Benign Degos' disease developing during pregnancy and followed for 10 years.
Degos' disease, or malignant atrophic papulosis, is a rare and often fatal multisystem vasculopathy of unknown etiology. The cutaneous manifestations comprise erythematous papules, which heal to leave scars with a pathognomonic central porcelain-white atrophic area and a peripheral telangiectatic rim. Involvement of the gastrointestinal tract is observed in 50% of cases, with intestinal perforation being the most common cause of death. Other organ systems can also be affected; 20% of cases involve the central nervous system. Systemic manifestations usually develop from weeks to years after onset of skin lesions or, in rare instances, may precede skin lesions. In the patient with Degos' disease reported in this article, the characteristic skin lesions developed during pregnancy, a precipitating event not previously reported. She has survived an unusually long time (10 years) without visceral or neurological involvement, despite florid cutaneous lesions. Moreover, we could detect the presence of antiphospholipid antibodies, the significance of which are currently unclear. These observations therefore confirm that there may be a strictly cutaneous form of Degos' disease with a favourable prognosis.


Physicians lead the way at America's top hospitals.
The 100 Top hospitals are selected annually based on seven critical parameters for each of the 6,200-plus U.S. hospitals with 25 or more beds. They include the previous year's risk-adjusted patient mortality and complication rates, severity-adjusted average patient lengths of stay, expenses, profitability, proportional outpatient revenue, and asset turnover ratio (a measure of facility and technological pace-keeping ability). The winners are selected from five comparable size groupings--small, medium, large community, teaching, and large academic hospitals. Conspicuous among the winners at every level are physician-led organizations. Even in the majority of hospitals headed by non-physician administrators, however, the managerial capabilities of medical directors are the key to success. The most common characteristic of these award-winning hospitals is that the leadership is working together and communicating the institution's goals effectively to all levels of the organization.


Chlorine-Doped Perovskite Oxide: A Platinum-Free Cathode for Dye-Sensitized Solar Cells.
Triiodide/iodide (I3-/I-) redox couple-mediated solar cells, batteries, and electrochromic devices require highly efficient and stable electrocatalysts for I3- reduction reaction (IRR) to overcome performance limitations, whereas the widely used platinum (Pt) cathode for IRR has limitations of high price and unfavorable durability. In this work, we present a halogen element (chlorine) doping strategy to design low-cost perovskite-type electrocatalysts with enhanced IRR activity and stability. The dye-sensitized solar cell (DSSC) assembled by the LaFeO2.965-δCl0.035 cathode delivers an attractive power conversion efficiency (PCE) of 11.4% with a remarkable PCE enhancement factor of 23% compared with Pt, which is higher than most of the reported non-Pt DSSC cathodes. Attractively, LaFeO2.965-δCl0.035 displays superior IRR activity/stability and structural stability in the I3-/I--based electrolyte compared to pristine LaFeO3 because chlorine doping facilitates the creation of oxygen vacancies (active sites) and enhances surface acidity simultaneously. This study provides a new way for designing outstanding IRR electrocatalysts, which could be applied to many redox couple-mediated photo/electrochemical devices.


Early periprosthetic hip joint infection managed by cementless one-stage revision - a case series.
Background: Early periprosthetic hip joint infection (PJI) is traditionally treated with debridement, antibiotics, and implant retention (DAIR). However, infection control rates after DAIR-treated periprosthetic hip joint infection do not exceed 77 %. Cementless one-stage revision of chronic PJI by the Cementless One-stage Revision of Infected Hip Arthroplasty (CORIHA) protocol has been evaluated positively with a 91 % success rate. We wanted to evaluate the effectiveness of cementless one-stage revision following the CORIHA protocol for early PJI in elective primary total hip arthroplasty, regarding risk of re-operation with exchange of implants. Methods: We identified 18 patients in our center with early ( ≤ 6 -week postoperative) PJI after primary total hip arthroplasty (THA) treated with one-stage cementless revision in the period January 2012-March 2018. Treatment followed the CORIHA protocol. Primary outcome was retention of implants at the most recent follow-up. Patients were followed for a minimum of 3 years. Results: Mean follow-up time was 60 months (39-105). All patients retained their implants, but two required superficial soft tissue debridement due to persistent wound seepage. Conclusion: Cementless one-stage revision appears to be an effective treatment of early PJI after primary THA and at least an equal choice of treatment compared with DAIR. Whether the potential benefit of a lower re-revision rate for postoperative PJI outweighs the increased surgical complexity of the CORIHA procedure needs further evaluation.


Quality of Evidence Supporting the Role of Supplement Curcumin for the Treatment of Ulcerative Colitis: An Overview of Systematic Reviews.
Curcumin is a potential complementary treatment for ulcerative colitis (UC). This overview systematically summarizes and evaluates the existing evidence of curcumin in the treatment of UC. Two researchers searched seven databases for systematic reviews (SRs)/meta-analyses (MAs) which are about randomized controlled trials (RCTs) on curcumin for UC. Two researchers use the Assessment of Multiple Systematic Reviews 2 (AMSTAR-2), the Risk of Bias in Systematic Reviews (ROBIS) scale, the list of Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system to assess the included SRs/MAs. Seven published SRs/MAs were included in our study. According to the results of the AMSTAR-2 assessment, all SRs/MAs are considered to be of very low quality. According to the ROBIS evaluation results, no SR/MA has been assessed as a low risk of bias. According to the results of the PRISMA checklist assessment, no SR/MA has been fully reported on the PRISMA checklist. According to GRADE, a total of 19 outcome indicators extracted from the included SRs/MAs were evaluated. The quality of evidence was 10 moderate, 6 low, and 3 very low. Curcumin may be an effective and safe complementary treatment for UC. However, further standard and comprehensive SRs/MAs and RCTs are needed to provide an evidence-based medical rationale for this.


Active Components of Traditional Chinese Medicinal Material for Multiple Myeloma: Current Evidence and Future Directions.
Multiple myeloma (MM) is a hematological malignancy characterized by clonal expansion of plasma cells in bone marrow, leading to the overproduction of monoclonal immunoglobulins. The clinical manifestations resulting from monoclonal proteins and malignant cells include signs of end-organ damage, such as hypercalcemia, renal failure, anemia, and bone lesions. Despite improvement in the survival of MM patients with use of myeloma-targeted and immunomodulatory therapies, MM remains an incurable disease. Moreover, patients with relapsed or refractory MM show poor survival outcomes. In recent years, there has been a growing interest in the use of traditional Chinese medicinal materials (TCMMs) for management of a wide spectrum of diseases. The bioactive ingredients derived from TCMMs hold great potential for the development of anticancer drugs. Here we summarize the evidence of the pharmacological effects of the active components in TCMMs on MM, including curcumin, resveratrol, baicalein, berberine, bufalin, cinobufagin, gambogic acid, ginsenoside, icariin, daidzin, formononetin, polysaccharides extracts from Hedyotis difus, and scutellarein. Available evidence indicates that the anti-MM effects of these bioactive ingredients are mediated via regulation of proliferation, apoptosis, autophagy, cell cycle, osteogenic differentiation, and drug resistance. In the future, the underlying mechanisms of the anti-MM effects of these components should be further investigated. Large-scale and well-designed clinical trials are also required to validate the efficacy of these bioactive constituents for MM.


Strain differentiation in microsporidia.
Microsporidia are obligate intracellular, spore-forming protozoa and are regarded as newly emerging pathogens . Enterocytozoon spp. as well as Encephalitozoon spp. are recognized as major aetiological agents in chronic diarrhoea of immnunocompromised patients. The detection and differentiation of strains within microsporidial species is a prerequisite for the elucidation of their hitherto unknown reservoirs and their mode of transmission . In Enterocytozoon bieneusi, the most prevalent human-pathogenic microsporidium, 6 different genotypes of the internal transcribed spacer (ITS) of the rRNA gene are known so far, with 12 polymorphic sites . This pathogen has infrequently been detected in 2 animal hosts only, pigs and rhesus macaques, and only the genotype of the latter has also been found in a human patient, too. Encephalitozoon cuniculi has a wider confirmed spectrum of animal hosts, but only one polymorphic site is known in the ITS, differing in 3 different numbers of a tetranucleotide repeat. Therefore, further genomic targets may have to be characterized, too. Few data are available on strain differentiation in Encephalitozoon intestinalis and E. hellem.


Analysis of Cell Wall-Related Genes in Organs of Medicago sativa L. under Different Abiotic Stresses.
Abiotic constraints are a source of concern in agriculture, because they can have a strong impact on plant growth and development, thereby affecting crop yield. The response of plants to abiotic constraints varies depending on the type of stress, on the species and on the organs. Although many studies have addressed different aspects of the plant response to abiotic stresses, only a handful has focused on the role of the cell wall. A targeted approach has been used here to study the expression of cell wall-related genes in different organs of alfalfa plants subjected for four days to three different abiotic stress treatments, namely salt, cold and heat stress. Genes involved in different steps of cell wall formation (cellulose biosynthesis, monolignol biosynthesis and polymerization) have been analyzed in different organs of Medicago sativa L. Prior to this analysis, an in silico classification of dirigent/dirigent-like proteins and class III peroxidases has been performed in Medicago truncatula and M. sativa. The final goal of this study is to infer and compare the expression patterns of cell wall-related genes in response to different abiotic stressors in the organs of an important legume crop.


Isolated fibrous dysplasia of the zygomatic bone.
Fibrous dysplasia is a nonneoplastic, hamartomatous, developmental disease of the bone of obscure etiology. The disease is generally presented as a continuously growing, painless mass at late childhood. It is mostly seen in the maxilla and the mandible in facial skeleton. Involvement of the zygomatic bone is far rarer. Fibrous dysplasia of the zygomatic bone may cause orbital dystopia, diplopia, proptosis, loss of visual acuity, swelling, mass formation, or facial asymmetry. We present 2 cases of fibrous dysplasia with isolated zygomatic bone involvement.


Surveillance of Salmonella spp. and Campylobacter spp. in poultry production flocks in The Netherlands.
In The Netherlands, a national programme for the surveillance of zoonotic bacteria in farm animals has been operative since 1997. We describe the results of the surveillance of Salmonella spp. in flocks of laying hens and broilers and of Campylobacter spp. in broiler flocks in the period 1999-2002. The prevalence of Salmonella spp. in laying-hen flocks has significantly decreased from 21.1% in 1999 to 13.4% in 2002. This decreasing trend might indicate that the control measures taken by the poultry industry were effective. S. Enteritidis was the predominant serovar in laying hens accounting for one third of the positive flocks. Although prevalence estimates for Salmonella spp. in broiler flocks did not yield a significant decreasing trend in 1999-2002, a decrease in Salmonella prevalence to 11% was measured in 2002. During the study period, S. Paratyphi B var. Java emerged in broilers to become the predominant serovar in 2002 accounting for one third of the positive flocks. The prevalence of Campylobacter spp. in broiler flocks did not increase nor decrease continuously between 1999 and 2002, which roughly corresponds with the monitoring results from the poultry industry. In this period, the estimated flock prevalence roughly averaged around 20%, with C. jejuni being the predominant species. The approach of monitoring presented in this paper can serve as a blueprint for monitoring schemes in farm animal populations to be developed in the context of the EC Zoonoses Directive.


Acute fatty liver of pregnancy after aspirin intake.
Acute fatty liver is a rare but fatal complication of pregnancy. Here we describe a patient presenting with stupor and jaundice after aspirin intake at 35 weeks of gestation. Supportive management and delivery resulted in uneventful discharge of the patient and the newborn. Differential diagnosis and management of this condition are discussed.


Target Analysis and Mechanism of Podophyllotoxin in the Treatment of Triple-Negative Breast Cancer.
As the original compound of many podophyllotoxin derivatives, podophyllotoxin has a beneficial antitumor effect. The mechanism of podophyllotoxin activity in triple-negative breast cancer still needs to be explored. We used cell proliferation assay, scratch and transwell experiments, and cell cycle and apoptosis analyses to observe the intervention effect of podophyllotoxin on breast cancer. Furthermore, we analyzed the differences between GSE31448, GSE65194, and GSE45827 in the Gene Expression Omnibus database (GEO) and explored the differential genes using a STRING database. Centiscape2.2, MCODE cluster analysis and KEGG pathway analysis were used to identify the most significant gene differences. Next, we utilized BATMAN-TCM and TCMSP databases for further screening to identify key genes. Finally, quantitative RT-PCR (qRT-PCR) and Western blotting were performed to detect the expression of key targets. Our research confirmed that podophyllotoxin could not only inhibit the migration and invasion of triple-negative breast cancer but also affect the cell cycle and induce apoptosis. In total, 566 differential genes were obtained by using the GEO database. After topological network analysis, cluster analysis, and molecular docking screening, we finally identified PLK1, CCDC20, and CDK1 as key target genes. The results of the qRT-PCR assay showed that the mRNA levels of PLK1, CDC20, and CDK1 decreased, while the expression of upstream P53 increased, after drug induction. The Gene Set Enrichment Analysis (GSEA) and conetwork analysis showed that PLK1 is a more critical regulatory factor. Further Western blotting analysis revealed that there was a negative regulatory relationship between the key gene PLK1 and P53 on the protein level. The results were presented as the mean ± standard deviation of triplicate experiments and P<0.05 was considered to indicate a statistically significant difference. Podophyllotoxin has an intervention effect on the development of triple-negative breast cancer. The expression of PLK1, CDC20, and CDK1 in the cell cycle pathway is inhibited by regulating P53. Our research shows that natural drugs inhibit tumor activity by regulating the expression of cyclins, and the combination of natural drugs and modern extensive database analysis has a wide range of potential applications in the development of antitumor therapies.


Overproduction of the Escherichia coli recA protein without stimulation of its proteolytic activity.
Plasmid pBEU14, which carries the Escherichia coli recA+ gene and which can be amplified by manipulation of growth temperature, was constructed. When pBEU14 deoxyribonucleic acid was amplified, a high rate of synthesis and accumulation of recA protein resulted. Amplification of the recA gene and protein did not cause induction of prophage lambda, indicating that the proteolytic activity of the recA protein was not stimulated.


[Adjustment disorders: a clinical study of a psychiatric hospital population in Tunisia].
The objectives of this study were to determine the frequency of adjustment disorders in psychiatric hospital and to establish the clinical and evolutional profiles of these disorders. A descriptive and retrospective study with approximately 115 patients hospitalized a first time in a psychiatric setting of the university hospital of Monastir in Tunisia for adjustment disorders according to the DSM-IV. The frequency of adjustment disorders in a psychiatric hospital was estimated at 11,8 %. The majority of patients were young (65,3 % between 16 and 20), female (60,9 %), of low professional and socio-economical status, and without any psychiatric history (59,1 %). The acute appearance of adjustment disorders caused by psychosocial stress factors which were usually various (60 %), recent (61,7 %) and with a high severity (69,6 %). The suicide attempts were frequent (53 %) representing the first reason for hospitalization. An evolution was favourable in 75,7 % of cases after a short hospitalization (about 8,2 days). Finally, the authors insist on the short hospitalization in order to provide evaluation, observation and treatment setting for these disorders.


The U-shaped curve: various health measures and alcohol drinking patterns.
To determine whether the well-known U-shaped relationship between average alcohol intake and mortality also holds for other health measures and for aspects of drinking other than weekly average alcohol intake, such as frequency of heavy-drinking episodes. This study was carried out within the framework of a general population survey conducted in Eindhoven, The Netherlands (N = 18,973). Apart from mortality, the following health measures were considered: self-assessed health (based on perceived general health and the Nottingham Health Profile questionnaire), a list of chronic conditions and a list of health complaints. Respondents were categorized as abstainers, light (1-14 units/week), moderate (15-28 units/week) and excessive drinkers (> or =29 units/week). Information on the frequency with which heavy-drinking episodes occurred was also available. Light or moderate drinkers had not only lower mortality but other health burdens were lower than for either abstainers or heavier drinkers. Frequent heavy-drinking episodes were observed to be directly related to increased mortality rates, although not significantly. A trend was observed for drinkers reporting seldom heavy-drinking episodes (once or twice in the previous 6 months) to report less health burdens and to have lower mortality rates than those reporting no heavy drinking episodes. A U-shaped pattern was observed for mortality as well as for several other health measures. Frequent heavy-drinking episodes were related to an increased likelihood of mortality (not significant but suggesting a J-shaped pattern) and were not related to other health measures.


Establishing a combined stimulation protocol hFSH followed by rFSH might represent a breakthrough in the IVF practice.
The article "Establishing a combined stimulation protocol hFSH followed by rFSH might represent a breakthrough in the IVF practice" by S. Gerli, G.C. Di Renzo, published in Eur Rev Med Pharmacol Sci 2013; 2013; 17 (15): 2091-2096 has been withdrawn.


Apolipoprotein E genotyping: accurate, simple, high throughput method using ABI Prism SNaPshot Multiplex System.
Apolipoprotein E (apo E) is an essential constituent of several plasma lipoproteins, and plays an important role in lipoprotein metabolism. The apo E gene exhibits two common functional polymorphisms, producing 3 isoforms known to be associated with the risks of developing cardiovascular disease and susceptibility to Alzheimer's disease. Numerous different methods have been established for determining the three apo E isoforms, yet there are disadvantages and ambiguities associated with all of them. We used a method adapted for multiplex automated primer extension analysis by improving a commercially available protocol (SNaPshot) and simultaneously typing apo E single nucleotide polymorphisms (SNPs) encoding for isoforms at codon 112 and 158. This protocol relies on the extension with fluorescent dideoxyNTPs of a primer that ends one nucleotide 5' of a given SNP (minisequencing). Improvement of the method is achieved by incorporating into the minisequencing reaction two pooled primers corresponding to both apo E SNPs followed by analysis on an ABI PRISM 310 DNA sequencer. We found full concordance with genotypes determined using universal heteroduplex. This method is readily available for many laboratories and is a simple, unequivocal easy to use technique suitable for large amount of clinical samples that may provide a significant improvement over previously reported methods for apo E genotyping.


Determinants of blood pressure in the first decades of life.
The blood pressure (BP) in children has been studied since the beginning of this century, and in the past decade the potential association between childhood BP levels and adult hypertension has gained increasing interest. From several longitudinal studies, many of them comprising large numbers of children and youngsters, it appears that the BP of children is significantly associated with BP on follow-up measurements and that childhood BP is related to adult levels. Whether the objective is to predict future BP, or the aim is to shed light on the early pathogenesis of primary hypertension, it is of major importance to find out why BP rises in some and stays the same in others. To achieve this, characteristics need to be detected that are related to changes in BP in the first decades of life. Although not many reports on these dynamic relations are presently available, age, height, body weight, initial BP level, and a family history of hypertension have been put forward as determinants of children's BP change over time. Moreover, there are data to support the effect of dietary factors, most notably certain electrolytes, on BP regulation early in life. Also, certain hemodynamic and neural characteristics, such as changes in cardiac output and left ventricular mass, renal blood flow, and sympathetic nervous system activity, may be related to a subsequent rise in BP and future hypertension. Findings from nonexperimental and experimental studies on determinants of BP in children and youngsters will be reviewed.


Laughter among deaf signers.
The placement of laughter in the speech of hearing individuals is not random but "punctuates" speech, occurring during pauses and at phrase boundaries where punctuation would be placed in a transcript of a conversation. For speakers, language is dominant in the competition for the vocal tract since laughter seldom interrupts spoken phrases. For users of American Sign Language, however, laughter and language do not compete in the same way for a single output channel. This study investigated whether laughter occurs simultaneously with signing, or punctuates signing, as it does speech, in 11 signed conversations (with two to five participants) that had at least one instance of audible, vocal laughter. Laughter occurred 2.7 times more often during pauses and at phrase boundaries than simultaneously with a signed utterance. Thus, the production of laughter involves higher order cognitive or linguistic processes rather than the low-level regulation of motor processes competing for a single vocal channel. In an examination of other variables, the social dynamics of deaf and hearing people were similar, with "speakers" (those signing) laughing more than their audiences and females laughing more than males.


Comprehensive intra-individual genomic and transcriptional heterogeneity: Evidence-based Colorectal Cancer Precision Medicine.
Despite advances in translating conventional research into multi-modal treatment for colorectal cancer (CRC), therapeutic resistance and relapse remain unresolved in advanced resectable and, particularly, non-resectable disease. Genome and transcriptome sequencing and editing technologies, coupled with interaction mapping and machine learning, are transforming biomedical research, representing the most rational hope to overcome unmet research and clinical challenges. Rapid progress in both bulk and single-cell next-generation sequencing (NGS) analyses in the identification of primary and metastatic intratumor genomic and transcriptional heterogeneity (ITH) and the detection of circulating cell-free DNA (cfDNA) alterations is providing critical insight into the origins and spatiotemporal evolution of genomic clones responsible for early and late therapeutic resistance and relapse. Moreover, DNA and RNA editing pave new avenues towards the discovery of novel drug targets. Breakthrough combinations of sequencing and editing systems with technologies exploring dynamic interaction networks within pioneering studies could delineate how coding and non-coding mutations perturb regulatory networks and gene expression. This review discusses latest data on genomic and transcriptomic landscapes in time and space, as well as early-phase clinical trials on targeted drug combinations, highlighting the transition from research to clinical Colorectal Cancer Precision Medicine, through non-invasive screening, individualized drug response prediction and development of multiple novel drugs. Future studies exploring the potential to target key transcriptional drivers and regulators will contribute to the next-generation pharmaceutical controllability of multi-layered aberrant transcriptional biocircuits.


Orbital angiolymphoid hyperplasia with eosinophilia. Presentation as chalazion.
Angiolymphoid hyperplasia with eosinophilia (ALHE) is an uncommon, benign slow-growing lesion primarily found in the head and neck region, with onset between the third and fourth decades, and a female predominance in the nonOriental population. Kimura's disease, occurring primarily in young Oriental males, is a similar lesion with peripheral blood eosinophilia, regional lymphadenopathy, and occasional nephrotic syndrome. Orbital ALHE is rare, previously reported in only nine patients. Orbital ALHE is a solitary lesion, with an older age of onset, between the fourth and eighth decades, than ALHE elsewhere. There is a male predominance, in contradistinction to ALHE elsewhere in nonOrientals. Orbital ALHE demonstrates the same histology as other locations, with exuberant capillary proliferation and an inflammatory infiltrate of eosinophils, lymphocytes, plasma cells, and mast cells. The maturity of the lesion, not necessarily the duration, determines the presence of lymphoid follicles and germinal centers. A distinctive endothelial cell lines and even extends into the vascular lumens. Peripheral blood eosinophilia occasionally occurs, and a few cases have been reported in conjunction with asthma. Therapeutic regimens for ALHE include excision, carbon dioxide and argon laser, irradiation, steroids, electrodesiccation, and cytotoxic agents. Orbital lesions have been treated successfully with excision, or biopsy with debulking, or steroids.


Antimicrobial treatment of grapes using sodium hypochlorite in winemaking and its effects on the chemical and sensory characteristics of wines.
This study was performed to examine the use of NaOCl as an alternative antimicrobial compound in winemaking because of the potential health problems that may arise as a result of the use of SO2. For this, the blank (non-treated), control (SO2-added), and sample (NaOCl-treated) wines were made, and microbial and chemical changes including sensory characteristics were analyzed during the fermentation periods. Treatment of grapes with NaOCl decreased the initial contaminating microbial population in grape must, resulting in higher growth of yeast and lactic acid bacteria. After 200 days of fermentation, the chemical analysis of sample wine revealed that it had higher ethanol content, redness (a*), and concentrations of fruity ester compounds and lower total acidity than the control. In the sensory analyses, the sample wine obtained a higher overall acceptability score (5.70) than the control (4.26). This result reveals that NaOCl can be used as an alternative to SO2 in winemaking for inhibiting the growth of contaminating microorganisms.


Prenatal Nicotine Exposure Disrupts Infant Neural Markers of Orienting.
Prenatal nicotine exposure (PNE) from maternal cigarette smoking is linked to developmental deficits, including impaired auditory processing, language, generalized intelligence, attention, and sleep. Fetal brain undergoes massive growth, organization, and connectivity during gestation, making it particularly vulnerable to neurotoxic insult. Nicotine binds to nicotinic acetylcholine receptors, which are extensively involved in growth, connectivity, and function of developing neural circuitry and neurotransmitter systems. Thus, PNE may have long-term impact on neurobehavioral development. The purpose of this study was to compare the auditory K-complex, an event-related potential reflective of auditory gating, sleep preservation and memory consolidation during sleep, in infants with and without PNE and to relate these neural correlates to neurobehavioral development. We compared brain responses to an auditory paired-click paradigm in 3- to 5-month-old infants during Stage 2 sleep, when the K-complex is best observed. We measured component amplitude and delta activity during the K-complex. Infants with PNE demonstrated significantly smaller amplitude of the N550 component and reduced delta-band power within elicited K-complexes compared to nonexposed infants and also were less likely to orient with a head turn to a novel auditory stimulus (bell ring) when awake. PNE may impair auditory sensory gating, which may contribute to disrupted sleep and to reduced auditory discrimination and learning, attention re-orienting, and/or arousal during wakefulness reported in other studies. Links between PNE and reduced K-complex amplitude and delta power may represent altered cholinergic and GABAergic synaptic programming and possibly reflect early neural bases for PNE-linked disruptions in sleep quality and auditory processing. These may pose significant disadvantage for language acquisition, attention, and social interaction necessary for academic and social success.


Independent contribution of left ventricular ejection time to the mean gradient in aortic stenosis.
Transvalvular mean pressure gradients (MPG) are important in the evaluation of aortic stenosis, but surprisingly they often differ in patients having similar valve effective orifice area (EOA) and stroke volume (SV). The study aim was to determine if these differences could be explained by variations in left ventricular ejection time (LVET). A pulse duplicator system with a constant SV of 75 ml and incremental increases of LVET from 250 to 450 ms was used to measure MPG by Doppler echocardiography in three fixed stenoses (0.5, 1.0 and 1.5 cm2). The same variables were also measured at rest in 192 patients with isolated aortic stenosis (EOA <1.5 cm2) as well as during stress in a subgroup of 24 patients. In vitro, the increase in LVET produced marked decreases of MPG ranging from -40 mmHg (-45%) for the 0.5-cm2 stenosis to -22 mmHg (-61%) for the 1.5-cm2 stenosis. In vivo, MPG measured by Doppler correlated strongly (R2 = 0.83) with the MPG predicted by the formula: MPGpred [SV/(50xEOAxLVET)]2, and on this basis the relative contributions of EOA, SV and LVET to the variance of MPG were found to be 36, 34 and 13%, respectively. During stress, the contribution of LVET to the increase in MPG was variable, but was sometimes as important as that of SV. LVET may significantly and independently influence MPG in aortic stenosis. Clinically, variations of up to 15 mmHg in MPG may be observed uniquely on the basis of a change in duration of LVET, and hence the MPG cannot be used as a stand-alone parameter for serial evaluations or for comparisons of aortic stenosis severity between patients. A correction of MPG for LVET (in ms) such as MPGc = MPGx(LVET/300)2 might be helpful for rendering comparisons of MPG more meaningful in patients with aortic stenosis.


p38 MAP kinase regulates TNF alpha-, IL-1 alpha- and PAF-induced RANTES and GM-CSF production by human bronchial epithelial cells.
RANTES and granulocyte macrophage-colony stimulating factor (GM-CSF) play an important role in the production of allergic inflammation of the airway through their chemotactic activity for eosinophils. Recent studies have indicated that p38 mitogen-activated protein (MAP) kinase regulates cytokine expression in various cells; however, the role of p38 MAP kinase in RANTES and GM-CSF production in human bronchial epithelial cells (BECs) has not yet been determined. In the present study, we examined serine phosphorylation of MKK3 and MKK6 which is the upstream regulator of p38 MAP kinase and p38 MAP kinase activation in tumour necrosis factor (TNF)-alpha, interleukin (IL)-1 alpha and platelet-activating factor (PAF)-stimulated BECs and the effect of SB 203580 as the specific inhibitor for p38 MAP kinase activity on RANTES and GM-CSF expression in order to clarify the intracellular signal regulating RANTES and GM-CSF production by human BECs. The results showed that TNF alpha, IL-1 alpha and PAF induced serine phosphorylation of MKK3 and MKK6, and p38 MAP kinase activation in BECs. SB 203580 inhibited p38 MAP kinase activity and RANTES and GM-CSF production by TNF alpha-, IL-1 alpha- or PAF-stimulated human BECs. These results indicate that p38 MAP kinase plays an important role in TNF alpha-, IL-1 alpha- or PAF-activated signalling pathway which regulates RANTES and GM-CSF production by BECs and that the specific inhibitor for p38 MAP kinase activity might be useful for the treatment of allergic inflammation of the airway.


Assessment of mental health outcomes and associated factors among workers in community-based HIV care centers in the early stage of the COVID-19 outbreak in Mali.
In Mali, the non-governmental association (NGO) ARCAD Santé PLUS launched the CovidPrev program in response to the COVID-19 outbreak to ensure continuity of HIV care-related activities. This study aimed to identify individual and structural factors associated with mental health disorders (MHD) in the NGO's healthcare workers (HCW) in the early stage of the outbreak. Data were collected between April 6 and 11, 2020 for 135 HCW in ARCAD Santé PLUS's 18 community-based HIV care centers. Outcomes corresponded to the PHQ-9, GAD-7 and ISI instruments for depression, anxiety and insomnia, respectively. A general mixture model with a negative binomial distribution was implemented. Most HCW were men (60.7%) and median age was 40 years IQR[33-46]. Symptoms of depression, anxiety and insomnia were declared by 71.9, 73.3, and 77% participants, respectively. Women were at greater risk of MHD. A lack of personal protection equipment and human resources, especially nurses, was associated with a high risk of MHD. Health policy must place non-front line HCW, including those in NGOs, at the core of the healthcare system response to the COVID-19 outbreak, as they ensure continuity of care for many diseases including HIV. The efficacy of public health strategies depends on the capacity of HCW to fully with and competently perform their duties.


Parametric Study of Effects of Atmospheric Pressure Plasma Treatment on the Wettability of Cotton Fabric.
In textiles processing, wettability of fabric plays a very important role in enhancing processes such as dyeing and printing. Although well-prepared cotton fabric has very good wettability, further enhancement of its wettability can effectively improve the subsequent dyeing and printing processes. Plasma treatment, especially atmospheric pressure plasma treatment (APPT), a continuous process, is now drawing attention of the industry. In this study, we investigated the effect of APPT under four operational parameters: (1) discharge power; (2) flow rate of oxygen; (3) jet travelling speed; and (4) jet-to-substrate distance on wettability (in terms of wickability and wetting area) of cotton fabric. Experimental results revealed that the four parameters interact with each other in affecting the wettability of the cotton fabric. The results are discussed comprehensively.


Somatic treatments for mood disorders.
Somatic treatments for mood disorders represent a class of interventions available either as a stand-alone option, or in combination with psychopharmacology and/or psychotherapy. Here, we review the currently available techniques, including those already in clinical use and those still under research. Techniques are grouped into the following categories: (1) seizure therapies, including electroconvulsive therapy and magnetic seizure therapy, (2) noninvasive techniques, including repetitive transcranial magnetic stimulation, transcranial direct current stimulation, and cranial electric stimulation, (3) surgical approaches, including vagus nerve stimulation, epidural electrical stimulation, and deep brain stimulation, and (4) technologies on the horizon. Additionally, we discuss novel approaches to the optimization of each treatment, and new techniques that are under active investigation.


Respiratory depression during VP shunting in Arnold Chiari malformation Type-II, a rare complication (Case reports and review of literature).
The VP Shunt is a common pediatric surgical procedure in our country. Hydrocephalus is commonly associated with meningomyelocele in Arnold Chiari malformation-II and the ventriculoperitoneal shunt insertion is the common surgical procedure for the management of hydrocephalus. The standard protocol is to rule out any hydrocephalus by preoperative MRI. If associated with hydrocephalus, insertion of the VP shunt is indicated before the repair of MMC whereas the absence of hydrocephalus indicates that the surgical repair of MMC is to be undertaken immediately. Anesthetic management of the patient during the insertion of ventriculoperitoneal shunt may pose problems. We report here two cases of ACM-II (lumbar MMC with associated hydrocephalus) who had respiratory depression / delayed emergence after an otherwise uneventful procedure. Although the VP shunt (first procedure) required postoperative ventilation which improved later, the phenomena of respiratory depression / delayed emergence did not occur after the MMC repair (second surgery). The possible mechanisms involved in these events and their various clinical aspects are discussed below.


3-Hydroxy-4,5-dimethyl-2(5H)-furanone levels in fortified Madeira wines: relationship to sugar content.
The maturation of Madeira wines usually involves exposure to relatively high temperatures and humidity levels >70%, which affect the aroma and flavor composition and lead to the formation of the typical and characteristic bouquet of these wines. To estimate the levels of sotolon [3-hydroxy-4,5-dimethyl-2(5H)-furanone] and their behavior over time, 86 aged Madeira wines samples (1-25 years old), with different sugar concentrations, respectively, 90 g L(-)(1) for Boal, 110 g L(-)(1) for Malvazia, 25 g L(-)(1) for Sercial, and 65 g L(-)(1) for Verdelho varieties, were analyzed. Isolation was performed by liquid-liquid extraction with dichloromethane followed by chromatographic analysis by GC-MS. The reproducibility of the method was found to be 4.9%. The detection and quantification limits were 1.2 and 2.0 microg L(-)(1), respectively. The levels of sotolon found ranged from not detected to 2000 microg L(-)(1) for wines between 1 and 25 years old. It was observed that during aging, the concentration of sotolon increased with time in a linear fashion (r = 0.917). The highest concentration of sotolon was found in wines with the highest residual sugar contents, considering the same time of storage. The results show that there is a strong correlation between sotolon and sugar derivatives: furfural, 5-methylfurfural, 5-hydroxymethylfurfural, and 5-ethoxymethylfurfural. These compounds are also well correlated with wine aging. These findings indicate that the kinetics of sotolon formation is closely related with residual sugar contents, suggesting that this molecule may come from a component like sugar.


(1Z)-1-(1-Benzo-furan-2-yl)ethanone oxime.
The title compound, C10H9NO2, is almost planar (r.m.s. deviation for the non-H atoms = 0.027 Å) and the conformation across the C=N bond is syn. Further, the O atom of the benzo-furan ring is syn to the CH3 group in the side chain. In the crystal, mol-ecules are linked into C(3) chains propagating in [010] by O-H⋯N hydrogen bonds.


Charge-state-derivation ion detection using a super-conducting nanostructure device for mass spectrometry.
Mass spectrometry (MS) is a method of analyzing ions based on their mass/charge (m/z) ratios. The m/z peak identification requires speculation on the ionic unit-charge states. This problem can be solved by using superconducting junction devices to measure the kinetic energies of single molecules. However, the kinetic energy measurement is followed by the dead time of 1-20 µs, which is fatally slow for modern high-resolution time-of-flight (TOF) analyzers. In this paper, we demonstrate that a superconducting nano-stripline detector (SSLD) composed of a 10-nm-thick and 800-nm-wide NbN strip realizes the charge-state derivation, and furthermore satisfies the ideal MS detector specifications such as a nano-second response, a short recovery time, a wide mass range, and no noise.


Melting of io by tidal dissipation.
The dissipation of tidal energy in Jupiter's satellite Io is likely to have melted a major fraction of the mass. Consequences of a largely molten interior may be evident in pictures of Io's surface returned by Voyager I.


MCL1 transgenic mice exhibit a high incidence of B-cell lymphoma manifested as a spectrum of histologic subtypes.
Viability-promoting genes such as BCL2 play an important role in human cancer but do not directly cause aggressive tumors. BCL2 transgenic mice develop lymphoma at low frequency, hindering studies of tumorigenesis and its inhibition in the presence of such gene products. MCL1 is a member of the BCL2 family that is highly regulated endogenously and that promotes cell viability and immortalization when introduced exogenously. Mice expressing an MCL1 transgene in hematolymphoid tissues have now been monitored for an extended period and were found to develop lymphoma with long latency and at high probability (more than 85% over 2 years). In most cases, the disease was widely disseminated and of clonal B-cell origin. A variety of histologic subtypes were seen, prominently follicular lymphoma and diffuse large-cell lymphoma. MCL1 thus sets the stage for the development of lymphoma as does BCL2, disease occurring with high probability and recapitulating a spectrum of subtypes as seen in human patients. These findings with the transgene underscore the importance of the normal, highly regulated pattern of MCL1 expression, in addition to providing a model for studying tumorigenesis and its inhibition in the presence of a viability promoting BCL2 family member. (Blood. 2001;97:3902-3909)


Bullous lichen planus arising in the skin graft donor site of a psoriatic patient.
The coexistence of psoriasis vulgaris and bullous disorders, particularly bullous pemphigoid, has been described previously. We present an unusual case of bullous lichen planus arising in the skin graft donor site of a psoriatic patient. To our knowledge, such an association has not been reported to date.


Grappling with herpes: herpes gladiatorum.
Initial reports of herpes gladiatorum, a skin infection of wrestlers caused by herpes simplex virus (HSV), focused on case histories and clinical presentations of this disease. To more adequately address broader epidemiologic questions concerning this skin infection, we surveyed members of four southeastern college wrestling teams, sampled high school and college athletic trainers nationwide, and obtained serum specimens from members of one college wrestling team for HSV antibody studies. Nine of 48 (18.8%) college wrestlers in the southeastern athletic conference reported histories of herpes gladiatorum. Wrestlers with a prior history of oral HSV infection (cold sores) were less likely to report HSV skin infection than wrestlers without cold sores (RR = 0.25; 95% C.I. 0.03 to 1.8), while wrestlers with exposure to opponents with cutaneous HSV lesions were at high risk to develop herpes gladiatorum (RR = 9.4; 95% C.I. 2.2 to 40.0). The national survey of athletic trainers indicated that 7.6% of college wrestlers and 2.6% of high school wrestlers had HSV skin infection during the 1984-85 season. Herpes gladiatorum is a common problem among college wrestlers, and morbidity associated with this skin disease can be significant.


1,1-Dicyano-2,2-diphenyl-1,2-dihydronaphthalene: photochromism and evidence for photochemically induced C[bond]CN bond cleavage.
The photoreactions of the 1,1-dicyano-2,2-diphenyl-1,2-dihydronaphthalene (DHN-1) have been studied by photochemical techniques under various conditions at room temperature. A transient species, T(C), with a major maximum at 545 nm in the UV-visible spectrum, detected in small yield in polar aprotic solvents and in large yield in trifluoroethanol (TFE) and hexafluoropropan-2-ol (HFP), is assigned as a carbocation (1-cyano-2,2-diphenylnaphthalenium), which is generated photochemically by elimination of CN(-). The decay of T(C) was found to be a first-order process in HFP, in which the longest lifetime of 0.4 s was observed; in TFE, the carbocation decays on the ms timescale, while the shortest lifetime of 1 micros was found in ethanol. The yield of T(C) increases strongly upon addition of water to alcohols or acetonitrile, and remains substantial in the presence of large amounts of water (1-20 M). On addition of water to TFE or HFP, the lifetime of the carbocation becomes much shorter. This is supported by pulse-induced charge formation due to the carbocation and release of CN(-); the conductivity decay is related to the lifetime of the carbocation under selected conditions. In addition, a major irreversible and a minor thermally reversible photoprocess were spectroscopically observed in solvents of low as well as high polarity. The former photoproduct, absorbing below 300 nm, is tentatively ascribed to benzobicyclohexenes A produced by phenyl-vinylmethane rearrangement. In the latter process, a longer-lived benzoquinodimethane derivative B, having a maximum at 400-430 nm, is formed; this is related to ring opening and closure and represents a new example of photochromic ten-electron electrocyclisation. The distinct differences between the photochromism of DHN and that of dihydroazulene (DHA) stem mainly from stereoelectronic effects. This study, however, has also revealed that photochemically induced bond heterolysis and photochemical/thermal electrocyclisation, representing two basic processes of photochromism, may occur in one molecular unit.


Changes in Physicochemical, Free Radical Activity, Total Phenolic and Sensory Properties of Orange (Citrus sinensis L.) Juice Fortified with Different Oleaster (Elaeagnus angustifolia L.) Extracts.
In Iran and other parts of Western Asia, the oleaster (Elaeagnus angustifolia L.) fruit is processed in the dried powdery form, and in recent times, increasingly applied/sprinkled in fruit juices such as those made from oranges (Citrus sinensis L.). To our best knowledge, the effectiveness of oleaster fruit extract in fortifying the orange juice has not yet been reported and the knowledge of this will greatly benefit the consumers, particularly those around the Western Asia region. This current work, therefore, investigated the changes in physicochemical, free radical activity, total phenolic compounds, and sensory properties of orange juice fortified with different oleaster fruit extracts. The orange juice mix formulation comprised different concentrations (5, 10, 15, 20, and 25%) of oleaster (alcoholic, aqueous, and hydro-alcoholic) extracts. The control comprised orange concentrate (4% w/v), sugar (8.5% w/v), and citric acid (0.1% w/v) brought to the desirable volume with water. As the free radical activity depicted the antioxidant properties, the physicochemical aspects of this work involved the determinations of Brix, density, ash, pH, total acidity, sucrose, and total sugar, whereas the sensory aspects involved the determinations of color and taste. Whilst the aqueous oleaster 20 and 25% extracts produced notable physicochemical differences in the orange juice mix, both free radical activity, and phenolic compounds significantly increased (p < 0.05) after 30 days despite resembling (p > 0.05) those of control at day 1. More so, the increases in aqueous, alcoholic, and hydro-alcoholic oleaster extracts would decrease (p < 0.05) the sensory color and taste of the orange juice mix in this study.


Adoptive transfer of genetically modified macrophages elucidated TGF-beta-mediated 'self-defence' of the glomerulus against local action of macrophages.
TGF-beta has several anti-inflammatory properties which may be relevant to prevention of or recovery from acute glomerular inflammation. Using genetically modified mesangial cells and a technique for in vivo macrophage transfer, this article provides evidence for TGF-beta-mediated 'self-defence' of the glomerulus against macrophages. Rat mesangial cells stably transfected with TGF-beta1 showed a blunted response to the macrophage-derived, proinflammatory cytokine IL-1beta. In contrast, mesangial cells expressing the dominant-interfering TGF-beta receptor showed an enhanced response to IL-1. Similarly, externally added TGF-beta1 inhibited the cytokine response of normal glomeruli, and isolated nephritic glomeruli producing active TGF-beta1 showed a depressed response to IL-1beta, compared to normal glomeruli. Consistent with these in vitro results, in vivo transfer of activated macrophages revealed that the TGF-beta-producing glomeruli are insensitive to the effector action of macrophages. These results indicate that TGF-beta1 functions as an endogenous 'defender' that counteracts local action of activated macrophages in the glomerulus.


A simplified procedure for developing multiplex PCRs.
We have developed a simplified method for multiplex PCR based on the use of chimeric primers. Each primer contains a 3' region complementary to sequence-specific recognition sites and a 5' region made up of an unrelated 20-nucleotide sequence. Identical reaction conditions, cycling times, and annealing temperatures have been established for any PCR primer pair comprising the chimeric motif. Under these conditions, efficient multiplex amplification is achieved easily and reproducibly by simple adjustment of the individual primer concentrations. No additional modification of either the reaction components or annealing temperatures is required. The use of tagged primers provides a method for primer design that eliminates the multiple optimization steps involved in developing multiplex PCR.


Analysis of the nitrous oxide reduction genes, nosZDFYL, of Achromobacter cycloclastes.
The structural gene, nosZ, for the monomeric N2O reductase has been cloned and sequenced from the denitrifying bacterium Achromobacter cycloclastes. The nosZ gene encodes a protein of 642 amino acid residues and the deduced amino acid sequence showed homology to the previously derived sequences for the dimeric N2O reductases. The relevant DNA region of about 3.6 kbp was also sequenced and found to consist of four genes, nosDFYL based on the similarity with the N2O reduction genes of Pseudomonas stutzeri. The gene product of A. cycloclastes nosF (299 amino acid residues) has a consensus ATP-binding sequence, and the nos Y gene encodes a hydrophobic protein (273 residues) with five transmembrane segments, suggesting the similarity with an ATP-binding cassette (ABC) transporter which has two distinct domains of a highly hydrophobic region and ATP-binding sites. The nosL gene encodes a protein of 193 amino acid residues and the derived sequence showed a consensus sequence of lipoprotein modification/processing site. The expression of nosZ gene in Escherichia coli cells and the comparison of the translated sequences of the nosDFYL genes with those of bacterial transport genes for inorganic ions are discussed.


Hardiness in Family Caregivers During Caring From Persons With Alzheimer's Disease: A Deductive Content Analysis Study.
Objective: This study was designed to describe the experiences of family Caregivers' hardiness in caring for Alzheimer's Patients. Methods: The deductive content analysis method was performed between April 2020 and February 2021 in one of the teaching hospitals in Iran. Fourteen family caregivers of Alzheimer's patients were selected using purposive and snowballing sampling and the data were collected by semi-structured interviews. After that, data were analyzed using Elo and Kingas steps. Results: The results of this study showed that based on the experiences of family caregivers, the family caregivers' hardiness in caring for Alzheimer's patients is a feature of cognitive ability to deal with stressful care situations and consists of five dimensions of commitment, control, challenge, communication and culture with 22 generic categories that they were nested into this five dimension. Conclusion: Family caregivers' hardiness is a trait related to the individual and environmental factors, and the prevailing social and cultural conditions affect the individual's perception and experience of hardship and threats, as well as his/her understanding of protective factors and how to use them. Therefore, hardiness should not be interpreted as a simple approach regardless of culture.


Genotype-phenotype correlations: sudden death in an infant with very-long-chain acyl-CoA dehydrogenase deficiency.
Very-long-chain acyl-coenzyme A (CoA) dehydrogenase deficiency (VLCADD) is an autosomal recessive disorder of fatty acid oxidation. The phenotype of VLCADD is heterogeneous, and patients are typically classified into three categories based upon onset of symptoms and clinical findings. As a result of early diagnosis and treatment, many patients with VLCADD have remained asymptomatic. A general genotype-phenotype correlation has been elicited. A genotype that is associated with residual enzyme activity is more likely to present with an attenuated phenotype. One prevailing mutation, the c.848T>C (p.V283A), has been associated with residual enzyme activity and has been identified in many asymptomatic individuals diagnosed through either newborn or family screening. We present a patient who died as a result of fatal hypoglycemia at 38 h of life before diagnosis of VLCADD could be established by newborn screening. Despite the early onset of the disease, the patient was found to have a missense mutation within the ACADVL gene with a c.848T>C, c.342+1G>C genotype. Genotype alone remains limited in its predictive ability to determine which affected individuals are at risk for fatal complications.


The significance of "positive" respiratory cytology determinations in a series of 327 patients.
The authors reviewed all "positive" respiratory cytology diagnoses rendered over the past ten years at a medical center. Three hundred twenty-seven patients (with a total of 689 "positive" respiratory cytology determinations) were classified as having nonmalignant respiratory tract disease by using a unique system of explicit, reproducible verification criteria. Five patients with false-positive results (1.5%) and seven false-positive patient determinations (1.0%) were encountered. None of these were typed cytologically as small cell anaplastic carcinoma, and none were bronchial determinations. Overall patient typing accuracy was 72.2%; 75.2% of all sputum and 61.2% of all bronchial determinations were typed accurately. Our lowest typing accuracy (53.3%) was encountered in patients with poorly differentiated carcinoma. The findings from this study confirm the continued need for systematic analysis of respiratory cytology data from large groups of patients. Only then can cytopathologists hope to improve upon the clinical value of this diagnostic modality.


Phase Equilibria and Thermoelectric Properties in the Pb-Ga-Te System in the Vicinity of the PbGa6Te10 Phase.
PbGa6Te10 is a promising thermoelectric (TE) material due to its ultralow thermal conductivity and moderated values of the Seebeck coefficient. However, the reproducible synthesis of the PbGa6Te10-based materials for the investigation and tailoring of physical properties requires detailed knowledge of the phase diagram of the system. With this aim, a combined thermal, structural, and microstructural study of the Pb-Ga-Te ternary system near the PbGa6Te10 composition is presented here, in which polycrystalline samples with the compositions (PbTe)1-x(Ga2Te3)x (0.67 ≤ x ≤ 0.87) and PbyGa6Te10 (0.85 ≤ y ≤ 1.5) were synthesized and characterized. Differential scanning calorimetry measurements revealed that PbGa6Te10 melts incongruently at 1007 ± 2 K and has a polymorphic phase transition at 658-693 K depending on composition. Powder X-ray diffraction of annealed samples confirmed that below 658 K, the trigonal modification of PbGa6Te10 exists (space groups P3121 or P3221) and above 693 K, the rhombohedral one (space group R32). A homogeneity range was found for PbyGa6Te10, y = 0.9-1.1, based on refined lattice parameters of PbyGa6Te10 in samples annealed at 873 K. The revised version of the PbTe-Ga2Te3 phase diagram in the vicinity of the PbGa6Te10 phase is proposed. Based on the new results of the phase equilibria, the TE properties of the PbyGa6Te10 samples were studied in detail. The deviation from the stoichiometric composition leads to a tuning of the charge transport in PbyGa6Te10, and as a result, the Seebeck coefficient and electrical conductivity were significantly modified over the homogeneity range. The Pb-deficient Pb0.9Ga6Te10 sample shows an improved power factor up to 9.5 μW m-1 K-2 and a reduced thermal conductivity as low as 0.17 W m-1 K-1 due to attuned chemical potential and additional scattering of phonons on point defects. Thus, the ZT parameter for this composition was improved up to ∼0.043 at 773 K, which is almost 4 times higher than that of the stoichiometric specimen. This work shows that the knowledge of phase equilibria and crystal chemistry plays a key role in improving the energy conversion efficiency for new functional TE materials.


The magnet process and the perceived work environment of nurses.
Several studies have described the work environment of nurses from magnet and nonmagnet hospitals, but there have been no studies of nurses from hospitals in the magnet application process. To compare the differences between characteristics of hospitals and nurses from three hospital types: magnet hospitals, hospitals in the process of applying for magnet certification, and nonmagnet hospitals, and how nurses from these hospitals perceive their work environment. In a national, cross-sectional survey of critical care nurses, the Perceived Nursing Work Environment (PNWE) instrument was administered to measure nurses' perceptions of their work environment. Data were available from 2,092 nurse surveys. Over a third of the respondents were from in-process hospitals and almost half were from nonmagnet hospitals. The majority of nurses were female and from large hospitals in the Atlantic region. The mean age of nurses was 39.5 years and the mean years of work experience in the intensive care unit (ICU) was 10.2 years. Higher nurse scores were significantly associated with magnet certification on one subscale of the PNWE, nursing competence. Nurses from magnet hospitals had a positive perception of nursing competence in their work environment. Further research is necessary to examine the nurse work environment and to determine if the characteristics of magnet hospitals have changed.


A useful protocol for analyses of mutations of the epidermal growth factor receptor gene.
Recent studies have reported that mutations of the epidermal growth factor receptor (EGFR) gene are associated with the responsiveness of tyrosine kinase inhibitors (TKIs), which are molecular targets for non-small cell lung cancer (NSCLC). To provide genetic analyses for NSCLC patients, a simple and reliable method using paraffin-embedded materials is needed. The DEXPAT DNA extraction kit was used for DNA extraction from paraffin-embedded materials. DNA was amplified using the nested PCR technique, then analyzed by direct sequencing for EGFR mutations (exons 18 to 21). The phenol/chloroform extraction for DNA was also performed for comparison. When the DEXPAT kit was used, distinct bands were observed in all products after nested PCR assays of paraffin-embedded materials. Distinct sequencing signals were obtained. Results from the sequencing analysis of paraffin-embedded materials and frozen materials were completely concordant. The current study suggests that DNA extraction with the DEXPAT kit followed by nested PCR is a simple and reliable technique for analyzing the EGFR gene status with paraffin-embedded samples.


Heat shock factor 1 contains two functional domains that mediate transcriptional repression of the c-fos and c-fms genes.
Heat shock factor 1 (HSF1), in addition to its pivotal role as a regulator of the heat shock response, functions as a versatile gene repressor. We have investigated the structural domains involved in gene repression using mutational analysis of the hsf1 gene. Our studies indicate that HSF1 contains two adjacent sequences located within the N-terminal half of the protein that mediate the repression of c-fos and c-fms. One region (NF) appears to be involved in quenching transcriptional activation factors on target promoters and binds to the basic zipper transcription factor NF-IL6 required for activation of c-fms and IL-1beta. The NF domain encompasses the leucine zipper 1 and 2 sequences as well as the linker domain between the DNA binding and leucine zipper regions. The function of this domain in gene repression is highly specific for HSF1, and the homologous region from conserved family member HSF2 does not restore repressive function in HSF2/HSF1 chimeras. In addition, HSF2 is not capable of binding to NF-IL6. The NF domain, although necessary for repression, is not sufficient, and a second region (REP) occupying a portion of the regulatory domain is required for repression. Neither domain functions independently, and both are required for repression. Furthermore, we constructed dominant inhibitors of c-fos repression by HSF1, which also blocked the repression of c-fms and IL-1beta, suggesting a shared mechanism for repression of these genes by HSF1. Our studies suggest a complex mechanism for gene repression by HSF1 involving the binding to and quenching of activating factors on target promoters. Mapping the structural domains involved in this process should permit further characterization of molecular mechanisms that mediate repression.


Effects of a chronic dietary exposure of the honeybee Apis mellifera (Hymenoptera: Apidae) to imidacloprid.
Previous studies have shown that imidacloprid and insecticidally active imidacloprid plant metabolites are rapidly metabolized by honeybees. Accordingly, no striking differences were expected between the acute and the chronic dietary toxicity of imidacloprid to honeybees. More recently, however, an unexpectedly high chronic dietary toxicity to honeybees was reported for imidacloprid and imidacloprid plant metabolites, and a novel pharmacologic mechanism unrelated to the parent toxophor was postulated. In an extensive literature survey, no further evidence was found for the reported high difference between the acute and the chronic dietary toxicity of imidacloprid and its plant metabolites to honeybees. The majority of data indicated a dietary no observed lethal-effect concentration >0.04 and 0.02 mg/L 50% sucrose solution, respectively, for an acute and a chronic dietary exposure of honeybees to either imidacloprid or its plant metabolites. Findings of chronic feeding studies with those plant metabolites where the toxophor had already been cleaved did not support the hypotheses of a novel pharmacologic mechanism unrelated to the parent toxophor. No increased treatment-related mortality or behavioral abnormalities were recorded in four independent research facilities during a 10-day dietary exposure of honeybees of different ages to sucrose solutions spiked with the respective metabolites at 0.0001, 0.001, and 0.010 mg/L 50% sucrose solution.


Ribosomal Lesions Promote Oncogenic Mutagenesis.
Ribosomopathies are congenital disorders caused by mutations in ribosomal proteins (RP) or assembly factors and are characterized by cellular hypoproliferation at an early stage. Paradoxically, many of these disorders have an elevated risk to progress to hyperproliferative cancer at a later stage. In addition, somatic RP mutations have recently been identified in various cancer types, for example, the recurrent RPL10-R98S mutation in T-cell acute lymphoblastic leukemia (T-ALL) and RPS15 mutations in chronic lymphocytic leukemia (CLL). We previously showed that RPL10-R98S promotes expression of oncogenes, but also induces a proliferative defect due to elevated oxidative stress. In this study, we demonstrate that this proliferation defect is eventually rescued by RPL10-R98S mouse lymphoid cells that acquire 5-fold more secondary mutations than RPL10-WT cells. The presence of RPL10-R98S and other RP mutations also correlated with a higher mutational load in patients with T-ALL, with an enrichment in NOTCH1-activating lesions. RPL10-R98S-associated cellular oxidative stress promoted DNA damage and impaired cell growth. Expression of NOTCH1 eliminated these phenotypes in RPL10-R98S cells, in part via downregulation of PKC-θ, with no effect on RPL10-WT cells. Patients with RP-mutant CLL also demonstrated a higher mutational burden, enriched for mutations that may diminish oxidative stress. We propose that oxidative stress due to ribosome dysfunction causes hypoproliferation and cellular insufficiency in ribosomopathies and RP-mutant cancer. This drives surviving cells, potentiated by genomic instability, to acquire rescuing mutations, which ultimately promote transition to hyperproliferation. SIGNIFICANCE: Ribosomal lesions cause oxidative stress and increase mutagenesis, promoting acquisition of rescuing mutations that stimulate proliferation.


Chronic activation of pDCs in autoimmunity is linked to dysregulated ER stress and metabolic responses.
Plasmacytoid dendritic cells (pDCs) chronically produce type I interferon (IFN-I) in autoimmune diseases, including systemic sclerosis (SSc) and systemic lupus erythematosus (SLE). We report that the IRE1α-XBP1 branch of the unfolded protein response (UPR) inhibits IFN-α production by TLR7- or TLR9-activated pDCs. In SSc patients, UPR gene expression was reduced in pDCs, which inversely correlated with IFN-I-stimulated gene expression. CXCL4, a chemokine highly secreted in SSc patients, downregulated IRE1α-XBP1-controlled genes and promoted IFN-α production by pDCs. Mechanistically, IRE1α-XBP1 activation rewired glycolysis to serine biosynthesis by inducing phosphoglycerate dehydrogenase (PHGDH) expression. This process reduced pyruvate access to the tricarboxylic acid (TCA) cycle and blunted mitochondrial ATP generation, which are essential for pDC IFN-I responses. Notably, PHGDH expression was reduced in pDCs from patients with SSc and SLE, and pharmacological blockade of TCA cycle reactions inhibited IFN-I responses in pDCs from these patients. Hence, modulating the IRE1α-XBP1-PHGDH axis may represent a hitherto unexplored strategy for alleviating chronic pDC activation in autoimmune disorders.


Cough associated with the detection of Mycoplasma hyopneumoniae DNA in clinical and environmental specimens under controlled conditions.
The association of cough with Mycoplasma hyopneumoniae (MHP) DNA detection in specimens was evaluated under conditions in which the MHP status of inoculated and contact-infected pen mates was closely monitored for 59 days post-inoculation (DPI). Seven-week-old pigs (n = 39) were allocated to five rooms (with one pen). Rooms contained 9 pigs each, with 1, 3, 6, or 9 MHP-inoculated pigs, respectively, except Room 5 (three sham-inoculated pigs). Cough data (2 × week) and specimens, tracheal swabs (2 × week), oral fluids (daily), drinker wipes (~ 1 × week), and air samples (3 × week) were collected. At 59 DPI, pigs were euthanized, and lung and trachea were evaluated for gross and microscopic lesions. Predictive cough value to MHP DNA detection in drinker and oral fluid samples were estimated using mixed logistic regression. Following inoculation, MHP DNA was first detected in tracheal swabs from inoculated pigs (DPI 3), then oral fluids (DPI 8), air samples (DPI 10), and drinker wipes (21 DPI). MHP DNA was detected in oral fluids in 17 of 59 (Room 1) to 43 of 59 (Room 3) samples, drinker wipes in 4 of 8 (Rooms 2 and 3) to 5 of 8 (Rooms 1 and 4) samples, and air samples in 5 of 26 (Room 2) or 3 of 26 (Room 4) samples. Logistic regression showed that the frequency of coughing pigs in a pen was associated with the probability of MHP DNA detection in oral fluids (P < 0.01) and nearly associated with drinker wipes (P = 0.08). Pathology data revealed an association between the period when infection was first detected and the severity of gross lung lesions. Dry, non-productive coughs suggest the presence of MHP, but laboratory testing and MHP DNA detection is required for confirmation. Based on the data from this study, oral fluids and drinker wipes may provide a convenient alternative for MHP DNA detection at the pen level when cough is present. This information may help practitioners in specimen selection for MHP surveillance.


Elevation of insulin-like growth factor-binding protein-1 mRNA expression following hormone replacement therapy.
The purpose of this study was to investigate the possible regulatory roles of insulin-like growth factors (IGF) and IGF binding protein-1 (IGFBP-1) on postmenopausal endometrium in women undergoing hormone replacement therapy (HRT). Endometrial tissues and blood samples were collected from 25 postmenopausal women with abnormal uterine bleeding before and after HRT. As a control, blood and endometrial samples were also obtained at mid-luteal phase (days 18-23 of the menstrual cycle) from 10 women with benign uterine leiomyoma during surgical intervention. Expression of mRNA for IGF-I, IGF-II, type 1-IGF receptor, IGFBP-1, oestrogen receptor (ER) and progesterone receptor (PR) in the endometrium was explored by a semiquantitative reverse transcription-polymerase chain reaction (RT-PCR). Serum concentrations of IGFBP-1, oestradiol, progesterone, follicle stimulating hormone (FSH) and sex hormone-binding globulin (SHBG) were also determined. In the endometrium obtained from postmenopausal women with abnormal uterine bleeding (before HRT), expression of IGFBP-1 was undetectable, whereas PR expression was abundant. HRT significantly up-regulated expression of IGFBP-1 but down-regulated PR. Moderate expression of IGF-I, IGF-II, type 1-IGF receptor and ER was identified in the postmenopausal endometrium before HRT. HRT significantly down-regulated IGF-I, up-regulated IGF-II, but had no effects on expression of type 1-IGF receptor and ER. In conclusion, up-regulation of IGFBP-1 collaboratively with down-regulation of IGF-I may account for the protective effect of progesterone in HRT on the endometrium.


School Notes: Managing Infectious Diseases in School and Child Care Settings.
The decision to exclude a child from day care or school leads to widespread educational, social, and economic ramifications for affected families. By understanding and improving how these decisions are made, health care providers and policy makers can promote child well-being throughout the state.


MUTYH, an adenine DNA glycosylase, mediates p53 tumor suppression via PARP-dependent cell death.
p53-regulated caspase-independent cell death has been implicated in suppression of tumorigenesis, however, the regulating mechanisms are poorly understood. We previously reported that 8-oxoguanine (8-oxoG) accumulation in nuclear DNA (nDNA) and mitochondrial DNA triggers two distinct caspase-independent cell death through buildup of single-strand DNA breaks by MutY homolog (MUTYH), an adenine DNA glycosylase. One pathway depends on poly-ADP-ribose polymerase (PARP) and the other depends on calpains. Deficiency of MUTYH causes MUTYH-associated familial adenomatous polyposis. MUTYH thereby suppresses tumorigenesis not only by avoiding mutagenesis, but also by inducing cell death. Here, we identified the functional p53-binding site in the human MUTYH gene and demonstrated that MUTYH is transcriptionally regulated by p53, especially in the p53/DNA mismatch repair enzyme, MLH1-proficient colorectal cancer-derived HCT116+Chr3 cells. MUTYH-small interfering RNA, an inhibitor for p53 or PARP suppressed cell death without an additive effect, thus revealing that MUTYH is a potential mediator of p53 tumor suppression, which is known to be upregulated by MLH1. Moreover, we found that the p53-proficient, mismatch repair protein, MLH1-proficient colorectal cancer cell line express substantial levels of MUTYH in nuclei but not in mitochondria, suggesting that 8-oxoG accumulation in nDNA triggers MLH1/PARP-dependent cell death. These results provide new insights on the molecular mechanism of tumorigenesis and potential new strategies for cancer therapies.


Study of liver cirrhosis over ten consecutive years in Southern China.
To investigate the etiology and complications of liver cirrhosis (LC) in Southern China. In this retrospective, cross-sectional study, we identified cases of liver cirrhosis admitted between January 2001 to December 2010 and reviewed the medical records. Patient demographics, etiologies and complications were collected, and etiological changes were illustrated by consecutive years and within two time periods (2001-2005 and 2006-2010). All results were expressed as the mean ± SD or as a percentage. The χ(2) test or Student's t-test was used to analyze the differences in age, gender, and etiological distribution, and one-way analysis of variance was applied to estimate the trends in etiological changes. We analyzed the relationship between the etiologies and complications using unconditioned logistic regression, and the risk of upper gastrointestinal bleeding (UGIB) and hepatocellular carcinoma (HCC) in the major etiological groups was evaluated as ORs. A P value less than 0.05 was considered significant. Statistical computation was performed using SPSS 17.0 software. In this study, we identified 6719 (83.16%) male patients and 1361 (16.84%) female patients. The average age of all of the patients was 50.5 years at the time of diagnosis. The distribution of etiological agents was as follows: viral hepatitis, 80.62% [hepatitis B virus (HBV) 77.22%, hepatitis C virus (HCV) 2.80%, (HBV + HCV) 0.58%]; alcohol, 5.68%; mixed etiology, 4.95%; cryptogenic, 2.93%; and autoimmune hepatitis, 2.03%; whereas the other included etiologies accounted for less than 4% of the total. Infantile hepatitis syndrome LC patients were the youngest (2.5 years of age), followed by the metabolic LC group (27.2 years of age). Viral hepatitis, alcohol, and mixed etiology were more prevalent in the male group, whereas autoimmune diseases, cryptogenic cirrhosis, and metabolic diseases were more prevalent in the female group. When comparing the etiological distribution in 2001-2005 with that in 2006-2010, the proportion of viral hepatitis decreased from 84.7% to 78.3% (P < 0.001), and the proportion of HBV-induced LC also decreased from 81.9% to 74.6% (P < 0.001). The incidence of mixed etiology, cryptogenic cirrhosis, and autoimmune diseases increased by 3.1% (P < 0.001), 0.5% (P = 0.158), and 1.3% (P < 0.001), respectively. Alcohol-induced LC remained relatively steady over the 10-year period. The ORs of the development of UGIB between HBV and other major etiologies were as follows: HCV, 1.07; alcohol, 1.89; autoimmune, 0.90; mixed etiology, 0.83; and cryptogenic, 1.76. The ORs of the occurrence of HCC between HBV and other major etiologies were as follows: HCV, 0.54; alcohol, 0.16; autoimmune, 0.05; mixed etiology, 0.58; and cryptogenic, 0.60. The major etiology of liver cirrhosis in Southern China is viral hepatitis. However, the proportions of viral hepatitis and HBV are gradually decreasing. Alcoholic LC patients exhibit a greater risk of experiencing UGIB, and HBV LC patients may have a greater risk of HCC.


Baseline characteristics of patients enrolled in the Canadian Fabry Disease Initiative.
The Canadian Fabry Disease Initiative [CFDI] is a longitudinal study evaluating all Canadians diagnosed with Fabry disease [FD]. The study has 3 cohorts: Cohort 1A which includes 81 subjects who were on enzyme replacement therapy [ERT] prior to October 2006, Cohort 1B which has ongoing enrolment of subjects newly started on ERT who are randomized to agalsidase alfa or agalsidase beta, and Cohort 1C where subjects who do not meet nationally accepted Canadian criteria for ERT are followed to assess the natural history of disease complications. The study currently enrols 244 patients [95 males and 149 females] with a mean age of 41.9+/-14.5years. There is a high prevalence of the c.427G>C mutation. Cohort 1A contains 82 patients [59 males, 23 females] of whom 42% are known to have cardiac complications of FD and 38% renal complications. Cohort 1B at the time of writing contained 37 patients [15 males, 22 females] of whom the indications for ERT were cardiac in 55% and renal in 60%. Cohort 1C at the time of writing contained 125 patients [22 males, 103 females]. Enrolment is ongoing in both Cohorts 1B and 1C. When compared to subjects in the Fabry Outcome Survey and the Fabry Registry, subjects in the CFDI are less likely to be male reflecting less ascertainment bias. The CFDI is a robust national data set that will contribute to available data on the natural history of FD and on the comparative efficacy of the two commercially available ERT products.


A simple, inexpensive, high pressure liquid chromatographic method for separating cytokinins in plant extracts.
Separation of a mixture of the main cytokinins occurring naturally in plant tissues was achieved by high pressure liquid chromatography using insoluble polyvinylpyrrolidone as the solid support. The separation of each cytokinin was first assessed over a range of salt and l-butanol concentrations and pH using a mixture of borate buffer and l-butanol as the mobile phase to determine the conditions necessary for optimum resolution. A discrete separation of zeatin, N-6-(Delta-2-isopentenyl)adenine, their related ribonucleosides, and kinetin was achieved using a simple isocratic elution with 0.025 m borate buffer at pH 6.8 and 4% (v/v) l-butanol. A number of cytokinin-active compounds were detected in cabbage extracts by the Amaranthus betacyanin bioassay using this separation technique.


Development of visual attention from age 7 to age 12 in children with familial high risk for schizophrenia or bipolar disorder.
Children with familial high risk of schizophrenia (FHR-SZ) or bipolar disorder (FHR-BP) are at increased risk of developing similar disorders and show cognitive deficits during childhood. The aim of this paper is to investigate visual attention and its developmental trajectories in children with FHR-SZ and with FHR-BP to increase our knowledge about potential cognitive endophenotypes of these two disorders. We compared the performance of 89 children with FHR-SZ (N = 32), FHR-BP (N = 22), and population-based controls (PBC, N = 35) at age 7 to that at age 12 as well as including 133 12-year-old children with FHR-SZ (N = 50), FHR-BP (N = 43) and PBC (N = 40) to investigate visual attention, as part of the Danish High Risk and Resilience Study. We used the TVA-based whole report paradigm, based on the Bundesen's Theory of Visual Attention (TVA) to investigate visual attention. Children with FHR-SZ that showed deficits in visual processing speed at age 7 improved to a level that was not significantly different from controls at age 12. All children improved over time. We found no attentional deficits in FHR children at age 12. On visual attention, children with FHR-SZ did not show developmental deficits or lags and, together with children with FHR-BP, they develop similarly to control children between age 7 to age 12. This emphasizes the potential of beneficial neuroplastic changes in cognitive deficits found at younger ages in children with FHR-SZ. It also highlights the importance of identifying and characterizing cognitive developmental trajectories of high-risk children and provides hope that visual attention may develop appropriately in these groups.


Effect of endotoxemia on hepatic portal and sinusoidal blood flow in rats.
A decrease in liver blood flow leads to dysfunction of hepatocytes and Kupffer cells, with subsequent local and systemic liberation of proinflammatory mediators that may maintain systemic inflammatory response syndrome (SIRS) and may lead to multiple organ dysfunction syndrome (MODS). There is only limited knowledge on the hepatic micro- and macrocirculation during sepsis or endotoxemia. Therefore, the aim of our study was to investigate alterations in hepatic portal blood flow (PBF) and sinusoidal blood flow (SBF) during endotoxemia. In male Wistar rats endotoxemia was induced by continuous infusion of 2 mg/kg/h lipopolysaccharides from Escherichia coli 026:B6 immediately after baseline measurements (n = 8). The control group (n = 8) received an equivalent volume of Ringer's solution. Mean arterial pressure (MAP), heart rate (HR), cardiac output (CO), PBF, and SBF were measured at baseline and 60 and 120 min after induction of endotoxemia. PBF was measured using an ultrasonic flow probe that was positioned around the portal vein. SBF was detected by in vivo videomicroscopy of the left liver lobe. In the LPS group MAP decreased, but CO remained at baseline values. During endotoxemia PBF decreased significantly from 23 +/- 3 to 15 +/- 4 mL/min (60 min) and 16 +/- 3 mL/min (120 min). SBF also significantly decreased to 68.5% (60 min) and 57.1% (120 min) of baseline value. Our results demonstrate that during early endotoxemia hepatic macro- and microcirculatory perfusion is significantly decreased despite unchanged CO. This early reduction of hepatic perfusion might be caused by an increased hepatic vessel resistance as a consequence of liberation of vasoconstrictive mediators or/and by a decrease in intestinal perfusion.


The effect of chromosome abnormalities on expression of SnoRNA in radioresistant and radiosensitive cell lines after irradiation.
In this paper, we have studied the role of chromosomal abnormalities in the expression of small nucleolar RNAs (snoRNAs) of radioresistant (K562) and radiosensitive (HL-60) leukemia cell line. Cells were exposed to an X-ray dose of 4 Gy. SnoRNA expression was investigated using NGS sequencing. The distribution of expressed snoRNAs on chromosomes has been found to be different for two cell lines. The most significant differences in the expression of snoRNAs were found in the K562 cell line based on the analysis of the dynamics of log2fc values. The type of clustering, the number and type of snoRNAs slightly differed in the chromosomes with trisomy and monosomy and had a pronounced difference in pairs with marker chromosomes in both cell lines. In this study, we have demonstrated that chromosomal abnormalities alter the expression of snoRNA after irradiation. Trisomies and monosomies do not have such a noticeable effect on the expression of snoRNAs as the presence of marker chromosomes.


Short-term combination therapy and long-term relapse prevention in the treatment of severe acne vulgaris.
Few long-term treatment regimens for severe acne vulgaris have been investigated in clinical trials. Data were combined from two consecutive, randomized, double-blind, controlled studies to evaluate the efficacy, safety and subject satisfaction of four nine-month regimens in severe acne vulgaris treatment. Subjects were first randomized to receive doxycycline (DCN) and adapalene 0.1% - benzoyl peroxide 2.5% (A/BPO) or vehicle once daily for 12 weeks. Subjects who had at least 50% global improvement were subsequently randomized to receive A/BPO or its vehicle once daily for 24 weeks. Over nine months, there were four regimens: A/BPO and DCN followed by A/BPO, vehicle and DCN followed by A/BPO, A/BPO and DCN followed by vehicle, and vehicle and DCN followed by vehicle. Among the four regimens, A/BPO and DCN followed by A/BPO led to the highest percentage of subjects rated "clear" or "almost clear" (50.0% vs. 40.4%, 26.2% and 25.0%, respectively), biggest reduction in total lesion counts (76% vs. 70%, 51% and 47%, respectively) and greatest subject satisfaction (85.0% vs. 75.5%, 63.3% and 52.4%, respectively) at week 36. It provided a faster onset of action compared to groups started with vehicle and DCN (P<.05 at week 2). Subjects receiving A/BPO and DCN followed by vehicle experienced deterioration once the active treatment was discontinued. All regimens were safe and well-tolerated. In conclusion, efficacious initial therapy and long-term treatment are both important. An initial combination therapy with adapalene-BPO and DCN followed by longer-term adapalene-BPO treatment is an efficacious and satisfactory new regimen for severe acne subjects.


Health-resource use and costs associated with fibromyalgia in France, Germany, and the United States.
Fibromyalgia (FM) is a chronic disorder characterized by widespread, persistent pain. Prospective and retrospective studies have demonstrated substantial health-care costs associated with FM in a number of countries. This study evaluated and compared health-resource use (HRU) and associated costs related to FM in routine clinical practice across the US, France, and Germany. Two separate, cross-sectional, observational studies of subjects with FM were conducted: one in the US and one in France and Germany. HRU related to prescription medication, physician office visits, diagnostic tests, and hospitalizations was abstracted from chart review; patient out-of-pocket costs and lost productivity were collected via subject self-report. Costs were assigned to HRU based on standard algorithms. Direct and indirect costs were evaluated and compared by simple linear regression. A total of 442 subjects (203 US, 70 France, 169 Germany) with FM were analyzed. The mean (standard deviation) age in the US, France, and Germany was 47.9 (10.9), 51.2 (9.5), and 49.2 (9.8), respectively (P = 0.085). Most subjects were female (95% US, 83% France, 80% Germany) (P < 0.001). Adjusted annual direct costs per subject for FM were significantly higher in the US ($7087) than in France ($481, P < 0.001) or Germany ($2417, P < 0.001). Adjusted mean annual indirect costs per subject for FM were lower in the US ($6431) than in France ($8718) or Germany ($10,001), but represented a significant proportion of total costs in all countries. The significant HRU and costs associated with FM in the US, France, and Germany documented in this study highlight the substantial global economic burden of FM. Indirect costs represented a significant proportion of the total costs, particularly in Europe. Comparisons between the three countries show differences in HRU, with significantly higher direct costs in the US compared with France and Germany.


Effects and toxicity of neoadjuvant chemotherapy preoperative followed by adjuvant chemoradiation in small cell neurdendocrine cervical carcinoma.
To determine the efficacy and toxicity of a combined-modality regimen of neoadjuvant chemotherapy (NACT) before primary radical surgery followed by adjuvant chemoradiation in small cell neuroendocrine cervical cancer (SCNEC) patients. The study was approved by the ethics committee of the present hospital. The records of 23 SCNEC patients who received NACT before primary radical surgery were reviewed at the Zhejiang Cancer Hospital between January 1998 and May 2010. All patients received one to four cycles of NACT and two to eight cycles of chemotherapy (NACT and adjuvant chemotherapy) on the basis of platinum, 17 (73.9%) patients received NACT using a regimen consisting of etoposide and cisplatin (EP). Eighteen (85.7%) patients received adjuvant chemotherapy using a regimen consisting of PE and EP. Kaplan-Meier and Cox regression methods were used for analyses. Of the 23 eligible patients, 18 had Stages I-IIA, five had Stages IIB-IIIB disease. Twelve patients (52.2%) developed grade 3 and 4 neutropenia. Fourteen patients (60.9%) developed grade 3 and 4 anemia. The majority of grade 3 and 4 neutropenia and non-hematologic toxicities were usually self-limited. Three patients (13.0%) who postoperative pathology showed pathologic complete response (CR) had better prognosis than those did not show pathologic CR; the median survival was 69.5 months (range, 51.1-177.1), 54.5 months (range: 7.3-81.5), respectively. In univariate analysis, lymphovascular space invasion (LSI) (p = 0.013), and deep stromal invasion (DSI) (p = 0.001) were considered poor prognostic factors. With a median follow-up for surviving patients was 40.8 months (range, 7-177), 12 patients recurred, 11 of which had died. The estimated three- and five-year overall survival (OS) rates for all patients were 55.8% and 39.9%, respectively. NACT before primary radical surgery followed by adjuvant chemoradiation or chemotherapy was well tolerated and seems to be effective for early stage SCNEC patients. Prospective clinical study is necessary and we hope that this research's results help to design a prospective clinical study.


Academic goals and emotions: results of a structural equation model and a cluster analysis.
Motivational researchers have suggested that the environment plays a key role in students' goal formation. However, some recent work (Seifert, 1996) suggests that students' emotions may play a role in goal formation. This study examined the relationship between environment, emotions, and goals. Do emotions and perceptions of teachers both contribute to goal orientation, or do emotions mediate the influence of perceptions of teachers on goal orientation? 559 Grade 10 students in Newfoundland and Labrador. Two structural equations were postulated: one in which students' affect mediated the influence of perceptions of teachers on goal orientation and one in which students' affect contributed to goal formation in addition to perceptions of teachers. A cluster analysis of affect scores was performed followed by between-group and within-group contrasts of goal orientation scores. The structural equation model in which emotions mediate the influence of perceptions of teachers on goal orientation fit the data better than the model in which perceptions of teachers directly predicted goal orientation. The cluster analysis showed that groups with different profiles of affect pursued different goals. Emotions seem to be directly linked to goal orientation. Teachers who are perceived as nurturing will foster feelings of self-assuredness and control in students which will lead to a learning orientation.


Community health workers caring for dependent elderly people.
Community Health Workers (CHWs) are a link between Family Health Strategy (FHS) professionals and the community. This study aims to analyze health care professionals' perceptions and health management about CHWs' role in caring for dependent elderly people. A qualitative study was carried out, from a hermeneutic-dialectic perspective, with 38 professionals working in elderly people's health in cities in the five regions of Brazil. The results identified CHWs as facilitators of access to elderly people dependent on the health care network, gaps in continuing education and the reduced number of these professionals to meet the demand in primary care. Respondents attributed great importance to CHW's performance, valued their participation in FHS, but pointed out a lack of knowledge and difficulties to supply the adequate amount in health care services and in assistance of elderly people with dependence and family. It is concluded that health professionals and managers consider CHWs to be a great workforce and essential to the dependent elderly people and their caregivers. The number of CHWs is insufficient in relation to FHS, and there is a lack of training to deal with various types of dependence.


Using nuclear envelope mutations to explore age-related skeletal muscle weakness.
Skeletal muscle weakness is an important determinant of age-related declines in independence and quality of life but its causes remain unclear. Accelerated ageing syndromes such as Hutchinson-Gilford Progerin Syndrome, caused by mutations in genes encoding nuclear envelope proteins, have been extensively studied to aid our understanding of the normal biological ageing process. Like several other pathologies associated with genetic defects to nuclear envelope proteins including Emery-Dreifuss muscular dystrophy, Limb-Girdle muscular dystrophy and congenital muscular dystrophy, these disorders can lead to severe muscle dysfunction. Here, we first describe the structure and function of nuclear envelope proteins, and then review the mechanisms by which mutations in genes encoding nuclear envelope proteins induce premature ageing diseases and muscle pathologies. In doing so, we highlight the potential importance of such genes in processes leading to skeletal muscle weakness in old age.


Limited regeneration in long acellular nerve allografts is associated with increased Schwann cell senescence.
Repair of large nerve defects with acellular nerve allografts (ANAs) is an appealing alternative to autografting and allotransplantation. ANAs have been shown to be similar to autografts in supporting axonal regeneration across short gaps, but fail in larger defects due to a poorly-understood mechanism. ANAs depend on proliferating Schwann cells (SCs) from host tissue to support axonal regeneration. Populating longer ANAs places a greater proliferative demand on host SCs that may stress host SCs, resulting in senescence. In this study, we investigated axonal regeneration across increasing isograft and ANA lengths. We also evaluated the presence of senescent SCs within both graft types. A sciatic nerve graft model in rats was used to evaluate regeneration across increasing isograft (~autograft) and ANA lengths (20, 40, and 60 mm). Axonal regeneration and functional recovery decreased with increased graft length and the performance of the isograft was superior to ANAs at all lengths. Transgenic Thy1-GFP rats and qRT-PCR demonstrated that failure of the regenerating axonal front in ANAs was associated with increased levels of senescence related markers in the graft (senescence associated β-galactosidase, p16(INK4A), and IL6). Lastly, electron microscopy (EM) was used to qualitatively assess senescence-associated changes in chromatin of SCs in each graft type. EM demonstrated an increase in the presence of SCs with abnormal chromatin in isografts and ANAs of increasing graft length. These results are the first to suggest that SC senescence plays a role in limited axonal regeneration across nerve grafts of increasing gap lengths.


New insights into the central PACAPergic system from the phenotypes in PACAP- and PACAP receptor-knockout mice.
Pituitary adenylate cyclase-activating polypeptide (PACAP) is a structurally highly conserved neuropeptide and displays pleiotropic activity, including functioning as a neurotransmitter, neuromodulator, and neurotrophic factor. A series of recent experiments, including genetic manipulation of PACAP and its receptors, has led to better understanding of both normal and pathological processes in which PACAP has been proposed to play a role, and sheds light on previously uncharacterized functions of endogenous PACAP. The aim of this article is to briefly review the recent advances in understanding the role of PACAP in the central nervous system from PACAP- and PACAP receptor-deficient mice, particularly with respect to behavioral and neurological features, including psychomotor behavior, feeding, stress responses, memory performance, ethanol sensitivity, chronic pain, and circadian rhythms. This article also discusses their potential involvement in human diseases.


Intestinal type cholangiocarcinoma of intrahepatic large bile duct associated with hepatolithiasis--a new histologic subtype for further investigation.
Intestinal metaplasia is regarded as a possible predisposing factor of cancer, particularly of the intestinal type adenocarcinoma. The clinicopathologic features of intestinal type adenocarcinoma have been well documented in the stomach, and intestinal metaplasia and intestinal type adenocarcinoma has also been reported in the gallbladder. However, regarding the intrahepatic bile ducts, the clinicopathologic features are not yet clear and there have been no reports in English literature on intestinal type intrahepatic cholangiocarcinoma. We report a case of intestinal type cholangiocarcinoma associated with hepatolithiasis in the large intrahepatic bile duct. The tumor showed mainly intraductal papillary growth primarily composed of absorptive columnar cells. Particularly, Paneth cell metaplasia of carcinoma cells was widespread, and goblet cells and neuroendocrine cells were also observed in the carcinoma tissue, to a varied degree. It showed an intraluminal spread along the dilated intrahepatic ducts with minimal ductal stromal invasion. In the vicinity of the tumor, intestinal metaplasia was also identified in the adjacent hyperplastic and dysplastic bile duct epithelium. Some bile ducts contained stones and the mural glands of the bile ducts showed hyperplastic change secondary to stones. This case is considered to provide the evidence supporting the concept of the metaplasia-dysplasia-carcinoma sequence via intestinal metaplasia in the stone-containing intrahepatic bile ducts.