[Carcinoma hepatoides of the stomach --case report and literature review].
Hepatoid differentiation in neoplastic tumors occurs not only in primary hepatic carcinoma but also in other malignant tumors, especially carcinomas. Stomach is the most frequent site of such tumors. Usually, at the time of diagnosis liver metastases are found and it is difficult to establish what was the primary site of hepatoid-like carcinoma. 83-year-old man was admitted to the hospital due to upper gastrointestinal haemorrhage. Beside weight loss (11 kg during the period of 3 months) he did not complain of any symptoms. Urgent gastroscopy revealed in the middle portion of the gastric corpus two ulcers 12 and 3 mm in diameters and just above them polyp 1.5 cm in diameter. The other parts of gastrointestinal tract were normal. Neoplastic infiltration of the whole thickness of the gastric wall was found in the histopathologic examination of the specimens taken from all these lesions. The lesion consisted of the hepatocyte-like cells with the droplets of bile visible among them. Morphological examination and immunohistochemical results (CKMNF+, CKhepatocyte+, Vimentin and CD68 negative) were consistent with very rare hepatoid type of gastric cancer--carcinoma hepatoides. The following investigations (USG, CT) showed tumor in the II, III and IV segments of the liver and thromboses in the left branch of vena porta and middle hepatic vena. The serum level of AFP was high (5837 ng/l). The possibility of gastric infiltration by primary hepatic tumor and primary gastric hepatoides carcinoma were considered in the differential diagnosis. Morphological characteristics of primary hepatic carcinoma may be identical with primary gastric hepatoides carcinoma. When the biopsy specimens are very small even immunohistochemical examination does not allow to establish the diagnosis.


Localized overexpression of alpha-internexin within nodules in multinodular and vacuolating neuronal tumors.
Multinodular and vacuolating neuronal tumors (MVNT) have been recently referred to as a distinctive neuronal tumor entity based on histopathological findings. They are characterized by multiple tumor nodules, vacuolar alteration and widespread immunolabeling for human neuronal protein HuC/HuD. Only 13 cases have been reported in the literature to date and little is known about the histopathology of these tumors. Herein, we report a case of MVNT with additional confirmation of immunohistochemical features. A 22-year-old woman presented with a continuous headache. MRI showed a subcortical white matter lesion with multiple satellite nodules in the frontal lobe appearing as T2/fluid-attenuated inversion recovery (FLAIR) hyperintensities. Histological examination of the resected lesion revealed well-defined multiple nodules composed of predominant vacuolating tumor cells. The tumor cells exhibited consistent immunolabeling for doublecortin, as well as HuC/HuD, both representative neuronal biomarkers associated with earlier stages of neuronal development. Immunopositivity for oligodendrocyte transcription factor 2 (Olig2) and S100 was also detected in tumor cells. Additionally, significant overexpression of alpha-internexin was observed in the background neuropil limited to tumor nodules. Neuronal nuclear antigen (NeuN), synaptophysin and neurofilament, markers for mature neurons, were either negative or weakly positive. The expression profile of neuronal biomarkers can be distinguished from that of classic neuronal tumors and is the immunohistochemical hallmark of MVNT. In summary, we identified the characteristic tumoral expression of HuC/HuD and doublecortin and the presence of abundant neuropil localized in MVNT tumor nodules, which exhibited widespread alpha-internexin expression. These results supported the presumption that MVNT is a distinct histopathological entity.


A phase 2 study of dalantercept, an activin receptor-like kinase-1 ligand trap, in patients with recurrent or metastatic squamous cell carcinoma of the head and neck.
Patients with platinum-refractory, recurrent or metastatic squamous cell carcinoma of the head and neck (RM-SCCHN) have limited options. Activin receptor-like kinase 1 (ALK1) is a type I receptor of the transforming growth factor β superfamily expressed on activated endothelial cells. Dalantercept is an ALK1 receptor fusion protein that acts as a ligand trap to block signaling through ALK1 and inhibits stages of angiogenesis involved in blood vessel maturation and stabilization. In a phase 1 study, dalantercept demonstrated clinical activity in patients with RM-SCCHN. The objective of the current study was to evaluate the activity of dalantercept in RM-SCCHN. Forty-six patients received dalantercept at doses of 80 mg (n = 2), 0.6 mg/kg (n = 13), or 1.2 mg/kg (n = 31) subcutaneously every 3 weeks. The primary endpoint was the overall response rate according to Response Evaluation Criteria in Solid Tumors (RECIST version 1.1). Secondary endpoints included progression-free survival and overall survival, safety and tolerability, and pharmacokinetic and pharmacodynamic assessments. Forty patients were evaluable for response (13 who received dalantercept 0.6 mg/kg and 27 who received dalantercept 1.2 mg/kg). The overall response rate was 5% (n = 2), and 35% of patients had stable disease; 44% of patients who received 1.2 mg/kg and 30.8% of those who received 0.6 mg/kg achieved disease control (partial response or stable disease). The median progression-fee survival was 1.4 months (95% confidence interval, 1.3-2.2 months), and the median overall survival was 7.1 months (95% confidence interval, 5.5-11.1 months). Drug-related adverse events (>15%) were anemia, fatigue, peripheral edema, headache, and hyponatremia. In an unselected, heavily pretreated population of patients with RM-SCCHN, dalantercept monotherapy resulted in a favorable safety profile but only modest dose-dependent activity, and it did not meet the primary efficacy objective of the study. Cancer 2016;122:3641-9. © 2016 American Cancer Society.


Tissue Non-Specific Genes and Pathways Associated with Diabetes: An Expression Meta-Analysis.
We performed expression studies to identify tissue non-specific genes and pathways of diabetes by meta-analysis. We searched curated datasets of the Gene Expression Omnibus (GEO) database and identified 13 and five expression studies of diabetes and insulin responses at various tissues, respectively. We tested differential gene expression by empirical Bayes-based linear method and investigated gene set expression association by knowledge-based enrichment analysis. Meta-analysis by different methods was applied to identify tissue non-specific genes and gene sets. We also proposed pathway mapping analysis to infer functions of the identified gene sets, and correlation and independent analysis to evaluate expression association profile of genes and gene sets between studies and tissues. Our analysis showed that PGRMC1 and HADH genes were significant over diabetes studies, while IRS1 and MPST genes were significant over insulin response studies, and joint analysis showed that HADH and MPST genes were significant over all combined data sets. The pathway analysis identified six significant gene sets over all studies. The KEGG pathway mapping indicated that the significant gene sets are related to diabetes pathogenesis. The results also presented that 12.8% and 59.0% pairwise studies had significantly correlated expression association for genes and gene sets, respectively; moreover, 12.8% pairwise studies had independent expression association for genes, but no studies were observed significantly different for expression association of gene sets. Our analysis indicated that there are both tissue specific and non-specific genes and pathways associated with diabetes pathogenesis. Compared to the gene expression, pathway association tends to be tissue non-specific, and a common pathway influencing diabetes development is activated through different genes at different tissues.


EEG Based Cortico-Muscular Connectivity During Standing Early Post Stroke.
In this exploratory study we studied brain activation and corticomuscular connectivity during standing in healthy individuals and persons with stroke within 40 days of cerebrovascular accident (CVA). EEG and EMG data were acquired during standing and analysis showed a trend of higher EEG power (hyper activation) in the stroke group. Direct corticomuscular connectivity between sensorimotor cortices and contralateral lower extremity muscles showed lower connectivity between affected motor, premotor, and sensory cortices, and contralateral lower extremity peripheral muscles with moderate effect size. The preliminary data in this paper suggest re-organization in left sensorimotor cortex role in controlling contralateral lower extremity muscles during standing. Correlational analysis in stroke group within 40 days of CVA showed a relationship between higher corticomuscular connectivity and better scores on balance assessments.Clinical Relevance- This study evaluates corticomuscular connectivity during standing in healthy controls and individuals with subacute stroke (within 40 days of injury). Better understanding of cortical control of standing post stroke is important to improve strategies used in mobility rehabilitation.


Combination of the tumor angiogenesis inhibitor bevacizumab and intratumoral oncolytic herpes virus injections as a treatment strategy for human gastric cancers.
Advanced gastric cancer is difficult to treat due to the frequency of liver metastases and peritoneal dissemination. A combination of two new strategies, including the anti-angiogenesis inhibitor bevacizumab and an oncolytic herpes virus is a promising treatment for advanced cancer. The effects of bevacizumab on oncolytic herpes virus replication and viral cytotoxicity were examined at varying bevacizumab concentrations and viral titers. In addition, the ability of these two new promising anticancer agents to inhibit tumor growth was studied. Histological examinations of CD31 and LacZ were used to assess angiogenesis and virus distribution within the tumor, respectively. Bevacizumab did not affect viral replication or viral cytotoxicity in vitro. The combination of bevacizumab and the oncolytic herpes virus hrR3 significantly reduced tumor growth in vivo in an experimental gastric cancer model. Bevacizumab inhibited angiogenesis caused by local injection of hrR3 and induced virus spread. Bevacizumab increased the distribution of the intratumorally injected oncolytic herpes virus within the tumor. Combination therapy consisting of bevacizumab and an oncolytic herpes virus is a promising new treatment strategy for gastric cancer.


Regulation of bacterial glycogen synthesis.
The formation of the alpha 1,4 glucosidic linkages of bacterial glycogen occurs first by synthesis of ADPglucose from ATP and alpha glucose 1-P and then transfer of the glucose moiety from the formed sugar nucleotide to a pre-existing glucan primer. Unlike mammalian glycogen synthesis, regulation occurs at the synthesis of the sugar nucleotide. Generally glycolytic intermediates activate ADPglucose synthesis while AMP, ADP and/or Pi inhibit ADPglucose synthesis. A variation of activator specificity is is seen when the enzyme is isolated from different bacteria and is thought to be related to the predominant type of carbon assimilation or dissimilation pathways present in the particular organism. Evidence indicating that the allosteric activation effects observed in vitro are physiologically pertinent for the regulation of glycogen synthesis is reviewed. The recent experiments in identifying the allosteric activator site of the Escherichia coli ADPglucose pyrophosphorylase as well as other chemical modification studies identifying amino acid residues essential for allosteric activation and for catalytic activity are discussed. Evidence is also presented for the covalent modification of the Rhodopseudomonas sphaeroides ADPglucose pyrophosphorylase by bromopyruvate at its allosteric activator site. Regulation of the biosynthesis of glycogen also occurs at the genetic level and the current evidence for the existence of a glycogen operon is presented. In addition the current studies concerning the cloning of the DNA region containing the Escherichia coli structural genes coding for the glycogen biosynthetic enzymes as well as the nucleotide sequence of the E. coli ADPglucose pyrophosphorylase are presented.


[Start of an adult living donor liver transplantation program in Switzerland].
The shortage of cadaver organs has prompted transplant centres to seek new sources of grafts. While living-donor left lobe transplantation (segments II and III) is an established procedure for children, living donor right liver transplantation (segments V, VI, VII, VIII), which can provide adequate liver mass for an average-sized adult patient, is technically more demanding and potentially associated with higher risks for the donor. In view of the permanent shortage of organs in Switzerland, we started an adult living donor liver transplantation programme in 1999 with the approval of the Clinical Ethics Committee of Geneva University Hospitals. Donor evaluation was performed only after the recipient had been officially registered for transplantation in the national waiting list. Preoperative evaluation consisted of a preliminary information phase with blood tests and Doppler ultrasonography, a second phase with radiological non invasive investigations (CT scan with volume measurements, magnetic resonance cholangiography) and a third phase including liver biopsy and angiography. A formal psychiatric evaluation was performed in all cases and detailed consent was required. Eight potential donors were investigated, 5 were not retained because of too small right liver or steatosis, and 3 were accepted (wife, son, sister). Living-donor hepatectomy was performed without interrupting the vascular blood flow. The liver graft was perfused ex-situ with University of Wisconsin solution. The grafts were anastomosed to the preserved vena cava of the recipient and the portal and arterial anastomoses were performed without interposition grafts, with short cold ischaemic times in the 3 cases. The graft-to-recipient weight ratio ranged from 1.04 to 1.12%. The grafts worked immediately; the post-operative course in the 3 recipients was unremarkable and no rejection episode occurred. Significant complications were observed in one donor (percutaneously drained bilioma and spontaneously resolved popliteal sensory palsy). Living-donor right liver transplantation is a potentially valuable solution to the increasing shortage of donor organs. The procedure can be performed safely provided stringent criteria for donor selection, for donor-recipient coupling (> 1% graft to body weight ratio) and for centre selection (experience in liver surgery, reduced and split liver transplantation) are applied.


Optoacoustic imaging using fiber-optic interferometric sensors.
An interferometric sensor based on nonmetallic silica optical fiber is presented as an ultrasonic wideband transducer for optoacoustic imaging applications. We have characterized the sensitivity of the optical fiber sensor by detecting optoacoustic signals from an optically absorbing object embedded in a tissue-mimicking phantom and have compared the signals recorded with those detected from the same phantom using an array of piezoelectric transducers. The optical fiber sensor was also scanned along the phantom surface in order to reconstruct two-dimensional optoacoustic images of the phantom. These images have been compared with images obtained using the Laser Optoacoustic Imaging System, LOIS-64B, demonstrating the feasibility of our fiber-optic sensor as a wideband ultrasonic transducer.


Temporal integration and 1/f power scaling in a circuit model of cerebellar interneurons.
Inhibitory interneurons interconnected via electrical and chemical (GABAA receptor) synapses form extensive circuits in several brain regions. They are thought to be involved in timing and synchronization through fast feedforward control of principal neurons. Theoretical studies have shown, however, that whereas self-inhibition does indeed reduce response duration, lateral inhibition, in contrast, may generate slow response components through a process of gradual disinhibition. Here we simulated a circuit of interneurons (stellate and basket cells) of the molecular layer of the cerebellar cortex and observed circuit time constants that could rise, depending on parameter values, to >1 s. The integration time scaled both with the strength of inhibition, vanishing completely when inhibition was blocked, and with the average connection distance, which determined the balance between lateral and self-inhibition. Electrical synapses could further enhance the integration time by limiting heterogeneity among the interneurons and by introducing a slow capacitive current. The model can explain several observations, such as the slow time course of OFF-beam inhibition, the phase lag of interneurons during vestibular rotation, or the phase lead of Purkinje cells. Interestingly, the interneuron spike trains displayed power that scaled approximately as 1/f at low frequencies. In conclusion, stellate and basket cells in cerebellar cortex, and interneuron circuits in general, may not only provide fast inhibition to principal cells but also act as temporal integrators that build a very short-term memory.NEW & NOTEWORTHY The most common function attributed to inhibitory interneurons is feedforward control of principal neurons. In many brain regions, however, the interneurons are densely interconnected via both chemical and electrical synapses but the function of this coupling is largely unknown. Based on large-scale simulations of an interneuron circuit of cerebellar cortex, we propose that this coupling enhances the integration time constant, and hence the memory trace, of the circuit.


Exposure to written content eliciting weight stigmatization: Neural responses in appetitive and food reward regions.
Neural activity in food reward- and appetite-related regions was examined in response to high-calorie (HC), low-calorie, and non-food pictures after exposure to written weight stigma (WS) content. Relationships with eating behavior (by Three-Factor Eating Questionnaire [TFEQ]), blood glucose, and subjective appetite were also explored. Adults with overweight and obesity were randomized to read either a WS (n = 20) or control (n = 20) article, and subsequently underwent brain scans while they rated pleasantness of food pictures. Fasting glucose, TFEQ, stigma experiences, and appetite were measured before reading the article, appetite after reading, and glucose and appetite again after scan. A priori region of interest analyses revealed significant group differences in activation to HC > low-calorie food cues in the caudate and thalamus whereas exploratory whole-brain analyses suggested significant differences in regions including left insula, left thalamus, left inferior temporal gyrus, right lingual gyrus, and bilateral middle occipital gyrus and superior parietal lobule (p < 0.005 uncorrected, k ≥ 200 m3 ). No significant relationships were observed between the pattern of activation and TFEQ, glucose, or subjective appetite in the WS group. Exposure to WS was associated with increased responsiveness to HC food content in the dorsal striatum and thalamus in individuals with overweight and obesity.


Detection of antibodies secreted from circulating Mycobacterium tuberculosis-specific plasma cells in the diagnosis of pediatric tuberculosis.
Diagnosis of tuberculosis (TB) in children is difficult because symptoms are often nonspecific or absent in infected children, diagnostic specimens are difficult to obtain from younger children, and >50% have negative TB cultures. Thus, there is an urgent need for improved diagnosis of pediatric TB. This study aimed to evaluate the diagnostic value of a new serological method, the ALS (antibodies in lymphocyte supernatant) assay, for the diagnosis of active TB in children with clinically identified TB. The ALS test is based on the concept that antigen-specific plasma cells are present in the circulation only at times of acute infection and not in latency. A cross-sectional study of pediatric patients (age range, 11 to 167 months) who were clinically identified as TB (n = 58) or non-TB (n = 16) patients was conducted, and they were monitored for 6 months. Healthy children (n = 58) were enrolled as controls. Spontaneous release of TB antigen-specific antibodies by in vitro-cultured, unstimulated peripheral blood mononuclear cells was assessed by an enzyme-linked immunosorbent assay using Mycobacterium bovis bacillus Calmette-Guérin (BCG) as the detecting antigen. Of the patients clinically diagnosed with TB, 15% had culture-confirmed TB, 64% were positive for TB by clinically established scoring charts (K. Edwards, P. N. G. Med. J. 30: 169-178, 1987; G. Stegen, K. Jones, and P. Kaplan, Pediatrics 43: 260-263, 1969; and stop TB Partnership, Childhood TB subgroup, World Health Organization, Int. J. Tuberc. Lung Dis. 10: 1091-1097, 2006), and 91% were TB positive by the ALS method. All TB patients had significantly higher BCG-specific ALS titers at enrollment (optical density [OD], 1.06 +/- 0.32) than healthy-control children (OD, 0.18 +/- 0.06) and non-TB children (OD, 0.21 +/- 0.10) (P = 0.001). The ALS titers declined in children with active disease from enrollment through 6 months following anti-TB therapy (P = 0.001). The ALS assay is a novel diagnostic method with potential applications in the diagnosis of pediatric TB and in subsequent monitoring of treatment effectiveness.


Profiling of microRNA in human and mouse ES and iPS cells reveals overlapping but distinct microRNA expression patterns.
Using quantitative PCR-based miRNA arrays, we comprehensively analyzed the expression profiles of miRNAs in human and mouse embryonic stem (ES), induced pluripotent stem (iPS), and somatic cells. Immature pluripotent cells were purified using SSEA-1 or SSEA-4 and were used for miRNA profiling. Hierarchical clustering and consensus clustering by nonnegative matrix factorization showed two major clusters, human ES/iPS cells and other cell groups, as previously reported. Principal components analysis (PCA) to identify miRNAs that segregate in these two groups identified miR-187, 299-3p, 499-5p, 628-5p, and 888 as new miRNAs that specifically characterize human ES/iPS cells. Detailed direct comparisons of miRNA expression levels in human ES and iPS cells showed that several miRNAs included in the chromosome 19 miRNA cluster were more strongly expressed in iPS cells than in ES cells. Similar analysis was conducted with mouse ES/iPS cells and somatic cells, and several miRNAs that had not been reported to be expressed in mouse ES/iPS cells were suggested to be ES/iPS cell-specific miRNAs by PCA. Comparison of the average expression levels of miRNAs in ES/iPS cells in humans and mice showed quite similar expression patterns of human/mouse miRNAs. However, several mouse- or human-specific miRNAs are ranked as high expressers. Time course tracing of miRNA levels during embryoid body formation revealed drastic and different patterns of changes in their levels. In summary, our miRNA expression profiling encompassing human and mouse ES and iPS cells gave various perspectives in understanding the miRNA core regulatory networks regulating pluripotent cells characteristics.


We are calling for adoption of universal, redistributive and solidarity-based policies with a rights-oriented approach to leave no one behind.
Serving in her present role since the economic crisis of 2008, Alicia Bárcena is no newcomer to regional and global emergencies, economic or otherwise. She also has extensive experience in the UN system, including as chief of staff to the UN Secretary-General and later, during Ban Ki-moon's tenure in that position, as Under-Secretary General for Management. From 2016 to 2017, she co-chaired the International Resource Panel at the UN Environment Program. A biologist trained in her home country of Mexico, she later received a master's degree in public administra-tion from Harvard University, USA. For decades, Ms Bárcena has devoted her professional career to issues of sustainable development, fi nancing of public policies, and the environment. She has received Doctor Honoris Causa degrees from the University of Oslo, Norway (2014); the University of Havana, Cuba (2016); and the Universidad Autónoma de México (2019). Today, she is a board member of the Global Partnership for Sus-tainable Development Data and a member of the University of Oslo/The Lancet Independent Panel on Global Governance for Health.


CycleGAN with mutual information loss constraint generates structurally aligned CT images from functional EIT images.
Electrical impedance tomography (EIT) has been employed in the field of medical imaging due to its cost effectiveness, safety profile and portability, but the images generated are relatively low resolution. To address these limitations, we create a novel method using EIT images to generate high resolution structurally aligned images of lungs like those from CT scans. A way to achieve this transformation is via Cycle generative adversarial networks (CycleGAN), which have demonstrated image-to-image translation capabilities across different modalities. However, a generic implementation yields images which may not be aligned with their input image. To solve this issue, we construct and incorporate a Mutual Information (MI) constraint in CycleGAN to translate functional lung EIT images to structural high resolution CT images. The CycleGAN is first trained on unpaired EIT and CT lung images. Afterwards, we generate CT image pairs from EIT images via CycleGANs constrained with MI loss and without this loss. Finally, through generating these 1560 CT image pairs and then comparing the visual results and quantitative metrics, we show that MI constrained CycleGAN produces more structurally aligned CT images, where Normalised Mutual Information (NMI) is increased to 0.2621+/- 0.0052 versus 0.2600 +/- 0.0066, p<0.0001 for non-MI constrained images. By this process, we simultaneously provide functional and structural information, and potentially enable more detailed assessment of lungs.Clinical Relevance- By establishing a structurally aligning generative process via MI Loss in CycleGAN, this study enables EIT-CT conversion, thereby providing functional and structural images for enhanced lung assessment, from just EIT images.


The Adult Roles Models Program: Feasibility, Acceptability, and Initial Outcomes.
We present the feasibility and acceptability of a parent sexuality education program led by peer educators in community settings. We also report the results of an outcome evaluation with 71 parents who were randomized to the intervention or a control group, and surveyed one month prior to and six months after the 4-week intervention. The program was highly feasible and acceptable to participants, and the curriculum was implemented with a high level of fidelity and facilitator quality. Pilot data show promising outcomes for increasing parental knowledge, communication, and monitoring of their adolescent children.


Implementing preventive chemotherapy through an integrated National Neglected Tropical Disease Control Program in Mali.
Mali is endemic for all five targeted major neglected tropical diseases (NTDs). As one of the five 'fast-track' countries supported with the United States Agency for International Development (USAID) funds, Mali started to integrate the activities of existing disease-specific national control programs on these diseases in 2007. The ultimate objectives are to eliminate lymphatic filariasis, onchocerciasis and trachoma as public health problems and to reduce morbidity caused by schistosomiasis and soil-transmitted helminthiasis through regular treatment to eligible populations, and the specific objectives were to achieve 80% program coverage and 100% geographical coverage yearly. The paper reports on the implementation of the integrated mass drug administration and the lessons learned. The integrated control program was led by the Ministry of Health and coordinated by the national NTD Control Program. The drug packages were designed according to the disease endemicity in each district and delivered through various platforms to eligible populations involving the primary health care system. Treatment data were recorded and reported by the community drug distributors. After a pilot implementation of integrated drug delivery in three regions in 2007, the treatment for all five targeted NTDs was steadily scaled up to 100% geographical coverage by 2009, and program coverage has since been maintained at a high level: over 85% for lymphatic filariasis, over 90% for onchocerciasis and soil-transmitted helminthiasis, around 90% in school-age children for schistosomiasis, and 76-97% for trachoma. Around 10 million people have received one or more drug packages each year since 2009. No severe cases of adverse effects were reported. Mali has scaled up the drug treatment to national coverage through integrated drug delivery involving the primary health care system. The successes and lessons learned in Mali can be valuable assets to other countries starting up their own integrated national NTD control programs.


Dutch healthcare reform: did it result in better patient experiences in hospitals? A comparison of the consumer quality index over time.
In 2006, the Dutch hospital market was reformed to create a more efficient delivery system through managed competition. To allow competition on quality, patient experiences were measured using the Consumer Quality index (CQI). We study whether public reporting and competition had an effect on the CQI between 2006 and 2009. We analyzed 8,311 respondents covering 31 hospitals in 2006, 22,333 respondents covering 78 hospitals in 2007 and 24,246 respondents covering 94 hospitals in 2009. We describe CQI trends over the period 2006-2009. In addition we compare hospitals that varied in the level of competition they faced and hospitals that were forced to publish CQI results publicly and those that were not. We corrected for observable covariates between hospital respondents using a multi level linear regression. We used the Herfindahl Hirschman Index to indicate the level of competition. Between 2006 and 2009 hospitals showed a CQI improvement of 0.034 (p < 0.05) to 0.060 (p < 0.01) points on a scale between one and four. Hospitals that were forced to publish their scores showed a further improvement of 0.027 (p < 0.01) to 0.030 (p < 0.05). Furthermore, hospitals that faced more competition from geographically close competitors showed a more pronounced improvement of CQI-scores 0.004 to 0.05 than other hospitals (p < 0.001). Our results show that patients reported improved experiences measured by the CQI between 2006 and 2009. CQI levels improve at a faster rate in areas with higher levels of competition. Hospitals confronted with forced public publication of their CQI responded by enhancing the experiences of their patients.


Transcriptomic Insights into Archaeal Nitrification in the Amundsen Sea Polynya, Antarctica.
Antarctic polynyas have the highest Southern Ocean summer primary productivity, and due to anthropogenic climate change, these areas have formed faster recently. Ammonia-oxidizing archaea (AOA) are among the most ubiquitous and abundant microorganisms in the ocean and play a primary role in the global nitrogen cycle. We utilized metagenomics and metatranscriptomics to gain insights into the physiology and metabolism of AOA in polar oceans, which are associated with ecosystem functioning. A polar-specific ecotype of AOA, from the "Candidatus Nitrosomarinus"-like group, was observed to be dominant in the Amundsen Sea Polynya (ASP), West Antarctica, during a succession of summer phytoplankton blooms. AOA had the highest transcriptional activity among prokaryotes during the bloom decline phase (DC). Metatranscriptomic analysis of key genes involved in ammonia oxidation, carbon fixation, transport, and cell division indicated that this polar AOA ecotype was actively involved in nitrification in the bloom DC in the ASP. This study revealed the physiological and metabolic traits of this key polar-type AOA in response to phytoplankton blooms in the ASP and provided insights into AOA functions in polar oceans.


Do gender differences in the relationship between living with children and alcohol consumption vary by societal gender inequality?
To better understand the relationship between alcohol consumption and living with children, we assessed whether the association varied for men and women across diverse countries and whether this relationship was moderated by country-level gender inequality. We used Hierarchical Linear Modelling to analyse data from 32 surveys conducted in 27 countries. Measures included whether the participant was a drinker versus abstainer in past 12 months, annual number of drinks consumed, whether the respondent lived with children, gender (male/female) and age of respondent, and country-level gender inequality measured using the Gender Inequality Index. Annual drinks consumed was significantly lower for women living with children. Men living with children were generally more likely to be drinkers, and the relationship between annual consumption and living with children was moderated by cultural gender equality: specifically, men in countries with higher gender equality drank less if they lived with children while the association for men in lower equality countries was nonsignificant. Although lower alcohol consumption was found generally for women living with children, this relationship was found only for men in countries where there was more gender equality. Given the high risk of harm to children from heavy consumption by adults with whom they live, prevention efforts need to strengthen prevention of heavy consumption by parents and other who live with children, especially for men who live with children in low gender equality countries.


Tales from the new frontier: pioneers' experiences with consumer-driven health care.
To conduct site visits to study the early experiences of firms offering consumer-driven health care (CDHC) plans to their employees and firms that provide CDHC products. A convenience sample of three firms offering CDHC products to their employees, one of which is also a large insurer, and one firm offering an early CDHC product to employers. We conducted onsite interviews of four companies during the spring and summer of 2003. These four cases were not selected randomly. We contacted organizations that already had a consumer-driven plan in place by January 2002 so as to provide a complete year's worth of experience with CDHC. The experience of the companies we visited indicated that favorable selection tends to result when a CDHC plan is introduced alongside traditional preferred provider organization (PPO) and health maintenance organization (HMO) plan offerings. Two sites demonstrated substantial cost-savings. Our case studies also indicate that the more mundane aspects of health care benefits are still crucial under CDHC. The size of the provider network accessible through the CDHC plan was critical, as was the role of premium contributions in the benefit design. Also, companies highlighted the importance of educating employees about new CDHC products: employees who understood the product were more likely to enroll. Our site visits suggest the peril (risk selection) and the promise (cost savings) of CDHC. At this point there is still far more that we do not know about CDHC than we do know. Little is known about the extent to which CDHC changes people's behavior, the extent to which quality of care is affected by CDHC, and whether web-based information and tools actually make patients become better consumers.


[Hemodynamics in the orbital vessels in patients with diabetes mellitus during medical treatment].
Diabetes mellitus is one of the major health problems in the 21st century. Diabetic retinopathy resulting in complete vision loss and disability is an early vascular complication in diabetes mellitus. Therefore, the treatment of diabetes has become a priority of modern medicine worldwide. The paper analyzes the possibilities of complex ultrasound diagnosis for estimating the orbital hemodynamics in diabetic patients during medical treatment and its efficiency monitoring at different stages.


A cis element within flowering locus T mRNA determines its mobility and facilitates trafficking of heterologous viral RNA.
The Arabidopsis flowering locus T (FT) gene encodes the mobile florigen essential for floral induction. While movement of the FT protein has been shown to occur within plants, systemic spread of FT mRNA remains to be unequivocally demonstrated. Utilizing novel RNA mobility assay vectors based on two distinct movement-defective viruses, Potato virus X and Turnip crinkle virus, and an agroinfiltration assay, we demonstrate that nontranslatable FT mRNA, independent of the FT protein, moves throughout Nicotiana benthamiana and mutant Arabidopsis plants and promotes systemic trafficking of viral and green fluorescence protein RNAs. Viral ectopic expression of FT induced flowering in the short-day N. tabacum Maryland Mammoth tobacco under long-day conditions. Recombinant Potato virus X bearing FT RNA spread and established systemic infection more quickly than the parental virus. The cis-acting element essential for RNA movement was mapped to the nucleotides 1 to 102 of the FT mRNA coding sequence. These data demonstrate that a plant self-mobile RNA molecule can mediate long-distance trafficking of heterologous RNAs and raise the possibility that FT RNA, along with the FT protein, may be involved in the spread of the floral stimulus throughout the plant.


[Changes in anxiety level of Wistar rats under the influence of maximally-diluted solution of a plant alkaloid].
A very dilute solution of Nux Vomica 200 plant alkaloid was applied onto the tongue of Wistar rats. The level of rats' anxiety was estimated by their behavior in elevated plus-maze. The dry application led to substantial changes in rats' behavior. In "passive" rats previously defined by the forced swimming tests changes in behavior were most prominent. The possible influence of the drug under study on the adaptive abilities of this group of animals is discussed.


Diversity of the fine specificity displayed by HLA-A*0201-restricted CTL specific for the immunodominant Melan-A/MART-1 antigenic peptide.
HLA-A*0201 melanoma patients often develop a CTL response to an immunodominant peptide derived from the melanocyte lineage-specific protein Melan-A/MART-1. We have shown previously that the antigenic peptide most often involved is the decapeptide Melan-A(26-35) (EAAGIGILTV). We also observed some clonal diversity in the fine specificity of Melan-A-specific CTL. To substantiate this observation, we have now tested a series of Melan-A(26-35) variant peptides containing single alanine substitutions for binding to HLA-A*0201 and recognition by polyclonal and monoclonal Melan-A-specific CTL. Substitution of several residues with alanine reduced peptide binding activity by > 10-fold. In contrast, substitution of E26 with alanine (AAAGIGILTV) resulted in a 5-fold higher binding activity as well as in stronger stability of the corresponding HLA-A*0201/peptide complexes. Interestingly, the peptide variant AAAGIGILTV was recognized more efficiently than the natural decapeptide by short term cultured, tumor-infiltrated lymph node cell cultures and a number of Melan-A-specific CTL clones derived from different individuals. Moreover, this analysis revealed that the fine specificity of the CTL response to the Melan-A immunodominant epitope is quite diverse at the clonal level. At least three distinct patterns of fine specificity were identified. This diversity appears to reflect the diversity of the TCR repertoire available for this Ag, since similar results were obtained with a panel of Melan-A-specific CTL clones derived from a single melanoma patient. These findings have important implications for the formulation of Melan-A peptide-based vaccines as well as for the monitoring of Melan-A-specific CTL responses in melanoma patients.


Induced Pluripotency: A Powerful Tool for In Vitro Modeling.
One of the greatest breakthroughs of regenerative medicine in this century was the discovery of induced pluripotent stem cell (iPSC) technology in 2006 by Shinya Yamanaka. iPSCs originate from terminally differentiated somatic cells that have newly acquired the developmental capacity of self-renewal and differentiation into any cells of three germ layers. Before iPSCs can be used routinely in clinical practice, their efficacy and safety need to be rigorously tested; however, iPSCs have already become effective and fully-fledged tools for application under in vitro conditions. They are currently routinely used for disease modeling, preparation of difficult-to-access cell lines, monitoring of cellular mechanisms in micro- or macroscopic scales, drug testing and screening, genetic engineering, and many other applications. This review is a brief summary of the reprogramming process and subsequent differentiation and culture of reprogrammed cells into neural precursor cells (NPCs) in two-dimensional (2D) and three-dimensional (3D) conditions. NPCs can be used as biomedical models for neurodegenerative diseases (NDs), which are currently considered to be one of the major health problems in the human population.


Community-based maternity care from the view of Iranian midwives: A phenomenological study.
Midwifery cares take place in diverse communities with different ethnics groups. Therefore, midwifery cares could be planned wisely and principally based on women's and their families' changeable demands which focus on social and cultural issues. This qualitative study explored the midwives' experiences of care in the community. This qualitative study was conducted by descriptive phenomenological approach. The subjects, selected by purposive sampling, comprised 13 midwives employed in Isfahan, Iran. Semi-structured interviews were audio-taped, transcribed, and simultaneously analyzed through Colaizzi's method. With descriptive analysis of participants' experiences, three main themes were explored (personal characteristics of the community midwife, social determinants of women's health, and achieving community-based midwifery skills). Knowledge of women's social status, gender inequality in health, and existence of social health risk factors for women in their community helps midwives to provide reproductive health care based on clients' needs and demands. Therefore, midwives should enhance the quality of their care through integrating professional skills with a full understanding of the social context.


Characterization of transcription organization and analysis of unique expression patterns of an alkyl hydroperoxide reductase C gene (ahpC) and the peroxide regulator operon ahpF-oxyR-orfX from Xanthomonas campestris pv. phaseoli.
We have analyzed the transcription organization of ahpC, ahpF, oxyR, and orfX from Xanthomonas campestris pv. phaseoli. ahpC was transcribed as a monocistronic 0.6-kb mRNA, while ahpF-oxyR-orfX were transcribed as a polycistronic approximately 3.0-kb-long mRNA. The novel transcription organization of these genes has not observed in other bacteria. Western analysis showed that oxidants (peroxides and superoxide anions), a thiol reagent (N-ethylmaleimide), and CdCl2 caused large increases in the steady-state level of AhpC. Growth at alkaline pH also moderately induced AhpC accumulation. Thermal and osmotic stresses did not alter the levels of AhpC. Northern blotting results confirmed that oxidant- and CdCl2-induced AhpC accumulation was due to increased levels of ahpC transcripts. Analysis of oxyR expression revealed a unique pattern. Unlike other bacterial systems, peroxides and a superoxide generator induced accumulation of OxyR. Northern blotting results confirmed that these oxidants induced expression of oxyR operon. This novel regulatory pattern could be generally important. The transcription organization and patterns of chemicals and stress induction of ahpC and oxyR differed from those of other bacteria and are likely to be important for X. campestris pv. phaseoli survival during exposure to oxidants.


Summarizing social disparities in health.
Reporting on health disparities is fundamental for meeting the goal of reducing health disparities. One often overlooked challenge is determining the best way to report those disparities associated with multiple attributes such as income, education, sex, and race/ethnicity. This article proposes an analytical approach to summarizing social disparities in health, and we demonstrate its empirical application by comparing the degrees and patterns of health disparities in all fifty states and the District of Columbia (DC). We used the 2009 American Community Survey, and our measure of health was functional limitation. For each state and DC, we calculated the overall disparity and attribute-specific disparities for income, education, sex, and race/ethnicity in functional limitation. Along with the state rankings of these health disparities, we developed health disparity profiles according to the attribute making the largest contribution to overall disparity in each state. Our results show a general lack of consistency in the rankings of overall and attribute-specific disparities in functional limitation across the states. Wyoming has the smallest overall disparity and West Virginia the largest. In each of the four attribute-specific health disparity rankings, however, most of the best- and worst-performing states in regard to overall health disparity are not consistently good or bad. Our analysis suggests the following three disparity profiles across states: (1) the largest contribution from race/ethnicity (thirty-four states), (2) roughly equal contributions of race/ethnicity and socioeconomic factor(s) (ten states), and (3) the largest contribution from socioeconomic factor(s) (seven states). Our proposed approach offers policy-relevant health disparity information in a comparable and interpretable manner, and currently publicly available data support its application. We hope this approach will spark discussion regarding how best to systematically track health disparities across communities or within a community over time in relation to the health disparity goal of Healthy People 2020.


Link between the renin-angiotensin system and insulin resistance: implications for cardiovascular disease.
The incidence of metabolic syndrome is rapidly increasing in the United States and worldwide. The metabolic syndrome is a complex metabolic and vascular disorder that is associated with inappropriate activation of the renin-angiotensin-aldosterone system (RAAS) in the cardiovascular (CV) system and increased CV morbidity and mortality. Insulin activation of the phosphatidylinositol-3-kinase (PI3K) pathway promotes nitric oxide (NO) production in the endothelium and glucose uptake in insulin-sensitive tissues. Angiotensin (Ang) II inhibits insulin-mediated PI3K pathway activation, thereby impairing endothelial NO production and Glut-4 translocation in insulin-sensitive tissues, which results in vascular and systemic insulin resistance, respectively. On the other hand, Ang II enhances insulin-mediated activation of the mitogen-activated protein kinase (MAPK) pathway, which leads to vasoconstriction and pathologic vascular cellular growth. Therefore, the interaction of Ang II with insulin signaling is fully operative not only in insulin-sensitive tissues but also in CV tissues, thereby linking insulin resistance and CV disease. This notion is further supported by an increasing number of experimental and clinical studies indicating that pharmacological blockade of RAAS improves insulin sensitivity and endothelial function, as well as reduces the incidence of new-onset diabetes in high-risk patients with CV disease. This article reviews experimental and clinical data elucidating the physiological and pathophysiological role of the interaction between insulin and RAAS in the development of insulin resistance as well as CV disease.


Neuropsychological test results and symptoms among workers with well-defined long-term exposure to lead.
Lead intoxication is a classical environmental hazard that can cause encephalopathy. During recent years several studies have suggested poor performances in psychological tests and increased numbers of subjective symptoms among workers with comparatively low blood lead concentrations. Forty-nine long-term lead-exposed male workers with time-weighted average blood lead concentrations between 1.3 and 3.3 mumol/l calculated from at least seven years' results have been compared with a referent group of 27 male industrial workers with normal blood lead concentrations and comparable intellectual backgrounds. Several indices of exposure were used. Both groups were examined with neuropsychological tests and a questionnaire covering neuropsychiatric symptoms. The exposed group performed less well in 11 of 14 non-verbal tests, and there were significant differences in tests of memory and reaction time. A non-linear dose-effect trend was indicated. The results are in accordance with those found in similar studies, and it is concluded that the blood lead concentration should be below 2.5 mumol/l to avoid the effects shown in this study.


NSAIDs and spontaneous abortions - true effect or an indication bias?
The aim of the study was to characterize the extent of indication bias resulting from the excessive use of NSAIDs on the days preceding a spontaneous abortion to relieve pain. We used data from a retrospective cohort study assessing the risk for spontaneous abortions following exposure to NSAIDs. Three definitions of exposure for cases of spontaneous abortions were compared, from the first day of pregnancy until the day of spontaneous abortion and until 3 and 2 days before a spontaneous abortion. Statistical analysis was performed using multivariate time programmed Cox regression. A sharp increase was observed in the dispensation of indomethacin, diclofenac and naproxen, and a milder increase was found in the use of ibuprofen during the week before a spontaneous abortion. Non- selective COX inhibitors in general and specifically diclofenac and indomethacin were found to be associated with spontaneous abortions when the exposure period was defined until the day of spontaneous abortion (hazard ratio (HR) 1.15, 95% confidence interval (CI) 1.04, 1.28; HR 1.31, 95% CI 1.08, 1.59 and HR 3.33, 95% CI 2.09, 5.29, respectively). The effect disappears by excluding exposures occurring on the day before the spontaneous abortion for non-selective COX inhibitors and on the last week before the spontaneous abortion for indomethacin. In general, decreasing HRs were found with the exclusion of exposures occurring on the days immediately before the spontaneous abortion. The increased use of NSAIDs during the last few days that preceded a spontaneous abortion to relieve pain associated with the miscarriage could bias studies assessing the association between exposure to NSAIDs and spontaneous abortions.


Blocking the proliferation of human tumor cell lines by peptidase inhibitors from Bauhinia seeds.
In cancer tumors, growth, invasion, and formation of metastasis at a secondary site play a pivotal role, participating in diverse processes in the development of the pathology, such as degradation of extracellular matrix. Bauhinia seeds contain relatively large quantities of peptidase inhibitors, and two Bauhinia inhibitors were obtained in a recombinant form from the Bauhinia bauhinioides species, B. bauhinoides cruzipain inhibitor, which is a cysteine and serine peptidase inhibitor, and B. bauhinioides kallikrein inhibitor, which is a serine peptidase inhibitor. While recombinant B. bauhinoides cruzipain inhibitor inhibits human neutrophil elastase cathepsin G and the cysteine proteinase cathepsin L, recombinant B. bauhinioides kallikrein inhibitor inhibits plasma kallikrein and plasmin. The effects of recombinant B. bauhinoides cruzipain inhibitor and recombinant B. bauhinioides kallikrein inhibitor on the viability of tumor cell lines with a distinct potential of growth from the same tissue were compared to those of the clinical cytotoxic drug 5-fluorouracil. At 12.5 µM concentration, recombinant B. bauhinoides cruzipain inhibitor and recombinant B. bauhinioides kallikrein inhibitor were more efficient than 5-fluorouracil in inhibiting MKN-28 and Hs746T (gastric), HCT116 and HT29 (colorectal), SkBr-3 and MCF-7 (breast), and THP-1 and K562 (leukemia) cell lines. Additionally, recombinant B. bauhinoides cruzipain inhibitor inhibited 40 % of the migration of Hs746T, the most invasive gastric cell line, while recombinant B. bauhinioides kallikrein inhibitor did not affect cell migration. Recombinant B. bauhinioides kallikrein inhibitor and recombinant B. bauhinoides cruzipain inhibitor, even at high doses, did not affect hMSC proliferation while 5-fluorouracil greatly reduced the proliferation rates of hMSCs. Therefore, both recombinant B. bauhinoides cruzipain inhibitor and recombinant B. bauhinioides kallikrein inhibitor might be considered for further studies to block peptidase activities in order to target specific peptidase-mediated growth and invasion characteristics of individual tumors, mainly in patients resistant to 5-fluorouracil chemotherapy.


Surgery-first approach in skeletal class III malocclusion treated with 2-jaw surgery: evaluation of surgical movement and postoperative orthodontic treatment.
The purpose of this study was to evaluate the surgical movement and postoperative orthodontic treatment (POT) of the surgery-first approach for the correction of skeletal class III malocclusion. The samples consisted of 11 patients with skeletal class III malocclusion who underwent nonextraction treatment and 2-jaw surgery (Le Fort I osteotomy impaction of the posterior maxilla, IPM; bilateral sagittal split ramus osteotomy setback of the mandible). The wafer was removed 4 weeks after surgery. Mean (SD) durations of POT and total treatment were 8.91 (3.14) and 12.18 (3.57) months, respectively. Lateral cephalograms were obtained during the initial examination (T0), immediately after surgery (T1), and after debonding (T2). Sixteen variables were measured. Paired t-test was performed for statistical analysis. The maxilla rotated clockwise, and the nasolabial angle increased by IPM (FH-palatal plane angle, FH-occlusal plane angle, P < 0.01; nasolabial angle, P < 0.05) and well maintained during POT. The mandible was repositioned backward by bilateral sagittal split ramus osteotomy setback of the mandible (SNB, Pog-N perp, P < 0.001) and relapsed forward during POT (SNB, P < 0.01; Pog-N perp, P < 0.05). U1-SN decreased by IPM (P < 0.001) and relapsed labially owing to class III mechanics during POT (P < 0.01); eventually, no significant difference was found between T0 and T2 stages. Although IMPA increased by POT, there was no significant difference between T0 and T2 stages. The mandible seems to relapse forward immediately after wafer removal and before labioversion of the lower incisors. Accurate prediction of POT is crucial in controlling dental alignment, incisor decompensation, arch coordination, and occlusal settling. Long-term wearing and selective grinding of the wafer for labioversion of the lower incisors and use of miniplates/miniscrews to control the inclination of the upper incisor and to prevent relapse of the mandible are needed.


Diminished endometrial expression of ghrelin and ghrelin receptor contributes to infertility.
The objectives were to investigate the presence, distribution and sex steroid hormone regulation of ghrelin and its receptor, growth hormone secretagogue receptor (GHSR), in human endometrium in relation to endometrial receptivity and fertility. Endometrial biopsies were obtained from women with unexplained infertility and healthy fertile volunteers. Ishikawa cells were used to mimic the action of ghrelin in endometrium. Immunostaining of GHSR was strong in luminal epithelium and stroma during mid-secretory phase. Ghrelin and GHSR expression is less intense in mid-secretory endometrium of infertile women compared to fertile controls. Treatment with estrogen and/or progesterone or their antagonists did not significantly change the relative expression of GHSR in Ishikawa and stromal cells. Ghrelin was present in and secreted from human blastocysts, which suggest that the communication between human blastocyst and endometrium might involve ghrelin. Low levels of GHSR in endometrium from women with unexplained infertility may in part explain the infertility.


Moxibustion's protective role against atherosclerosis: Inhibition of Ca2+ overload-triggered oxidative stress and inflammatory response via P2Y12/PI3K/AKT pathway.
This study aims to investigate the protective mechanism of moxibustion in combating atherosclerosis (AS). Apolipoprotein E (ApoE)-deficient mice, aged 8 weeks, were randomly assigned into four groups: the model group (n = 6), SC79 group (n = 6), moxibustion group (n = 6), and moxibustion+SC79 group (n = 6). All mice were fed with a high-fat diet (HFD). Concurrently, 8-week-old C57BL/6 mice of the same genetic background were utilized as the control group (n = 6) and were given a regular diet. Macrophages were isolated via flow cytometry. The intracellular Ca2+ expression in macrophages was evaluated, and aortic plaques were quantitatively assessed through en face oil red O and Masson staining. The presence of macrophages and smooth muscle cells in AS plaques was determined by MAC-3 and α-smooth muscle actin (α-SMA) immunohistochemistry. The relative fluorescence intensity of nuclear factor-κB (NF-κB) in macrophages was identified by immunofluorescence staining. The expressions of proteins related to the P2Y12/phosphatidylinositol 3-hydroxy kinase (PI3K)/protein kinase B (AKT) signaling pathway were examined by Western blotting. Moxibustion reduced free Ca2+ expression in macrophage cytoplasm, inhibiting Ca2+ influx and oxidative stress. Significant reductions in atherosclerotic plaque formation and inflammation markers, including TNF-α and IL-1β, were noted in the moxibustion group. Moxibustion modulated the P2Y12/PI3K/AKT pathway, impacting various inflammatory and oxidative stress-related proteins. Introduction of the AKT activator SC79 counteracted moxibustion's benefits, highlighting the P2Y12/PI3K/AKT pathway's central role. Moxibustion, through the P2Y12/PI3K/AKT signaling pathway, can inhibit Ca2+ overload-induced oxidative stress and inflammatory response, decrease macrophage infiltration, and increase the content of smooth muscle cells and collagen, thereby exerting a protective effect against AS.


Plasma Gradient of Soluble Urokinase-Type Plasminogen Activator Receptor Is Linked to Pathogenic Plasma Proteome and Immune Transcriptome and Stratifies Outcomes in Severe COVID-19.
Disease caused by SARS-CoV-2 coronavirus (COVID-19) led to significant morbidity and mortality worldwide. A systemic hyper-inflammation characterizes severe COVID-19 disease, often associated with acute respiratory distress syndrome (ARDS). Blood biomarkers capable of risk stratification are of great importance in effective triage and critical care of severe COVID-19 patients. Flow cytometry and next-generation sequencing were done on peripheral blood cells and urokinase-type plasminogen activator receptor (suPAR), and cytokines were measured from and mass spectrometry-based proteomics was done on plasma samples from an Indian cohort of COVID-19 patients. Publicly available single-cell RNA sequencing data were analyzed for validation of primary data. Statistical analyses were performed to validate risk stratification. We report here higher plasma abundance of suPAR, expressed by an abnormally expanded myeloid cell population, in severe COVID-19 patients with ARDS. The plasma suPAR level was found to be linked to a characteristic plasma proteome, associated with coagulation disorders and complement activation. Receiver operator characteristic curve analysis to predict mortality identified a cutoff value of suPAR at 1,996.809 pg/ml (odds ratio: 2.9286, 95% confidence interval 1.0427-8.2257). Lower-than-cutoff suPAR levels were associated with a differential expression of the immune transcriptome as well as favorable clinical outcomes, in terms of both survival benefit (hazard ratio: 0.3615, 95% confidence interval 0.1433-0.912) and faster disease remission in our patient cohort. Thus, we identified suPAR as a key pathogenic circulating molecule linking systemic hyperinflammation to the hypercoagulable state and stratifying clinical outcomes in severe COVID-19 patients with ARDS.


Combinatorial motif analysis of regulatory gene expression in Mafb deficient macrophages.
Deficiency of the transcription factor MafB, which is normally expressed in macrophages, can underlie cellular dysfunction associated with a range of autoimmune diseases and arteriosclerosis. MafB has important roles in cell differentiation and regulation of target gene expression; however, the mechanisms of this regulation and the identities of other transcription factors with which MafB interacts remain uncertain. Bioinformatics methods provide a valuable approach for elucidating the nature of these interactions with transcriptional regulatory elements from a large number of DNA sequences. In particular, identification of patterns of co-occurrence of regulatory cis-elements (motifs) offers a robust approach. Here, the directional relationships among several functional motifs were evaluated using the Log-linear Graphical Model (LGM) after extraction and search for evolutionarily conserved motifs. This analysis highlighted GATA-1 motifs and 5'AT-rich half Maf recognition elements (MAREs) in promoter regions of 18 genes that were down-regulated in Mafb deficient macrophages. GATA-1 motifs and MafB motifs could regulate expression of these genes in both a negative and positive manner, respectively. The validity of this conclusion was tested with data from a luciferase assay that used a C1qa promoter construct carrying both the GATA-1 motifs and MAREs. GATA-1 was found to inhibit the activity of the C1qa promoter with the GATA-1 motifs and MafB motifs. These observations suggest that both the GATA-1 motifs and MafB motifs are important for lineage specific expression of C1qa. In addition, these findings show that analysis of combinations of evolutionarily conserved motifs can be successfully used to identify patterns of gene regulation.


Leisure-time physical activity: association with activity levels in other domains.
To explore whether participation in leisure-time physical activity (LTPA) is associated with participation in occupational, housework, and transport-related physical activity. Population-based cross-sectional study covering a multistage sample of 972 subjects age 20 to 69 years. Physical activity was measured using the long version of the International Physical Activity Questionnaire. A LTPA score was calculated as follows: min/wk of walking + min/wk of moderate-intensity physical activity + (min/wk of vigorous-intensity physical activity x 2). Similar scores were generated for each domain. For categorical analyses, the scores were divided into 3 categories: 0 min/wk, 10-149 min/wk, and > or = 150 min/wk. The proportion of subjects practicing less than 150 min/wk of physical activity in each domain was: leisure-time (69.8%), occupational (58.3%), housework (35.0%), transportation (51.9%). Subjects with a transport-related physical activity score equal to or above 150 min/wk were 40% less likely to be sedentary in leisure-time in comparison with those who did not practice transport-related physical activity. Housework and occupational physical activity were not related to participation in LTPA. Future physical activity campaigns should focus on other domains instead of LTPA alone, particularly supporting transport-related physical activity as a strategy of health promotion.


Genome-Scale Metabolic Modeling Reveals Sequential Dysregulation of Glutathione Metabolism in Livers from Patients with Alcoholic Hepatitis.
Alcoholic hepatitis (AH) is the most severe form of alcoholic liver disease for which there is no efficacious treatment aiding most patients. AH manifests differently in individuals, with some patients showing debilitating symptoms more so than others. Previous studies showed significant metabolic dysregulation associated with AH. Therefore, we sought to analyze how the activity of metabolic pathways differed in the liver of patients with varying degrees of AH severity. We utilized a genome-scale metabolic modeling approach that allowed for integration of a generic human cellular metabolic model with specific RNA-seq data corresponding to healthy and multiple liver disease states to predict the metabolic fluxes within each disease state. Additionally, we performed a systems-level analysis of the transcriptomic data and predicted metabolic flux data to identify the regulatory and functional differences in liver metabolism with increasing severity of AH. Our results provide unique insights into the sequential dysregulation of the solute transport mechanisms underlying the glutathione metabolic pathway with increasing AH disease severity. We propose targeting of the solute transporters in the glutathione pathway to mimic the flux activity of the healthy liver state as a potential therapeutic intervention for AH.


Combination of pose and rank consensus in docking-based virtual screening: the best of both worlds.
The use of high-throughput docking (HTD) in the drug discovery pipeline is today widely established. In spite of methodological improvements in docking accuracy (pose prediction), scoring power, ranking power, and screening power in HTD remain challenging. In fact, pose prediction is of critical importance in view of the pose-dependent scoring process, since incorrect poses will necessarily decrease the ranking power of scoring functions. The combination of results from different docking programs (consensus scoring) has been shown to improve the performance of HTD. Moreover, it has been also shown that a pose consensus approach might also result in database enrichment. We present a new methodology named Pose/Ranking Consensus (PRC) that combines both pose and ranking consensus approaches, to overcome the limitations of each stand-alone strategy. This approach has been developed using four docking programs (ICM, rDock, Auto Dock 4, and PLANTS; the first one is commercial, the other three are free). We undertook a thorough analysis for the best way of combining pose and rank strategies, and applied the PRC to a wide range of 34 targets sampling different protein families and binding site properties. Our approach exhibits an improved systematic performance in terms of enrichment factor and hit rate with respect to either pose consensus or consensus ranking alone strategies at a lower computational cost, while always ensuring the recovery of a suitable number of ligands. An analysis using four free docking programs (replacing ICM by Auto Dock Vina) displayed comparable results.


[Adolescence and cochlear implant].
During adolescence, the identity is constructed and the communication changes. The cochlear implant may disturb the identity's construction. The restrictions and advantages may be misunderstood due to the communication difficulties. It is important to take time to discuss and explain the limits of this hearing aid. It must not be perceived as a miracle resolving all auditory and oral communication problems. The hearing aid is effective for motivated and informed adolescents. The outcome depends on the level of auditory experience and oral language development before implantation. It can be very positive. (full article translated in English available on www.ent-review.com).


Axillary lymph node dissection for breast cancer utilizing Harmonic Focus®.
For patients with axillary lymph node metastases from breast cancer, performance of a complete axillary lymph node dissection (ALND) is the standard approach. Due to the rich lymphatic network in the axilla, it is necessary to carefully dissect and identify all lymphatic channels. Traditionally, these lymphatics are sealed with titanium clips or individually sutured. Recently, the Harmonic Focus®, a hand-held ultrasonic dissector, allows lymphatics to be sealed without the utilization of clips or ties. We hypothesize that ALND performed with the Harmonic Focus® will decrease operative time and reduce post-operative complications. Retrospective review identified all patients who underwent ALND at a teaching hospital between January of 2005 and December of 2009. Patient demographics, presenting pathology, treatment course, operative time, days to drain removal, and surgical complications were recorded. Comparisons were made to a selected control group of patients who underwent similar surgical procedures along with an ALND performed utilizing hemostatic clips and electrocautery. A total of 41 patients were included in this study. Operative time was not improved with the use of ultrasonic dissection, however, there was a decrease in the total number of days that closed suction drainage was required, although this was not statistically significant. Complication rates were similar between the two groups. In this case-matched retrospective review, there were fewer required days of closed suction drainage when ALND was performed with ultrasonic dissection versus clips and electrocautery.


Updates on human papillomavirus and genital warts and counseling messages from the 2010 Sexually Transmitted Diseases Treatment Guidelines.
In April 2009, experts on sexually transmitted diseases (STDs) were convened to review updates on STD prevention and treatment in preparation for the revision of the Centers for Disease Control and Prevention (CDC) STD Treatment Guidelines. At this meeting, there was a discussion of important updates on human papillomavirus (HPV), genital warts, and cervical cancer screening. Key questions were identified with assistance from an expert panel, and systematic reviews of the literature were conducted searching the English-language literature of the PubMed computerized database (US National Library of Medicine). The available evidence was reviewed, and new information was incorporated in the 2010 CDC STD Treatment Guidelines. Two HPV vaccines are now available, the quadrivalent HPV vaccine and the bivalent HPV vaccine; either vaccine is recommended routinely for girls aged 11 or 12 years. The quadrivalent HPV vaccine may be given to boys and men aged 9-26 years. A new patient-applied treatment option for genital warts, sinecatechins 15% ointment, is available and recommended for treatment of external genital warts. This product is a mixture of active ingredients (catechins) from green tea. Finally, updated counseling guidelines and messages about HPV, genital warts, and cervical cancer are included. This manuscript highlights updates to the 2010 CDC STD Treatment Guidelines for HPV and genital warts. Important additions to the 2010 STD Treatment Guidelines include information on prophylactic HPV vaccine recommendations, new patient-applied treatment options for genital warts, and counseling messages for patients on HPV, genital warts, cervical cancer screening, and HPV tests.


Stat3 mediates interleukin-6 [correction of interelukin-6] inhibition of human endothelial nitric-oxide synthase expression.
Chronic activation of the acute phase response (APR) is associated with atherosclerosis. Elevated levels of interleukin-6, the major inducer of the APR, are associated with an increased risk of cardiovascular events. One of the clinical hallmarks of atherogenesis is endothelial dysfunction, characterized by a decrease in endothelial production of nitric oxide (NO). We hypothesized that interleukin-6 (IL-6) decreases endothelial NO synthase (eNOS) expression. We now show that IL-6 treatment of human aortic endothelial cells (HAEC) decreases steady-state levels of human eNOS mRNA and protein. This decrease in eNOS expression is caused in part by IL-6 inhibition of transactivation of the human eNOS promoter. To explore the mechanism by which IL-6 affects eNOS expression, we examined activation of signal transducer and transactivator-3 (Stat3). The IL-6 receptor (IL-6R) is expressed in HAEC, and Stat3 is phosphorylated in response to IL-6 stimulation of the IL-6R. We identified four consensus sequences for Stat3 binding (SIE) in the eNOS promoter at positions -1520, -1024, -840, and -540. Transfection of eNOS promoter mutants revealed that the SIE at -1024 mediates Stat3 inhibition of eNOS promoter activity. Gel-shift analysis of nuclear extracts from HAEC treated with IL-6 confirms that Stat3 binds to a complex containing the SIE at -1024. RNA silencing of STAT3 blocks the inhibitory effect of IL-6 on eNOS expression. Our data show that IL-6 has direct effects upon endothelial cells, inhibiting eNOS expression in part through Stat3. Decreased levels of eNOS may be an important component of the pro-atherogenic effect of the APR.


Secretory NPC2 Protein-Mediated Free Cholesterol Levels Were Correlated with the Sorafenib Response in Hepatocellular Carcinoma.
Hepatocellular carcinoma (HCC) is the most common primary malignant tumor in the world. Sorafenib is the first-line drug for patients with advanced HCC. However, long-term treatment with sorafenib often results in reduced sensitivity of tumor cells to the drug, leading to acquired resistance. Identifying biomarkers which can predict the response to sorafenib treatment may represent a clinical challenge in the personalized treatment era. Niemann-Pick type C2 (NPC2), a secretory glycoprotein, plays an important role in regulating intracellular free cholesterol homeostasis. In HCC patients, downregulation of hepatic NPC2 is correlated with poor clinical pathological features through regulating mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) activation. This study aimed to investigate the roles of secretory NPC2-mediated free cholesterol levels as biomarkers when undergoing sorafenib treatment and evaluate its impact on acquired sorafenib resistance in HCC cells. Herein, we showed that NPC2 downregulation and free cholesterol accumulation weakened sorafenib's efficacy through enhancing MAPK/AKT signaling in HCC cells. Meanwhile, NPC2 overexpression slightly enhanced the sorafenib-induced cytotoxic effect. Compared to normal diet feeding, mice fed a high-cholesterol diet had much higher tumor growth rates, whereas treatment with the free cholesterol-lowering agent, hydroxypropyl-β-cyclodextrin, enhanced sorafenib's tumor-inhibiting ability. In addition, sorafenib treatment induced higher NPC2 secretion, which was mediated by inhibition of the Ras/Raf/MAPK kinase (MEK)/ERK signaling pathway in HCC cells. In both acquired sorafenib-resistant cell and xenograft models, NPC2 and free cholesterol secretion were increased in culture supernatant and serum samples. In conclusion, NPC2-mediated free cholesterol secretion may represent a candidate biomarker for the likelihood of HCC cells developing resistance to sorafenib.


[Temporal lobe epilepsy and adult hippocampal neurogenesis].
Temporal lobe epilepsy (TLE) is a common and severe neurological disorder which is often intractable. It can not only damage the normal structure and function of hippocampus, but also affect the neurogenesis in dentate gyrus (DG). It is well documented from researches on the animal models of TLE that after a latent period of several days, prolonged seizure activity leads to a dramatic increase in mitotic activity in the hippocampal DG. However, cell proliferation returns to baseline levels within 3-4 weeks after status epilepticus (SE). Meanwhile, there are two major abnormalities of DG neurogenesis, including the formation of hilar basal dendrites and the ectopic migration of newborn granule cells into the polymorphic cell layer, which may affect epileptogenesis and seizure onset. However, the specific contribution of these abnormalities to seizures is still unknown. In other words, whether they are anti-epileptic or pro-epileptic is still under heated discussion. This article systematically reviews current knowledge on neurogenesis and epilepsy based on the results of studies in recent years and discusses the possible roles of neurogenesis in epileptogenesis and pathologic mechanisms, so as to provide information for the potential application of neurogenesis as a new clinical therapeutic target for temporal lobe epilepsy.


Real-World Experience With CMV inSIGHT T Cell Immunity Testing in High-Risk Kidney and Pancreas Transplant Recipients.
Cytomegalovirus (CMV)-specific cell-mediated immunity is important for control of CMV after transplant. Assays exist to measure this, but their place in therapy is unclear, particularly in CMV high-risk recipients, without pretransplant exposure. The objective of this study was to evaluate predictive potential of a positive assay to determine freedom from DNAemia and describe subsequent 3-month CMV outcomes. Adult CMV high-risk kidney and/or pancreas transplant recipients were included if a CMV inSIGHT T Cell Immunity Panel (TCIP, Eurofins Viracor) was ordered and resulted between 1 August, 2019 and 30 July, 2022. Seventy-six patients were included in our study; 49 tested during prophylaxis and 27 during treatment. Most TCIP assays obtained in the prophylaxis cohort were negative (n = 46, 93.9%). Rate of post-TCIP CMV infection was 10.2%. In those tested during treatment, 33.3% were positive and rate of post-TCIP CMV recurrence was 22.2%. The positive predictive value of the assay to successfully predict immunity was 66.7% during both prophylaxis and treatment. There were 4 cases of TCIP predictive failure with progressive CMV replication. At time of replication, 2 patients had concomitant clinical confounders thought to influence immune control of viral replication. All patients had intensification of immunosuppression prior to recurrent replication, but after TCIP was collected. The data obtained from the TCIP are not static, immune control of CMV in latency can change and must be evaluated in clinical context. Timing of TCIP after transplant is significant, and patient-specific factors remain important to assess the likelihood of CMV in each unique patient-specific scenario. A CMV stewardship program can aid in application and interpretation of results.


"The tolerance benefits of multicultural experiences depend on the perception of available mental resources": Correction to Tadmor et al. (2018).
Reports an error in "The tolerance benefits of multicultural experiences depend on the perception of available mental resources" by Carmit T. Tadmor, Ying-yi Hong, Melody M. Chao and Ayala Cohen (Journal of Personality and Social Psychology, Advanced Online Publication, Jul 23, 2018, np). In the article, the legend labels for Figure 4 are missing. The correct labels are Regulated-writing for the black bar and Free-writing for the gray bar. All versions of this article have been corrected. (The following abstract of the original article appeared in record 2018-34852-001.) Multicultural experience has been shown to lead to greater intergroup tolerance via reduced need for cognitive closure (NFCC). However, the requisite metacognitive conditions that facilitate this effect have yet to be examined. In 6 studies, we systematically demonstrated that the ameliorative effects of multicultural experience on intergroup bias are achieved only when individuals perceived that they had sufficient mental resources. Mental resources were either (a) measured during the Hong Kong "Umbrella Revolution" (Study 1), (b) experimentally manipulated in the lab through a classic depletion task (Study 2), or (c) subjectively recalled (Studies 3, 4, 5, and 6). We further showed that the moderating effects of perceived resource availability on the tolerance benefits of multicultural experience were mediated by reduced levels of NFCC (Studies 1, 5, and 6). This effect was consistent across a variety of targeted outgroups (Mainland Chinese, Arabs, Russians, Blacks, Asian Americans, and homosexuals), regardless of whether multicultural experience was measured or manipulated, and across samples (Hong Kongers, Jewish Israelis, and U.S.-born Americans). Overall, by integrating the literature on multicultural experiences with that on perceived resource depletion, we demonstrate the state-dependent nature of the advantages of multicultural experiences as well as afford a more nuanced view of the downstream influence of perceived mental depletion. (PsycINFO Database Record


Learning how to be a student: an overview of instructional practices targeting school readiness skills for preschoolers with autism spectrum disorder.
Due to difficulties associated with autism spectrum disorder (ASD), many children with ASD will require additional support to actively participate in classroom activities. Therefore, it is important that professionals who work with young children with ASD know what skills to teach and how to teach them. Using the recent evidence-based practice review conducted by the National Professional Development Center on ASD, we have identified studies that targeted school readiness behaviors which can have implications for academic skill development. In this article, we evaluate (a) the types of skills that have been taught to preschool children with ASD, (b) the strategies used to teach specific skills, and (c) other descriptive information, such as who delivered the intervention and the setting in which the intervention took place. We conclude by offering suggestions for future research and considerations for professional development.


Enhanced survival of multi-species biofilms under stress is promoted by low-abundant but antimicrobial-resistant keystone species.
Multi-species biofilms are more resistant against stress compared to single-species biofilms. However, the mechanisms underlying this common observation remain elusive. Therefore, we studied biofilm formation of well-known opportunistic pathogens (Acinetobacter baumanii, Enterococcus faecium, Escherichia coli, Staphylococcus haemolyticus and Stenotrophomonas maltophilia) in various approaches. Synergistic effects in their multi-species biofilms were observed. Using metatranscriptomics, changes in the gene expression of the involved members became evident, and provided explanations for the improved survivability under nutrient limitation and exposure to disinfectants. Genes encoding proteins for vitamin B6 synthesis and iron uptake were linked to synergism in the multi-species biofilm under nutrient-limited conditions. Our study indicates that sub-lethal concentrations of an alcohol-based disinfectant enhance biofilm yields in multi-species assemblages. A reduction of the dominant taxa in the multi-species biofilm under disinfectant pressure allowed minor taxa to bloom. The findings underline the importance of minor but antimicrobial-resistant species that serve as "protectors" for the whole assemblage due to upregulation of genes involved in defence mechanisms and biofilm formation. This ultimately results in an increase in the total yield of the multi-species biofilm. We conclude that inter-species interactions may be crucial for the survival of opportunistic pathogens; especially under conditions that are typically found under hospital settings.


DRESS syndrome: a detailed insight.
Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a serious and potentially fatal adverse effect to therapeutic medications. The incidence of this condition varies among different ethnicities because of the difference in the genetic makeup. Though fever, rash and eosinophilia are essential features for the diagnosis of this syndrome, these vary from patient to patient along with the involvement of various organs such as liver, kidney, lungs, pancreas, etc. Some of the atypical features are dysphagia, agranulocytosis, and chylous ascites. Phenytoin, phenobarbitone, carbamazepine, and allopurinol are the most common drugs responsible for developing this syndrome, although the list is fairly long. Among the criteria used for the diagnosis of DRESS syndrome, European Registry of Severe Cutaneous Adverse Reactions to Drugs and Collection of Biological Samples (RegiSCAR) criteria is the most commonly used one. The management of this syndrome involves early removal of the causative agent and treatment with anti-histamines and emollients in the mild form, corticosteroids in the moderate form and plasmapheresis in the severe form along with other alternatives drugs. Healthcare professionals should be more vigilant about the early manifestations of this syndrome, as early diagnosis and treatment improve outcomes considerably.


Glucose concentrations after insulin-induced hypoglycemia and glycemic variability in healthy and diabetic cats.
Little information is available about posthypoglycemic hyperglycemia (PHH) in diabetic cats, and a causal link between hypoglycemia and subsequent hyperglycemia is not clear. Fluctuations in blood glucose concentrations might only represent high glycemic variability. Insulin induces PHH in healthy cats, and PHH is associated with poorly regulated diabetes and increased glycemic variability in diabetic cats. Six healthy cats, 133 diabetic cats. Insulin (protamine-zinc and degludec; 0.1-0.3 IU/kg) administered to healthy cats. Blood glucose curves were generated with portable glucose meter to determine the percentage of curves with PHH. Data from insulin-treated diabetic cats with blood glucose curves showing hypoglycemia included data of cats with and without PHH. Post-hypoglycemic hyperglycemia was defined as blood glucose concentrations <4 mmol/L followed by blood glucose concentrations >15 mmol/L within 12 hours. Glycemic variability was calculated as the standard deviation of the blood glucose concentrations. In healthy cats, all insulin doses caused hypoglycemia but PHH was not observed; glycemic variability did not differ between insulin preparations. Among diabetic cats with hypoglycemia, 33 (25%) had PHH. Compared with cats without PHH, their daily insulin dose was higher (1.09 ± 0.55 versus 0.65 ± 0.56 IU/kg; P < .001), serum fructosamine concentration was higher (565 ± 113 versus 430 ± 112 µmol/L; P < .001), remission was less frequent (10% versus 56%; P < .001), and glycemic variability was larger (8.1 ± 2.4 mmol/L versus 2.9 ± 2.2 mmol/L; P < .001). Insulin-induced hypoglycemia did not cause PHH in healthy cats but it occurred in 25% of diabetic cats with hypoglycemia, particularly when diabetes was poorly controlled. Glycemic variability was increased in cats with PHH.


A Systematic Review on Improving the Family Experience After Consent for Deceased Organ Donation.
The demand for transplanted organs outweighs the supply and intensifies the need to improve care for donor families. Studies have shown inadequate care by hospital staff can increase posttraumatic stress disorder and complicated grief in these families but putting solutions into practice remains slow. This systematic review identified factors that relieve or contribute to distress for deceased organ donor families in the time since the decision to donate. Additionally, it provides insights into potential improvements at public health, educational, and health system levels to address these deficiencies. Search terms included organ don*, famil* or relati*, family-centered, grief, and experience*. The search covered original research articles, published in English, from 2014 to July 2021. Four key themes emerged among the studies. (a) Understanding factors that affect the emotional aftermath can help staff prevent posttraumatic stress disorder and complicated grief. (b) Improving communication by hospital staff includes: avoiding medical jargon, providing adequate audio and visual explanations, and understanding that the next of kin is struggling to comprehend the tragedy and the information they are being told. (c) End-of-life care such as memory making, bringing in palliative care resources, and parting ceremonies can assist with familial coping as well as staff interactions. (d) Families want more support in the months and years after the donation decision. Changes at multiple levels can improve the quality of care for families whose relative gave the gift of life, but more research and translation into practice are needed.


Concerted motions networking pores and distant ferroxidase centers enable bacterioferritin function and iron traffic.
X-ray crystallography, molecular dynamics (MD) simulations, and biochemistry were utilized to investigate the effect of introducing hydrophobic interactions in the 4-fold (N148L and Q151L) and B-pores (D34F) of Pseudomonas aeruginosa bacterioferritin B (BfrB) on BfrB function. The structures show only local structural perturbations and confirm the anticipated hydrophobic interactions. Surprisingly, structures obtained after soaking crystals in Fe2+-containing crystallization solution revealed that although iron loads into the ferroxidase centers of the mutants, the side chains of ferroxidase ligands E51 and H130 do not reorganize to bind the iron ions, as is seen in the wt BfrB structures. Similar experiments with a double mutant (C89S/K96C) prepared to introduce changes outside the pores show competent ferroxidase centers that function akin to those in wt BfrB. MD simulations comparing wt BfrB with the D34F and N148L mutants show that the mutants exhibit significantly reduced flexibility and reveal a network of concerted motions linking ferroxidase centers and 4-fold and B-pores, which are important for imparting ferroxidase centers in BfrB with the required flexibility to function efficiently. In agreement, the efficiency of Fe2+ oxidation and uptake of the 4-fold and B-pore mutants in solution is significantly compromised relative to wt or C89S/K96C BfrB. Finally, our structures show a large number of previously unknown iron binding sites in the interior cavity and B-pores of BfrB, which reveal in unprecedented detail conduits followed by iron and phosphate ions across the BfrB shell, as well as paths in the interior cavity that may facilitate nucleation of the iron phosphate mineral.


Desiccation Tolerance in Chlorophyllous Fern Spores: Are Ecophysiological Features Related to Environmental Conditions?
Fern spores of most species are desiccation tolerant (DT) and, in some cases, are photosynthetic at maturation, the so-called chlorophyllous spores (CS). The lifespan of CS in the dry state is very variable among species. The physiological, biochemical, and biophysical mechanisms underpinning this variability remain understudied and their interpretation from an ecophysiological approach virtually unexplored. In this study, we aimed at fulfilling this gap by assessing photochemical, hydric, and biophysical properties of CS from three temperate species with contrasting biological strategies and longevity in the dry state: Equisetum telmateia (spore maturation and release in spring, ultrashort lifespan), Osmunda regalis (spore maturation and release in summer, medium lifespan), Matteuccia struthiopteris (spore maturation and release in winter, medium-long lifespan). After subjection of CS to controlled drying treatments, results showed that the three species displayed different extents of DT. CS of E. telmateia rapidly lost viability after desiccation, while the other two withstood several dehydration-rehydration cycles without compromising viability. The extent of DT was in concordance with water availability in the sporulation season of each species. CS of O. regalis and M. struthiopteris carried out the characteristic quenching of chlorophyll fluorescence, widely displayed by other DT cryptogams during drying, and had higher tocopherol and proline contents. The turgor loss point of CS is also related to the extent of DT and to the sporulation season: lowest values were found in CS of M. struthiopteris and O. regalis. The hydrophobicity of spores in these two species was higher and probably related to the prevention of water absorption under unfavorable conditions. Molecular mobility, estimated by dynamic mechanical thermal analysis, confirmed an unstable glassy state in the spores of E. telmateia, directly related to the low DT, while the DT species entered in a stable glassy state when dried. Overall, our data revealed a DT syndrome related to the season of sporulation that was characterized by higher photoprotective potential, specific hydric properties, and lower molecular mobility in the dry state. Being unicellular haploid structures, CS represent not only a challenge for germplasm preservation (e.g., as these spores are prone to photooxidation) but also an excellent opportunity for studying mechanisms of DT in photosynthetic cells.


Cross-bridge elasticity in single smooth muscle cells.
In smooth muscle, a cross-bridge mechanism is believed to be responsible for active force generation and fiber shortening. In the present studies, the viscoelastic and kinetic properties of the cross-bridge were probed by eliciting tension transients in response to small, rapid, step length changes (delta L = 0.3-1.0% Lcell in 2 ms). Tension transients were obtained in a single smooth muscle cell isolated from the toad (Bufo marinus) stomach muscularis, which was tied between a force transducer and a displacement device. To record the transients, which were of extremely small magnitude (0.1 microN), a high-frequency (400 Hz), ultrasensitive force transducer (18 mV/microN) was designed and built. The transients obtained during maximal force generation (Fmax = 2.26 microN) were characterized by a linear elastic response (Emax = 1.26 X 10(4) mN/mm2) coincident with the length step, which was followed by a biphasic tension recovery made up of two exponentials (tau fast = 5-20 ms, tau slow = 50-300 ms). During the development of force upon activation, transients were elicited. The relationship between stiffness and force was linear, which suggests that the transients originate within the cross-bridge and reflect the cross-bridge's viscoelastic and kinetic properties. The observed fiber elasticity suggests that the smooth muscle cross-bridge is considerably more compliant than in fast striated muscle. A thermodynamic model is presented that allows for an analysis of the factors contributing to the increased compliance of the smooth muscle cross-bridge.


Urinary tract infections in the female patient.
Recent investigations into the pathogenesis of urinary tract infections have led to significant understanding of the interaction between uropathogens and the urogenital tract. This understanding provides the potential for the development of new types of therapy. A practical approach to the management of lower urinary tract infections in female patients is discussed, as are new therapies for nonbacterial cystitis, including the urgency-frequency syndrome.


It's (a) Shame: Why Poverty Leads to Support for Authoritarianism.
The literature has widely discussed and supported the relationship between poverty and support for authoritarian leaders and regimes. However, there are different claims about the mediating mechanism and a lack of empirical tests. We hypothesize that the effect of poverty on support for authoritarianism is mediated by shame: People living in poverty frequently experience social exclusion and devaluation, which is reflected in feelings of shame. Such shame, in turn, is likely to increase support for authoritarianism, mainly due to the promise of social re-inclusion. We support our hypothesis in two controlled experiments and a large-scale field study while empirically ruling out the two main alternative explanations offered in the literature: stress and anxiety. Finally, we discuss how the present findings can support policymakers in efficiently addressing the negative political consequences of poverty.


High-dose chemotherapy and autologous peripheral blood stem cell transplantation for primary breast cancer refractory to neoadjuvant chemotherapy.
The role of high-dose chemotherapy (HDCT) in patients with refractory breast cancer is not well established. Forty-two female patients (median age of 46 years) with breast cancer refractory to neoadjuvant chemotherapy received HDCT (cyclophosphamide, carmustine and thiotepa) supported by an autologous peripheral blood stem cells transplant. Their disease had been refractory (defined as less than partial response) to one (18 patients) or two (24 patients) regimens of neoadjuvant chemotherapy. Twenty-nine patients had surgery before HDCT. The best response after surgery, HDCT, and radiation therapy was assessed 60 days after transplantation. Thirty patients had complete remission, eight had a PR, one had a minor response, and three had progressive disease. In seven of 13 patients whose disease was inoperable before HDCT, it became operable. After a median follow-up of 42 months, 21 patients were alive, and 15 remained disease free. Five-year overall survival (OS) was 57% (CI, 50-64%), and the estimated 5-year progression-free survival was 40% (CI, 32-48%). Both OS and PFS were better in patients whose disease became operable after chemotherapy than in those whose disease remained inoperable. A randomized study is warranted in this patient population.


Spectroscopic (vibrational, NMR and UV-vis.) and quantum chemical investigations on 4-hexyloxy-3-methoxybenzaldehyde.
In this study, the 4-hexyloxy-3-methoxybenzaldehyde compound as one of the derivatives of vanillin which is a well known flavoring agent, C14H20O3, has been investigated by experimentally and extensively utilizing density functional theory (DFT) at the B3LYP/6-311++G(d,p) level. In this context, the optimized geometry, vibrational frequencies, (1)H and (13)C NMR chemical shifts, UV-vis. (in gas phase and in methanol solvent) spectra, HOMO-LUMO analysis, molecular electrostatic potential (MEP), thermodynamic parameters and atomic charges of 4-hexyloxy-3-methoxybenzaldehyde have been calculated. In addition, theoretically predicted IR, Raman and UV-vis. (in gas phase and in methanol solvent) spectra of the mentioned molecule have been constructed. The results calculated were compared with the experimental data.