to whole target systems has the potential to relate elements of protein sequence to the structure-activity relationship (SAR) of small molecules that can modulate protein action. Grouping potential drug discovery targets into families based on the relatedness of their SAR provides a means to translate the information from genome-sequencing efforts into knowledge that will aid in the discovery of drugs.


Salidroside Protects Acute Kidney Injury in Septic Rats by Inhibiting Inflammation and Apoptosis.
To clarify the protective effect and mechanism of salidroside (SLDS) on acute kidney injury (AKI) in septic rats. We pretreated rats with different doses of SLDS and analyzed the impact of SLDS on the survival of septic rats. We evaluated the levels of inflammatory factors in rats, the expression of NF-ƙB p65 in the kidney, and the apoptosis of kidney tubular epithelial cells (KTECs). SLDS significantly decreased the mortality of septic rats, and it reduced the levels of TNF-α, IL-1β, and IL-17A in plasma and kidneys and decreased the levels of serum creatinine, plasma renal injury molecule-1 and plasma neutrophil gelatin-associated lipocalin. Moreover, SLDS could significantly decrease the expression of NF-ƙB p65 in kidney tissues and the apoptotic number of KETCs, while reducing the mRNA levels of Caspase-3 and Bax mRNA, and increasing the level of Bcl-2 mRNA. SLDS pretreatment protects against AKI in septic rats by inhibiting the inflammation of kidney and the apoptosis of KTECs.


HspBP1 is a dual function regulatory protein that controls both DNA repair and apoptosis in breast cancer cells.
The Hsp70-binding protein 1 (HspBP1) belongs to a family of co-chaperones that regulate Hsp70 activity and whose biological significance is not well understood. In the present study, we show that when HspBP1 is either knocked down or overexpressed in BRCA1-proficient breast cancer cells, there were profound changes in tumorigenesis, including anchorage-independent cell growth in vitro and in tumor formation in xenograft models. However, HspBP1 did not affect tumorigenic properties in BRCA1-deficient breast cancer cells. The mechanisms underlying HspBP1-induced tumor suppression were found to include interactions with BRCA1 and promotion of BRCA1-mediated homologous recombination DNA repair, suggesting that HspBP1 contributes to the suppression of breast cancer by regulating BRCA1 function and thereby maintaining genomic stability. Interestingly, independent of BRCA1 status, HspBP1 facilitates cell survival in response to ionizing radiation (IR) by interfering with the association of Hsp70 and apoptotic protease-activating factor-1. These findings suggest that decreased HspBP1 expression, a common occurrence in high-grade and metastatic breast cancers, leads to genomic instability and enables resistance to IR treatment.


Clinical utility of ictal eyes closure in the differential diagnosis between epileptic seizures and psychogenic events.
The presence of ictal eye closure (IEC) has been considered to represent an additional clinical sign supporting the diagnosis of psychogenic non-epileptic events (PNEEs). We undertook a systematic review to evaluate sensitivity, specificity and likelihood ratios (LR) of IEC in the differential diagnosis between PNEEs and epileptic seizures. Six studies (total of 1496 events; 1021 epileptic seizures and 475 PNEEs) were included. Pooled accuracy measures of IEC for the diagnosis of PNEE were: sensitivity 58% (0.579) (95% CI 0.534-0.623), specificity 80% (0.895) (95% 0.875-0.9131)%, pLR 5.524 (95% CI 4.546-6.714) and nLR 0.47 (95% CI 0.422-0.524). However, a sensitivity analysis including only the studies performing an IEC assessment blinded to the diagnoses yielded results indicative of a rather low diagnostic value of IEC (pLR 3.056) compared with the analysis including unblinded studies (pLR 12.754). Further studies evaluating the occurrence of IEC through direct observation by means of video-EEG recording and blind to both EEG tracings and patient diagnosis are therefore required to definitely estimate the diagnostic utility of this sign in the differential diagnosis between epileptic seizures and PNEEs.


Essential role for the PKC target MARCKS in maintaining dendritic spine morphology.
Spine morphology is regulated by intracellular signals, like PKC, that affect cytoskeletal and membrane dynamics. We investigated the role of MARCKS (myristoylated, alanine-rich C-kinase substrate) in dendrites of 3-week-old hippocampal cultures. MARCKS associates with membranes via the combined action of myristoylation and a polybasic effector domain, which binds phospholipids and/or F-actin, unless phosphorylated by PKC. Knockdown of endogenous MARCKS using RNAi reduced spine density and size. PKC activation induced similar effects, which were prevented by expression of a nonphosphorylatable mutant. Moreover, expression of pseudophosphorylated MARCKS was, by itself, sufficient to induce spine loss and shrinkage, accompanied by reduced F-actin content. Nonphosphorylatable MARCKS caused spine elongation and increased the mobility of spine actin clusters. Surprisingly, it also decreased spine density via a novel mechanism of spine fusion, an effect that required the myristoylation sequence. Thus, MARCKS is a key factor in the maintenance of dendritic spines and contributes to PKC-dependent morphological plasticity.


Lymphatic changes in retroperitoneal lipomatosis.
Retroperitoneal lipomatosis is a condition in which excessive fat deposits in the retroperitoneum can exert a mass effect, with displacement of normal structures. In the case presented, it displaced lymph nodes and simulated adenopathy in nonopacified nodes. The specific diagnosis of retroperitoneal lipomatosis as the cause of the mass effect can be made by computerized tomography.


The impact of household fuel usage on adverse pregnancy outcomes in rural Ma'anshan City, Anhui Province: a birth cohort study.
The combustion of cooking fuels generates detrimental gases significantly impacting human health, particularly for vulnerable populations like expectant mothers. Prenatal exposure of such hazardous emissions raises the probability of adverse pregnancy outcomes, including preterm birth (PTB) and low birth weight (LBW). Our research aims to explore the association between cooking fuel utilization and adverse birth outcomes in rural Ma'anshan, Anhui Province. A prospective cohort study was executed, employing the Maternal and Infant Health Assessment questionnaire to classify fuels into clean (natural gas, electricity) and polluting energy sources (coal, coal gas, firewood). Multivariate logistic regression models were conducted to evaluate the association between fuel consumption and postpartum maternal and infant outcomes. Among the 442 surveyed pregnant women, 38.2% (N=169) utilized polluting fuels. After adjusting for covariates such as age and BMI, the relative risks of preterm birth, low birth weight, and postpartum hemorrhage in the polluting fuel group compared to the clean fuel group were OR: 3.27, 95% CI: 1.34, 8.00; OR: 3.50, 95% CI: 1.12, 10.90; and OR: 3.18, 95% CI: 1.06, 9.46, respectively. These results indicate that the usage of polluting fuels during pregnancy may heighten the risk of adverse birth outcomes. Consequently, additional research is advised to mitigate the harmful emissions generated by cooking fuels and advocate for clean energy adoption, enhancing maternal and infant well-being.


Defective transcription elongation in human cancers imposes targetable proteotoxic vulnerability.
Successful cancer therapy is contingent on identifying cancer-specific aberrant phenotypes and their associated vulnerabilities. We recently reported that a subset of almost every cancer type contains a genome-wide defect in RNA Polymerase II-mediated transcription elongation (TEdef), which impairs the expression of long genes and confers resistance to anti-tumor immune attack. Using a combination of computational analysis and laboratory experiments, we report that tumor cells with TEdef have widespread overexpression of the components of the protein homeostasis machinery (mostly composed of short genes), including protein folding and clearance. Accordingly, TEdef cells were characterized by abnormally high levels of insoluble protein aggregates in the cytoplasm and autophagy influx. We present evidence that TEdef cells exhibit impaired clearance of misfolded protein aggregates through the ubiquitin-proteasome system, and thus rely on autophagy for their degradation. As such, while these cells were highly resistant to proteasome inhibitors, they were acutely sensitive to inhibitors of autophagy in vitro and in vivo. This study reveals a major aberrant phenotype that is observed in ∼15-25% of all cancers and characterizes a unique cellular vulnerability that can be readily exploited in the clinic to improve treatment efficacy.


5' and 3' RACE Method to Obtain Full-Length 5' and 3' Ends of Ciona robusta Macrophage Migration Inhibitory Factors Mif1 and Mif2 cDNA.
The 5' and 3' RACE is a method to obtain full-length 5' and 3' ends of cDNA using known cDNA sequences from expressed sequence tags (ESTs), subtracted cDNA, differential display, or library screening. Here is described the identification of full-length 5' and 3' ends of Ciona robusta Mif1 and Mif2 cDNA by using 5' and 3' RACE method.


Cytogenetic observations on translocations in species A of the Anopheles gambiae complex.
The ovarian polytene chromosomes of females of species A of the Anopheles gambiae complex, from colonies suspected of containing heterozygous translocations, were examined. In three lines, the presence of translocations was confirmed and the chromosomes involved in the interchanges identified. The usefulness of cytogenetic methods for the detection of translocations is discussed.


[Effect of Acute Myeloid Leukemia Cells on the Proliferation and Apoptosis of Bone Marrow-Derived Mesenchymal Stromal Cells].
To investigate the effect of acute myeloid leukemia cells in leukemia-microenvironment on proliferation and apoptosis of bone marrow-derived mesenchymal stromal cells (BM-MSC). Acute myeloid leukemia (AML) murine models overexpressing MLL-AF9 were established. The number of BM-MSC of wild type (WT) and AML-derived mice were analyzed by flow cytometry. Morphology and growth differences between WT and AML-derived BM-MSC were analyzed by inverted fluorescence microscope. Proliferation and apoptosis of BM-MSC between these two groups were detected by Brdu and Annexin V/PI. Compared with WT-derived BM-MSC, the number and proliferation rate of AML-derived BM-MSC significantly increased (P<0.01, P<0.001), while apoptosis rate decreased (P<0.05). When cultured in vitro, BM-MSC grew faster under conditional medium. AML cells can promote proliferation and inhibit apoptosis of BM-MSC.


The parotid gland is the main source of human salivary epidermal growth factor.
To clarify the production of human epidermal growth factor (EGF) by different salivary glands, we measured its concentration by radioimmunoassay separately in whole saliva, in parotid gland (PG) saliva and in mixed submandibular (SMG) and sublingual gland (SLG) saliva. Also, we studied the presence of EGF in PG and SMG by immunohistochemistry. The mean (geometric) concentrations of EGF in PG saliva (2704 pg/ml, +/- SEM interval 2393-3056 pg/ml, n = 20) was higher (p less than 0.001) than in whole saliva (864 pg/ml, +/- 733-1019 pg/ml, n = 29), which in turn was higher (p less than 0.001) than in mixed SMG + SLG saliva (357 pg/ml, +/- 296-430 pg/ml, n = 16). No sex difference existed in any salivary gland EGF. Immunohistochemistry revealed EGF in the acinar cells of both PG and SMG, but only in PG there were prominent EGF deposits in luminal spaces. Our data suggest that EGF is produced by both PG and SMG, but that more of it is secreted from the PG. This result is new and challenges the general view that human salivary EGF is mainly from SMG. In mouse almost all salivary EGF comes from SMG and its amount is androgen dependent. Thus there are great differences in sources and regulation of salivary EGF between man and mouse.


Association of malaria and curable sexually transmitted infections with pregnancy outcomes in rural Burkina Faso.
Malaria and curable sexually transmitted infections (STIs) are severe infections associated with poor pregnancy outcomes in sub-Saharan countries. These infections are responsible for low birth weight, preterm birth, and miscarriage. In Burkina Faso, many interventions recommended by the World Health Organization were implemented to control the impact of these infections. After decades of intervention, we assessed the impact of these infections on pregnancy outcomes in rural setting of Burkina Faso. Antenatal care and delivery data of pregnant women attending health facilities in 2016 and 2017 were collected in two rural districts namely Nanoro and Yako, in Burkina Faso. Regression models with likelihood ratio test were used to assess the association between infections and pregnancy outcomes. During the two years, 31639 pregnant women received antenatal care. Malaria without STI, STI without malaria, and their coinfections were reported for 7359 (23.3%), 881 (2.8 %), and 388 (1.2%) women, respectively. Low birth weight, miscarriage, and stillbirth were observed in 2754 (10.5 %), 547 (2.0 %), and 373 (1.3 %) women, respectively. Our data did not show an association between low birth weight and malaria [Adjusted OR: 0.91 (0.78 - 1.07)], STIs [Adjusted OR: 0.74 (0.51 - 1.07)] and coinfection [Adjusted OR: 1.15 (0.75 - 1.78)]. Low birth weight was strongly associated with primigravidae [Adjusted OR: 3.53 (3.12 - 4.00)]. Both miscarriage and stillbirth were associated with malaria [Adjusted OR: 1.31 (1.07 - 1.59)], curable STI [Adjusted OR: 1.65 (1.06 - 2.59)], and coinfection [Adjusted OR: 2.00 (1.13 - 3.52)]. Poor pregnancy outcomes remained frequent in rural Burkina Faso. Malaria, curable STIs, and their coinfections were associated with both miscarriage and stillbirth in rural Burkina. More effort should be done to reduce the proportion of pregnancies lost associated with these curable infections by targeting interventions in primigravidae women.


Gambling and crime: An exploration of gambling availability and culture in an English prison.
There is evidence that prisoners have the highest rate of problem gambling in any population, but little is known about the nature of in-prison gambling, the motives for it or how it relates to prior gambling behaviour. To investigate the prevalence and type of gambling prior to prison and the prevalence, type, and reasons for gambling in prison. Two hundred and eighty-two male volunteers in a Category B male prison in England completed a questionnaire which included the Problem Gambling Severity Index (PGSI). One hundred and twenty-six (45%) reported gambling in prison, with eighty-one (30%) of participants reporting that gambling was a normal part of prison life. Pre-prison behaviour, whether type of index offence or prior gambling, had little relationship to in-prison gambling. Frequency of gambling in prison increased with increasing PGSI risk category. The most common types of gambling in prison were card/dice games, sports and ball games, while the most common motives were entertainment, excitement or sense of challenge and to win prizes, with significant differences in motive between PGSI risk categories. Prison canteen items formed the most common currency gambled. People within the higher PGSI risk category were more likely to have borrowed items from other prisoners. Our research has added to existing literature by identifying high rates of gambling in prison and showing that prisoners' perceptions of gambling are as a normal part of prison life. Findings suggest that screening and support should be available to manage gambling in prison, including support to reduce gambling-related debt, particularly given associations between debt and violence in prison. Relief from boredom and need for excitement were among the most common reasons for gambling in prison, indicating that there is a need to provide a more appropriately stimulating prison environment.


Oropharyngeal dysphagia: manifestations and diagnosis.
Swallowing disorders (dysphagia) have been recognized by the WHO as a medical disability associated with increased morbidity, mortality and costs of care. With increasing survival rates and ageing of the population, swallowing disorders and their role in causing pulmonary and nutritional pathologies are becoming exceedingly important. Over the past two decades, the study of oropharyngeal dysphagia has been approached from various disciplines with considerable progress in understanding its pathophysiology. This Review describes the most frequent manifestations of oropharyngeal dysphagia and the clinical as well as instrumental techniques that are available to diagnose patients with dysphagia. However, the clinical value of these diagnostic tests and their sensitivity to predict outcomes is limited. Despite considerable clinical research efforts, conventional diagnostic methods for oropharyngeal dysphagia have limited proven accuracy in predicting aspiration and respiratory disease. We contend that incorporation of measurable objective assessments into clinical diagnosis is needed and might be key in developing novel therapeutic strategies.


Correlation of left ventricular myocardial work indices with invasive measurement of stroke work in patients with advanced heart failure.
This study aimed to explore the correlation between left ventricular (LV) myocardial work (MW) indices and invasively-derived LV stroke work index (SWI) in a cohort of patients with advanced heart failure (AHF) considered for heart transplantation. Left ventricular MW has emerged as a promising tool for diagnostic and prognostic purposes in heart failure (HF) but its relationship with hemodynamic data derived from right heart catheterization (RHC) has not been assessed in patients with advanced heart failure yet. Consecutive patients with AHF considered for heart transplantation from 2016 to 2021 performing RHC and echocardiography as part of the workup were included. Conventional LV functional parameters and LV MW indices, including LV global work index (GWI), LV global constructive work (GCW), LV global wasted work (GWW), LV global work efficiency (GWE), and other were calculated and compared with invasively-measured LV SWI. The population included 44 patients. Median time between RHC and echocardiography was 0 days (IQR: 0-24). Median age was 60 years (IQR: 54-63). For the most part, etiology of HF was non-ischemic (61.4%) and all patients were either on class NYHA II (61.4%) or III (27.3%). Median left ventricular ejection fraction was 25% (IQR: 22.3-32.3), median NT-proBNP 1,377 pg/ml (IQR: 646-2570). LV global longitudinal strain (GLS) significantly correlated with LV SWI (r = -0.337; p = 0.031), whereas, LV ejection fraction (EF) did not (r = 0.308; p = 0.050). With regard to LV MW indices, some of them demonstrated correlation with LV SWI, particularly LV GWI (r = 0.425; p = 0.006), LV GCW (r = 0.506; p = 0.001), LV global positive work (LV GPW; r = 0.464; p = 0.003) and LV global systolic constructive work (GSCW; r = 0.471; p = 0.002). Among LV MW indices, LV GCW correlated better with invasively-derived SWI, potentially representing a powerful tool for a more comprehensive evaluation of myocardial function.


Blocking CTGF-Mediated Tumor-Stroma Interplay in Pancreatic Cancer.
As the major feature of pancreatic ductal adenocarcinoma (PDAC), desmoplastic stroma poses a significant obstacle for treatment. Recent studies revealed that connective tissue growth factor (CTGF) aggravates the fibrotic environment and drives cancer initiation and progression, thus suggesting CTGF as a novel target for PDAC treatment.


National Evaluation of Hospital Performance on the New Commission on Cancer Melanoma Quality Measures.
To increase adherence to cancer management guidelines, the Commission on Cancer (CoC) developed and approved five melanoma quality measures in 2015. Our objectives were to evaluate formally the national performance of these melanoma measures and to examine patient, tumor, and hospital characteristics associated with adherence. From the National Cancer Data Base (2012), patients with invasive, nonmetastatic melanoma were identified. Inclusion and exclusion criteria were based on the CoC definition for each measure. Patient-level and hospital-level adherence rates were calculated for the five measures. A hospital was deemed "compliant" if it met the CoC standard, which requires 80 % of patients to receive the measure-specific recommended care. Patient, tumor, and hospital characteristics potentially associated with higher likelihood of adherence at the patient-level were estimated using hierarchical random-effects logistic regression models. A total of 31,598 patients from 1343 hospitals were examined. Patient-level adherence rates varied from 31.6 % (Measure 5: ≥10 axillary lymph nodes removed/examined) to 72.6 % (Measure 1: sentinel lymph node biopsy (SLNB) appropriateness measure). Hospital-level adherence rates, ranged from 19.3 % of hospitals (N = 538 hospitals for Measure 5) to 44.8 % of hospitals (N = 1090 hospitals for Measure 3: completion lymph node dissection after positive SLNB). No hospital-level factors (e.g., teaching status) were consistently associated with better adherence. National adherence rates to the five new CoC melanoma quality metrics are low, and most hospitals would not meet the CoC requirement of 80 % adherence. Feedback for performance of these measures to hospitals, decisions support tools, and educational initiatives are needed to improve guideline adherence.


A new method for targeted drug delivery using polymeric microcapsules: implications for treatment of Crohn's disease.
Recent research and clinical evidence suggest that thalidomide could potentially be used to treat inflammation associated with Crohn's disease. However, systemic side effects associated with large doses of this drug have limited its widespread use. Treatment with thalidomide would prove more efficacious if the drug could be delivered directly to target areas in the gut, thereby reducing systemic circulation. Microcapsule encapsulation could enable direct delivery of the drug. To assess the latter, we designed and tested drug-targeting release characteristics of alginate-poly-L-lysine-alginate (APA) microcapsules in simulated gastrointestinal environments. The results show that APA capsules enabled delivery of thalidomide in the middle and distal portions of the small intestine. We also compared the APA membrane formulation with an earlier designed alginate chitosan (AC) membrane thalidomide formulation. The results show that both APA and AC capsules allow for successful delivery of thalidomide in the gut and could prove beneficial in the treatment of Crohn's disease. However, further research is required.


The National Provider Identifier Taxonomy: Does it Align With a Surgeon's Actual Clinical Practice?
The taxonomy code(s) associated with each National Provider Identifier (NPI) entry should characterize the provider's role (e.g., physician) and any specialization (e.g., orthopedic surgery). While the intent of the taxonomy system was to monitor medical appropriateness and the expertise of care provided, this system is now being used by researchers to identify providers and their practices. It is unknown how accurate the taxonomy codes are in describing a provider's true specialization. Department websites of orthopedic surgery and general surgery from three large academic institutions were queried for practicing surgeons. The surgeon's specialty and subspeciality information listed was compared to the provider's taxonomy code(s) listed on the National Plan and Provider Enumeration System (NPPES). The match rate between these data sources was evaluated based on the specialty, subspecialty, and institution. There were 295 surgeons (205 general surgery and 90 orthopedic surgery) and 24 relevant taxonomies (8 orthopedic and 16 general or plastic) for analysis. Of these, 294 surgeons (99%) selected their general specialty taxonomy correctly, while only 189 (64%) correctly chose an appropriate subspecialty. General surgeons correctly chose a subspecialty more often than orthopedic surgeons (70 versus 51%, P = 0.002). The institution did not affect either match rate, however there were some differences noted in subspecialty match rates inside individual departments. In these institutions, the NPI taxonomy is not accurate for describing a surgeon's subspecialty or actual practice. Caution should be taken when utilizing this variable to describe a surgeon's subspecialization as our findings might apply in other groups.


Chloropyrimidines as a new class of antimicrobial agents.
In the course of our investigations of pyrimidines as antimycotic agents, we have identified a sub-class, with significant in vitro activity against mycobacteria. The salient feature of these pyrimidine derivatives (3a-o and 7a,b) is their appended aryl, heteroaryl and alkylthio substituent at position 6 and also alkylthio substituent at position 2. The rational design, synthesis, and evaluation of the in vitro antibacterial activity against six pathogenic bacteria including virulent and non-virulent strains of Mycobacterium tuberculosis is described. Some of the synthesized compounds (3c, 3h, 3i, 3o) have displayed only potent in vitro antimycobacterial activity with MIC of 0.75 microg/mL except 3i which also demonstrated activity against Escherichia coli at 12.5 microg/mL concentration. Only two compounds, 3a and 3b, demonstrated antibacterial activity against Pseudomonas aeruginosa and E. coli with MIC 12.5 microg/mL. All the synthesized compounds were also evaluated for their antimycotic activity against five pathogenic fungi but only some of them 3j-n and 7a,b were found most potent against Aspergillus fumigatus and Trichophyton mentagrophytes.


Cyclic population changes in three mouse species in the same woodland.
In two forest areas of West Berlin the population-changes in three mouse species have been investigated over 28 years (1952-1979). Significant changes in absolute density have been established for the Short-Tailed Vole (Microtus agrestis) at 5-year intervals, for the Common Vole (Microtus arvalis) at 4-year intervals, and for the Yellow-Necked Field Mouse (Apodemus flavicollis) at 3-year intervals. The investigations were based on a total of 43,535 small vertebrates, 90% of which had been found in the pellets of breeding Tawny Owls. The remaining 10% belonged to pellets collected in the territories of breeding Long-Eared Owls. It is assumed that, for those prey animals whose percentage in the total prey of a predator is fairly high, the percentage proportionally approximates the real fluctuations in their (absolute) density.


Hypersensitivity of DNA in transcriptionally active chromatin to ionizing radiation.
We have examined the size distribution of single-strand fragments of total 3H-labeled DNA and of DNA sequences complementary to specific probes in gamma-irradiated and unirradiated mouse L929 cells. Those DNA sequences which hybridize to rDNA or to poly(A+)RNA have lower number average molecular weights and sustain 5--6-times the number of single-strand breaks as do satellite DNA sequences or the bulk DNA. We therefore conclude that transcriptionally active DNA sequences are more susceptible to ionizing radiation-induced damage than are inactive sequences, and suggest that these differential susceptibilities are a likely consequence of differences in their chromatin organization.


Novel Diagnostic Autoantibodies Against Endothelial Protein C Receptor in Patients With Ulcerative Colitis.
There have been many reports on serologic autoantibodies in inflammatory bowel diseases (IBD),1 consisting of ulcerative colitis (UC) and Crohn's disease (CD), and recently Kuwada et al2 reported a new autoantibody against integrin αvβ6 with high sensitivity and specificity for UC. Concurrently, we had discovered autoantibodies against endothelial protein C receptor (EPCR) in Takayasu arteritis (TAK), which is sometimes complicated by UC.3 Interestingly, this autoantibody was found in most patients with TAK associated with UC, and we found that the positivity rate in patients with UC without TAK was also high, suggesting that anti-EPCR antibody is a candidate autoantibody useful for the diagnosis of UC.4 To clarify the diagnostic usefulness of anti-EPCR antibodies in patients with IBD and their relationship to several disease subphenotypes and their disease activities, we analyzed the serum samples from patients with IBD and non-IBD control subjects in Japan and the United States.


Atrial natriuretic peptide negatively regulates follicle-stimulating hormone-induced porcine oocyte maturation and cumulus expansion via cGMP-dependent protein kinase pathway.
This study examined the effect of atrial natriuretic peptide (ANP) on porcine cumulus-enclosed oocyte (CEO) maturation and cumulus expansion. ANP negatively regulated follicle-stimulating hormone (FSH)-stimulated germinal vesicle breakdown (GVBD; 90.1, 81.2 and 68.2% for FSH, FSH+10nM ANP and FSH+1 microM ANP, respectively), first polar body emission (PB1; 86.1, 75.3 and 53.3% for FSH, FSH+1 nM ANP and FSH+1 microM ANP, respectively) and cumulus expansion (CEI; 3.47, 3.16 and 2.43 for FSH, FSH+1 nM ANP and FSH+1 microM ANP, respectively) in a dose-dependent manner when CEOs were cultured in the maturation medium containing porcine follicular fluid (pFF). This negative effect showed a time-dependent manner after preincubation with 100 nM ANP for 5h (78.4% PB1), 10h (81.7% GVBD and 74.1% PB1), 20 h (78.5% GVBD and 68.9% PB1), and 44 h (75.3% GVBD and 60.5% PB1), respectively. ANP also significantly inhibited FSH-induced porcine oocyte GVBD (47.6% versus 83.8%) and PB1 emission (22.4% versus 45.2%) when CEOs were cultured in pFF-free maturation medium. cGMP analog 8-Br-cGMP (10 microM to 1mM) mimicked the effects of ANP on GVBD, PB1, and CEI. The negative effect of ANP was completely reversed by KT5823 (a specific inhibitor of cGMP-dependent protein kinase), while C-ANP-(4-23) (an analogue of ANP and specific binder for natriuretic peptide receptors-C) was ineffective in oocyte maturation. Neither ANP nor C-ANP-(4-23) had an effect on spontaneous porcine oocyte maturation and cumulus expansion. These results suggested that ANP negatively regulates FSH-activated porcine oocyte meiotic resumption, meiotic maturation and cumulus expansion. The function of ANP on porcine oocyte maturation is via the cGMP dependent protein kinase (PKG) pathway.


Left ventricle assist devices and driveline's infection incidence: a single-centre experience.
Different left ventricular assist devices (LVADs) are provided of different driveline exit sites: HeartWare HVAD presents abdominal power-cable-supply, while the Jarvik 2000 LVAD is powered by a retroauricular driveline. We analyzed 93 LVAD-implanted patients from January-2009 to October-2016 (41 HeartWare and 52 Jarvik 2000), hypothesizing a different incidence of infection, according to driveline exit site. The two populations were propensity matched for the demographic data and preoperative variables, and the outcomes were further analyzed. Nine driveline infections (DLIs) were in each LVAD group recorded (22% for HVAD and 17% for Jarvik 2000). The incidence of the complication was similar between groups (p = 0.97), even during time (p = 0.27 within 6 months and p = 0.16 over 6 months of support). Age at implant (p = 0.01), revision for bleeding (p = 0.05), days of postoperative intubation (p = 0.002), and ICU stay (p < 0.001), as well as days on device (p < 0.001) were identified as risk factors for DLIs. The type of device and the driveline exit site were not statistically co-related to infections. Similar infection-freedom survival was identified (p = 0.87). Younger age at implant, revision for bleeding, prolonged mechanical ventilation, delayed rehabilitation, as well as long time LVAD support were identified as risk factors for exit site DLIs. Despite similar incidence of DLIs, the different management and care of the retroauricular exit site makes it more appropriate and comfortable in long-term support.


HDL particle size: a marker of the gender difference in the metabolic risk profile.
A low plasma HDL-cholesterol concentration is an important risk factor for coronary heart disease (CHD) and is often accompanied by increased triglyceride concentrations. Women have generally higher HDL-cholesterol and lower triglyceride concentrations and concomitantly are at lower risk of CHD than men. As HDL particle size is a new and potentially important marker of CHD risk, we have examined the potential gender difference in HDL particle size, assessed by nondenaturing 4-30% polyacrylamide gradient gel electrophoresis, in a sample of men (n=231) and women (n=183). Overall, men were characterized by a less favorable lipoprotein--lipid profile, which was accompanied by smaller HDL particle size compared to women. However, when men and women were matched for HDL particle size and compared for their metabolic profile, it was found that both genders were characterized by similar plasma lipoprotein--lipid profile despite the fact that women were characterized by higher levels of total body fat but lower waist girth than men. In summary, HDL particle size is a strong marker of the gender-related difference in the determination of the metabolic risk profile.


[Increase of body mass and risk of hypertension in pregnancy].
Hypertension in pregnancy is one of the reasons of high rate of perinatal risk. In case of women with high BMI, the rate of hypertension is higher than in pregnant women with normal BMI. The etiology and the role of the environmental factors remain unknown. The main aim of the study was to assess the influence of high BMI before pregnancy on the risk of hypertension in pregnancy and body mass gain in pregnancy and the frequency of hypertension. The study was conducted in 2005-2007 in 126 women treated in High Risk Pregnancy Medical University Lodz. The study group consisted of 33 pregnant women with hypertension and normal weight and 35 hypertensive obese women. Control groups constituted 27 pregnant normal weight and normotensive women and 31 obese normotensive pregnant women. Pregnancy body mass index, body mass gain in pregnancy and frequency of hypertension were estimated. Mean value of BMI before pregnancy and in III trimester of pregnancy in pregnant women with normal BMI did not differ in study and control group. In pregnant obese women the rate of hypertension was higher in case of higher BMI. The body mass gain during pregnancy in normal weight women is higher in the group where hypertension occurs, if compared with normotensive women. The risk factor of hypertension for normal weight women is a high body mass gain during pregnancy. In obese women the risk of hypertension in pregnancy is high but not correlated with body mass gain during pregnancy.


A plasma cytokine and angiogenic factor (CAF) analysis for selection of bevacizumab therapy in patients with metastatic colorectal cancer.
This study intends to identify biomarkers that could refine the selection of patients with metastatic colorectal cancer (mCRC) for bevacizumab treatment. Pretreatment 36 plasma cytokines and angiogenic factors (CAFs) were first measured by protein microarray analysis in patients who received first-line bevacizumab-containing therapies (discovery cohort, n = 64), and further evaluated by enzyme-linked immunosorbent assay in patients treated on regimens with or without bevacizumab (validation cohort, n = 186). Factor levels were correlated with clinical outcomes, predictive values were assessed using a treatment by marker interaction term in the Cox model. Patients with lower pretreatment levels of hepatocyte growth factor (HGF) or VEGF-A(121) gain much more benefit from bevacizumab treatment as measured by progression-free survival (PFS) and overall survival (OS), while angiopoietin-like 4 (ANGPTL4) levels negatively correlated with PFS and response rate following bevacizumab (all adjusted interaction P < 0.05). A baseline CAF signature combining these three markers has greater predictive ability than individual markers. Signature-negative patients showed impaired survival following bevacizumab treatment (PFS, 7.3 vs 7.0 months; hazard ratio [HR] 1.03; OS, 29.9 vs 21.1 months, HR 1.33) compared with signature-positive patients (PFS, 6.5 vs 11.9 months, HR 0.52; OS, 28.0 vs 55.3 months, HR 0.67). These promising results warrant further prospective studies.


Inter-Ligand Energy Transfer Process in an Ir-Complex with Expanding π-Conjugated Ligand.
The inter-ligand energy transfer (ILET) process in heteroleptic iridium complex, [Ir(dfppy)2 (bpy-Im2 )]+ , where dfppy=2-(2,4-difluorophenyl)pyridine and bpy-Im2 =4,4'-bis(1,2-diphenyl-1H-benzo[d]imidazole)-2,2',-bipyridine, was investigated using a femtosecond transient absorption (fs-TA) spectroscopic technique. The photophysical properties of [Ir(dfppy)2 (bpy-Im2 )]+ with significantly expanding π-conjugated ligand are compared to those of [Ir(dfppy)2 (bpy)]+ (bpy=2,2'-bipyridine) and a free bpy-Im2 ligand. The emission spectrum of [Ir(dfppy)2 (bpy-Im2 )]+ shows no shift upon changing the solvent polarity, whereas the free ligand bpy-Im2 showed bathochromic fluorescence shifts with increasing solvent polarity, which is attributed to intramolecular charge transfer (ICT). The unique photophysical properties of [Ir(dfppy)2 (bpy-Im2 )]+ are due to the fast ILET process from 3 MLCTdfppy to 3 MLCT/3 LCbpy-Im2 , resulting in the phosphorescence emission originating from 3 MLCT/3 LCbpy-Im2 . On the other hand, the TA bands of bpy-Im2 are observed at 540 and 480 nm, corresponding to the singlet and triplet manifolds, respectively. In contrast, the TA spectrum of [Ir(dfppy)2 (bpy-Im2 )]+ showes broad bands centered at 420 and 600 nm, attributed to the transitions from 3 MLCTdfppy and 3 MLCT/3 LCbpy-Im2 , respectively. Time-resolved spectroscopic results confirm the efficient ILET dynamics from 3 MLCTdfppy to 3 MLCT/3 LCbpy-Im2 in [Ir(dfppy)2 (bpy-Im2 )]+ . From the relaxation times determined by singular value decomposition analysis and simple sequential kinetic model, we infer that the ILET process from 3 MLCTdfppy to 3 MLCT/3 LCbpy-Im2 occurs with a time constant of ca. 4 ps. The presented results in this study show that the introduction of an expanding π-conjugated ligand can lead to the efficient ILET dynamics for improving the OLED performance.


Assessment of the prognostic value of the World Health Organization clinical staging system for HIV/AIDS in HIV-infected children and adolescents in a cohort in Belo Horizonte, Brazil.
This study aimed to evaluate the prognostic value of WHO clinical staging system in HIV-infected children and adolescents in Belo Horizonte, Brazil. WHO clinical stages were evaluated for risk of disease progression in 335 patients admitted from 1989 to 2003. In Kaplan-Meier analysis, age, clinical stage, CD4% <15% and viral load >5 log(10) were statistically significant. In Cox proportional hazards model, the relative risk of disease progression for Stage 4 at admission and in the worst moment were 3.47 [confidence interval (CI) 95% CI = 1.92-6.26] and 2.89 (95% CI = 1.44-5.79). Stages 2 and 3 were neutral as predictors of risk either of disease progression. CD4% <15% and viral load > 5 log(10) remained statistically significant in multivariate analysis. WHO clinical Stage 4 was a good predictor of risk of progression in this cohort. The findings support WHO proposition to start antiretroviral treatment for patients at a more advanced clinical stage.