Prophylactic surgery to reduce breast cancer risk: a brief literature review.
Prophylactic mastectomy reduces the likelihood of developing breast cancer among women at heightened risk for breast cancer, but at significant personal cost. Women at increased breast cancer risk on the basis of hormonal history, family history and/or genetic mutation carrier status may consider bilateral prophylactic mastectomy with or without reconstruction to reduce their cancer risk and/or decrease their chances of cancer mortality. Women having received mastectomy as treatment for breast cancer may request contralateral mastectomy to decrease the chances of developing a second breast primary. The potential oncologic value of these procedures must be weighed carefully on a case-by-case basis against the operation's physical and psychological morbidity. The purpose of this literature review is to provide a practice-oriented summary of recent clinical studies attempting to address the relative risks and benefits of preventive surgery for breast cancer. Data are included regarding the psychological factors surrounding patient selection and quality of life outcomes, which become the cornerstone of patient satisfaction and acceptance. Taken together, these data support the Society of Surgical Oncology position statement regarding the proper application of prophylactic surgery for breast cancer.


The Ancient Evolutionary History of Polyomaviruses.
Polyomaviruses are a family of DNA tumor viruses that are known to infect mammals and birds. To investigate the deeper evolutionary history of the family, we used a combination of viral metagenomics, bioinformatics, and structural modeling approaches to identify and characterize polyomavirus sequences associated with fish and arthropods. Analyses drawing upon the divergent new sequences indicate that polyomaviruses have been gradually co-evolving with their animal hosts for at least half a billion years. Phylogenetic analyses of individual polyomavirus genes suggest that some modern polyomavirus species arose after ancient recombination events involving distantly related polyomavirus lineages. The improved evolutionary model provides a useful platform for developing a more accurate taxonomic classification system for the viral family Polyomaviridae.


[Experimental study on transfection of pleiotrophin gene into adipose-derived stem cells of mice].
To study the transfection and expression of pleiotrophin (Ptn) gene in mice adipose-derived stem cells (ADSCs) so as to provide a new approach for the treatment of ischemic injury. ADSCs from clean inbred C57BL/6W mice (weighing, 15-20 g) were isolated and cultured in vitro. The cell surface markers (CD29 and CD44) of ADSCs were identified by flow cytometry. The ADSCs were transfected with plasmid pIRES2-LEGFPN1 (containing Ptn gene coding sequence) as experimental group (group A) and with plasmid pLEGFP-N1 (containing GFP gene coding sequence) as control group (group B). After ADSCs were transfected by different plasmids respectively, the cells containing Ptn gene were selected by G418 (the best selected concentration was 200 microg/mL), and the immunophenotype of the cells was identified by flow cytometry after transfection. Meanwhile, real-time fluorescence quantitative PCR and Western blot were used to analyse the expression levels of Ptn mRNA and PTN protein in selected cells. The mice ADSCs were isolated and cultured successfully in vitro. The positive rates of the cell surface markers CD29 and CD44 of ADSCs were 99.5% and 95.8%, respectively; the double positive rate of CD44 and CD29 was 93.6%. The positive rates of the cell surface markers CD29 and CD44 of ADSCs were 99.1% and 95.6%, respectively after transfection of Ptn gene; the double positive rate of CD44 and CD29 was 93.4%. The expression levels of Ptn gene and PTN protein in group A were significantly higher than those in group B (P < 0.05). The ADSCs can be stablely transfected by Ptn gene, the transfected ADSCs can express PTN protein highly, which is a new idea for tissue engineering of vascular reconstruction.


Remembering Hospice.
This book review essay discusses The Crisis of US Hospice Care: Family and Freedom at the End of Life (2019), by Harold Braswell.


Alcohol-induced modulation of signaling pathways in liver parenchymal and nonparenchymal cells: implications for immunity.
Alcoholic liver injury involves a complex array of derangements in cellular signaling of hepatic parenchymal and nonparenchymal cells as well as cells of the immune system. In the hepatocyte, chronic ethanol abuse leads to lipid accumulation and liver steatosis. Multiple pathways are affected to promote lipid accumulation in the ethanol-exposed hepatocyte. Chronic ethanol renders Kupffer cells hyperresponsive to endotoxin, which results in production of inflammatory cytokines and the tumor necrosis factor-alpha via a toll-like receptor 4 dependent pathway, leading to inflammation and hepatic necrosis. Dysfunction of the innate and adaptive immune responses caused by ethanol contributes to impaired antiviral response, inflammatory injury, and autoimmune activation. Recent developments in the literature are reviewed in a model that suggests lipid accumulation, dysregulation of immunity, and impaired antiviral and autoimmune responses as three distinct, though interwoven, pathophysiological mechanisms of alcoholic liver injury.


[Free radial activity in patients with pneumoconioses].
The authors examined indicators of the effect of free radicals (MDA, SOD, GSHPx, selenium) in 20 patients with notified simple silicosis or miner's pneumoconiosis, in 11 patients with complicated silicosis or miner's pneumoconiosis and in 10 patients exposed to fibrogenic dust without an X-ray finding of pneumoconiosis. No statistically significant differences between individual groups were found. Subsequent investigations should be focused on subjects with incipient pneumoconiosis who are not yet entitled to damages.


Peripheral electrical stimulation: titrating neuromuscular blocking agent levels.
Objective monitoring of the response to neuromuscular blocking agents is essential to ensure the patient receives the maximum benefit from the drug without harm. Peripheral nerve stimulation using a train-of-four mode of four quick pulses is an intervention the critical care nurse uses at the bedside to monitor the level of neuromuscular blockage for each patient. The nurse can use this objective evaluation and a dosage protocol to titrate effective levels of neuromuscular blocking agents for ventilated patients.


Multiple processing of Ig-Hepta/GPR116, a G protein-coupled receptor with immunoglobulin (Ig)-like repeats, and generation of EGF2-like fragment.
Ig-Hepta/GPR116 is a member of the LNB-TM7 subfamily of G protein-coupled receptors (GPCRs), also termed the adhesion GPCRs, whose members have EGF, cadherin, lectin, thrombospondin, or Ig repeats in their long N-terminus. In this study, we established that Ig-Hepta is processed at multiple sites yielding the following four fragments: (i) presequence (amino acid residues 1-24), (ii) proEGF2 (25-223, alpha-fragment), (iii) Ig repeats (224-993, beta-chain), and (iv) TM7 (994-1349, gamma-chain). The proEGF2 region is converted to EGF2 (52-223) by the processing enzyme furin and remains attached to the beta- and gamma-chains. Expression of some mRNA species was affected by the presence of alpha-fragment. These results suggest that the furin-processed alpha-fragment is involved in cellular signaling.


Arsenic, cadmium, and selenium exposures and bone mineral density-related endpoints: The HORTEGA study.
Experimental data suggest that trace elements, such as arsenic (As), cadmium (Cd), and selenium (Se) can influence the bone remodeling process. We evaluated the cross-sectional association between As, Cd, and Se biomarkers with bone mineral density (BMD) measured at the calcaneus, in a representative sample of a general population from Spain. As secondary analyses we evaluated the associations of interest in subgroups defined by well-established BMD determinants, and also conducted prospective analysis of osteoporosis-related incident bone fractures restricted to participants older than 50 years-old. In N = 1365 Hortega Study participants >20 years-old, urine As and Cd were measured by inductively coupled-plasma mass spectrometry (ICPMS); plasma Se was measured by atomic absorption spectrometry (AAS) with graphite furnace; and BMD at the calcaneus was measured using the Peripheral Instaneuous X-ray Imaging system (PIXI). As levels were corrected for arsenobetaine (Asb) to account for inorganic As exposure. The median of total urine As, Asb-corrected urine As, urine Cd, and plasma Se was 61.3, 6.53 and 0.39 μg/g creatinine, and 84.9 μg/L, respectively. In cross-sectional analysis, urine As and Cd were not associated with reduced BMD (T-score < -1 SD). We observed a non-linear dose-response of Se and reduced BMD, showing an inverse association below ~105 μg/L, which became increasingly positive above ~105 μg/L. The evaluated subgroups did not show differential associations. In prospective analysis, while we also observed a U-shape dose-response of Se with the incidence of osteoporosis-related bone fractures, the positive association above ~105 μg/L was markedly stronger, compared to the cross-sectional analysis. Our results support that Se, but not As and Cd, was associated to BMD-related disease. The association of Se and BMD-related disease was non-linear, including a strong positive association with osteoporosis-related bone fractures risk at the higher Se exposure range. Considering the substantial burden of bone loss in elderly populations, additional large prospective studies are needed to confirm the relevance of our findings to bone loss prevention in the population depending on Se exposure levels.


Elevated 18-hydroxy-corticosterone in inbred salt-sensitive rats.
Rats susceptible to the hypertensive effect of dietary salt (SS/Jr) have excess 18-hydroxydeoxycorticosterone (18-OH-DOC) and 19-nor-DOC compared to control rats (SR/Jr). This may be caused by an abnormal adrenal 11 beta-hydroxylase, which catalyzes the 11 beta, 18, and 19-hydroxylations of DOC. A comparison of the urinary products of this enzyme including 18-OH-DOC, 19-nor-DOC, corticosterone (B), and 18-OH-B have not been described in the SS/Jr. Therefore, these steroid products were measured at 7 and 12 weeks of age in 36 weanling male and female, SS/Jr and SR/Jr (n = 9 in each group), on a low-salt diet. In both the male and female SS/Jr urinary free levels of 18-OH-DOC, 19-nor-DOC, and 18-OH-B were elevated, while B was not different at 6 and 10 weeks of age. The largest increases were in 18-OH-B levels, and these levels correlated with 18-OH-DOC and B but not 19-nor-DOC. The high degree of correlation between these steroids probably reflects their closely related dependence on adrenal 11 beta-hydroxylase biosynthesis.


Plasminogen activator inhibitor-1 potentiates LPS-induced neutrophil activation through a JNK-mediated pathway.
Plasminogen activator inhibitor-1 (PAI-1), a member of the serine protease inhibitor superfamily, modulates fibrinolysis by interacting with proteolytic mediators, including urokinase plasminogen activator (uPA). Although the roles of uPA and PAI-1 in plasmin generation and the degradation of fibrin are well known, recent evidence also suggests that they can participate in acute inflammatory conditions that involve neutrophil activation. In the present experiments, we found that the addition of PAI-1 to LPS- stimulated neutrophils resulted in enhanced nuclear translocation of NF-kappaB and increased production of the proinflammatory cytokines IL-1beta, Tnf-alpha, and Mip-2. uPA and the kringle domain (KD) of uPA potentiated cytokine expression and NF-kappaB activation by neutrophils cultured with LPS, and had additive effects when combined with PAI-1. The c-Jun N-terminal kinase (JNK) was activated after exposure of resting neutrophils to PAI-1 or the uPA KD. Enhanced JNK activation, but not that of other kinases induced by LPS, was present in neutrophils cocultured with PAI-1 or uPA KD. Inhibition of JNK activation prevented the potentiation of expression of proinflammatory cytokines induced by PAI-1 or uPA KD in LPS stimulated neutrophils. These results demonstrate that PAI-1 and uPA KD enhance LPS-induced neutrophil responses through their effects on JNK mediated pathways.


Prevalence of cryptococcal antigenemia and cost-effectiveness of a cryptococcal antigen screening program--Vietnam.
An estimated 120,000 HIV-associated cryptococcal meningitis (CM) cases occur each year in South and Southeast Asia; early treatment may improve outcomes. The World Health Organization (WHO) recently recommended screening HIV-infected adults with CD4<100 cells/mm(3) for serum cryptococcal antigen (CrAg), a marker of early cryptococcal infection, in areas of high CrAg prevalence. We evaluated CrAg prevalence and cost-effectiveness of this screening strategy in HIV-infected adults in northern and southern Vietnam. Serum samples were collected and stored during 2009-2012 in Hanoi and Ho Chi Minh City, Vietnam, from HIV-infected, ART-naïve patients presenting to care in 12 clinics. All specimens from patients with CD4<100 cells/mm(3) were tested using the CrAg lateral flow assay. We obtained cost estimates from laboratory staff, clinicians and hospital administrators in Vietnam, and evaluated cost-effectiveness using WHO guidelines. Sera from 226 patients [104 (46%) from North Vietnam and 122 (54%) from the South] with CD4<100 cells/mm(3) were available for CrAg testing. Median CD4 count was 40 (range 0-99) cells/mm(3). Nine (4%; 95% CI 2-7%) specimens were CrAg-positive. CrAg prevalence was higher in South Vietnam (6%; 95% CI 3-11%) than in North Vietnam (2%; 95% CI 0-6%) (p = 0.18). Cost per life-year gained under a screening scenario was $190, $137, and $119 at CrAg prevalences of 2%, 4% and 6%, respectively. CrAg prevalence was higher in southern compared with northern Vietnam; however, CrAg screening would be considered cost-effective by WHO criteria in both regions. Public health officials in Vietnam should consider adding cryptococcal screening to existing national guidelines for HIV/AIDS care.


An exploration of competitiveness and caring in relation to psychopathology.
Social mentality theory outlines how specialist systems have evolved to facilitate different types of social behaviour such as caring for offspring, forming alliances, and competing for resources. This research explored how different types of self-experience are linked to the different social mentalities of competitive social ranking (focusing on gaining and defending one's social position/status/rank) in contrast to caring (being helpful to others). Perceived low social rank (with feelings of being inferior and unfavourable social comparison, SC) has been linked to depression, but a caring sense of self has less so. We hypothesized therefore that depression, in both clinical and non-clinical populations, would be primarily linked to competitive and rank focused sense of self rather than a caring sense of self. Students (N = 312) and patients with depression (N = 48) completed self-report scales measuring: self-experience related to competitiveness and caring; social rank; social safeness; and depression, anxiety, and stress. The data suggest that in students, and particularly in patients, competitiveness (and feeling unsuccessful in competing for resources) is strongly associated with depression. Although caring shares a small correlation with depression in students, and with depression, anxiety, and stress in patients, when controlling for the rank variable of submissive behaviour this relationship ceases to be significant. Submissive behaviour was found to be a full mediator between caring and depression. We also found that how safe and comfortable one feels in one's social relationships (social safeness), was a full mediator between competitiveness and depression. So, it is the feeling of being unable to compete where one does not feel secure in one's social environment that is particularly linked to depression. The results of this study suggest that self-experience is complex and multifaceted and is linked to different social roles that are socially contextualized. In addition, perceived low social rank and perceived failures in being able to 'attract' others and compete for social resources, are strongly linked to depression, whereas experiencing oneself as caring and helpful is not when submissiveness is controlled for.


Is Hyperthyroidism a Possible Etiology of Early Onset Dementia?
Dementia, a disabling syndrome of the elderly characterized by the decline in memory and cognition, is increasing in incidence and affects not only the individual but also their family and close ones. Hyperthyroidism can mimic many other diseases and untreated hyperthyroidism can lead to adverse problems of various systems including the heart, bones, muscles, menstrual cycle, and fertility. In this article, we have tried to evaluate the association between hyperthyroidism and dementia, as well as the impact of hyperthyroidism management in the treatment and prevention of dementia. Studies available in the PubMed database have been used, excluding animal studies and including studies of adults above the age of 50. The analysis of studies reveals that thyroid dysfunction can lead to cognitive impairment. It has not been able to prove that hyperthyroidism can lead to an earlier onset of dementia. But subclinical hyperthyroidism, thyroid-stimulating hormone (TSH) levels below the normal range, and high free thyroxine (T4) levels increase the risk of dementia among the elderly. The possible mechanisms involved in this association have also been discussed. Thus, we concluded that it is essential to detect and manage hyperthyroidism at an earlier stage since hyperthyroidism increases the risk of dementia. The possibility of using antithyroid treatment in euthyroid dementia is yet to be studied extensively.


Defect density in multiwalled carbon nanotubes influences ovalbumin adsorption and promotes macrophage activation and CD4(+) T-cell proliferation.
Carbon nanotubes (CNTs) are of great interest for the development of drugs and vaccines due to their unique physicochemical properties. The high surface area to volume ratio and delocalized pi-electron cloud of CNTs promote binding of proteins to the surface forming a protein corona. This unique feature of CNTs has been recognized for potential delivery of antigens for strong and long-lasting antigen-specific immune responses. Based on an earlier study that demonstrated increased protein binding, we propose that carboxylated multiwalled CNTs (MWCNTs) can function as an improved carrier to deliver antigens such as ovalbumin (OVA). To test this hypothesis, we coated carboxylated MWCNTs with OVA and measured uptake and activation of antigen-presenting cells (macrophages) and their ability to stimulate CD4(+) T-cell proliferation. We employed two types of carboxylated MWCNTs with different surface areas and defects (MWCNT-2 and MWCNT-30). MWCNT-2 and MWCNT-30 have surface areas of ~215 m(2)/g and 94 m(2)/g, respectively. The ratios of D- to G-band areas (I D/I G) were 0.97 and 1.37 for MWCNT-2 and MWCNT-30, respectively, samples showing that MWCNT-30 contained more defects. The increase in defects in MWCNT-30 led to increased binding of OVA as compared to MWCNT-2 (1,066±182 μg/mL vs 582±41 μg/mL, respectively). Both types of MWCNTs, along with MWCNT-OVA complexes, showed no observable toxicity to bone-marrow-derived macrophages up to 5 days. Surprisingly, we found that MWCNT-OVA complex significantly increased the expression of major histocompatibility complex class II on macrophages and production of pro-inflammatory cytokines (tumor necrosis factor-α and interleukin 6), while MWCNTs without OVA protein corona did not. The coculture of MWCNT-OVA-complex-treated macrophages and OVA-specific CD4(+) T-cells isolated from OT-II mice demonstrated robust proliferation of CD4(+) T-cells. This study provides strong evidence for a role for defects in carboxylated MWCNTs and their use in the efficient delivery of antigens for the development of next-generation vaccines.


Paediatric tympanoplasty.
Much debate exists over the management of mucosal chronic suppurative otitis media in children, with the majority of it centred around the correct timing to perform either a myringoplasty (an operative repair of the tympanic membrane) or type I tympanoplasty (reconstruction of the tympanic membrane when there is an intact and mobile ossicular chain). Further discussion will use the term tympanoplasty to mean both of the above definitions. We present the findings of a recent survey of UK ENT consultants questioning their opinions on various management aspects of mucosal CSOM in the paediatric population. We also present an extensive review of the literature to provide us with published evidence in order to analyse the results of the questionnaire.


Exercise and sport in mental health: a review of the literature.
A literature survey was conducted of the most prominent psychological effects and therapeutic applications of physical activity in mental health. This paper primarily reviews the literature comparing therapeutic exercise and sport with more traditional therapies and activities. Commentary on research methods is also presented.


Dynamic critical behavior of failure and plastic deformation in the random fiber bundle model.
The random fiber bundle (RFB) model, with the strength of the fibers distributed uniformly within a finite interval, is studied under the assumption of global load sharing among all unbroken fibers of the bundle. At any fixed value of the applied stress sigma (load per fiber initially present in the bundle), the fraction U(t)(sigma) of fibers that remain unbroken at successive time steps t is shown to follow simple recurrence relations. The model is found to have stable fixed point U*, filled (sigma) for applied stress in the range 0 < or = sigma < or = sigma(c), beyond which total failure of the bundle takes place discontinuously [abruptly from U*, filled (sigma(c)) to 0]. The dynamic critical behavior near this sigma(c) has been studied for this model analyzing the recurrence relations. We also investigated the finite size scaling behavior near sigma(c). At the critical point sigma = sigma(c), one finds strict power law decay (with time t) of the fraction of unbroken fibers U(t)(sigma(c)) (as t--> infinity). The avalanche size distribution for this mean-field dynamics of failure at sigma < sigma(c) has been studied. The elastic response of the RFB model has also been studied analytically for a specific probability distribution of fiber strengths, where the bundle shows plastic behavior before complete failure, following an initial linear response.


In vitro genotoxicity study of silver nanoparticles and titanium dioxide nanoparticles.
Nanoparticles are widely used in cosmetic, pharmaceutical, and food industries, but their safety and genetic toxicity are still unclear. In this study, the genotoxicity of silver nanoparticles (AgNPs) and titanium dioxide nanoparticles (titanium dioxide nanoparticles) were evaluated by in vitro comet assay and PIG-A assay in TK6 cells. We exposed TK6 cells to two types of nanoparticles at the highest concentration of 200 μmol/L for 4 h and conducted the in vitro comet assay. We examined the mutation results of PIG-A gene in vitro after 4 h, 24 ho and 10 days of exposure, respectively. We also examined the endocytosis of nanoparticles in TK6 cells exposed to nanoparticles for 24 h. In the endocytosis assay, with the increase of nano-material concentration, the side scatter (SSC) of TK6 cells in flow cytometry showed a concentration-dependent and time-dependent increase, indicating that TK6 cells could uptake both types of nanoparticles. In the comet assay, AgNPs could induce a concentration-dependent increase in DNA tail intensity. However, titanium dioxide NPs could not induce the concentration-dependent increase of DNA fluorescence intensity of comet tail. In the PIG-A assay, both AgNPs and TiO2NPs did not induce PIG-A gene mutation frequency in TK6 cells. The results showed that AgNPs could induce DNA damage in TK6 cells, but could not induce increase of PIG-A gene mutation frequency. TiO2NPs neither induce DNA damage in TK6 cells nor increase PIG-A mutation frequency. Further tests are needed to determine whether TiO2NPs are genotoxic.


Attentional and perceptual contributions to the identification of extrafoveal stimuli: adult age comparisons.
Gerontological researchers have been cautioned that conclusions about age differences in attention may have been inferred from data that, in fact, reflected age differences in perceptual processing of stimuli falling outside the fovea (Cerella, 1985). Presumably, the experimental manipulations on which Cerella based his caution induced a broad focus of attention so that changes in perceptual processing would not be confounded with changes in attention. Experiment 1 tested this by comparing a condition similar to Cerella's with another in which attention was narrowly focused at fixation. The results replicated Cerella's findings. In addition, there were greater age differences when attention had been narrowly focused, showing that attentional effects can be separated from the effects reported by Cerella. Experiment 2 showed that age differences in extrafoveal perception could be removed by increasing the duration of the target from 200 to 2000 ms, suggesting that the perceptual deficits in older adults are due to differentially lengthened processing of stimuli outside the fovea.


Kidney transplantation for primary focal segmental glomerulosclerosis: outcomes and response to therapy for recurrence.
For a subset of adults and children with primary focal segmental glomerulosclerosis (FSGS), proteinuria and renal dysfunction recur after kidney transplantation (KTx). Predicting recurrence and response to plasmapheresis (PP) or other interventions remains problematic. The prevalence, recurrence rate, outcomes, and treatment responses of patients with FSGS were determined among 1573 KTx recipients. Although 5.0% carried some diagnosis of FSGS, only 1.9% (n=30) met strict diagnostic criteria for primary FSGS including biopsy-proven FSGS, lack of secondary factors, negative family history, and progression to end-stage renal disease within 10 years. Of these, 47% had recurrent FSGS compared with 8% of those not meeting strict criteria (P<0.001). Recurrence was more common in children compared with adults (86% vs. 35%, P=0.01). Graft survival was lower for recipients with primary FSGS compared with all others and inferior graft survival was attributable to recurrent FSGS. Fourteen patients received PP preemptively (pre-KTx) or therapeutically (post-KTx) for recurrent disease. Four pediatric patients additionally received anti-CD20 (rituximab) therapy. Of the different treatment approaches, only PP combined with rituximab was associated with prolonged remission of proteinuria. The results indicate that patients at high risk for FSGS recurrence can be identified and may benefit from carefully planned peritransplant interventions.


The discomforts of pregnancy.
During pregnancy, women may experience one or more of a wide variety of discomforts. Every pregnancy is different; discomforts felt during one pregnancy may not appear in another. Most discomforts experienced during pregnancy are thought to be the result of abundant hormonal changes. As pregnancy progresses, other discomforts are attributed to physical changes associated with the enlarging uterus. Selected discomforts of pregnancy are presented with suggestions for clinical management. Nurses can do something to decrease discomforts associated with pregnancy.


[Expert opinions on clinical application of interferon-γ release assay of Mycobacterium tuberculosis (2021 edition)].
Interferon-γ release assay (IGRA) is an in vitro immunological technique for Mycobacterium tuberculosis diagnosis, which is recommended by the World Health Organization. As one of the auxiliary diagnosis methods for active tuberculosis in diagnostic criteria of China, the method and technique have been developed in recent years, and a wealth of clinical applied experience has been accumulated in the clinical application in China. Based on the "Opinions of applications of IGRA in China (2014 edition)" issued by Chinese Society for Tuberculosis, Chinese Medical Association, it was revised and improved according to the latest developments and clinical experience, and the expert opinions were presented in six parts: principles and technical advances, quality control, application of latent tuberculosis infection diagnosis, auxiliary diagnosis of active tuberculosis, application in special populations, and the influence of common drugs on IGRA results, with a view to providing guidance for the clinical application of IGRA in China.


Postmenopausal women with abdominal obesity choosing a nutritional approach for weight loss: A decisional needs assessment.
To identify the decisional needs of postmenopausal women with abdominal obesity choosing between two nutritional approaches for weight loss: a low-fat diet or a diet rich in fruit and vegetables. Our descriptive qualitative study was based on the Ottawa Decision Support Framework. Four focus groups were conducted with postmenopausal women. A thematic content analysis was performed to determine the decisional needs influencing the choice of a low-fat diet or a diet rich in fruit and vegetables. Seventeen postmenopausal women participated in the study (median age 59 years). Most frequently reported decisional needs for each nutritional approach were sufficient levels of nutritional skills and knowledge, consideration of the physiological impacts and the sensory aspect of approaches, food availability, social support, finances and motivation. Partners, friends and daughters were considered as the most important individuals involved in the decision. We identified several decisional needs influencing postmenopausal women when choosing between a low-fat diet and a diet rich in fruit and vegetables. These findings could inform the design of decision support interventions that address the decisional needs of women for making and implementing informed decisions about a nutritional approach for weight loss.


Current and emerging factor VIII replacement products for hemophilia A.
Hemophilia A is a congenital X-linked bleeding disorder caused by coagulation factor VIII (FVIII) deficiency. Routine infusion of factor replacement products is the current standard of care; however, the development of alloantibodies against FVIII remains a challenge. The treatment of hemophilia has undergone major advances over the past century to improve safety, effectiveness, manufacturing, and convenience of factor products. Major recent advances in the treatment of hemophilia A include the emergence of extended half-life products, factor VIII orthologs, and gene therapy products. Extended half-life products were designed to decrease the frequency of infusions, but only modest half-life extension is achieved. Factor VIII orthologs featuring lower cross-reactivity with anti-FVIII antibodies may be less susceptible to inactivation by inhibitors. Meanwhile, gene therapy may potentially provide a cure for hemophilia A, thus abrogating the need for protein-based factor replacement. This review aims to discuss current and emerging FVIII replacement products for hemophilia A.


Silencing cathepsin L expression reduces Myzus persicae protein content and the nutritional value as prey for Coccinella septempunctata.
Gut-expressed aphid genes, which may be more easily inhibited by RNA interference (RNAi) constructs, are attractive targets for pest control efforts involving transgenic plants. Here we show that expression of cathepsin L, which encodes a cysteine protease that functions in aphid guts, can be reduced by expression of an RNAi construct in transgenic tobacco. The effectiveness of this approach is demonstrated by up to 80% adult mortality, reduced fecundity, and delayed nymph production of Myzus persicae (green peach aphids) when cathepsin L expression was reduced by plant-mediated RNAi. Consistent with the function of cathepsin L as a gut protease, M. persicae fed on the RNAi plants had a lower protein content in their bodies and excreted more protein and/or free amino acids in their honeydew. Larvae of Coccinella septempunctata (seven-spotted ladybugs) grew more slowly on aphids having reduced cathepsin L expression, suggesting that prey insect nutritive value, and not just direct negative effects of the RNAi construct, needs to be considered when producing transgenic plants for RNAi-mediated pest control.


Key role of alkanoic acids on the spectral properties, activity, and active-site stability of iron-containing nitrile hydratase from Brevibacterium R312.
Interaction of n-butyric acid with dialyzed nitrile hydratase from Brevibacterium R312, which is characterized by a charge-transfer band at 680 nm and EPR signals typical of a low-spin Fe(III) with delta g = 0.22, leads to a form displaying different spectral properties (lambda = 710 nm, delta g = 0.31). Butyric acid also acts as a competitive inhibitor of nitrile-hydratase-catalyzed hydration of acrylonitrile with a Ki value of 0.9 mM. Formation of the complex between the enzyme and butyric acid is highly dependent on the concentration of the latter and on pH. When stored with high levels of butyric acid, nitrile hydratase is completely inactive. The active uncomplexed enzyme is restored under the high dilution conditions used for the enzymatic assays, while the complexed form is favored at acidic pH and is not formed at pH above 8. Furthermore, the inhibitory potency of butyric acid decreases upon increasing pH (IC50 increases from 0.8 mM at pH 6.2 to 12 mM at pH 8.2). These data show that nitrile hydratase interacts with the acid form of butyric acid with a high affinity (Ki' approximately 4 microM at pH 7.2). At pH < 3, the visible spectrum of the enzyme disappears, presumably because of demetallation, whereas that of the complex exhibits a charge-transfer band shifted to 800 nm, the presence of butyric acid preventing nitrile hydratase from demetallation. Other linear carboxylic acids such as valeric and hexanoic acids behave similarly; they act as inhibitors of nitrile hydratase and protect the enzyme during storage. A structure of the nitrile hydratase active site interacting with butyric acid is tentatively proposed in which the latter is hydrogen-bonded to the Fe(III)-OH moiety. This interaction between butyric acid and nitrile hydratase should be considered when deducing the nature of nitrile hydratase active site and mechanisms, from spectral and enzymatic data, since most results published previously have been obtained on nitrile hydratase containing large amounts of butyric acid and interpreted without taking into account the presence of this acid in the active site.


The trinuclear gallium-bridged Ferrocenophane [{Fe(eta5-C5H4)2}3Ga2]: synthesis, bonding, structure, and coordination chemistry.
The trinuclear ferrocenophane [{Fe(eta(5)-C(5)H(4))(3)}(2)Ga(2)] (3) featuring two sp(2)-hybridized gallium atoms in bridging positions between three ferrocene-1,1'-diyl units represents a novel type of ferrocene derivative. Compound 3 is obtained by thermal treatment of 1,1'-bis(dimethylgallyl)ferrocene (1) in nondonor solvents or in diethyl ether as solvent and subsequent thermal decomplexation. The [1.1]ferrocenophane [{Fe(eta(5)-C(5)H(4))(2)}(2){GaMe}(2)] (2) is an intermediate in the formation of 3. The reaction of 3 with an excess of trimethylgallium leads back to 1 and proves the reversibility of the multistep reaction sequence. Theoretical calculations reveal a carousel-type D(3h) structure for 3. The compound can best be described as being composed of three only weakly interacting ferrocenediyl units covalently connected by gallium atoms without any pi-bond contribution in the Ga--C bonds. Owing to steric constraints 3 cannot be reduced to the dianion 3(2-), which would feature a Ga--Ga bond. Compound 3 represents a stereochemically rigid difunctional Lewis acid allowing the formation of the adducts 3 a-3 d possessing linear donor-aceptor-aceptor-donor arrangements. Crystal structure data for 3 a-3 d show a symmetry-reduced chiral ferrocenophane core (D(3h)-->D(3)). A polymeric rodlike structure is observed for 3 b and 3 d caused by pi-stacking effects (3 b) or by a difunctional donor-acceptor interaction (3 d). In solution, the chirality of the adducts is lost by rapid interconversion of the enantiomers. A cyclic voltammogram of 3 b in pyridine reveals three quasi-reversible oxidation steps at -356, -154, and 8 mV, indicating only weak electron delocalization in the cationic species. The redox potentials of the pyridine adduct 3 b are compared with those of other pyridine-stabilized gallyl-sustituted ferrocene derivatives and with ferrocene itself.


Evaluation of postoperative analgesic efficacy of transversus abdominis plane block after abdominal surgery: A comparative study.
The transversus abdominis plane (TAP) block is an effective method of providing postoperative analgesia in patients undergoing midline abdominal wall incisions, by blocking the abdominal wall neural afferents via the bilateral lumbar triangles of Petit. We evaluated its analgesic efficacy in patients during the first 48 postoperative hours after abdominal surgery, in a randomized, controlled single-blind clinical trial. Sixty patients (mean age 36.2 ± 9.6 years) of either sex of ASA grade 1 and 2 who underwent major gynecological or surgical operation were randomized either to receive standard care, including patient-controlled tramadol analgesia (n = 30), or to undergo TAP block (n = 30) in addition to standard care. After completion of surgery, 20 ml of 0.375% levobupivacaine was deposited into the transversus abdominis neurofascial plane via the bilateral lumbar triangles of Petit. Each patient was assessed in the postanesthesia care unit and at 2, 4, 6, 12, 24, and 48 h postoperatively. The TAP block reduced Visual Analog Scale pain scores at most (2, 4, 6, 12, 24 h), but not at all time (36, 48 h) points assessed. Patients undergoing TAP block had reduced tramadol requirement in 24 h (210.05 ± 20.5 vs. 320.05 ± 10.6; P < 0.01) and 48 h (508.25 ± 20.6 vs. 550.25 ± 20.6; P < 0.01), and a longer time to the first PCA tramadol request (in minutes), compared to the control group (178.5 ± 45.6 vs. 23.5 ± 3.8; P < 0.001). The TAP block provided highly effective postoperative analgesia in the first 24 postoperative hours after major abdominal surgery, and no complications due to the TAP block were detected.


Development and validation of a Multidimensional Sense of Humor Scale.
Personal sense of humor has been recognized as a coping mechanism. Sense of humor as a construct, however, is multidimensional. Existing efforts to assess overall sense of humor are, for a number of reasons, deficient. The present study reports the development and factor analysis of a new Multidimensional Sense of Humor Scale that may be useful in a variety of research and clinical applications.


A Renal Inflammatory Myofibroblastic Tumor Similar to Cystic Renal Cell Carcinoma: One Case Report.
We describe and analyze the clinical course and imaging findings of a case of a renal inflammatory myofibroblastic tumor (IMT) that is similar to cystic renal cell carcinoma. "Solitary cysts" on the left kidney were found during a health examination of a 60-year-old female. The patient also had hypertension. She had undergone surgeries twice for limb trauma fracture and had no definite record of hepatitis. There was no tenderness with percussion of the kidney area or edema in the lower extremity. The renal function results, including serum creatinine, blood urea nitrogen, and blood urea, were within the normal range. No gross hematuria or microscopic hematuria was found. An 8.7 cm × 9.2 cm mixed echogenic mass at the upper pole of the left kidney was observed with ultrasound, the majority of which was an anechoic mass that was slightly protruding from the renal capsule and had well-circumscribed borders. After a bolus injection of an ultrasound contrast agent, the mass had rapid enhancement with fast fading. An approximately 9.4 cm × 10.1 cm round-like cyst lesion at the upper pole of the left kidney was revealed by computed tomography (CT) examination of the abdomen; it had edge finishing with well-circumscribed borders. The upper inner wall of the lesion was thick with crescentic soft tissue. The solid content had gradual enhancement on enhanced CT scans. A kidney tumor was considered based on the CT findings. Based on the preoperative examination, the left renal cystic masses were resected. Intraoperative frozen sections were used to further clarify the nature of the lesion, and no significant malignant cells were observed; therefore, the kidney was not removed. The pathological diagnosis was renal IMT. After surgery, the patient recovered and did not have recurrence or metastasis over the course of long-term follow-up. CT images of our patient with renal cystic disease are categorized as Fuhrman grade IV and typically indicate the presence of malignant lesions. However, gradual enhancement of the solid content in our case is different from typical cystic renal cell carcinoma. The nature of the lesion was further identified using intraoperative frozen sections, which helped avoid unnecessary nephrectomy.


Myosin heavy chain isoforms influence surface EMG parameters: a study of the trapezius muscle in cleaners with and without myalgia and in healthy teachers.
The present study had two aims: (1) to investigate potential differences in proportion of myosin heavy chain isoforms in the trapezius muscle between female cleaners with and without trapezius myalgia and healthy teachers, and (2) to elucidate if myosin heavy chain composition and surface electromyogram (EMG) during an isokinetic endurance test of shoulder flexors are significantly related. The subjects were divided into three groups: (1) 25 female cleaners with diagnosed work-related trapezius myalgia; (2) 25 female cleaners without work-related trapezius myalgia; (3) a control group of 21 healthy female teachers who were not exposed to repetitive or static muscle work. All subjects performed a test involving150 forward flexions using an isokinetic dynamometer. During the test surface EMG was recorded from the trapezius muscle. Muscle samples were obtained from the descending part of the trapezius muscle. The fibre type area percentage based on ATPase staining and the proportions of different MHC isoforms as determined by gel electrophoresis. The trapezius was dominated by MHC I (71%), followed by MHC IIA (22-24%), and MHC IIX (5-7%); no significant differences between the three groups of subjects were found. The proportion of MHC I correlated negatively with MHC IIA ( r=-0.78; P<0.001) and MHC IIX ( r=-0.53; P<0.001). Significant correlations existed between the proportion of the MHC isoforms and the corresponding proportion of the fibre type area; 27-45% of the variance was explained. The multivariate analysis of the three groups of subjects revealed that MHC variables showed intercorrelations with EMG (both amplitude and frequency variables). However, the directions of the relationships differed among the three groups; the cleaners with myalgia and the teachers showed the greatest similarities in patterns. Intrinsic muscle properties appear to influence the frequency content of the EMG, which is in contrast to some of the theoretical models of the EMG. Our data could suggest that monotonous work such as professional cleaning can change the relationships between muscle structure and the frequency content of the EMG.


Explaining the impact of poverty on old-age frailty in Europe: material, psychosocial and behavioural factors.
Previous research found poverty to be associated with adverse health outcomes among older adults but the factors that translate low economic resources into poor physical health are not well understood. The goal of this analysis was to assess the impact of material, psychosocial, and behavioural factors as well as education in explaining the poverty-health link. In total, 28 360 observations from 11 390 community-dwelling respondents (65+) in the Survey of Health, Ageing and Retirement in Europe (2004-13, 10 countries) were analysed. Multilevel growth curve models were used to assess the impact of combined income and asset poverty risk on old-age frailty (frailty index) and associated pathway variables. In total, 61.8% of the variation of poverty risk on frailty level was explained by direct and indirect effects. Results stress the role of material and particularly psychosocial factors such as perceived control and social isolation, whereas the role of health behaviour was negligible. We suggest to strengthen social policy and public health efforts in order to fight poverty and its deleterious health effects from early age on as well as to broaden the scope of interventions with regard to psychosocial factors.


IL-4 down-regulates IL-2 receptor p75 by accelerating its endocytosis.
We examined the effects of interleukin 4 (IL-4) on the expression of IL-2 receptor p75 (IL-2R p75) or beta chain on various human T cells. IL-4 promptly down-regulated surface IL-2 receptor (IL-2R) p75 in these cells. Although IL-2-induced IL-2R p75 down-regulation was seen more quickly, IL-2 did not contribute to the process of the IL-4-induced decrease of IL-2R p75. Northern blotting revealed that IL-4 did not reduce the expression of IL-2R p75 mRNA. Studies using Pronase E, which digests cell surface IL-2R p75, or brefeldin A, which blocks intracytoplasmic protein transport from endoplasmic reticulum to the Golgi apparatus, suggest that IL-4-induced IL-2R p75 down-regulation is controlled after IL-2R p75 is expressed on the cell surface. We found that IL-4 accelerated the endocytosis of IL-2R p75, which was monitored by [125I]Mik-beta 3 monoclonal antibody that recognizes non-IL-2-binding epitope on IL-2R p75. These findings demonstrate that IL-4 down-regulates IL-2R p75 mainly by accelerating its endocytosis.


Striated muscle heteroplasia in the uterine round ligament. A report of 30 cases.
The presence of nonneoplastic mature striated muscle, ie, striated muscle heteroplasia, is described in the proximal stumps of the round ligaments of the uterus. It was an incidental finding in 30 (2.8%) of 1064 surgical specimens studied without clinical or pathologic significance. It is deemed to represent aberrant persistence, differentiation, and maturation of gubernacular rhabdomyoblasts, which normally involute in female fetuses. The reasons for its sporadic occurrence in normal adult women are unknown.


Combined nitritation-anammox: advances in understanding process stability.
Efficient nitrogen removal from wastewater containing high concentrations of ammonium but little organic substrate has recently been demonstrated by several full-scale applications of the combined nitritation-anammox process. While the process efficiency is in most cases very good, process instabilities have been observed to result in temporary process failures. In the current study, conditions resulting in instability and strategies to regain efficient operation were evaluated. First, data from full-scale operation is presented, showing a sudden partial loss of activity followed by recovery within less than 1 month. Results from laboratory-scale experiments indicate that these dynamics observed in full scale can be caused by partial inhibition of the ammonia oxidizing bacteria (AOB), while anammox inhibition is a secondary effect due to temporarily reduced O(2) depletion. Complete anammox inhibition is observed at 0.2 mg O(2) · L(-1), resulting in NO(2)(-) accumulation. However, this inhibition of anammox is reversible within minutes after O(2) depletion. Thus, variable AOB activity was identified as the key to reactor stability. With appropriate interpretation of the online NH(4)(+) signal, accumulation of NO(2)(-) can be detected indirectly and used to signal an imbalance of O(2) supply and AOB activity (no suitable online NO(2)(-) electrode is currently available). Second, increased abundance of nitrite-oxidizing bacteria (NOB; competing with anammox for NO(2)(-)) is known as another cause of instability. Based on a comparison of parallel full-scale reactors, it is suggested that an infrequent and short-term increased O(2) supply (e.g., for maintenance of aerators) that exceeds prompt depletion of oxygen by AOB may have caused increased NOB abundance. The volumetric air supply as a proxy for O(2) supply thus needs to be linked to AOB activity. Further, NOB can be washed out of the system during regular operation if the system is operated at a sludge age in the range of 45 days and by controlling the air supply according to the NO(3)(-) concentration in the treated effluent. Early detection of growing NOB abundance while the population is still low can help guide process operation and it is suggested that molecular methods of quantifying NOB abundance should be tested.


Caspase-independent cell death and mitochondrial disruptions observed in the Apaf1-deficient cells.
Apaf1 is a critical molecule in the mitochondria-dependent apoptotic pathway. Here we show that Apaf1-deficient embryonic fibroblasts died at a later phase of apoptotic induction, although these cells were resistant to various apoptotic stimulants at an early phase. Neither caspase 3 activation nor nuclear condensation was observed during this cell death of Apaf1-deficient cells. Electron microscopic examination revealed that death in response to apoptotic stimulation resembled necrosis in that nuclei were round and swollen with low electron density. Necrosis-like cell death was also observed in wild-type cells treated with z-VAD-fmk. Mitochondria were not only morphologically abnormal but functionally affected, since mitochondrial transmembrane potential (DeltaPsim) was lost even in cells with intact plasma membrane integrity. These mitochondrial alterations were also observed in the wild-type cells dying of apoptosis. Combined, these data suggest that cells without caspase activation, such as Apaf1-deficient cells or cells treated with caspase inhibitors, die of necrosis-like cell death with mitochondrial damage in response to "apoptotic stimulation."


Clinical Outcomes of Liver Transplantation in Patients With Hepatorenal Syndrome: A Single Center Study in China.
Liver transplantation (LT) is an optimal treatment for hepatorenal syndrome (HRS) patients but renal function recovery is not universal after operation. The aim of this study is to explore the association between stages of hepatorenal syndrome-acute kidney injury (HRS-AKI) and incidence of post-operation chronic kidney disease (CKD). Data of HRS-AKI patients who received LT were collected from the First Affiliated Hospital of Sun Yat-sen University from 2016 to 2020. A survival and incidence curve and multivariable model were established to analyze the impacts of HRS-AKI stages and variables on 90-day survival and CKD within 12 months. A total of 62 HRS-AKI patients were enrolled in this study. Overall, 35 (57%), 17 (27%), and 10 (16%) patients were diagnosed as stages 1, 2, and 3, respectively. The patients at stage 3 had the poorest outcomes with the lowest rate of 90-day survival and the highest incidence of CKD in 12 months. Stage 3 (SHR = 7.186, 95% CI, 1.661-32.043) and postoperative renal replacement therapy (RRT) (SHR = 3.228, 95% CI, 1.115-9.345) were found as useful indicators for poor prognosis. In our study, the classification of HRS-AKI stages can be used to predict the prognosis of HRS patients after LT. The peak serum creatinine level is a risky predictor in high HRS-AKI stage patients.


Molecular-Layer-Defined Asymmetric Schottky Contacts in Organic Planar Diodes for Self-Powered Optoelectronic Synapses.
Optoelectronic synapses have been utilized as neuromorphic vision sensors for image preprocessing in artificial visual systems. Self-powered optoelectronic synapses, which can directly convert optical power into electrical power, are promising for practical applications. The Schottky junction tends to be a promising candidate as the energy source for electrical operations. However, fully utilizing the potential of Schottky barriers is still challenging. Herein, organic self-powered optoelectronic synapses with planar diode architecture are fabricated, which can simultaneously sense and process ultraviolet (UV) signals. The photovoltaic operations are facilitated by the built-in potential originating from the molecular-layer-defined asymmetric Schottky contacts. Diverse synaptic behaviors under UV light stimulation without external power supplies are facilitated by the interfacial carrier-capturing layer, which emulates the membranes of synapses. Furthermore, retina-inspired image preprocessing functions are demonstrated on the basis of synaptic plasticity. Therefore, our devices provide the potential for the development of power-efficient and advanced artificial visual systems.


Mono-Locus and Pyramided Resistant Grapevine Cultivars Reveal Early Putative Biomarkers Upon Artificial Inoculation With Plasmopara viticola.
One of the most economically important grapevine diseases is Downy mildew (DM) caused by the oomycete Plasmopara viticola. A strategy to reduce the use of fungicides to compensate for the high susceptibility of V. vinifera is the selection of grapevine varieties showing pathogen-specific resistance. We applied a metabolomics approach to evaluate the metabolic modulation in mono-locus resistant genotypes carrying one locus associated with P. viticola resistance (Rpv) (BC4- Rpv1, Bianca- Rpv3-1, F12P160- Rpv12, Solaris- Rpv10), as well as in pyramided resistant genotypes carrying more than one Rpv (F12P60- Rpv3-1; Rpv12 and F12P127- Rpv3-1, Rpv3-3; Rpv10) taking as a reference the susceptible genotype Pinot Noir. In order to understand if different sources of resistance are associated with different degrees of resistance and, implicitly, with different responses to the pathogen, we considered the most important classes of plant metabolite primary compounds, lipids, phenols and volatile organic compounds at 0, 12, 48, and 96 h post-artificial inoculation (hpi). We identified 264 modulated compounds; among these, 22 metabolites were found accumulated in significant quantities in the resistant cultivars compared to Pinot Noir. In mono-locus genotypes, the highest modulation of the metabolites was noticed at 48 and 96 hpi, except for Solaris, that showed a behavior similar to the pyramided genotypes in which the changes started to occur as early as 12 hpi. Bianca, Solaris and F12P60 showed the highest number of interesting compounds accumulated after the artificial infection and with a putative effect against the pathogen. In contrast, Pinot Noir showed a less effective defense response in containing DM growth.


Comparison of Corrosion Performance of Extruded and Forged WE43 Mg Alloy.
Adjusting the microstructure through the deformation process is one of the ways to improve the properties of Mg alloys. Most studies have focused on the influence of the microstructure after deformation treatment on the mechanical properties of Mg alloys. In this paper, extruded and forged Mg-Gd-Y-Nd-Zr alloys were selected to investigate the corrosion performance of two deformed magnesium alloys immersed in 0.6 M NaCl solution using a hydrogen evolution test, a weight loss test, an immersion experiment, and an electrochemical test. The results showed that WE43 alloys undergoing different deformation treatments presented different microstructures, which led to different corrosion behaviors and corrosion resistance. The extruded WE43 alloy showed uniform corrosion, while the forged WE43 alloy suffered severe local galvanic corrosion. Meanwhile, the corrosion rate of the forged WE43 alloy was about four times faster than that of the extruded WE43 alloy.


Pyoderma Gangrenosum Mimicking Necrotizing Fasciitis on Magnetic Resonance Imaging: A Case Report and Literature Review.
BACKGROUND Pyoderma gangrenosum (PG) is a sterile neutrophilic dermatosis that can be associated with systemic diseases, such as ulcerative colitis, polyarthritis, diabetes mellitus, myelodysplastic syndrome, and/or myeloid leukemia, and is often misdiagnosed as a necrotizing infection. Few reports have described imaging studies of PG; however, necrotizing fasciitis (NF) exhibits distinct imaging characteristics. If deep fascial involvement is not demonstrated on magnetic resonance imaging (MRI), NF is excluded. CASE REPORT We present a case of PG mimicking NF on MRI in a 67-year-old woman with acute myeloblastic leukemia. After undergoing a second cycle of decitabine therapy, she was admitted for pain in her lower left leg. The condition was initially misdiagnosed as NF because MRI findings demonstrated signal intensity in the fascia. MRI revealed fasciitis that exhibited linear fluid signal intensity in the fascia of lower left leg. Despite broad-spectrum antibiotics, the lesion rapidly progressed to a swollen hemorrhagic patch with bullae and an ulcer. Skin biopsy results ultimately led to the diagnosis of PG, based on histopathological findings. The patient was treated with intravenous steroids and regular wound dressing. The skin lesion on the lower left leg exhibited a good response. CONCLUSIONS Despite the presence of a lesion that invaded the fascia on MRI, our patient was diagnosed with PG following a skin biopsy and completely recovered with steroid treatment. To distinguish PG from NF, it is more important to identify the characteristic clinical features than to rely solely on imaging findings.


Electron paramagnetic resonance study of radiation damage in photosynthetic reaction center crystals.
Electron paramagnetic resonance (EPR) was used to simultaneously study radiation-induced cofactor reduction and damaging radical formation in single crystals of the bacterial reaction center (RC). Crystals of Fe-removed/Zn-replaced RC protein from Rhodobacter ( R.) sphaeroides R26 were irradiated with varied radiation doses at cryogenic temperature and analyzed for radiation-induced free radical formation and alteration of light-induced photosynthetic electron transfer activity using high-field (HF) D-band (130 GHz) and X-band (9.5 GHz) EPR spectroscopies. These analyses show that the formation of radiation-induced free radicals saturated at doses 1 order of magnitude smaller than the amount of radiation at which protein crystals lose their diffraction quality, while light-induced RC activity was found to be lost at radiation doses at least 1 order of magnitude lower than the dose at which radiation-induced radicals exhibited saturation. HF D-band EPR spectra provide direct evidence for radiation-induced reduction of the quinones and possibly other cofactors. These results demonstrate that substantial radiation damage is likely to have occurred during X-ray diffraction data collection used for photosynthetic RC structure determination. Thus, both radiation-induced loss of photochemical activity in RC crystals and reduction of the quinones are important factors that must be considered when correlating spectroscopic and crystallographic measurements of quinone site structures.


Exploration of the Adsorption Reduction of the Pigment Aggregates Strength under the Effect of Surfactants in Water-Dispersion Paints.
This article presents the results of studying the disaggregation of titanium dioxide in water-dispersion compositions based on an acrylic film-forming agent under the action of a surfactant. The possibility of using polyether siloxane copolymer (PC) and sodium polyacrylate (NaPA) in paint and varnish compositions as modifying additives of the dispersing effect is proved. The correlation between the dispersing effect of surfactants and the amount of their adsorption on the pigment is proved. NaPA, which provides a greater reduction in adsorption strength, demonstrates a greater dispersing effect than PC. It was found that the larger the size of the aggregates of pigment particles, the greater the disjoining pressure created by the surfactant. An equation is derived that generalizes the cumulative contribution of surfactant concentration and the content of the film-forming agent in suspensions to the average particle diameter of pigment. The introduction of NaPA in the amount of 0.25 g/dm3 into the paint allows the rate of acid corrosion to be reduced by 2 times, the number of pores in the coating to be decreased, and the adhesion of the coating to be significantly increased (by 2 points according to ISO 11845: 2020).


Pseudomegadactyly. A unique presentation of chronic granulomatous paronychia.
An interesting case of chronic paronychia of the big toe for the last 6 years resulting in granulomatous reaction and hypertrophy of nail plate and bed is being reported. An increased rate of longitudinal growth of nails may occur in association with infection around the nail, in bullous, ichthyosiform erythroderma and in psoriasis as already reported, but a unique feature in this patient was the increase in size of the nail plate in all directions, along with simultaneous increase in the surface area of the nail bed.


Identification of three factors influencing trail making test performance using multichannel near-infrared spectroscopy.
Recent advances in medical care have facilitated the survival of patients with stroke or traffic-related injuries. However, such patients may suffer from higher brain dysfunction; i.e., an impaired ability to plan and perform behaviors based on prior knowledge. The Trail Making Test (TMT) is a cognitive task that is used to evaluate higher brain dysfunction caused by frontal lobe injury. TMT consists of two tasks; TMT-A involves connecting consecutive numbers, and TMT-B involves connecting numbers and letters alternately. In this study, using near-infrared spectroscopy (NIRS) and the achievement value (TMT score), we investigated the effects of three factors on TMT performance: knowledge of the TMT, the order of TMT-A and TMT-B performance, and gender. The subjects were 48 healthy adults, consisting of college graduates and undergraduates (age: 22.8 ± 2.5 years, education: 16.0 ± 1.2 years, 24 males and 24 females). We measured the changes in oxygenated hemoglobin (oxy-Hb) levels using NIRS, showing that the increase in oxy-Hb was higher in subjects who had no knowledge of the TMT than those who had prior knowledge. In both TMT-A and TMT-B, the subjects who performed their first task displayed higher oxy-Hb levels. Moreover, the oxy-Hb level in males was higher than that in females. In contrast, only the order of TMT performance showed noticeable effect on the TMT score. In the present study, using NIRS we have shown that either knowledge of the TMT, the order of the TMT, or gender affects TMT performance, providing invaluable information for interpreting TMT results.


Modulation of antioxidant defence system in response to berberine in Candida albicans.
Emergence of multidrug resistant species of Candida is evolving, which advocates an urgent need for the development of new therapeutic strategies and antifungal drugs. Activation of antioxidant defence system in Candida albicans is known as forefront mechanism to escape drug toxicity. This study evaluated the role of antioxidant defence genes in the susceptibility to fluconazole in C. albicans and also determined the effect of berberine on growth, antioxidant enzymes and the expression of their genes in C. albicans isolates. Expression of major antioxidant genes was significantly increased in fluconazole-resistant isolates in comparison with the susceptible group. Antifungal susceptibility against berberine showed MIC values ranging from 125 to 500 μg/ml. Berberine treatment caused upregulation of mRNA expression and enzymatic activities of the targeted major antioxidants. Interestingly, C. albicans exhibited efficient antioxidant response at lower concentrations but could not sufficiently alleviate berberine-induced oxidative stress occurring at concentrations greater than 250 μg/ml. Therefore, berberine could serve as a potent Reactive Oxygen Species (ROS)-inducing agent, disrupting the antioxidant system especially in fluconazole-resistant C. albicans to overcome antifungal drug resistance. TAKE AWAYS: Evaluated the role of antioxidant enzymes in FLC resistance in C. albicans Studied the effect of berberine on growth of different C. albicans isolates Investigated the modulation of antioxidant enzymes by berberine in C. albicans Studied the effect of berberine on antioxidant gene expression in C. albicans.


Dengue Virus Infection Is through a Cooperative Interaction between a Mannose Receptor and CLEC5A on Macrophage as a Multivalent Hetero-Complex.
Dengue fever is a mosquito-borne viral pandemic disease that is widespread in the tropical and subtropical areas. Dengue virus uses human mannose-binding receptor (MR) and DC-SIGN on macrophages as primary receptors, and CLEC5A as signaling receptor to sense the dengue virus invasion and then to signal and stimulate macrophages to secrete cytokines. But the interplay between MR/DC-SIGN and CLEC5A is unknown. Here we demonstrate a plausible mechanism for the interaction, i.e. MR/DC-SIGN first attracts the virus with high avidity, and the virus concurrently interacts with CLEC5A in close proximity to form a multivalent hetero-complex and facilitate CLEC5A-mediated signal transduction. Our study suggests that the cooperation between a high-avidity lectin-virus interaction and a nearby low-avidity signaling receptor provides a necessary connection between binding and signaling. Understanding this mechanism may lead to the development of a new antiviral strategy.


Value of anaerobic culture in bacterial surveillance program for platelet concentrates.
Short-term aerobic bacterial culture (STABC) has been used routinely in Hong Kong since 1998 to reduce bacterial contamination in platelet concentrates (PCs) with good results. With more countries implementing routine aerobic and anaerobic cultures of PCs, a prospective study was conducted to determine the value of anaerobic culture to STABC. PC tested by STABC was used as control. Twenty milliliters of the PC selected for this study was aliquoted and pooled for 7 days aerobic and anaerobic culture. If the initial culture was positive, samples retrieved from the original PC and their associated components were cultured for confirmation and microbiologic identification. A total of 10,035 PC units (2007 pools) were tested. The confirmed positive rates by aerobic and anaerobic cultures per pool were 3 (0.15%) and 13 (0.65%), respectively, which was equivalent to an increased yield from 0.03 to 0.13 percent of PC if anaerobic culture was added. Of the 10 bacteria detected by anaerobic culture only, 9 were found to be Propionibacterium acnes and the remaining one Peptostreptococcus sp. Their mean detection time from inoculation was 92.16 hours (range, 50.4-124.8 hr). Addition of anaerobic culture to our routine STABC would significantly increase the detection rate of bacterial contaminated PC. However, since only slow-growing bacteria were detected, and because their clinical significance was uncertain, it is concluded that there was no clear justification to introduce anaerobic culture locally if 5-day shelf life for PCs was to be maintained.


ABCC11/MRP8 Expression in the Gastrointestinal Tract and a Novel Role for Pepsinogen Secretion.
ATP-binding cassette (ABC) transporters are involved in chemotherapy resistance. Multidrug-resistance protein 8 (ABCC11/MRP8) is also involved in 5-fluorouracil (5-FU) metabolism. 5-FU and its derivatives are widely used in the treatment of gastrointestinal tract cancers, but little is known about the contribution of ABCC11/MRP8 to gastrointestinal tract and related cancers. Here, we report our investigation of ABCC11/MRP8 expression in normal and cancerous gastrointestinal tract tissues and reveal its novel role in the gastric mucosa. In tissue microarray and surgically resected cancer specimens, immunohistochemical (IHC) staining revealed significantly reduced expression of ABCC11/MRP8 in gastrointestinal tract cancers compared with other cancers. In contrast, strong ABCC11/MRP8 expression was observed in normal gastric mucosa. Additional immuno-fluorescence assays revealed co-localization of ABCC11/MRP8 and pepsinogen I in normal gastric chief cells. Quantitative PCR and Western blot analysis also revealed significant expression of ABCC11/MRP8 in fundic mucosa where the chief cells are mainly located. Furthermore, the ABCC11 mRNA-suppressed NCI-N87 gastric cancer cell line failed to secret pepsinogen I extracellularly. Thus, low expression of ABCC11/MRP8 is consistent with chemotherapeutic regimens using 5-FU and its derivatives in gastrointestinal tract cancers. Our results indicated a novel function of ABCC11/MRP8 in the regulation of pepsinogen I secretion in the normal gastric chief cells.


Ischemic damage prevention by coenzyme Q10 treatment of the donor before orthotopic liver transplantation: biochemical and histologic findings.
This study was undertaken to determine whether pretreatment of the donor rat with coenzyme Q10 (CoQ10) would protect against hepatic ischemia induced for 30 minutes at normothermic body temperature. Fresh liver transplants were used as controls (minus warm ischemia of 30 minutes) and gave a 1-week survival rate of 84.6%. CoQ10 was administered intravenously (10 mg/kg body weight) to the donor rat 1 hour before induction of warm ischemia (group A). In another group (B), the same dose was given intravenously not only to the donor rat but also to the recipient rat 1 hour before grafting. None of the placebo group survived more than 2 days. The 1-week survival rates of the groups pretreated with CoQ10 were 45.5% for group A and 50% for group B. There was no significant difference between groups A and B. A statistically significant difference was demonstrated between the placebo group and both CoQ10-treated groups (p less than 0.05). It was therefore assumed that CoQ10, accumulated in the donor liver, was a primary factor in improving survival. Serum glutamic oxaloacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT), serum alkaline phosphatase (SALP), total bilirubin, and total protein were measured by means of light and electron microscopic examination of the liver 6 months after transplantation. Long-term-surviving rats with transplanted, ischemically damaged liver that was pretreated with CoQ10 showed a decrease in the activity of SGOT and SGPT and an increase in levels of total protein to the normal range (as well as to those levels exhibited by fresh-liver-transplanted rats) with practically no change in levels of SALP, total bilirubin, or in histologic findings. These results indicate that donor pretreatment with CoQ10 is useful for increasing survival after warm ischemic damage of rat liver grafts.


Pandemic influenza A(H1N1) 2009 and respiratory syncytial virus associated hospitalizations.
To determine the contribution of influenza and respiratory syncytial virus (RSV) as the cause of lower respiratory tract infection (LRTI) associated hospitalizations during the first year of the influenza A(H1N1) 2009 pandemic and to assess the severity of illness during the second pandemic wave. Patients admitted with LRTI from April 2009 through March 2010 were assessed for the presence of influenza and RSV. Pandemic influenza virus was detected by means of a nested RT-PCR assay and/or the CDC's real time-PCR protocol. RSV was detected using a one-step RT-PCR assay. The characteristics of patients admitted during the first and second pandemic outbreaks were compared. 657 patients with LRTI were admitted during the study period. Pandemic influenza virus was detected in 180 and RSV in 133. Influenza was the most common cause of infection in adults, while RSV was more common in children. There were no differences in disease severity between the first and second pandemic outbreaks. Pandemic influenza virus was associated to increased numbers of hospitalizations and deaths; particularly in adults. The severity of the first and second pandemic outbreaks was similar. RSV continues to be the main pathogen responsible for hospitalizations in young children.


Graft failure in a patient with systemic lupus erythematosus (SLE) treated with high-dose immunosuppression and autologous stem cell rescue.
A 32-year-old female with WHO grade IV, dialysis dependent, lupus nephritis was treated with high-dose immunosuppression and autologous stem cell rescue. Stem cells were mobilized with cyclophosphamide (CY) and G-CSF, and 4.07 x 10(6) CD34+ cells/kg were obtained after CD34+ cell selection using the CellPro column. The preparative regimen consisted of CY, and antithymocyte globulin (ATG), with methylprednisolone. After apparent primary engraftment of neutrophils on day 9, the patient developed recurrent neutropenia on day 19. She showed no evidence of engraftment by day 35, and back-up unmanipulated stem cells were given without effect. Subsequently, she received unmanipulated peripheral stem cells (2 x 10(6) CD34+ cells/kg) from an HLA-identical sibling. The patient remained pancytopenic and expired on day 62 from disseminated fungal infection. An autopsy revealed no evidence of hematopoietic recovery. Progenitor cell assays were performed with the patient's stem cells, which were collected prior to transplantation, and serum collected day 27. Morphologic examination of the patient's cell colonies grown in the presence of her serum revealed abnormal shapes and non-adherent cells. There were significantly fewer BFU-e colonies and a trend toward fewer CFU-GM colonies with the patient's cells and serum compared to normal donor cells. We concluded that a substance present in her serum mediated graft failure and prevented engraftment after additional stem cell infusions.


Blocked exchanges revisited.
This paper reconsiders the topic of blocked exchanges. It has been argued by some philosophers and social theorists that in order to encourage people to make donations of, e.g., blood, the sale of such items should be banned by law or public policy. In this paper I argue that (a) donations made without the option of selling are morally diminished and (2) selling such items isn't morally wrong or even insignificant in all cases since prudence (which is a moral virtue, pace Kant) may require that one sell them.


[Images of growth zones of the femoral head, neck and greater trochanter in MR examination].
The possibilities of MR imaging were evaluated in 36 children with 58 normal hips. The analysed children were divided into 3 groups, basing on age at the time of investigation i.e. children less than 5 years old, age ranging from 5 to 12 years, and over 12 years of age. MRI allowed visualisation of all growth zones of the proximal femur. On T-1 weighted images the growth cartilage of the femoral head, neck, and greater trochanter were of intermediate signal intensity. On sequences using fat saturation and on gradient echo images the cartilage was of high signal intensity. The growth zone of the subtrochanteric cartilage was of low signal intensity on T-1 weighted images and high signal intensity on sequences using fat saturation and on gradient echo images. T-1 weighted images together with FLASH 3D FAT SAT seem to be sufficient for the analysis of the growth zones of the proximal femur.


Development, characterization, and evaluation of ketorolac tromethamine-loaded biodegradable microspheres as a depot system for parenteral delivery.
Ketorolac tromethamine, a potent nonnarcotic analgesic agent and 800 times more potent than aspirin, is indicated for the short-term management of moderate to such severe painful states as post operative pain, acute musculoskeletal pain, and dental pain. It Given every 6 hr intramuscularly in patients for acute pain, to avoid frequent dosing and patient inconvenience Ketorolac from ethamine was found suitable for parenteral depot system by biodegradable microspheres for the present study. Ketorolac tromethamine-loaded microspheres were prepared by o/w emulsion solvent evaporation technique using different polymers viz. polycaprolactone, poly-dl-lactide (Resomer) and poly lactic acid (PLA). To tailor the release profile of drug for several days, blends of Resomer and PLA were prepared with polycaprolactone in different ratios. Higher encapsulation efficiency was obtained with microspheres made with pure Resomer. Surface topography was studied by scanning electron microscopy, which showed spherical shape of microspheres. Residual solvent analysis was carried out to determine the residual amount of dichloromethane in microspheres and the content was found within permissible limits. Differential scanning calorimetric studies also were carried out to study any drug polymer interactions. We concluded that with careful selection of different polymers and their combinations, we can tailor the release of ketorolac tromethamine for long periods.


Primary eosinophilic gastrointestinal disorders in children who have received food oral immunotherapy.
Food oral immunotherapy (OIT) involves the administration of the food allergen causing the symptoms, in order to induce tolerance. Primary eosinophilic gastrointestinal disorders (PEGDs) are characterised by an eosinophil-rich inflammation affecting different locations of the digestive tract. We present a series of patients with PEGDs in a group of children following OIT with milk and/or egg. A prospective study during the period 2006-2014 was performed in paediatric patients subjected to OIT with milk and/or egg. When these children present persistent gastrointestinal symptoms, they are referred to the Paediatric Gastroenterology Unit for evaluation. Primary eosinophilic gastrointestinal disorders were diagnosed in eight of the 128 cases of OIT (6.25%). The time to PEGDs development was variable: two cases showed symptoms during OIT, and the rest with a median time of 29 months (15-48 months). Food treatment discontinuation was not required in four of the five cases of eosinophilic oesophagitis, although food removal was necessary in patients with eosinophilic gastroenteritis. We report the highest prevalence of PEGDs in children subjected to OIT, and the first cases of eosinophilic gastroenteritis following food OIT. The monitoring of new digestive signs and symptoms after OIT is crucial for the diagnosis of these disorders, and prolonged follow-up is required. The management of such patients and the need or not to eliminate the food should be assessed on an individualised basis, according to the severity of the condition, its evolution and response to different treatment alternatives.


Thanatomicrobiome composition profiling as a tool for forensic investigation.
Thanatomicrobiome, or the postmortem microbiome, has been recognized as a useful microbial marker of the time and location of host death. In this mini-review, we compare the experimental methods commonly applied to thanatomicrobiome studies to the state-of-the-art methodologies in the microbiome field. Then, we review present findings in thanatomicrobiome studies, focusing on the diversity of the thanatomicrobiome composition and prediction models that have been proposed. Finally, we discuss potential improvements and future directions of the field.


Self-regulation of inflammatory cell trafficking in mice by the leukocyte surface apyrase CD39.
Leukocyte and platelet accumulation at sites of cerebral ischemia exacerbate cerebral damage. The ectoenzyme CD39 on the plasmalemma of endothelial cells metabolizes ADP to suppress platelet accumulation in the ischemic brain. However, the role of leukocyte surface CD39 in regulating monocyte and neutrophil trafficking in this setting is not known. Here we have demonstrated in mice what we believe to be a novel mechanism by which CD39 on monocytes and neutrophils regulates their own sequestration into ischemic cerebral tissue, by catabolizing nucleotides released by injured cells, thereby inhibiting their chemotaxis, adhesion, and transmigration. Bone marrow reconstitution and provision of an apyrase, an enzyme that hydrolyzes nucleoside tri- and diphosphates, each normalized ischemic leukosequestration and cerebral infarction in CD39-deficient mice. Leukocytes purified from Cd39-/- mice had a markedly diminished capacity to phosphohydrolyze adenine nucleotides and regulate platelet reactivity, suggesting that leukocyte ectoapyrases modulate the ambient vascular nucleotide milieu. Dissipation of ATP by CD39 reduced P2X7 receptor stimulation and thereby suppressed baseline leukocyte alphaMbeta2-integrin expression. As alphaMbeta2-integrin blockade reversed the postischemic, inflammatory phenotype of Cd39-/- mice, these data suggest that phosphohydrolytic activity on the leukocyte surface suppresses cell-cell interactions that would otherwise promote thrombosis or inflammation. These studies indicate that CD39 on both endothelial cells and leukocytes reduces inflammatory cell trafficking and platelet reactivity, with a consequent reduction in tissue injury following cerebral ischemic challenge.


Bird communities in two fragments of Cerrado in Itirapina, Brazil.
The Cerrado domain is a mosaic of vegetation types at the local scale, and this environmental heterogeneity leads to high regional bird diversity. Therefore, we aimed to survey quantitative and qualitatively the bird fauna of two fragments of Cerrado and to compare them with an adjacent protected area (Estação Ecológica de Itirapina), in order to assess the heterogeneity of bird diversity in the region. The present study was conducted during 12 months from October 2006 to September 2007 in the municipality of Itirapina, Southeastern Brazil. Altogether we recorded 210 bird species. Fifty-six of them had never been detected in Estação Ecológica de Itirapina, and eleven species are new records for the whole Itirapina region. The list also includes six species that are endangered in Sao Paulo State and five endemic species of the Cerrado domain. Most species were recorded in less than 50% of the visits and exhibited low relative abundance. Primarily insectivorous species were the most common, followed by omnivores. Frugivorous birds were poorly represented. Carnivores were more abundant than usually observed in fragments. The similarity among fragments was higher than between fragments and the protected area. Considering the vegetation heterogeneity in the Cerrado domain, our results reinforce the importance of conserving fragments in order to sample this diversity.


Some observations on the role of LH receptor binding inhibitor of ovine corpora lutea in ovarian processes.
Preliminary studies, both in vitro and in vivo were carried out to understand the physiological significance of LH receptor binding inhibitors isolated from ovine corpora lutea. Among the four active fractions tested, while UM-2R-III administered intraperitoneally suppressed both hMG and hCG-induced stimulation of uterine weights in immature mice, UM-2R-IX reduced the hCG-induced uterine weight. Fraction UM-2R-III inhibited both FSH and LH-stimulated cyclic AMP production by rat granulosa cells. Intraperitoneal injections of UM-2R-III and IX to adult cycling rats on the day of proestrus partially blocked ovulation. Similar i.p. treatment of cycling rats in 2 doses on day 1 of diestrus, prevented implantation/or early pregnancy (on 10th day of pregnancy) in 70 to 80% of rats. As the plasma levels of progesterone were low in the treated animals compared to the control, the decrease was attributed to the inadequate development of the corpus luteum. Of these fractions, UM-2R-IX was more effective at 5 to 10 times less doses compared to UM-2R-III. Further studies are needed to assess the route and dose of administering the active LHRBR components.


Stereoselective Synthesis and Structural Confirmation of the Specialized Pro-Resolving Mediator Resolvin E4.
Herein, we report the stereoselective and convergent synthesis of resolvin E4, a newly identified specialized pro-resolving mediator. This synthesis proves the absolute configuration and exact olefin geometry. Key elements of the successful strategy include a highly stereoselective MacMillan organocatalytic oxyamination, a Midland Alpine borane reduction, and the use of a 1,4-pentadiyne unit as a linchpin building block. The application of reaction telescoping in several of the synthetic transformations enabled the preparation of the resolvin E4 methyl ester in 10% yield over 10 steps (longest linear sequence). The physical property (UV-Vis and LC-MS/MS) data of synthetic resolvin E4 matched those obtained from biologically produced material.


Transcriptional regulation of the methuselah gene by dorsal protein in Drosophila melanogaster.
The Drosophila methuselah (mth) mutant has an approximately 35 percent increase in average lifespan, and enhanced resistance to various forms of stress, including starvation, high temperature, and dietary paraquat. To examine the transcriptional regulation of mth, we used luciferase assays employing Drosophila S2 cells. Two positive control elements were found at -542 to -272 (PE1) and +28 to +217 (PE2), where putative binding sites for transcription factors including Dorsal (Dl) were identified. Cotransfection of a Dl expression plasmid with a mth-luciferase reporter plasmid resulted in decreased reporter activity. PE1 and PE2, the minimal elements for strong promoter activity, were required for maximal repression by Dl protein. The N-terminal Rel homology domain (RHD) of Dl was not sufficient for repression of mth. We demonstrated by chromatin affinity precipitation (ChAP) assays in S2 cells that Dl bound to the putative PE1 binding site. Unexpectedly, semi-quantitative RT-PCR analysis revealed that the level of mth transcripts was reduced in dl flies. However, the in vivo result support the view that mth expression is regulated by dl, since it is well known that Dl functions as both a transcriptional activator and repressor depending on what other transcription factors are present. These findings suggest that both innate immunity and resistance to stress are controlled by Dl protein.


Steroid-independent translocation of the glucocorticoid receptor by the antidepressant desipramine.
The glucocorticoid receptor (GR) is a ligand-regulated transcription factor that in its unactivated form resides primarily in the cytoplasm. After being bound by steroid, the GR undergoes a conformational change and translocates to the nucleus, where it influences gene transcription. Because the GR mediates negative feedback exerted by circulating glucocorticoid hormones on the hypothalamic-pituitary-adrenal (HPA) axis, it has been hypothesized that abnormalities in GR expression and/or function may underlie the HPA axis hyperactivity described in patients with major depression. In further support of this hypothesis, animal studies have shown that long term in vivo treatment with antidepressants enhances glucocorticoid feedback inhibition, possibly through a direct effect on the GR. To examine this latter possibility, we evaluated translocation of the GR from the cytoplasm to the nucleus after 24-hr in vitro treatment of L929 cells (mouse fibroblasts) with the tricyclic antidepressant desipramine (0.1-10 microM) in the presence or absence of the synthetic steroid dexamethasone. In addition, GR-mediated gene transcription was measured with the use of L929 cells stably transfected with the mouse mammary tumor virus-chloramphenicol acetyltransferase reporter gene. Desipramine was found to (i) induce GR translocation from the cytoplasm to the nucleus in the absence of steroids (with no effect alone on GR-mediated gene transcription) and (ii) potentiate dexamethasone-induced GR translocation and dexamethasone-induced GR-mediated gene transcription. Treatment with desipramine for 24-96 hr had no effect on the expression of GR protein as measured by cytosolic radioligand receptor binding. We suggest that one important aspect of the effects of antidepressants in vivo may be to facilitate GR-mediated feedback inhibition on the HPA axis, by facilitating GR translocation and function, and thereby reverse glucocorticoid hypersecretion in depression.


Challenges of introducing participant observation to community health research.
Participant observation elicits unique observation data from both an insider's and an outsider's perspectives. Despite the growing tendency to adopt participant observation strategies in health care research regarding health-related beliefs and types of behavior, the use of participant observation in current research is mostly limited to structured clinical settings rather than community settings. In this paper, we describe how we use participant observation in a community health research study with Chinese-born immigrant women. We document discrepancies between these women's beliefs and types of behavior regarding health and health promotion. We further discuss the ethnical, time, and setting challenges in community health research using participant observation. Possible solutions are also discussed.


First report of Rhizoctonia solani AG-4 HGI Causing Stem Canker on Fagopyrum tataricum (Tartary buckwheat) in China.
Tartary buckwheat (Fagopyrum tataricum) is an ideal functional food source, which is well known to be gluten-free and rich in proteins, fats, vitamins, minerals, and flavonoids of various pharmaceutical uses, such as rutin, quercitin and epicatechin (Zhou, M et al. 2018). The Rhizoctonia solani AG-4 HGIII causing severe canker disease was first isolated from common buckwheat (F. esculentum) in Inner Mongolia of China (Zhou, H et al. 2015). In 2018, sunken lesion and dark brown symptoms were observed on the root and stem of ten days old Tartary buckwheat in Liangshan (28°21'N, 103°19''E), Sichuan Province and Fenghuang (28°19' N, 109°48' E), Hunan Province in China. In the beginning, water soaked spots appeared on the stem base, where gradually became rotten and necrotic, finally resulting in the damping-off and death of buckwheat seedlings. This disease had over 40% incidence and lead to serious losses to the buckwheat production in 2018. To isolate the pathogens on Tartary buckwheat, ten plants with typical symptoms were collected from each location. The infected tissue was taken and cut into 3mm pieces from the margin between healthy and diseased tissue, surface sterilized with 1% sodium hypochlorite solution for 4 min, washed three times with sterile distilled water, dried on sterilized filter paper and then placed on potato dextrose agar (PDA) with 100 mg/ml streptomycin sulfate. After incubation at 28℃ in the dark for 2 days, mycelial tips of four fungal cultures were transferred to PDA plates for purification. Initially, colonies were pale white, and then turned brown after 2 days incubation. The mycelium was hairy and concentrically whorled in the culture medium. Microscopic observation showed that the hyphae characteristically branched at right angles and had constriction at the base of hyphal branches. Nuclear staining showed that the hyphae cells were multinuclear. These morphological features revealed that the isolates belonged to R. solani (Sneh et al. 1991). Subsequently, the ribosomal DNA (rDNA) internal transcribed spacer (ITS) region of one isolate was amplified by PCR (White et al. 1990) and sequenced (GeneBank accession no. MT078642) by Shanghai Majorbio Bio-pharm Technology Co.,Ltd. DNA was extracted by Fungal genomic DNA Extraction Kit, D3390-02, OMEGA. The BLAST similarity analysis showed a 99.96% match with R. solani AG-4 HGI (GenBank accession no. JQ343830) and 99.85% identity to R. solani AG-4 HGI isolate SX-8 (GenBank accession no. KJ170346) (Suli, Sun et al. 2015). Furthermore, the phylogenetic analysis performed by the neighbour-joining method (MEGA 7 software) showed that the isolate was clearly clustered with the group of R. solani AG-4 HGI (Ireland et al. 2015). Pathogenicity was tested in the greenhouse condition to satisfy Koch's postulates. Tartary buckwheat plants of seven days old and fifty days old were respectively inoculated near the base of the stem neck with one mycelial plug contacted directly. Ten plants in a pot were inoculated as one treatment, four pots were used for replicates. Control plants were inoculated with PDA medium plugs without fungi. All the plants were kept at 26℃ with 14 h light, 10 h dark and 96% humidity. After five days (Suli, Sun et al. 2015), over 90% of the inoculated plants exhibited necrotic brown lesions on stems that was similar to those symptoms observed in the field, whereas control plants remained asymptomatic. The visible characteristics and ITS sequence of the pathogen re-isolated from symptomatic plants were in accordance with the original isolate (R. solani AG-4 HGI). Based on disease symptoms in the fields, morphological characteristics, ITS sequence analysis, and pathogenicity assay, we concluded that R. solani AG-4 HGI was the principle cause of Tartary buckwheat blight in Liangshan, Sichuan Province and Fenghuang, Hunan Province in China. Previously, R. solani AG-4 HGI has been identified as a Chinese chive pathogen (Shi, Y et al. 2017). To the best of our knowledge, this is the first report of the natural occurrence of Rhizoctonia solani AG-4 HGI affecting Tartary Buckwheat in China. This finding is helpful for the early diagnosis and identification of the disease, which will be the guiding of effective control methods to the devastating disease at the early stage.


Preparation of Esterified Bacterial Cellulose for Improved Mechanical Properties and the Microstructure of Isotactic Polypropylene/Bacterial Cellulose Composites.
Bacterial cellulose (BC) has great potential to be used as a new filler to reinforce isotactic polypropylene (iPP) due to its high crystallinity, biodegradability, and efficient mechanical properties. In this study, esterification was used to modify BC, which improved the surface compatibility of the iPP and BC. The results indicated that the cellulose octoate (CO) changed the surface properties from hydrophilic to lipophilic. Compared to the pure iPP, the tensile strength, charpy notched impact strength, and tensile modulus of the iPP/BC composites increased by 9.9%, 7.77%, and 15.64%, respectively. However, the addition of CO reinforced the iPP/CO composites. The tensile strength, charpy notched impact strength, and tensile modulus of the iPP/CO composites increased by 14.23%, 14.08%, and 17.82% compared to the pure iPP. However, the elongation at break of both the composites is decreased. The SEM photographs and particle size distribution of the composites showed improvements when the change of polarity of the BC surface, interface compatibility, and dispersion of iPP improved.


[An information extraction method of spectral images based on 3D spectral angle statistics].
A novel information extraction method of spectral images based on 3D spectral angle statistics is proposed. By computing the spectral angle between adjacent pixels of the image in the horizontal, vertical and diagonal direction respectively, a 3D information statistical model was then constructed. This model reflects the similarity between adjacent pixels which represent some kind of materials. Uniform areas and edge information of the same material, which will be used for the training sample collection in supervised classification, can be extracted from the image if different threshold values are set and slices are extracted from different axes in the statistical model. Compared with the traditional statistical tools, such as the histogram and scatter diagram, this statistical method has higher robustness and reliability. And it can obtain more information extracted from the spectral images.


MicroRNAs and other non-coding RNAs as targets for anticancer drug development.
The first cancer-targeted microRNA (miRNA) drug - MRX34, a liposome-based miR-34 mimic - entered Phase I clinical trials in patients with advanced hepatocellular carcinoma in April 2013, and miRNA therapeutics are attracting special attention from both academia and biotechnology companies. Although miRNAs are the most studied non-coding RNAs (ncRNAs) to date, the importance of long non-coding RNAs (lncRNAs) is increasingly being recognized. Here, we summarize the roles of miRNAs and lncRNAs in cancer, with a focus on the recently identified novel mechanisms of action, and discuss the current strategies in designing ncRNA-targeting therapeutics, as well as the associated challenges.


Crohn's disease with persistence of Clostridium difficile, surgical elimination.
Clostridium difficile has been associated with increased activity of Crohn's disease in some patients, and in them its eradication has proved beneficial. We have seen a patient unresponsive to two courses of vancomycin with persistence of C. difficile colonization and toxin production in whom surgical intervention eliminated the C. difficile cytotoxin and organism.


102T/C polymorphism of serotonin receptor type 2A gene is not associated with schizophrenia in either Chinese or British populations.
Several pieces of evidence implicate serotonin receptors in the aetiology of schizophrenia, and recently a number of studies have reported a genetic association between the 102T/C polymorphism of serotonin receptor type 2A gene and schizophrenia. Unfortunately a number of failures to replicate these positive associations in both Caucasian and Chinese populations have also been reported. We have examined the 102T/C polymorphism by PCR amplification and restriction analysis of DNA from: 202 schizophrenics and 202 controls from Shanghai; 112 schizophrenics and 224 parents from Chengdu, Cina; and 253 schizophrenics and 244 controls from the the UK. We find no evidence of association or transmission disequilibrium between the 102T/C polymorphism and schizophrenia in any of the groups we have examined. We conclude that either the original positive reports occurred by chance or any effect must be minimal, and urge caution in interpreting small positive results derived using data from different centres.