Screening for HIV-related neurocognitive impairment in clinical practice: challenges and opportunities.
With increasingly successful management of HIV, focus has shifted away from AIDS-related complications to other chronic co-morbidities. For HIV-related cognitive problems, the true aetiopathogenesis and epidemiology remains unclear. Rather than a systematic review, this paper presents the challenges and the opportunities we faced in establishing our own clinical service. Papers were identified using Pubmed and the terms "screening", "HIV" and "neurocognitive". This article covers the background of HIV-associated neurocognitive disorders (HAND) with a focus on HIV-related neurocognitive impairment (NCI), detailing classification, prevalence, diagnostic categories and diagnostic uncertainties. Screening is discussed, including a comparison of the available screening tools for cognitive deficits in HIV-infected patients and the importance of practice effects. Discussed also are the normal ranges and the lack thereof and potential investigations for those found to have impairments. We conclude by discussing the role of NCI screening in routine clinical care at the current time.


Chinese authors do need CONSORT: reporting quality assessment for five leading Chinese medical journals.
Only a few Chinese medical journals have recommended CONSORT in their "Instruction for authors or Guide for authors". This study aims to evaluate the reporting quality of randomized controlled trials (RCTs) published in the five leading Chinese medical journals indexed by MEDLINE. We identified RCTs published from 2004 to January 2007 in five leading Chinese medical journals by searching three important Chinese databases systematically, namely CNKI (China National Knowledge Infrastructure/Chinese Academic Journals full text Database), VIP (a full text database of China) and CBM disc (China Biomedicine Database Disc) and assessed the quality of each RCT by using the Consolidated Standards for Reporting of Trials (CONSORT) and the 5-point Jadad scale. One hundred and forty two RCTs were included. Based on the items in the revised CONSORT statement, 130 (91.55%) of the 142 RCTs mentioned "randomization" in the title or abstract, but only 38 (26.76%) RCTs described the method to generate the random sequence; only 6 RCTs had adequate allocation concealment; 24 (17.61%) RCTs mentioned "masking", but only 7 described the process of masking. Three out of 40 items were reported clearly in all included trials, while five items were not mentioned at all. The quality of RCTs was low as assessed by the Jadad scale and 22 RCTs were high-quality research (>/=3 points). The reporting quality of RCTs published in the five leading Chinese medical journals is low. Chinese journals should adopt the CONSORT statement to improve the reporting quality of Chinese randomized controlled trials.


Prevalence and correlates of fire-setting in the United States: results from the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC).
To estimate the prevalence, sociodemographic correlates, comorbidity, and rates of mental health service utilization of fire-setters in the general population. A face-to-face survey of more than 43,000 adults aged 18 years and older residing in households was conducted during the 2001-2002 period. Diagnoses of mood, anxiety, substance use disorders, and personality disorders were based on the Alcohol Use Disorder and Associated Disabilities Interview Schedule-DSM-IV Version (AUDADIS-IV). The prevalence of lifetime fire-setting in the US population was 1.13 (95% CI, 1.0-1.3). Being male, never married, and US-born and having a yearly income over $70,000 were risk factors for lifetime fire-setting, while being Asian or Hispanic and older than 30 years were protective factors for lifetime fire-setting. The strongest associations with fire-setting were with disorders often associated with deficits in impulse control, such as antisocial personality disorder (ASPD) (odds ratio [OR] = 21.8; CI, 6.6-28.5), drug dependence (OR = 7.6; 95% CI, 5.2-10.9), bipolar disorder (OR = 5.6; 95% CI, 4.0-7.9), and pathological gambling (OR = 4.8; 95% CI, 2.4-9.5). Associations between fire-setting and all antisocial behaviors were positive and significant. A lifetime history of fire-setting, even in the absence of an ASPD diagnosis, was strongly associated with substantial rates of Axis I comorbidity, a history of antisocial behavior, a family history of other antisocial behaviors, decreased functioning, and higher treatment-seeking rates. Our findings suggest that fire-setting may be better understood as a behavioral manifestation of a broader impaired control syndrome and part of the externalizing spectrum. Fire-setting and other antisocial behaviors tend to be strongly associated with each other and increase the risk of lifetime and current psychiatric disorders, even in the absence of a DSM-IV diagnosis of ASPD.


Assessment of sarcopenia in patients with fibromyalgia.
Fibromyalgia is a chronic disorder characterized by persistent widespread musculoskeletal pain. Patients with fibromyalgia have reduced physical activity and increased sedentary rate. The age-associated reduction of skeletal muscle mass and function is called sarcopenia. The European Working Group on Sarcopenia in Older People developed a practical clinical definition and consensus diagnostic criteria for sarcopenia. Loss of muscle function is common in fibromyalgia and in the elderly. The goal of this study is to determine whether the reduction of muscle function in fibromyalgia is related to sarcopenia according to the European Working Group on Sarcopenia in Older People criteria. Forty-five patients with fibromyalgia and thirty-nine healthy control female subjects were included. All the participants were assessed by Fibromyalgia Impact Questionnaire and SARC-F questionnaire. Muscle mass was evaluated by bioimpedance analysis, muscle strength by handgrip strength test and physical performance with the Short Physical Performance Battery. Fibromyalgia Impact Questionnaire and SARC-F scores were statistically significantly higher in the fibromyalgia group than in the control group, showing severe disease and a higher risk of sarcopenia in the fibromyalgia group (p < 0.001). Muscle strength and physical performance were statistically significantly lower in the group with fibromyalgia than in the control group (p < 0.001). There was no statistical difference between fibromyalgia and control groups regarding skeletal muscle mass (p = 0.263). Our study demonstrated a significant reduction in muscle function in fibromyalgia patients without any loss of muscle mass. Loss of muscle function without decrease in muscle mass is called dynapenia.


TWO NEW SPECIES OF STILLABOTHRIUM (CESTODA: RHINEBOTHRIIDEA) FROM STINGRAYS FROM NORTHERN AUSTRALIA AND ONE NEW COMBINATION.
A study of cestode specimens that were collected during survey work on elasmobranchs collected from Taiwan and Northern Territory, Australia, revealed the presence of 1 new combination into the genus Stillabothrium (Rhinebothriidea: Escherbothriidae) and 2 new species of the genus. Phyllobothrium biacetabulatum, collected from Rhinobatos schlegelii, is transferred to Stillabothrium and its description is emended, as is the diagnosis for the genus Stillabothrium and the family Escherbothriidae. Stillabothrium biacetabulatum n. comb. differs from existing species of the genus in that the face of its bothridia is laced with a network of longitudinal and horizontal muscle fibers that do not contribute to the formation of septa. Stillabothrium lunae n. sp. is described from Himantura leoparda and differs from existing species of the genus in that its bothridium possesses an anterior field of 7-8 loculi that are wider than long. Stillabothrium mariae n. sp. is described from Maculabatis astra. This species differs from all species of Stillabothrium except Stillabothrium campbelli in possessing 10-12 horizontally oriented bothridial loculi. Stillabothrium mariae n. sp. differs from S. campbelli in having longer bothridia and from all other species of Stillabothrium in that it lacks, rather than possesses, conspicuous septa and loculi that are longer than wide in the posterior region of its bothridia. Bayesian and parsimony-bootstrap analysis of 28S rDNA revealed S. biacetabulatum n. comb., S. lunae n. sp., and S. mariae n. sp. to be part of Clade 1 of Stillabothrium, with S. biacetabulatum n. comb. being the sister species to S. mariae n. sp. Stillabothrium lunae n. sp. was found to be the sister species to Stillabothrium borneoense.


The legal investigation of a decision not to operate on an infant with Down's syndrome and a duodenal atresia: a report from the Netherlands.
It is well-known that in the Netherlands it has for several years been possible to carry out voluntary euthanasia quite openly, provided certain strict conditions are fulfilled. This situation has arisen because courts in the Netherlands have decided that doctors who end the lives of their patients under these conditions are in a "conflict of duties" situation, and therefore should not be convicted of any criminal offence. It has, however, not been known what view a Netherlands court might take about life and death decisions concerning patients who are not capable of giving consent -- for example, infants. This report briefly outlines my experience in the case of an infant with Down's syndrome and duodenal atresia -- a blockage of the digestive system that must be operated upon if the infant is to survive. A decision was taken not to operate, and this decision resulted in the Netherlands courts considering whether criminal proceedings were justified.


Children with juvenile idiopathic arthritis: are health outcomes better for those diagnosed younger?
Children living with juvenile idiopathic arthritis (JIA) have swollen, painful and stiff joints, which may have an impact on all spheres of their life, as well as their family. While children diagnosed in their preschool years may be at risk for worse physical outcomes than children diagnosed later in life, it is not clear whether they have worse psychological outcomes and whether these outcomes have an impact on their everyday life. The aim of this study was to examine the association between age at diagnosis and health outcomes in families of children with JIA. Parents of children with JIA (n = 182) who attended rheumatology clinics at the Montreal Children's Hospital and British Columbia Children's Hospital completed measures assessing socio-demographic attributes, their child's health status, health-related quality of life and pain level, as well as their own level of psychological distress and coping behaviours. Regression models explored the association between age at diagnosis and health outcomes while adjusting for sex, age, severity and duration of the disease. Parents of children diagnosed with JIA before 5 years of age found their child to have a better health-related quality of life in terms of psychosocial functioning than parents of children diagnosed later [β = -0.91 (-1.63, -0.19)]. Children diagnosed younger were also found to be less limited in schoolwork or activities with friends because of emotional or behavioural problems than children diagnosed later [odds ratio = 0.07 (0.01, 0.42)]. Children diagnosed younger seem to show good psychosocial adjustment, which may also be true for their caregivers. Perhaps more attention to psychosocial adjustment should be given to families of children who are diagnosed with the disease at an older age.


Diversity within bacterial isolates hybridizing with Comamonas probe ppT.
Diversity within bacteria isolated from activated sludge and the Baltic sea and recognized by the rRNA targeted oligonucleotide probe ppT (designed by BRAUN-HOWLAND et al., 1993 to recognize C. testosteroni) was studied. The partial nucleotide sequences of 16S genes of the isolates revealed that the activated sludge and Baltic sea isolates each formed a separate group distinct from C. testosteroni. The analysis of phage and bacteriocin sensitivity as well as whole cell protein patterns revealed the same grouping, but in these characters also intragroup variation was observed. As a conclusion, neither of the studied groups were C. testosteroni, but they probably belong to two previously unknown species common in activated sludge or the Baltic sea.


[The effect of desloratadine on use of rescue beta2-agonists and symptoms in patients suffering from seasonal allergic rhinitis and asthma].
Seasonal allergic rhinitis (SAR) and intermittent asthma are frequently comorbid and share some pathophysiological, clinical and epidemiological bases which has been confirmed by ARIA (Allergic Rhinitis and its Impact on Asthma) WHO position paper. Therapeutical consequences of H1 receptor antagonists treatment in patients with both SAR and asthma are not clear. The aim of this study was to evaluate the effect of desloratadine (5 mg daily) on rescue medication use, symptoms of SAR and asthma. One hundred and ninteen patients (59 men), mean age 29.64 +/- 8.34 years, suffering from SAR and asthma were recruited. After 14 days of screening during the pollen season desloratadine in an open manner was introduced. During the treatment phase mean beta2 agonist weekly demand decreased from 11.73 +/- 8.91 (screening) to 4.89 +/- 7.09 (p < 0.001, Wilcoxon test). Mean symptoms score decreased from 13.37 +/- 5.93 to 5.19 +/- 4.7 and from 5.69 +/- 3.83 to 2.09 +/- 2.45 for SAR and asthma respectively (p < 0.001). Eight mild adverse events were reported with the most frequent-sleepiness (6.9% of study group). Desloratadine in the dosis of 5 mg daily confirmed its efficacy and safety in the treatment of patients with SAR and asthma. Decrease of beta2-agonist use and reduction of diseases symptoms was documented in patients with seasonal allergic rhinitis and asthma.


[Expression and function of hepatocellular carcinoma-related gene pp1158].
To study in vitro and in vivo protein expression and biological function of gene pp1158, a hepatocellular carcinoma (HCC)-related gene. pp1158 was expressed with fusion expression vector pET-32a in E. Coli-BL21 (DE3), and rabbit anti-pp1158 fusion protein polyclonal antibody was prepared. The biological function and differential expressions of pp1158 were studied by in vitro colony formation assay nude mouse in vivo tumor formation assay of transfected BEL7402 cell line and immunohistochemistry and Western blot. Differential expression of pp1158 in human fetal tissues were examined by Northern blot. In vitro experiment showed that pp1158 inhibited colony formation rate of transfected BEL 7402 cells, with an inhibition rate of 58.3% (P < 0.01). Tumor formation assay indicated that tumor formation of pCMV-Script-1158 transfected BEL 7402 cell line was significantly inhibited (P < 0.05) as compared with that of the control group. Immunohistochemical assay showed that pp1158 was expressed in human tissue in the following sequence: normal liver >/= noncancerous liver tissue > HCC. Western blot indicated that a 60kD protein (pp1158 protein) was expressed in BEL 7402 cells transfected with pCMV-Script-pp1158 DNA, while it was detected in BEL 7402 cells transfected with pCMV-Script vector DNA. Northern blot showed pp1158 was expressed in the placenta at a very high level, heart, liver, muscle, pancreas and lung but expressed poorly in the brain and kidney. pp1158 is a new candidate tumor suppressor gene of HCC.


Myelodysplastic syndromes: analysis of 51 cases. Therapy with low doses of arabinosyl cytosine of leukaemic transformation.
Clinical, haematological, cytogenetic features and therapeutic problems of 51 patients with MDS were examined. Patients were distributed in 5 FAB subgroups: RA 21, SA 7, RAEB 8, RAEB-t 9 and MMCL 6 patients. Leukaemic transformation occurred in 3 RA, 3 RAEB, 7 RAEB-t and 3 MMCL patients. No SA patient suffered from leukaemic transformation. Cytogenetic alterations occurred in 13 of 29 examined patients; 5q- was the most common abnormality. We did not find any relation between chromosomal anomalies and FAB subgroups. Leukaemic transformation, however, was more frequent in patients with cytogenetic aberrations. In some cases it was not easy to determine the precise diagnostic allocation according to FAB subgroups; it is possible, however, to subdivide MDS prognosis into 2 classes. The more satisfactory therapy of leukaemic transformation is often due to low doses of Ara-C; this therapy allowed a better survival and sometimes to obtain CR which in a M6 ANLL patient continued for 24 months.


[Macrovascular diseases-based on the data of Japanese cohort study (JCDM) including 1,016 very elderly diabetic individuals older than 75 years old].
LDL-cholesterol and glucose are risk for ischemic heart disease (IHD) in middle-aged diabetic individuals; however, the risk among elderly, especially very elderly, is not well-known. We performed a prospective cohort study (JCDM) with 5.5 years of follow-up. Four thousand fourteen type 2 diabetic patients without previous IHD or cerebrovascular attack (CVA) (1,936 women: 67.4 +/- 9.5 years, > or = 75 years, n = 1,016) were recruited. One hundred fifty-three IHDs and 104 CVAs occurred over 5.5 years. Lower HDL-cholesterol (HDL-C) was correlated with IHD in patients > or = 75 years old. In contrast, systolic BP, HbA1c, LDL-C and non-HDL-C were correlated in subjects < 65 years old, and LDL-C/HDL-C ratio was correlated in all subjects. HDL-C was correlated with CVA in patients > or = 75 years old. These age-dependent differences in risk are important for developing individualized strategies to prevent atherosclerotic disease.


Kit ligand 2 promotes murine oocyte growth in vitro.
Oocyte-granulosa cell communication, mediated by paracrine factors, is essential for oocyte development. Kit ligand (KITL) is expressed in granulosa cells as soluble (KITL1) or membrane-associated (KITL2) proteins. However, the relative biopotency of each isoform during oocyte development is unknown. Our initial results showed that Kitl2 was down-regulated in cultured granulosa cells. To determine the effect of the two isoforms of KITL on oocyte growth, Kitl-deficient fibroblasts were transfected with constructs expressing either KITL1 or KITL2, and growing oocytes were isolated from 12-day-old mice and cultured on the transfected fibroblasts for 2 days. At the end of culture, oocyte diameters were measured, the incidence of spontaneous germinal vesicle breakdown (GVBD) was noted, and oocytes were analyzed for KIT receptor expression. Oocyte growth occurred only in the presence of the KITL2-producing fibroblasts, and suppression of KITL2 expression impaired oocyte growth. Up-regulation of KIT expression occurred in the presence of KITL2 but not KITL1. The presence of KITL2 inhibited spontaneous GVBD. Meiosis inhibitors did not attenuate the GVBD that occurred in the absence of KITL2, suggesting that this process reflects oocyte degeneration rather than meiotic progression. These results indicate that KITL2 is the principal KITL isoform required for oocyte growth and survival in vitro.


Clipping Effect on the Grain Nitrogen and Protein Fractions of Ancient and Old Wheats Grown in a Mediterranean Environment.
This study is the first to assess the effects of clipping, cultivar, season, and their interactions on the protein composition of six old and ancient wheat cultivars (n = 6). For this, nitrogen content, the proportion of wheat protein fractions, and the molecular weight distribution of the extractable and unextractable glutenin polymers were investigated as a function of cultivar and clipping in two consecutive seasons. The relationships between genotypic variation in grain nitrogen and protein fraction content under clipping and non-clipping conditions were also assessed. Clipping delayed and shortened the grain filling period of all of the cultivars. The protein composition of some cultivars behaved differently to clipping due to differences in the environmental conditions of S1 (exceptional dry season) and S2 (rainy season). In S1, clipping decreased the ratio of gliadins over glutenins (GLI/GLU) (<1) of Cappelli and Giovanni Paolo, while in S2, clipping improved the GLI/GLU of Giovanni Paolo, Monlis, and Norberto. The unextractable polymeric proteins were not affected by clipping. Khorasan was shown to be indifferent to clipping in S1 and S2. These results suggest that it is possible to have ancient/old wheats suitable for a dual-purpose system, in different climatic conditions, while maintaining good grain quality traits. The increased market demand for ancient and old wheats presents an economic opportunity for farmers who adopt the dual-purpose technique to cultivate these resilient crops again and increase their profit margins and revenues.


Health professionals' decision-making in wound management: a grounded theory.
To develop a conceptual understanding of the decision-making processes used by healthcare professionals in wound care practice. With the global move towards using an evidence-base in standardizing wound care practices and the need to reduce hospital wound care costs, it is important to understand health professionals' decision-making in this important yet under-researched area. A grounded theory approach was used to explore clinical decision-making of healthcare professionals in wound care practice. Interviews were conducted with 20 multi-disciplinary participants from nursing, surgery, infection control and wound care who worked at a metropolitan hospital in Australia. Data were collected during 2012-2013. Constant comparative analysis underpinned by Strauss and Corbin's framework was used to identify clinical decision-making processes. The core category was 'balancing practice-based knowledge with evidence-based knowledge'. Participants' clinical practice and actions embedded the following processes: 'utilizing the best available information', 'using a consistent approach in wound assessment' and 'using a multidisciplinary approach'. The substantive theory explains how practice and evidence knowledge was balanced and the variation in use of intuitive practice-based knowledge versus evidence-based knowledge. Participants considered patients' needs and preferences, costs, outcomes, technologies, others' expertise and established practices. Participants' decision-making tended to be more heavily weighted towards intuitive practice-based processes. These findings offer a better understanding of the processes used by health professionals' in their decision-making in wound care. Such an understanding may inform the development of evidence-based interventions that lead to better patient outcomes.


Rasmussen syndrome of chronic focal encephalitis.
Rasmussen syndrome of chronic focal encephalitis is a relatively rare disease, which presents with epilepsia partialis continua and hemiparesis in childhood. Though first described in the 1950s it still remains somewhat of an enigma. The immunological process involved in its pathogenesis is better understood now but the exact relationship to viral infections is still unclear. Medical treatment remains disappointing while results of surgical treatment are mixed. There are emerging insights into the disease, which are reviewed and a case study of a patient with Rasmussen syndrome is presented.


Grape berry yeast communities: influence of fungicide treatments.
The yeast communities colonising grape berry surfaces were evaluated for the influence of fungicide treatments in an organic vineyard (copper/sulphur-based products) and a conventional vineyard (commonly used fungicides). Analysis of yeast abundance and diversity was carried out on grape berries and juice during fermentation, using culture-dependent and -independent approaches. Yeast abundance was as generally reported for mature grapes and it was slight higher from grapes treated with conventional fungicides. Initial grape samples showed less yeast species diversity in the organic vineyard compared with the conventional one. In both vineyards, the dominant yeast were Candida zemplinina and Hanseniaspora uvarum (>50%), respectively, typical species that colonise surfaces of mature grape berries. Metschnikowia pulcherrima was widely found in the conventional samples while it was only occasionally found in organic ones. Saccharomyces cerevisiae was isolated only at the end of natural fermentation (conducted in sterile condition), with lower levels in the organic samples. S. cerevisiae strains showed less intraspecies diversity in the organic samples (two genotypes), in comparison with the conventional samples (six genotypes).


[Impact of low T3 syndrome on adverse cardiovascular events in adult patients with acute viral myocarditis].
Objective: To determine the impact of low T3 syndrome on adverse cardiovascular events in adult patients with acute viral myocarditis. Methods: The study population consisted of 134 consecutive patients admitted between January 2002 and March 2018 with diagnoses of acute viral myocarditis (onset of symptoms<1 month,patients were divided into low serum free triiodothyronine (FT3, n=20) group and normal FT3 (n=114) group. General information, clinical presentation,electrocardiography at admission,laboratory tests,echocardiography features were analyzed. Low T3 syndrome was defined as a state with decreased FT3 and total triiodothyronine (TT3), normal or decreased free thyroxine (FT4) and total thyroxine (TT4) as well as normal thyroid stimulating hormone (TSH). Composite adverse cardiovascular events included death, persistent ventricular tachycardia (VT) or ventricular fibrillation (VF) and cardiac arrest. Risk factors related with composite adverse cardiovascular events in adult patients with acute viral myocarditis were analyzed by logistic regression analysis. Results: Systolic blood pressure was significantly lower (P<0.01),while heart rate (P=0.004) and the prevalence of VT/VF were significantly higher (P=0.017) in low T3 group than in the normal T3 group. Level of white blood cell,C response protein,fasting glucose (all P<0.01) as well as creatinine (P=0.035) were significantly higher, while level of FT3 and left ventricular ejection fraction (LVEF) were significantly lower (both P<0.01) in low T3 group than in normal T3 group. Multivariate logistic regression analysis revealed that LVEF at admission less than 40% (OR=6.615,95%CI 1.186-36.907, P=0.031) and FT3 level less than 1.79 ng/L (OR=9.131, 95%CI 1.577-52.857, P=0.014) were independent risk factors of increased composite adverse cardiovascular events in patients with acute viral myocarditis. Conclusion: Low FT3 increases the risk of adverse cardiovascular events in adult patients with acute viral myocarditis.


Redefining functional sensitivity of thyroglobulin assay on Immulite platform: implications in thyroid cancer management.
Circulating thyroglobulin (Tg) measurement after thyrotropin stimulation is a pivotal tool in the management of patients affected by differentiated thyroid carcinoma. The Tg assay on Immulite platform has a declared functional sensitivity of 0.9 ng/mL and it is widely used in clinical practice and research on thyroid carcinoma. Recently, thyroglobulin measured during thyroxine treatment was found to be adequate for thyroid carcinoma follow-up if functional sensitivity at 0.2-0.3 ng/mL was reached by assay methods. Thus, the present study was then undertaken to evaluate the imprecision of Immulite Tg assay at very low concentrations. The detection limit was calculated on zero calibrator and Tg-free pooled sera replicates and was 0.14 and 0.16 ng/mL, respectively. Different serum pools with Tg concentrations ranging from 0.16 to 2.50 ng/mL were assayed according to the National Academy of Clinical Biochemistry guidelines to estimate functional sensitivity. By interpolating the imprecision profile with a coefficient of variation of 20%, the functional sensitivity was 0.36 ng/mL. The Immulite-Tg assay was directly compared with a high-sensitive immunoradiometric Tg assay in sera from 93 patients with thyroid carcinomas. No significant differences in sensitivity and specificity were observed by using the newly defined functional sensitivity. In conclusion, the Immulite Tg assay showed a lower functional sensitivity than expected and performed comparably to high-sensitive immunoradiometric assay in patients with thyroid carcinoma.


Synthesis of Highly Uniform and Compact Lithium Zinc Ferrite Ceramics via an Efficient Low Temperature Approach.
LiZn ferrite ceramics with high saturation magnetization (4πMs) and low ferromagnetic resonance line widths (ΔH) represent a very critical class of material for microwave ferrite devices. Many existing approaches emphasize promotion of the grain growth (average size is 10-50 μm) of ferrite ceramics to improve the gyromagnetic properties at relatively low sintering temperatures. This paper describes a new strategy for obtaining uniform and compact LiZn ferrite ceramics (average grains size is ∼2 μm) with enhanced magnetic performance by suppressing grain growth in great detail. The LiZn ferrites with a formula of Li0.415Zn0.27Mn0.06Ti0.1Fe2.155O4 were prepared by solid reaction routes with two new sintering strategies. Interestingly, results show that uniform, compact, and pure spinel ferrite ceramics were synthesized at a low temperature (∼850 °C) without obvious grain growth. We also find that a fast second sintering treatment (FSST) can further improve their gyromagnetic properties, such as higher 4πMs and lower ΔH. The two new strategies are facile and efficient for densification of LiZn ferrite ceramics via suppressing grain growth at low temperatures. The sintering strategy reported in this study also provides a referential experience for other ceramics, such as soft magnetism ferrite ceramics or dielectric ceramics.


Predicting the fate of sediment and pollutants in river floodplains.
Geological processes such as erosion and sedimentation redistribute toxic pollutants introduced to the landscape by mining, agriculture, weapons development, and other human activities. A significant portion of these contaminants is insoluble, adsorbing to soils and sediments after being released. Geologists have long understood that much of this sediment is stored in river floodplains, which are increasingly recognized as important nonpoint sources of pollution in rivers. However, the fate of contaminated sediment has generally been analyzed using hydrodynamic models of in-channel processes, ignoring particle exchange with the floodplain. Here, we present a stochastic theory of sediment redistribution in alluvial valley floors that tracks particle-bound pollutants and explicitly considers sediment storage within floodplains. We use the theory to model the future redistribution and radioactive decay of 137Cs currently stored on sediment in floodplains at the Los Alamos National Laboratory (LANL) in New Mexico. Model results indicate that floodplain storage significantly reduces the rate of sediment delivery from upper Los Alamos Canyon, allowing 50% of the 137Cs currently residing in the valley floor to decay radioactively before leaving LANL. A sensitivity analysis shows that the rate of sediment overturn in the valley (and hence, the total amount of radioactive 137Cs predicted to leave LANL) is significantly controlled by the rate of sediment exchange with the floodplain. Our results emphasize that flood plain sedimentation and erosion processes can strongly influence the redistribution of anthropogenic pollutants in fluvial environments. We introduce a new theoretical framework for examining this interaction, which can provide a scientific basis for decision-making in a wide range of river basin management scenarios.


The autism/neuroprotection-linked ADNP/NAP regulate the excitatory glutamatergic synapse.
Activity-dependent neuroprotective protein (ADNP), essential for brain formation, was discovered as a leading de novo mutated gene causing the autism-like ADNP syndrome. This syndrome is phenotypically characterized by global developmental delays, intellectual disabilities, speech impediments, and motor dysfunctions. The Adnp haploinsufficient mouse mimics the human ADNP syndrome in terms of synapse density and gene expression patterns, as well as in developmental, motor, and cognitive abilities. Peripheral ADNP was also discovered as a biomarker for Alzheimer's disease and schizophrenia, with nasal administration of the ADNP snippet peptide NAP (enhancing endogenous ADNP activity) leading to partial cognitive and functional protection at the cellular, animal and clinical settings. Here, a novel formulation for effective delivery of NAP is provided with superior brain penetration capabilities. Also provided are methods for treating pertinent clinical implications such as autism, cognitive impairments, olfactory deficits, and muscle strength using the formulation in the Adnp haploinsufficient mouse. Results showed a dramatically specific increase in brain/body bioavailability with the new formulation, without breaching the blood brain barrier. Additional findings included improvements using daily intranasal treatments with NAP, at the behavioral and brain structural levels, diffusion tensor imaging (DTI), translatable to clinical practice. Significant effects on hippocampal and cerebral cortical expression of the presynaptic Slc17a7 gene encoding vesicular excitatory glutamate transporter 1 (VGLUT1) were observed at the RNA and immunohistochemical levels, explaining the DTI results. These findings tie for the first time a reduction in presynaptic glutamatergic synapses with the autism/Alzheimer's/schizophrenia-linked ADNP deficiency coupled with amelioration by NAP (CP201).


Trimipramine in the treatment of duodenal ulcer. A multicenter, open study.
Sixty patients with endoscopically confirmed duodenal ulcers were treated with 50 mg of trimipramine daily. After the end of the treatment 45 patients showed healed ulcers. Ulcer healing was not related to serum concentration of trimipramine, but seemed to be influenced by smoking habits and duration of the total and actual disease history.


In search of an animal model for postmenopausal diseases.
The purpose of this review is to discuss the use of the aged ovariectomized ewe as a cost-effective large animal model to study coronary artery disease (CAD), osteoporosis, osteoarthritis (OA), and oral bone loss--conditions seen after menopause. Earlier studies from our laboratory showed a significant decline in the bone mineral density (BMD) of the iliac crest following ovariectomy in sheep, while subsequent studies demonstrated decreased bone loss (measured by dual energy X-ray absorptiometry (DXA)) in the lumbar vertebrae following ovariectomy. We examined the effects of estrogen deficiency and estrogen therapy on the terminal aorta of the aged ovariectomized (OVX) ewes and demonstrated subintimal thickening in the distal aorta of animals that were estrogen deficient when compared to the control groups. A popular model to study OA is the knee joint of sheep following medial or lateral meniscus removal combined with exercise, but there is a need for an estrogen-deficient large animal model of OA to study articular cartilage changes occurring after menopause. We saw an effect of ovariectomy on the biomechanical properties (aggregate modulus and shear modulus) of articular cartilage. Estrogen deficiency had a detrimental effect on the articular cartilage of the knee even though the cartilage of the OVX animals appeared grossly normal. In another study, 13.5 months following ovariectomy, we found an increase in estrogen receptor binding capacity of the articular cartilage suggesting that articular cartilage is a sex-hormone sensitive tissue. There is intense interest in the correlation between systemic osteoporosis and bone loss of the mandible and maxilla. We studied mandibular bone loss in OVX sheep using DXA. The mean BMD of the OVX group versus sham and estradiol-treated animals was lower, indicating that systemic bone loss in OVX ewes may be accompanied by oral bone loss. Coronary artery disease, osteoporosis, osteoarthritis (OA) and oral bone loss all have a major impact on women's heath after menopause and we found that certain characteristics of these conditions can be reproduced in the skeletally mature or aged estrogen-deficient sheep. It is premature to promote the sheep as the only model to study estrogen deficiency and the many differences from small animal omnivores and non-human primates need to be overcome and a search for more economical models must continue. This model, however, may offer the opportunity to study postmenopausal conditions and the safety and efficacy of new therapeutic agents.


Further validity evidence of the Behavioral Inhibition Observation System (BIOS).
The Behavioral Inhibition Observation System (BIOS) is a brief clinician-report scale for detecting behavioral inhibition (BI) from direct observation. This study aims to compare the validity coefficients obtained in the natural context of use of the BIOS (i.e., a clinical situation) with those obtained using the BIOS after standardized observation. The participants were 74 randomly selected preschool children who were exposed to systematic observation. The results indicate excellent internal consistency (α = .91) and moderate to good inter-rater reliability for all items (ICC from .55 to .88). The correlations with observational measures of BI ranged from .40 to .70, and were mostly equivalent to those of the previous study. The correlations with parents', teachers', and clinicians' measures of BI and related constructs ranged from .30 to .60, and were also equivalent to those obtained in the natural context of use of the BIOS (i.e., clinical situation). The validity coefficients obtained with the BIOS in a non-structured natural observation are mostly equivalent to those obtained in an experimental situation, thus supporting that the BIOS is a cost-efficient instrument for measuring BI from observation in a clinical situation.


Diagnostic value of long noncoding RNAs for hepatocellular carcinoma: A PRISMA-compliant meta-analysis.
Increasing evidences have shown that long noncoding RNAs (lncRNAs) are involved in cancer diagnosis and prognosis. However, the overall diagnostic accuracy of lncRNAs for hepatocellular carcinoma (HCC) remains unclear. Herein, we perform a meta-analysis to assess diagnostic value of lncRNAs for HCC. The online PubMed, Cochrane, Web of Science, and Embase database were searched for eligible studies published until October 5, 2016. Study quality was evaluated with the Quality Assessment for Studies of Diagnostic Accuracy (QUADAS). All statistical analyses were conducted with Stata 12.0 and Meta-Disc 1.4. We included 19 studies from 10 articles with 1454 patients with HCC and 1300 controls. The pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and AUC for lncRNAs in the diagnosis of HCC were 0.83 (95% confidence interval [CI]: 0.76-0.88), 0.80 (95% CI: 0.73-0.86), 4.2 (95% CI: 3.00-5.80), 0.21 (95% CI: 0.15-0.31), 20 (95% CI: 11-34), and 0.88 (95% CI: 0.85-0.91), respectively. Additionally, the diagnostic value of lncRNAs varied based on sex ratio of cases and characteristics of methods (specimen type and reference gen). This meta-analysis suggests lncRNAs show a moderate diagnostic accuracy for HCC. However, prospective studies are required to confirm its diagnostic value.


The Impact of Mindfulness on Stress and Burnout of New Graduate Nurses as a Component of a Nurse Residency Program.
This evidence-based practice project assessed the impact of integrating mindfulness training into an existing nurse residency program. Stress and burnout are endemic in healthcare. The transition to practice is associated with stress and anxiety for newly graduated nurses. Evidence supports mindfulness-based interventions to mitigate stress and burnout and improve the workplace environment and patient outcomes. This project employed a pre/post design to measure burnout, stress, and mindfulness, comparing means and standard deviations between intervention and comparison nurse residency cohorts. Mindfulness training was integrated at 4 points within the 1st 6 months of the residency program. The intervention cohort reported significantly less burnout and stress and more mindfulness at 6 months than the comparison group. Mindfulness training can be feasibly integrated into an existing nurse residency program to decrease stress and burnout for new graduate nurses during the transition to practice.


Engagement of African Americans with Rapid HIV Testing and HIV Care.
African Americans and Blacks experience the greatest human immunodeficiency virus (HIV) burden of any racial group in the US and globally. A number of challenges contribute to the higher rates of HIV infection among African Americans, including a lack of awareness of HIV status. African Americans account for nearly 50% of the newly estimated HIV/acquired immunodeficiency syndrome (AIDS) diagnoses, with the majority being tested only after developing symptoms of AIDS. Moreover, African Americans are more likely to postpone medical care after finding out that they are HIV positive. The aim of this study was to describe African Americans' likelihood of using salivary rapid testing (SRT) methods and entry into healthcare if HIV positive. Focus groups were conducted among 38 African Americans. The purpose of this study was to (1) describe personal factors, social resources, socio-demographic factors, cognitive appraisal, and health and coping behaviors which predict or influence the likelihood of African Americans' participation in SRT and, if positive, subsequent entry into healthcare and (2) to evaluate HIV Testing Survey items and modify them to be culturally and linguistically appropriate. A modified Comprehensive Health Seeking and Coping Paradigm guided the study (CHSCP). Of the 38 African American adults who participated in the study, 16 were female between the ages of 18-49 and the mean age was 23 years and there were 22 males, aged between 18-49 and the mean age was 29.5 years. Eight themes emerged from the data: familiarity, stigma, fear, access, immediacy, ease, degree of responsibility, and trust. Gender specific themes were health maintenance (women) and illness management (men). Sub-themes within gender-specific themes were stoicism (women) and anger (men). Identifying the factors that influence the likelihood of HIV testing uptake can provide information on which to base development of interventions to facilitate HIV testing and earlier linkage to healthcare.


Ion transport in a polymer-plastic solid soft matter electrolyte in the light of solvent dynamics and ion association.
Ion transport in a recently demonstrated promising soft matter solid plastic-polymer electrolyte is discussed here in the context of solvent dynamics and ion association. The plastic-polymer composite electrolytes display liquid-like ionic conductivity in the solid state, compliable mechanical strength (approximately 1 MPa), and wide electrochemical voltage stability (> or = 5 V). Polyacrylonitrile (PAN) dispersed in lithium perchlorate (LiClO(4))-succinonitrile (SN) was chosen as the model system for the study (abbreviated LiClO(4)-SN:PAN). Systematic observation of various mid-infrared isomer and ion association bands as a function of temperature and polymer concentration shows an effective increase in trans conformer concentration along with free Li(+) ion concentration. This strongly supports the view that enhancement in LiClO(4)-SN:PAN ionic conductivity over the neat plastic electrolyte (LiClO(4)-SN) is due to both increase in charge mobility and concentration. The ionic conductivity and infrared spectroscopy studies are supported by Brillouin light scattering. For the LiClO(4)-SN:PAN composites, a peak at 17 GHz was observed in addition to the normal trans-gauche isomerism (as in neat SN) at 12 GHz. The fast process is attributed to increased dynamics of those SN molecules whose energy barrier of transition from gauche to trans has reduced under influences induced by the changes in temperature and polymer concentration. The observations from ionic conductivity, spectroscopy, and light scattering studies were further supplemented by temperature dependent nuclear magnetic resonance (1)H and (7)Li line width measurements.


Decipher the complexity of cis-regulatory regions by a modified Cas9.
Understanding complex mechanisms of human transcriptional regulation remains a major challenge. Classical reporter studies already enabled the discovery of cis-regulatory elements within the non-coding DNA; however, the influence of genomic context and potential interactions are still largely unknown. Using a modified Cas9 activation complex we explore the complexity of renin transcription in its native genomic context. With the help of genomic editing, we stably tagged the native renin on chromosome 1 with the firefly luciferase and stably integrated a programmable modified Cas9 based trans-activation complex (SAM-complex) by lentiviral transduction into human cells. By delivering five specific guide-RNA homologous to specific promoter regions of renin we were able to guide this SAM-complex to these regions of interest. We measured gene expression and generated and compared computational models. SAM complexes induced activation of renin in our cells after renin specific guide-RNA had been provided. All possible combinations of the five guides were subjected to model analysis in linear models. Quantifying the prediction error and the calculation of an estimator of the relative quality of the statistical models for our given set of data revealed that a model incorporating interactions in the proximal promoter is the superior model for explanation of the data. By applying our combined experimental and modelling approach we can show that interactions occur within the selected sequences of the proximal renin promoter region. This combined approach might potentially be useful to investigate other genomic regions. Our findings may help to better understand the transcriptional regulation of human renin.


Serial assessments of delayed encephalopathy after carbon monoxide poisoning using magnetic resonance spectroscopy and diffusion tensor imaging on 3.0T system.
To elucidate the still unclear mechanism of delayed encephalopathy after carbon monoxide (CO) poisoning, we serially performed single-voxel proton magnetic resonance spectroscopy ((1)H-MRS) and diffusion tensor imaging (DTI) on a 3.0T system and intelligence tests in 2 patients, while they were undergoing hyperbaric oxygenation therapy. The chronological changes in (1)H-MRS- and DTI-derived parameters indicated the following: (1) White matter demyelination, aerobic metabolism inhibition, and cytotoxic edema persisted for at least 3 months even after starting the hyperbaric oxygenation therapy; (2) the axonal function and structural integrity of the white matter were initially severely impaired and then gradually and partially improved for 5 months, showing changes similar to those in the scores of the intelligence tests. The results demonstrated that brain damage after CO poisoning may persist longer than expected, and that the (1)H-MRS- and DTI-derived parameters are good indicators of the clinical progress of a patient. The combination of (1)H-MRS and DTI on a 3.0T system is useful for monitoring the changes in brain damage and the clinical symptoms of patients with delayed encephalopathy after CO poisoning.


Alkali absorption and citrate excretion in calcium nephrolithiasis.
The role of net gastrointestinal (GI) alkali absorption in the development of hypocitraturia was investigated. The net GI absorption of alkali was estimated from the difference between simple urinary cations (Ca, Mg, Na, and K) and anions (Cl and P). In 131 normal subjects, the 24 h urinary citrate was positively correlated with the net GI absorption of alkali (r = 0.49, p < 0.001). In 11 patients with distal renal tubular acidosis (RTA), urinary citrate excretion was subnormal relative to net GI alkali absorption, with data from most patients residing outside the 95% confidence ellipse described for normal subjects. However, the normal relationship between urinary citrate and net absorbed alkali was maintained in 11 patients with chronic diarrheal syndrome (CDS) and in 124 stone-forming patients devoid of RTA or CDS, half of whom had "idiopathic" hypocitraturia. The 18 stone-forming patients without RTA or CDS received potassium citrate (30-60 mEq/day). Both urinary citrate and net GI alkali absorption increased, yielding a significantly positive correlation (r = 0.62, p < 0.0001), with the slope indistinguishable from that of normal subjects. Thus, urinary citrate was normally dependent on the net GI absorption of alkali. This dependence was less marked in RTA, confirming the renal origin of hypocitraturia. However, the normal dependence was maintained in CDS and in idiopathic hypocitraturia, suggesting that reduced citrate excretion was largely dietary in origin as a result of low net alkali absorption (from a probable relative deficiency of vegetables and fruits or a relative excess of animal proteins).


UCP2 transports C4 metabolites out of mitochondria, regulating glucose and glutamine oxidation.
Uncoupling protein 2 (UCP2) is involved in various physiological and pathological processes such as insulin secretion, stem cell differentiation, cancer, and aging. However, its biochemical and physiological function is still under debate. Here we show that UCP2 is a metabolite transporter that regulates substrate oxidation in mitochondria. To shed light on its biochemical role, we first studied the effects of its silencing on the mitochondrial oxidation of glucose and glutamine. Compared with wild-type, UCP2-silenced human hepatocellular carcinoma (HepG2) cells, grown in the presence of glucose, showed a higher inner mitochondrial membrane potential and ATP:ADP ratio associated with a lower lactate release. Opposite results were obtained in the presence of glutamine instead of glucose. UCP2 reconstituted in lipid vesicles catalyzed the exchange of malate, oxaloacetate, and aspartate for phosphate plus a proton from opposite sides of the membrane. The higher levels of citric acid cycle intermediates found in the mitochondria of siUCP2-HepG2 cells compared with those found in wild-type cells in addition to the transport data indicate that, by exporting C4 compounds out of mitochondria, UCP2 limits the oxidation of acetyl-CoA-producing substrates such as glucose and enhances glutaminolysis, preventing the mitochondrial accumulation of C4 metabolites derived from glutamine. Our work reveals a unique regulatory mechanism in cell bioenergetics and provokes a substantial reconsideration of the physiological and pathological functions ascribed to UCP2 based on its purported uncoupling properties.


Web-Based Therapist Training in Interpersonal Psychotherapy for Depression: Pilot Study.
Training mental health professionals to deliver evidence-based therapy (EBT) is now required by most academic accreditation bodies, and evaluating the effectiveness of such training is imperative. However, shortages of time, money, and trained EBT clinician teachers make these challenges daunting. New technologies may help. The authors have developed the first empirically evaluated comprehensive Internet therapist training program for interpersonal psychotherapy (IPT). The aim of this study was to examine whether (1) the training protocol would increase clinicians' knowledge of IPT concepts and skills and (2) clinicians would deem the training feasible as measured by satisfaction and utility ratings. A total of 26 clinicians enrolled in the training, consisting of (1) a Web-based tutorial on IPT concepts and techniques; (2) live remote training via videoconference, with trainees practicing IPT techniques in a role-play using a case vignette; and (3) a Web-based portal for therapists posttraining use to help facilitate implementation of IPT and maintain adherence over time. Trainees' knowledge of IPT concepts and skills improved significantly (P<.001). The standardized effect size for the change was large: d=2.53, 95% CI 2.23-2.92. Users found the technical features easy to use, the content useful for helping them treat depressed clients, and felt the applied training component enhanced their professional expertise. Mean rating of applied learning was 3.9 (scale range from 1=very little to 5=a great deal). Overall satisfaction rating was 3.5 (range from 1=very dissatisfied to 4=very satisfied). Results support the efficacy and feasibility of this technology in training clinicians in EBTs and warrant further empirical evaluation.


Application of oxygen vectors to Aspergillus terreus cultivation.
Research was undertaken to examine the effects of adding an oxygen carrier (n-dodecane, n-tetradecane, or n-hexadecane) on lovastatin production by Aspergillus terreus in both shaking-flask and 5-l fermentor cultivations. In the shaking-flask cultivation, an addition of 2.5% (w/v) n-dodecane to the medium gave about a 1.4-fold increase (0.51 g/l) in lovastatin production. This improvement was related to morphological changes in the fungal cells, and resulted mainly from the formation of small, uniform, compact pellets of A. terreus. In contrast, in the 5-l fermentor cultivation, the lovastatin production was only one-ninth of that achieved without n-dodecane addition independent of the pellet density. This adverse effect of adding the oxygen carrier to the medium was attributed to an uncontrolled, high dissolved oxygen level (higher than 60%) which resulted in unfavorable morphological changes and the formation of star-like pellets. However, when this dosage of n-dodecane was added 24 h after the start of the 5-l fermentor cultivation, lovastatin production was further enhanced due to its foam suppressing activity in the fungal fermentation.


Phage T4 endonuclease V stimulates DNA repair replication in isolated nuclei from ultraviolet-irradiated human cells, including xeroderma pigmentosum fibroblasts.
The repair mode of DNA replication has been demonstrated in isolated nuclei from UV-irradiated human cells. Nuclei are incubated in a mixture containing [(3)H]thymidine triphosphate and bromodeoxyuridine triphosphate in a 1:5 ratio. The (3)H at the density of parental DNA in alkaline CsCl density gradients is then a measure of repair. In nuclei prepared from WI38 cells 30 min after irradiation, repair replication is UV dependent and proceeds at approximately the in vivo rate for 5 min. Repair replication is reduced in irradiated nuclei or in nuclei prepared immediately after irradiation. It is Mg(2+)-dependent and stimulated by added ATP and deoxyribonucleoside triphosphates. No repair replication is observed in nuclei from xeroderma pigmentosum (complementation group A) cells. However, upon addition of coliphage T4 endonuclease V, which specifically nicks DNA containing pyrimidine dimers, repair replication is observed in nuclei from irradiated xeroderma pigmentosum cells and is stimulated in WI38 nuclei. The reaction then persists for an hour and is dependent upon added ATP and deoxyribonucleoside triphosphates. The repair label is in stretches of roughly 35 nucleotides, as it is in intact cells. Added pancreatic DNase does not promote UV-dependent repair synthesis. Our results support the view that xeroderma pigmentosum (group A) cells are defective in the incision step of the DNA excision repair pathway, and demonstrate the utility of this system for probing DNA repair mechanisms.


The impact on quality of life on families of children on an elimination diet for Non-immunoglobulin E mediated gastrointestinal food allergies.
The impact on health related quality of life (HRQL) has been well studied in children with Immunoglobulin E (IgE)-mediated food allergy. However limited data exists on related quality of life (QOL) of families who have a child suffering from food protein induced non-IgE mediated gastrointestinal allergies. We aimed to establish the QOL of families with children at the beginning of following an elimination diet for non-IgE mediated gastrointestinal food allergies. A prospective, observational study was performed. Parents of children aged 4 weeks-16 years who improved after 4-8 weeks of following an elimination diet for suspected non-IgE mediated allergies were included. The Family Impact Module (FIM) of the Pediatric Quality of Life (PedsQL™) was used and we compared our data to two historical cohorts: one with sickle cell disease and another with intestinal failure. One hundred and twenty three children with a median age of 20 months were included (84 boys). The total FIM Score was 57.43 (SD 22.27) and particularly low for daily activities and worry. Factors that impacted significantly included age (p < 0.0001), number of foods excluded (p = 0.008), symptom severity (p = 0.041) and chronic nasal congestion (p = 0.012). Children with non-IgE mediated food allergies had worse scores in all domains (p < 0.0001) compared to sickle cell disease and worse physical (p = 0.04), emotional (p = 0.04) and worry (p = 0.01) domains compared to intestinal failure. This study found that parent QOL and family functioning was worse in those families who had a child on an elimination diet for non-IgE mediated allergies compared to those with sickle cell disease and intestinal failure, highlighting the impact this disease has on families.


[The whole genome-wide screening of the longevity-related gene of Uyghur population in Hotan, Xinjiang].
Objective: To discuss the whole genome-wide screening of the longevity-related gene of Uyghur population in Hotan, Xinjiang. Methods: The whole gene scanning using genome-wide association study (GWAS) based on the pooling DNA and the SNP-Map strategy in the longevity group (≥90 years old) and control group (persons who died before 70 years old) was carried out. Then, through detecting varieties of SNP locus, the frequencies of genotype and allele were calculated by sequencing and PCR- restriction fragment length polymorphism (RFLP) method. Results: There was no significant difference of rs6450874, rs6800573 and rs6741735 genotypes and alleles frequency distributions between the two groups, however, there were statistical differences of rs1718307, rs4449651, rs11217987 and rs2907092 genotypes and alleles frequency distributions between the two groups. The TT genotype of rs11217987 (OR=1.462, P=0.034) and the GG genotype of rs2907092 (OR=3.000, P=0.018) were positively correlated to the longevity. And the T allele of rs11217987 (OR=1.382, 95%CI: 1.075-1.776) and the G allele of rs2907092 (OR=1.672, 95%CI: 1.267-2.205) had strong potential function to prolong life. The TT genotype of rs4449651 (OR=6.892, P=0.009) and rs1718307 (OR=4.036, P<0.001) were positively correlated to the longevity. Moreover, the T allele of both SNPs (OR=1.793, 95%CI: 1.298-2.477; OR=1.830, 95%CI: 1.391-2.407) had strong potential function to prolong life. Conclusions: The GWAS test can effectively and extensively analyze human longevity-related genes. And rs1718307, rs4449651, rs11217987 and rs2907092 are related to the longevity of Uyghur population in Hotan, Xinjiang.


Beta-blockade and oxygen delivery to muscle during exercise.
The most commonly observed effect of beta-blockade on cardiovascular function has been a reduction in heart rate both at rest and during exercise. The body attempts to compensate by increasing stroke volume and (or) increasing the extraction of O2 from the blood to maintain O2 delivery to the muscle. This paper examines the roles of muscle mass involved in the exercise as well as the time course of change in cardiac output and peripheral blood flow in an attempt to understand whether O2 supply is limited by beta-blockade. Experiments are reported in which the kinetics of cardiac output response at the onset of submaximal cycle exercise were slowed in subjects taking oral propranolol. Taken in consideration with other data from our laboratory and with data in the literature, it was concluded that beta-blockade does impair O2 transport. The degree of impairment is dependent on the total muscle mass involved and the metabolic demand.


Time and dose dependencies for priming effect of glucose on insulin secretion.
Short-term exposure to glucose increases insulin secretion during subsequent stimulation. This priming effect of glucose was further investigated in the perfused rat pancreas. A 5-min pulse of 27.7 mM glucose enhanced the response to a second pulse of the sugar after a 5- or 30-min period of 3.9 mM glucose. With a 10-min pulse of 27.7 mM glucose, the priming effect tended to persist also after a 60-min but not after a 90-min rest period. The priming effects of glucose were also evaluated from enhancement of stimulation 15 min later with 3-isobutyl-l-methylxanthine (IBMX). A 10-min pulse of 8.3 and 27.7, but not 5.6 mM glucose enhanced IBMX-induced insulin secretion. Cycloheximide did not abolish the priming effect of glucose on IBMX-induced insulin secretion. Conclusions are 1) priming is rapidly induced; 2) it persists longer than the time of induction; 3) threshold concentrations of glucose that induce priming are similar to those that initiate insulin secretions; and 4) mechanisms causing priming may not involve protein synthesis.


STUB1/CHIP is required for HIF1A degradation by chaperone-mediated autophagy.
The transcription factor HIF1 is mostly regulated by the oxygen-dependent proteasomal degradation of the labile subunit HIF1A. Recent data showed degradation of HIF1A in the lysosome through chaperone-mediated autophagy (CMA). However the molecular mechanism involved has not been elucidated. This study shows that the KFERQ-like motif, that has been identified in all CMA substrates, is required to mediate the interaction between HIF1A and the chaperone HSPA8. Moreover, mutations in the KFERQ-like motif of HIF1A preclude the interaction with the CMA receptor LAMP2A, thus inhibiting its lysosomal degradation. Importantly, we show for the first time that the ubiquitin ligase STUB1 is required for degradation of HIF1A in the lysosome by CMA. Indeed, mutations in STUB1 that inhibit either the ubiquitin ligase activity or its ability to bind to HSPA8, both prevent degradation of HIF1A by CMA. Moreover, we show that HIF1A binds to and is translocated into intact lysosomes isolated from rat livers. This new pathway for degradation of HIF1A does not depend on the presence of oxygen and is activated in response to nutrient deprivation such that the levels of HIF1A bound to CMA positive lysosomes significantly increase in starved animal livers and the binding of HIF1A to LAMP2A increases in response to serum deprivation. Moreover, excessive degradation of HIF1A by CMA compromises cells' ability to respond to and survive under hypoxia, suggesting that this pathway might be of pathophysiological importance in conditions that combine hypoxia with starvation.


Systemic infusion of FLK1(+) mesenchymal stem cells ameliorate carbon tetrachloride-induced liver fibrosis in mice.
Fibrosis is the common end stage of most liver diseases, for which, unfortunately, there is no effective treatment available currently. It has been shown that mesenchymal stem cells (MSCs) from bone marrow (BM) could engraft in the lung after bleomycin exposure and ameliorate its fibrotic effects. This study was designed to evaluate the effect of Flk1 MSCs from murine BM (termed here Flk1 mMSCs) on fibrosis formation induced by carbon tetrachloride (CCl4). A CCl(4)-induced hepatic fibrosis model was used. Flk1 mMSCs were systemically infused immediately or 1 week after mice were challenged with CCl(4). Control mice received only saline infusion. Fibrosis index and donor-cell engraftment were assessed 2 or 5 weeks after CCl(4) challenge. We found that Flk1 mMSCs transplantation immediately, but not 1 week after exposure to CCl(4), significantly reduced CCl(4)-induced liver damage and collagen deposition. In addition, levels of hepatic hydroxyproline and serum fibrosis markers in mice receiving immediate Flk1 mMSCs transplantation after CCl(4) challenge were significantly lower compared with those of control mice. More importantly, histologic examination suggested that hepatic damage recovery was much better in these immediately Flk1 mMSCs-treated mice. Immunofluorescence, polymerase chain reaction, and fluorescence in situ hybridization analysis revealed that donor cells engrafted into host liver, had epithelium-like morphology, and expressed albumin, although at low frequency. These results suggest that Flk1 mMSCs might initiate endogenous hepatic tissue regeneration, engraft into host liver in response to CCl(4) injury, and ameliorate its fibrogenic effects.


Effect of Tibiofemoral Rotation Angle on Graft Failure After Anterior Cruciate Ligament Reconstruction.
Coronal and sagittal malalignment of the knee are well-recognized risk factors for failure after anterior cruciate ligament (ACL) reconstruction (ACLR). However, the effect of axial malalignment on graft survival after ACLR is yet to be determined. To evaluate whether increased tibiofemoral rotational malalignment, namely, tibiofemoral rotation angle (TFA) and tibial tubercle-trochlear groove (TT-TG) distance, is associated with graft failure after ACLR. Cohort study; Level of evidence, 3. In this retrospective matched control study of a single center's database, 151 patients who underwent revision ACLR because of graft failure (ACLR failure group, defined as symptomatic patients with anterior knee instability and an ACL graft tear appreciated on magnetic resonance imaging [MRI] and confirmed during arthroscopic surgery) were compared with a matched control group of 151 patients who underwent primary ACLR with no evidence of failure after ≥2-year follow-up (intact ACLR group). Patients were matched by sex, age, and meniscal injury during primary ACLR. Axial malalignment was assessed on preoperative MRI through the TFA and the TT-TG distance. Sagittal alignment was measured through the posterior tibial slope on MRI. The optimal TFA cutoff associated with graft failure was identified by a receiver operating characteristic curve. The Kaplan-Meier curve with log-rank analysis was performed to evaluate the influence of the TFA on ACLR longevity. The mean age was 25.7 ± 10.4 years for the ACLR failure group and 25.9 ± 10.0 years for the intact ACLR group. Among all the included patients, 174 (57.6%) were male. In the ACLR failure group, the mean TFA was 5.8°± 4.5° (range, -5° to 16°), while it was 3.0°± 3.3° (range, -3° to 15°) in the intact ACLR group (P < .001). Neither the TT-TG distance nor the posterior tibial slope presented statistical differences between the groups. The receiver operating characteristic curve suggested an optimal TFA cutoff of 4.5° for graft failure (area under the curve = 0.71; P < .001; sensitivity, 68.2%; specificity, 75.5%). Considering this a threshold, patients who had a TFA ≥4.5° had 6.6 times higher odds of graft failure compared with patients with a TFA <4.5° (P < .001). Survival analysis demonstrated a 5-year survival rate of 81% in patients with a TFA <4.5°, while it was 44% in those with a TFA ≥4.5° (P < .001). An increased TFA was associated with increased odds of ACLR failure when the TFA was ≥4.5°. Measuring the TFA in patients with ACL tears undergoing reconstruction may inform the surgeon about additional factors that may require consideration before ACLR for a successful outcome.


Analysis of near-field components of a plasmonic optical antenna and their contribution to quantum dot infrared photodetector enhancement.
In this paper, we analyze near-field vector components of a metallic circular disk array (MCDA) plasmonic optical antenna and their contribution to quantum dot infrared photodetector (QDIP) enhancement. The near-field vector components of the MCDA optical antenna and their distribution in the QD active region are simulated. The near-field overlap integral with the QD active region is calculated at different wavelengths and compared with the QDIP enhancement spectrum. The x-component (E(x)) of the near-field vector shows a larger intensity overlap integral and stronger correlation with the QDIP enhancement than E(z) and thus is determined to be the major near-field component to the QDIP enhancement.


Moments of hyper-Rayleigh spectra of selected rare gas mixtures.
In this work we have analyzed spectral moments characterizing properties of the collisionally hyper-Rayleigh scattered light. This is a supplementary study undertaken in order to complete the series of our previously published papers on the collisional hyper-Rayleigh scattering spectral profiles. In order to evaluate the moments we have extended the theory so that it could embrace the (hyper)polarizabilities of higher rank. Using the expressions developed on the grounds of the theoretical principles and applying appropriate computational methods with ab initio hyperpolarizability values as an input, we have obtained desirable moment values for three diatomic noble gas systems: HeNe, HeAr, and NeAr, at several temperature points. The semiclassical and the quantum treatments have been taken into account, and the moments were calculated both from the sum rule method as well as from the spectral profiles. The results were compared and discussed.


Tissue-specific concentration changes of estrone and estradiol during spontaneous and ACTH-induced parturition in sheep.
Changes in estrogen production are considered important in the sequence of events leading to parturition. We sought tissue-specific changes in the concentration of unconjugated estrone (E1) and estradiol (E2) in intrauterine fetal (amnion, chorion) and maternal (endometrium, myometrium) tissues during normal pregnancy, labour, and ACTH-induced labour in sheep. The mean concentrations of E1 and E2 in the fetal membranes were higher than in endometrium and myometrium. In amnion there were no consistent changes in estrone concentrations with gestation, although estradiol concentrations increased between day 130 and term. In the endometrium there were increases in both estrone and estradiol between day 100 and term, whereas in the myometrium increases in the concentrations of E1 and E2 occurred between days 130-135 and term. Animals showing a labourlike pattern of uterine contractions after intrafetal ACTH administration did not show significant differences in estrone or estradiol concentrations in amnion, chorion, or endometrium compared with saline-infused controls. However, there was a progressive increase in the concentration of estrone and estradiol in the myometrium during ACTH-induced labour. We conclude that changes in the concentrations of estrone and estradiol in intrauterine tissues vary between the tissues studied and the two estrogens. In general, estrogen concentrations increased towards term, but this trend was more marked in the maternal than fetal tissues. The changes in estrone concentrations in myometrium, but not in the other tissues, were replicated during ACTH-induced labour. Our results would be compatible with the suggestion that tissue-specific changes in estrogen concentrations may contribute to the local intrauterine steroid milieu during pregnancy and at term.


Repairs of complex groin wounds with contralateral rectus abdominis myocutaneous flaps.
Management of complex groin wounds posterior to complications of vascular prosthetic surgery, malignant tumor excision, and irradiation therapy for recurrent cancers continued to pose a difficult task in reconstructive surgery. Pedicled and microsurgical myocutaneous flaps are valuable tools for wound repairs, but applications of these flaps are limited when the healthy vascular vessels are not available around the wound. In this report, we present our experience on the use of the contralateral rectus abdominis myocutaneous flaps for the coverage of the groin complex wounds in 13 patients. All the flaps were completely survived and the wounds healed uneventfully. The results suggest that the contralateral myocutaneous flap can be used for the repair of the groin wound with presence of significant comorbidities in the area, in which the ipsilateral local flaps and microsurgical flaps are not available.


[Safety and feasibility of gastrectomy after neoadjuvant chemotherapy for gastric cancer].
The aim of this study was to evaluate the safety and feasibility of gastrectomy after neoadjuvant chemotherapy in patients with gastric cancer. Forty-five patients received neoadjuvant chemotherapy and curative gastrectomy between December 2002 and May 2011. Surgical complications were evaluated according to the Clavien- Dindo classification. The median age of the patients was 63 years. Twenty-three patients received a PTX and CDDP regimen, 20 received an S-1 and CDDP regimen, 1 received an S-1 regimen, and 1 received an CPT-11 and CDDP regimen as neoadjuvant chemotherapy. Distal gastrectomy was performed in 6 patients, and total gastrectomy was performed in 39 patients. The median operation time was 268 minutes, and the median blood loss was 249.5 mL. Complications more severe than grade 2 were observed in 10 patients: anatomic bleeding( grade 3a) was observed in 2 patients; abdominal abscess( grade 2), in 1 patient; and pancreatic fistula( grade 2), in 7 patients. No surgical mortality was observed. The results of our study suggest that gastrectomy after neoadjuvant chemotherapy for the treatment of patients with gastric cancer is safe and feasible.


[Application of DNA methyltransferase inhibitors for myelodysplastic syndrome].
Epigenetic research plays an important role in the malignant tumor genotyping and tumor clinical treatment recently. Epigenetics is the study of changes in gene function that are mitotically and/or meiotically heritable and that do not entail a change in DNA sequence, including DNA methylation and histone modifications. DNA methylation is one of the most important epigenetic modifications often occurring on the cytosine of CpG islands located in gene promoter regions, which is thought to be closely correlated with tumorigenesis. The inducibility and reversibility of DNA methylation provide us an insight into tumor development and treatment. Aberrant DNA hypermethylation is associated with the progress of myelodysplastic syndrome (MDS). The DNA methyltransferase inhibitors (azacytidine and decitabine) have achieved suc-cess in treating high-and intermediate-risk MDS. This will bring new ideas to understand the cause and develop the treat-ment of MDS. This review mainly introduces the latest progress of the action mechanism of those two medicines, the clini-cal effect and new problems during the clinical application on MDS.


Effects of ethyl-eicosapentaenoic acid omega-3 fatty acid supplementation on hot flashes and quality of life among middle-aged women: a double-blind, placebo-controlled, randomized clinical trial.
To compare the effects of enriched ethyl-eicosapentaenoic acid (E-EPA) omega-3 fatty acid supplementation with those of placebo on hot flashes (HFs) and quality of life among middle-aged women. Women were considered for participation if they were between 40 and 55 years of age and had moderate to severe psychological distress. A total of 120 women were randomly assigned to E-EPA or placebo for 8 weeks. Only women with HFs were included in this analysis (E-EPA, n = 45; placebo, n = 46). Outcomes were changes from baseline to week 8 postintervention regarding hot flash (HF) frequency (number of HFs per day), intensity and score (frequency x intensity), and Menopause-specific Quality of Life questionnaire scores. At baseline, the average number of HFs was 2.8 per day. After 8 weeks, HF frequency and score decreased significantly in the E-EPA group compared with the placebo group. There was no difference in the change in HF intensity between groups. Frequency of HFs declined by a mean of 1.58 per day (95% CI, -2.18 to -0.98) in the E-EPA group and by 0.50 per day (95% CI, -1.20 to 0.20) in the placebo group. The odds of being a responder among those taking E-EPA were about three times greater than among those taking placebo (odds ratio, 2.70; 95% CI, 1.03-7.03; P = 0.04). Menopause-Specific Quality of Life scores improved significantly over time in both groups but no significant differences were noted between them. Supplementation with E-EPA omega-3 fatty acid reduced HF frequency and improved the HF score relative to placebo. These results need to be confirmed by a clinical trial specifically designed to evaluate HFs in more symptomatic women.


Reciprocal regulation of K+ channels by Ca2+ in intact human T lymphocytes.
The requirement for increased [Ca2+]i during T cell activation is well established. In the present study, we have used the cell-attached configuration of the patch-clamp technique and Ca2+ spectrofluorometry to investigate the regulation of K+ channel activity by intracellular calcium [Ca2+]i in intact human T lymphocytes. The predominant ion current in resting human T cells is a voltage-dependent K+ current, K(V), which is susceptible to second-messenger regulation. We report here that K(V) channel activity is reversibly inhibited at all relevant membrane potentials by a rise in [Ca2+]i induced by Ca2+ ionophore or the mitogens, concanavalin A or phytohemagglutinin. Consistent with this Ca2+ dependence, lowering [Ca2+]i with Ca(2+)-depleted medium can induce K(V) channel activity in otherwise quiet patches. We have also found two Ca(2+)-activated K+ channels (K(Ca)), a 9 pS channel and an inwardly rectifying 11-25 pS channel, similar to those we found in rat thymic T cells and human B cells. The sensitivity of these K(Ca) channels to [Ca2+]i suggests reciprocal regulation with that of K(V) channels. A considerable lag between mitogen treatment and induction of 9 pS K(Ca) activity, the decrease in this channel's activity in the continued presence of high [Ca2+]i or upon patch excision, and the decreased sensitivity of K(V) to Ca2+i block in disrupted cells all argue for the involvement of intracellular factors. During [Ca2+]i-mediated inhibition of K(V) channels, the recruitment of distinct K(Ca) channels is likely to play a central role in maintaining cell hyperpolarization and a sustained driving force for Ca2+ influx during T-cell activation.


Purification and characterization of human sarcomeric mitochondrial creatine kinase.
In order to set the basis for detailed clinical investigations, mitochondrial creatine kinase (Mi-CK) was purified to homogeneity from human cardiac muscle. Biophysical characterization by SDS-PAGE, gel permeation chromatography and by electron microscopy of negatively stained single molecules demonstrated that, similar to other vertebrate Mi-CKs, human sarcomeric Mi-CK occurs in two different oligomeric forms, dimers and octamers, that are readily interconvertible. The apparent MTs of Mi-CK protomers, dimers and octamers were 43,600 +/- 800, 79,700 +/- 800 and 371,000 +/- 3000, respectively. In addition, isoelectric focussing proved to be a suitable technique for routinely distinguishing Mi-CK from cytosolic MM-CK and gave pl values of 8.30 +/- 0.04 and 7.44 +/- 0.04 for octameric and dimeric human sarcomeric Mi-CK. Circumstantial evidence suggests that both the highly symmetrical structure and the high pI value of Mi-CK octamers are crucial determinants for the physiological functions of this enzyme.


Diffusive spreading of time-dependent pressures in elastic microfluidic devices.
Here we show that transient flow of Newtonian fluids in viscoelastic PDMS microfluidic channels can be described by a diffusive pressure spreading mechanism analogous to the electric telegrapher's equation. The pressure diffusion constant D(p) = 1/R(x)C(x) of a channel with length l is determined by the hydrodynamic resistance R(x) and capacitance C(x) per unit length of the channel. l(2)/D(p) sets the timescale for the transmission of pressure steps along the channel and the relaxation after a pressure step in steady state flow. For oscillatory flows, the channel acts as a low-pass filter with a cutoff frequency omega(cutoff) = 2piD(p)l(-2), so that pressure and flow rate pulses disperse and get smoothed while they travel along the channel. The combination of different microparticle tracking techniques allows the determination of pressure and flow profiles at any point in the channel and excellent agreement with theoretical predictions is obtained.


Mutations in the embB gene and their association with ethambutol resistance in multidrug-resistant Mycobacterium tuberculosis clinical isolates from Poland.
Ethambutol (EMB) continues to be used as part of a standard drug regimen for the treatment of tuberculosis (TB). Mutations in the embB gene and those within its conserved EMB resistance determining region (ERDR) in particular have repeatedly been associated with resistance to EMB in Mycobacterium tuberculosis. The aim of this study was to examine the mutational "hot spots" in the embB gene, including the ERDR, among multidrug-resistant (MDR) M. tuberculosis clinical isolates and to find a possible association between embB mutations and resistance to EMB. An 863-bp fragment of the embB gene was sequenced in 17 EMB-resistant and 33 EMB-susceptible MDR-TB isolates. In total, eight embB mutation types were detected in 6 distinct codons of 27 (54%) M. tuberculosis isolates. Mutations in codon 306 were most common, found in both EMB-resistant (9) and EMB-susceptible (11) isolates. Only mutations in codons 406 and 507 were found exclusively in four and one EMB-resistant isolates, respectively. Sequence analysis of the ERDR in the embB gene is not sufficient for rapid detection of EMB resistance, and the codon 306 mutations are not good predictive markers of resistance to EMB.


Subchronic Oral Toxicity of Sodium p-Hydroxybenzoate in Sprague-Dawley Rats.
p-Hydroxybenzoic acid (p-HBA), which exists extensively in plants, is well known for its anti-inflammatory effects, but various adverse side effects have also been reported. Previous research has found that acid translated to its sodium salt improves the safety profile of compounds. Therefore, we hypothesized that p-HBA translated to sodium p-hydroxybenzoate would improve its safety profile. In the present study, we evaluated the toxicity of sodium p-hydroxybenzoate after 90 days of repeated oral toxicity experiments according to OECD guidelines in male and female Sprague-Dawley rats. Sodium p-hydroxybenzoate was administered orally to SD rats at doses of 0, 125, 250, and 500 mg/kg body weight (BW)/day for 90 days. All animals survived to the end of the study, and no sodium p-hydroxybenzoate treatment-associated mortality or clinical changes were observed during the study period. Sodium p-hydroxybenzoate did not promote any clinical signs of toxicologically relevant effects, including changes in body weight, food intake and urinalysis parameters, in male or female SD rats. Dose-related alterations in hematological parameters, organ weights and histopathological findings in hepatic tissue were examined in animals of both sexes in the 500 mg/kg BW/day group. Based on the study, the no-observed-adverse-effect level (NOAEL) for sodium p-hydroxybenzoate was determined to be 250 mg/kg BW/day in both male and female rats.


Pain and quality of life in persons with spinal cord injury: Mediating effects of mindfulness, self-efficacy, social support, and functional independence.
To identify mediating roles of mindfulness, self-efficacy, social support, and functional independence in the relationship between pain and quality of life (QOL) in persons with spinal cord injury (SCI). A cross-sectional descriptive study was conducted using a sample of 272 persons with SCI living in the United States. The participants completed self-report standardized questionnaires on a Qualtrics survey. A parallel mediation analysis adjusting for covariates was performed to test the hypotheses. Findings showed significant direct effects of pain on functional independence, self-efficacy, mindfulness, and social support. Self-efficacy, mindfulness, and social support had significant direct effects on QOL. In the mediation analysis, mindfulness, self-efficacy, and social support significantly mediated the relationship between pain and QOL, controlling for other variables in the model. This study adds to the extant literature by providing evidence that mindfulness, self-efficacy, and social support not only directly contribute to QOL but are likely to mitigate the negative effect of pain on QOL in persons with SCI. Identifying these potential factors that can assuage the adverse effects of pain on QOL is a first step toward active intervention to facilitate the adjustment of persons with SCI.


Comparison between Traditional Chinese Medicine Constitution and Blood Biochemical Markers Associated with Left and Right Mammary Hyperplasia in Rural Areas of Southwest China.
Hyperplasia of mammary glands (HMG) is the breast disease with the highest clinical incidence. Many traditional Chinese medicine (TCM) doctors suggest that the treatment of HMG should be based on the left and right breast pain difference. However, these views are based on case reports, and an objective basis has not been established for treatment according to left-side and right-side differences. We enrolled 150 patients who met the clinical diagnostic criteria of HMG. The incidence bias was determined according to the score difference between bilateral breast pain and mass in patients with HMG. A left group, right group, and bilateral group were included, and TCM constitution was investigated in each group. Blood biochemical indicators were measured for 120 fasting patients. We conducted a network pharmacology study of the key herb qingpi and chenpi, which are used by TCM doctors to treat different lateral HMG. In patients with biased onset of HMG, the results showed that the frequency and constitution score of stagnant blood in the L group were higher than those of the R group, and the frequency and constitution score of phlegm-dampness in the R group were higher than those of the L group. Both the L and R groups had high proportion of stagnant Qi. The results indicated that the concentration of coagulation factor VIII (FVIII) was higher in the L group than that in the R group, and the concentration of lipoprotein a (Lp-α) was higher in the R group than that in the L group. The results showed that sinensetin and neohesperidin contained in qingpi might interfere with platelet activation, thrombogenesis, prolactin signaling pathway, and atherosclerosis process, in removing "blood stasis" and eventually treating the left-leaning group of HMG patients. Sitosterol and citromitin contained in chenpi could regulate lipid metabolism by interfering with regulation of lipolysis in adipocytes, salivary secretion, estrogen signaling pathway, and thyroid hormone signaling pathway. Chenpi could eliminate "phlegm turbidity" and treat HMG patients in the right-leaning group. We preliminarily confirmed that the clinical pathogenesis of HMG is not a left-right equilibrium and TCM constitution, coagulation function, and lipid metabolism may be used as the objective basis for the difference between the left and right in HMG pathogenesis. For left-sided HMG patients, the doctor can consider qingpi, herb of activating blood and removing stasis, to treat HMG. However, for right-sided HMG, we think doctors should apply herb of activating Qi and eliminating phlegm, such as chenpi.


CD47 regulates renal tubular epithelial cell self-renewal and proliferation following renal ischemia reperfusion.
Defects in renal tubular epithelial cell repair contribute to renal ischemia reperfusion injury, cause acute kidney damage, and promote chronic renal disease. The matricellular protein thrombospondin-1 and its receptor CD47 are involved in experimental renal ischemia reperfusion injury, although the role of this interaction in renal recovery is unknown. We found upregulation of self-renewal genes (transcription factors Oct4, Sox2, Klf4 and cMyc) in the kidney of CD47(-/-) mice after ischemia reperfusion injury. Wild-type animals had minimal self-renewal gene expression, both before and after injury. Suggestive of cell autonomy, CD47(-/-) renal tubular epithelial cells were found to increase expression of the self-renewal genes. This correlated with enhanced proliferative capacity compared with cells from wild-type mice. Exogenous thrombospondin-1 inhibited self-renewal gene expression in renal tubular epithelial cells from wild-type but not CD47(-/-) mice, and this was associated with decreased proliferation. Treatment of renal tubular epithelial cells with a CD47 blocking antibody or CD47-targeting small interfering RNA increased expression of some self-renewal transcription factors and promoted cell proliferation. In a syngeneic kidney transplant model, treatment with a CD47 blocking antibody increased self-renewal transcription factor expression, decreased tissue damage, and improved renal function compared with that in control mice. Thus, thrombospondin-1 via CD47 inhibits renal tubular epithelial cell recovery after ischemia reperfusion injury through inhibition of proliferation/self-renewal.


Ice-cap. A high-throughput method for capturing plant tissue samples for genotype analysis.
High-throughput genotype screening is rapidly becoming a standard research tool in the post-genomic era. A major bottleneck currently exists, however, that limits the utility of this approach in the plant sciences. The rate-limiting step in current high-throughput pipelines is that tissue samples from living plants must be collected manually, one plant at a time. In this article I describe a novel method for harvesting tissue samples from living seedlings that eliminates this bottleneck. The method has been named Ice-Cap to reflect the fact that ice is used to capture the tissue samples. The planting of seeds, growth of seedlings, and harvesting of tissue are all performed in a 96-well format. I demonstrate the utility of this system by using tissue harvested by Ice-Cap to genotype a population of Arabidopsis seedlings that is segregating a previously characterized mutation. Because the harvesting of tissue is performed in a nondestructive manner, plants with the desired genotype can be transferred to soil and grown to maturity. I also show that Ice-Cap can be used to analyze genomic DNA from rice (Oryza sativa) seedlings. It is expected that this method will be applicable to high-throughput screening with many different plant species, making it a useful technology for performing marker assisted selection.


Mammography: EUSOBI recommendations for women's information.
This paper summarises the basic information to be offered to women who undergo mammography. After a delineation of the general aim of early diagnosis of breast cancer, the main difference between screening mammography and diagnostic mammography is explained. The best time for scheduling mammography in fertile women is defined. The need to bring images and reports from the previous mammogram (and from other recent breast imaging examinations) is highlighted. The technique and procedure of mammography are briefly described with particular attention to discomfort and pain experienced by a fraction of women who undergo the test. Information is given on the recall during a screening program and on the request for further work-up after a diagnostic mammography. The logic of the diagnostic mammography report and of classification systems such as BI-RADS and R1-R5 is illustrated, and brief but clear information is given about the diagnostic performance of the test, with particular reference to interval cancers. Moreover, the breast cancer risk due to radiation exposure from mammography is compared to the reduction in mortality obtained with the test, and the concept of overdiagnosis is presented. Finally, five frequently asked questions are answered.


Multiple functions of a Zic-like gene in the differentiation of notochord, central nervous system and muscle in Ciona savignyi embryos.
Multiple functions of a Zic-like zinc finger transcription factor gene (Cs-ZicL) were identified in Ciona savignyi embryos. cDNA clones for Cs-ZicL, a beta-catenin downstream genes, were isolated and the gene was transiently expressed in the A-line notochord/nerve cord lineage and in B-line muscle lineage from the 32-cell stage and later in a-line CNS lineage from the 110-cell stage. Suppression of Cs-ZicL function with specific morpholino oligonucleotide indicated that Cs-ZicL is essential for the formation of A-line notochord cells but not of B-line notochord cells, essential for the CNS formation and essential for the maintenance of muscle differentiation. The expression of Cs-ZicL in the A-line cells is downstream of beta-catenin and a beta-catenin-target gene, Cs-FoxD, which is expressed in the endoderm cells from the 16-cell stage and is essential for the differentiation of notochord. In spite of its pivotal role in muscle specification, the expression of Cs-ZicL in the muscle precursors is independent of Cs-macho1, which is another Zic-like gene encoding a Ciona maternal muscle determinant, suggesting another genetic cascade for muscle specification independent of Cs-macho1. Cs-ZicL may provide a future experimental system to explore how the gene expression in multiple embryonic regions is controlled and how the single gene can perform different functions in multiple types of embryonic cells.


An autoantibody to human plasma prekallikrein blocks activation of the contact system.
A patient without a history of bleeding or thromboembolism presented with an activated partial thromboplastin time (aPTT) of 55.1 s (normal 24-38 s). Incubation of the patient plasma with an equal volume of normal plasma failed to correct the aPTT, suggesting the presence of an inhibitor. The MRVVT (modified Russell Viper venom time) was normal, and the anti-cardiolipin antibody titres were not elevated, indicating that the presence of a lupus anticoagulant was unlikely. Plasma prekallikrein (PK) measured by a coagulant assay (2 U/dl) was very low, but PK was in the low normal range (approximately 65%) when measured by an enzymatic assay (amidolytic) or by an antigenic assay (ELISA). The purified patient IgG reacted with purified PK, the heavy chain, and the 28 kD fragment of the heavy chain, indicating that it contained an autoantibody to PK. The purified IgG did not directly inhibit the amidolytic activity of kallikrein, but it did inhibit the activation of PK to kallikrein by activated factor XII. Activation of the contact system by dextran sulphate, as reflected by the cleavage of HK on a Western blot, was inhibited when the patient IgG was added to pooled normal plasma. The antibody appears to be oligoclonal with IgG1 being most abundant, followed by IgG4. This report appears to be the first of a spontaneously occurring antibody to prekallikrein.


Effects of FK506-binding protein 12 and FK506 on autophosphorylation of epidermal growth factor receptor.
FK506-binding proteins and cyclophilins are intracellular proteins that express peptidylproline cis-trans-isomerase (PPIase) activity. The effects of FK506-binding protein 12 (FKBP12) and the cyclophilins 18 and 23 on autophosphorylation of the epidermal growth factor (EGF) receptor prepared from plasma membranes of the human epidermoid cell line A431 have been investigated. Whereas FKBP12 inhibited EGF receptor tyrosine kinase activity in a concentration-dependent manner, the cyclophilins did not affect autophosphorylation. In contrast to the wild-type enzyme, several variants of FKBP12 with greatly reduced PPIase activity were unable to suppress EGF receptor tyrosine kinase significantly. Pervanadate an inhibitor of protein tyrosine phosphatases, abolished the effect of FKBP12 on EGF receptor autophosphorylation. Finally, FK506 and rapamycin, which are known to block the PPIase activity of FKBP12, induced a significant stimulation of EGF receptor autophosphorylation in intact A431 cells suggesting suppression of EGF receptor autophosphorylation by intracellular FKBP12 in vivo. Taken together the data point to an inhibitory function of FKBP12 in EGF receptor signaling, possibly induced by stimulation of a protein tyrosine phosphatase coupled to the EGF receptor. Both PPIase activity and substrate specificity of FKBP12 seem to be indispensable for this effect.


Management of osteoarthritis (OA) with the pharma-standard supplement FlexiQule (Boswellia): a 12-week registry.
This registry study assessed the pharma-standard supplement FlexiQule (Boswellia extract in capsules) in the management of symptoms associated to osteoarthritis (OA) also managed with the 'standard management' (SM) in comparison with a group of patients managed only with SM. The 12- week registry included patients with symptomatic knee arthrosis. They were able to walk on a treadmill for a walking test and to complete the WOMAC questionnaire. 32 patients used the supplement and 34 acted as controls (SM). No safety problems were observed. At 12 weeks, the Karnofsky scale was significantly improved in both groups: the variation was higher (p<0.05) in the supplement group. The WOMAC score was decreased significantly more in the supplement+SM group in comparison with controls considering pain, stiffness and physical functions (p<0.05). For social and emotional functions the decrease in score was also more evident in the supplement group (p<0.05). Both groups improved in pain-free and total walking distance at 12 weeks. Pain-free walking distance (treadmill) was higher (p<0.05) with the supplement (from 93.4;11.6 m to 271.3;19.3 m) than in controls (from 90.5;13.5 m to 158.3;22.3)(p<0.05). The improvement in total walking distance was also higher in the supplement group (p<0.05) (from 164.3;23.2 to 322.3;22.3 m) in comparison with the SM- only group ( from 158.3;18,4 to 240.2;19.3 m). The need for concomitant drugs and medical attention during the registry was reduced more in the supplement group (p<0.05). In conclusion the difference between SM and the Flexiqule+SM was in favor of the management with the supplement for all target measurements. The product is safe and well tolerated.