Men's sexual issues after breast cancer in their wives: a qualitative study.
Husbands of women with breast cancer may experience problems in their sexual relationships with their wives. Adjustment to sexual issues can be affected by cultural norms and beliefs. Understanding men's perceptions and responses to their new sexual status after diagnosis of their wife's disease and during its treatment may help clinicians to better support the couple. The objective of this study was to explore the sexual issues of Iranian men after breast cancer in their wives. A qualitative research method based on the grounded theory approach was used. In-depth interviews were conducted with a purposive sampling of Iranian men experiencing breast cancer in their wives. Data analysis was based on the constant comparative method. Eighteen men were interviewed. Five main themes emerged: sexual relationship changes, sexual avoidance, sexual abstinence, sexual restraint, and efforts to normalize the relationship. The participants experienced problems in their sex lives. Because cultural and religious beliefs were important factors affecting the men's sexual adjustment, health system providers should encourage husbands to tolerate and adjust to their sexual issues in the context of their culture and religion. The findings of this study could help nurses and other healthcare professionals recognize sexual issues in the husbands of women with breast cancer and promote the couples' healthy sexual life.


Tarsal-related cysts: Different diagnoses with similar presentations.
To study different tarsal cysts that share similar presentations and are commonly misdiagnosed clinically as a chalazion. A retrospective review of medical charts of all consecutive patients who presented eyelid tarsal-related pathology that needed surgical excision between 2010 and 2016 to a tertiary hospital was done. The data collected included preoperative, intraoperative and postoperative observations. Complete ophthalmologic examination at presentation, surgical procedures needed, complications, histopathological findings, response to treatment and follow-ups were recorded. Out of 850 patients who had an eyelid tarsal-related pathology, ten patients were found to have an eyelid cystic lesion related to the tarsus. All patients presented with an eyelid mass with no sign of local inflammation. All lesions were fixed to the tarsus with freely mobile overlying skin. Five patients had a recurrent lesion that was misdiagnosed and surgically treated as a chalazion. All patients underwent a surgical removal of these cysts, and a histopathological examination was performed. An intratarsal keratinous cyst was found in six patients and epithelial inclusion cyst was in one patient. Two patients found to have cystic structure lined by double cuboidal epithelium with numerous goblet cells consistent with benign lacrimal duct cyst (Dacryops). Cysts related to the tarsal plate could have similar presentations. Careful clinical evaluation and histopathological examination play an important role in giving the right diagnosis and in providing the appropriate management.


[Characteristics of heroin dependent patients admitted to a methadone treatment program].
Methadone is largely used as the primary opioid substitution therapy for the treatment of heroin addiction; the objective of the study was to describe the clinical characteristics of heroin abusers admitted into a methadone maintenance program (MMP) in metropolitan Barcelona. Cross-sectional study in patients enrolled in MMP since its introduction in 1992 through December 2010. Socio-demographic data, drug use characteristics, prevalence of blood-borne infections (human immunodeficiency virus [HIV], and hepatitis B [HBV] and C [HCV]) and psychiatric co-morbidity were assessed at entry. One thousand and six hundred seventy eight patients (82.8% male). A total of 608 (36.2%) patients were admitted during 1992-1996, 566 (33.7%) between 1997-2001, 305 (18.2%) between 2002-2006 and 199 (11.9%) in the last period. Age at admission to methadone increased significantly (28 years in period 1992-1996 vs. 37 years in the last period [P<.005]). The percentage of patients with a history of intravenous drug use decreased significantly (89.5% in first period vs. 56.4% in period 2007-2010 [P<.05]). Prevalence of HIV, HCV and HBV (HBcAb+) was 53.7, 73.6 and 61.3%, respectively. The prevalence of HIV decreased over time from 66.2% in first period to 43.5% in 2007-2010 (P<.05); the prevalence of HCV decreased significantly from 82.8% in 1992-1996 to 69.8% in last period (P<.05). Twenty five percent of patients had psychiatric co-morbidity at admission and the prevalence of psychiatric co-morbidity increased over time (21% in 1992-1996 and 32% in 2007-2010; P<.05). Age at first opioid substitution therapy is increasing over time, as well as the proportion of patients with psychiatric co-morbidity. There were significant reductions in blood-borne infections.


Synthesis and activity of novel 16-dehydropregnenolone acetate derivatives as inhibitors of type 1 5α-reductase and on cancer cell line SK-LU-1.
Testosterone (T) plays a crucial role in prostate growth. In androgen-dependent tissues T is reduced to dihydrotestosterone (DHT) because of the presence of the 5α-reductase enzyme. This androgen is more active than T, since it has a higher affinity for the androgen receptor (AR). When this mechanism is altered, androgen-dependent diseases, including prostate cancer, could result. The aim of this study was to synthesize several 16-dehydropregnenolone acetate derivatives containing a triazole ring at C-21 and a linear or alicyclic ester moiety at C-3 of the steroidal skeleton. These steroids were designed as potential inhibitors of the activity of both types (1 and 2) of 5α-reductase. The cytotoxic activity of these compounds was also evaluated on a panel of PC-3, MCF7, and SK-LU-1 human cancer cell lines. The results from this study showed that with the exception of steroids 20-oxo-21-(1H-1,2,4-triazole-1-yl)pregna-5,16-dien-3β-yl-propionate and 20-oxo-21-(1H-1,2,4-triazole-1-yl)pregna-5,16-dien-3β-yl-pentanoate, the compounds exhibit a lower inhibitory activity for both isoenzymes of 5α-reductase than finasteride. Furthermore the 3β-hydroxy-21-(1H-1,2,4-triazole-1-yl)pregna-5,16-dien-20-one and 20-oxo-21-(1H-1,2,4-triazole-1-yl)pregna-5,16-dien-3β-yl-acetate derivatives display 80% cytotoxic activity on the SK-LU-1 cell line. These results also indicated that the triazole derivatives, which have a hydroxyl or acetoxy group at C-3, could have an anticancer effect, whereas the derivatives with a alicyclic ester group at C-3 do not show biological activity.


Amino acid and 22Na+ uptake in membrane vesicles from confluent simian virus 40 transformed Balb/c3T3 and Balb/c3T3.
The studies reported here were carried out to characterize further previously described changes in membrane localized amino acid transport associated with simian virus 40 transformation of the mammalian cell line, Balb/c3T3. Membrane vesicles were prepared from confluent cultures of both simian virus 40 transformed Balb/c3T3 (SV3T3) and the untransformed parent line, Balb/c3T3 (3T3). An initial, externally imposed out greater than in, 100 mM a+ gradient produces acceleration of early ingress of alpha-aminoisobutyric acid (AlB) in vesicles from both cell lines, but transient, concentrative uptake (overshooting) only in SV3T3 vesicles. Early ingress of L-leucine is also accelerated in SV3T3 vesicles by a Na+ gradient, and overshooting is also demonstrable. Na+-gradient independent AIB permeability of SV3T3 and 3T3 membranes was estimated using uptake data, a first order rate equation and measurements of vesicle size derived from quasi-elastic light-scattering studies. AIB permeability of SV3T3 membranes is greater than that of 3T3 membranes (113 A/min and 43 A/min, respectively), suggesting that overshooting in 3T3 vesicles is not attenuated by a Na+-independent AIB "leak". Na+ permeability of the two membranes is similar, ruling out the possibility that a slower rate of Na+ equilibration across the SV3T3 membrane allows development of the overshoot. In SV3T3 vesicles the height of a Na+-gradient dependent overshoot varies with the initial [Na+]o/[Na+]i ratio, and ln[Na+]o/[Na+]i is linearly related to ln AIB uptake at overshoot peak/AIB uptake at equilibrium, consistent with the possibility that for [Na+]o/[Na+]i ratios in the range studied, AIB overshoot is energized by a constant proportion of the energy available from the initial electrochemical gradient for Na+. These results are consistent with the possibility that Na+-gradient dependent overshooting in SV3T3 vesicles is produced by Na+-amino acid carrier interactions resulting in either an increase in maximum transport velocity or an increase in carrier affinity for AIB.


A Metagenomic and Amplicon Sequencing Combined Approach Reveals the Best Primers to Study Marine Aerobic Anoxygenic Phototrophs.
Studies based on protein-coding genes are essential to describe the diversity within bacterial functional groups. In the case of aerobic anoxygenic phototrophic (AAP) bacteria, the pufM gene has been established as the genetic marker for this particular functional group, although available primers are known to have amplification biases. We review here the existing primers for pufM gene amplification, design new ones, and evaluate their phylogenetic coverage. We then use samples from contrasting marine environments to evaluate their performance. By comparing the taxonomic composition of communities retrieved with metagenomics and with different amplicon approaches, we show that the commonly used PCR primers are biased towards the Gammaproteobacteria phylum and some Alphaproteobacteria clades. The metagenomic approach, as well as the use of other combinations of the existing and newly designed primers, show that these groups are in fact less abundant than previously observed, and that a great proportion of pufM sequences are affiliated to uncultured representatives, particularly in the open ocean. Altogether, the framework developed here becomes a better alternative for future studies based on the pufM gene and, additionally, serves as a reference for primer evaluation of other functional genes.


Racial/Ethnic Pay Disparities among Registered Nurses (RNs) in U.S. Hospitals: An Econometric Regression Decomposition.
To detect the presence of racial and ethnic pay disparities between minority and white hospital RNs using a national sample. The National Sample Survey of Registered Nurses, 2008, which is representative at both the state and national level. Cross-sectional data were analyzed using multivariate regression and regression decomposition. Differences between groups were decomposed into differences in the possession of characteristics and differences in the value of the same characteristic between different groups, the latter being a commonly used measure of wage discrimination. As the majority of minority hospital RNs are employed within the most densely populated (central) counties of metropolitan statistical areas (MSAs), only hospital RNs employed in the central counties of MSAs were selected. Regression decomposition found that black and Hispanic RNs earned less than whites and Asians, while Asian RNs earned more than white RNs. The majority of pay variation between white RNs, versus Asian, black, or Hispanic RNs was due to unexplained differences in the value of the same characteristic between groups. Differences in earnings between underrepresented and overrepresented hospital RNs is suggestive of discrimination.


Author Correction: Increased autophagy in EphrinB2-deficient osteocytes is associated with elevated secondary mineralization and brittle bone.
An amendment to this paper has been published and can be accessed via a link at the top of the paper.


Binding characteristics of delta opioid receptors in different regions of the brain of young and old male rats as studied with the highly selective ligand [D-Pen2-D-Pen5] enkephalin.
The present experiments were performed to study the binding characteristics of delta opioid receptors in membrane preparations obtained from the brain of adult male rats, and to analyze whether aging modifies these binding parameters. The binding characteristics of delta opioid receptors were evaluated on membrane preparations derived from dissected brain regions (hypothalamus, amygdala, mesencephalon, corpus striatum, hippocampus, thalamus, frontal poles, anterior and posterior cortex) collected from male rats of 3 and 24 months of age; the highly selective ligand 3H-[D-Pen2-D-Pen5] enkephalin (3H-DPDPE) was used. The results obtained in young rats show that the distribution of delta opioid receptors is different in the various brain areas examined; these receptors appear to be maximally concentrated in the frontal poles, anterior and posterior cortex; lower concentrations were found in the other structures considered. Kd (dissociation constant) for the delta sites was found very similar in all areas. The distribution of delta opioid receptors in the brain of 24-month-old rats was similar to that observed in young animals; this result was surprising in view of the fact that aging modifies the number of other types of brain opioid receptors (mu and kappa).


Effects of inflammatory and anti-inflammatory environments on the macrophage mitochondrial function.
Mitochondrial response to inflammation is crucial in the metabolic adaptation to infection. This study aimed to explore the mitochondrial response under inflammatory and anti-inflammatory environments, with a focus on the tricarboxylic acid (TCA) cycle. Expression levels of key TCA cycle enzymes and the autophagy-related protein light chain 3b (LC3b) were determined in raw 264.7 cells treated with lipopolysaccharide (LPS) and metformin (Met). Additionally, reactive oxygen species (ROS) levels and mitochondrial membrane potential were assessed using flow cytometry. Moreover, 8-week-old C57BL/6J mice were intraperitoneally injected with LPS and Met to assess the mitochondrial response in vivo. Upon LPS stimulation, the expression of key TCA enzymes, including citrate synthase, α-ketoglutarate dehydrogenase, and isocitrate dehydrogenase 2, and the mitochondrial membrane potential decreased, whereas the levels of LC3b and ROS increased. However, treatment with Met inhibited the reduction of LPS-induced enzyme levels as well as the elevation of LC3b and ROS levels. In conclusion, the mitochondrial TCA cycle is affected by the inflammatory environment, and the LPS-induced effects can be reversed by Met treatment.


Differentiation in human chorionic villus cultures: hCG and HLA expression.
The present report describes methods to separate, culture, and study syncytio-cytotrophoblast and mesenchymal core of the first-trimester human chorionic villus. The cultured outer layer cells (syncytio-cytotrophoblast) are multinucleated, pleomorphic, and active in the formation of human chorionic gonadotrophin (hCG). The mesenchymal core cells are more fibroblast-like in appearance, do not show multinucleation, and have less hCG in their culture media. Both cultured cell types express HLA (ABC) Class I histocompatibility antigens but not HLA (DR) Class II antigens. These and previous studies from this laboratory postulate different embryonic origins: (1) Syncytio-cytotrophoblast cultures of chorionic villus derive from differentiated trophoblast and preserve multinucleation as well as hCG hormone function. (2) Cells cultured from the chorionic villus core originate from extraembryonic mesenchyme. (3) Amniocytes (AF cells) cultured from amniotic fluid resemble the multipotential and early-stage trophoblast, retaining pleomorphism, multinucleation, and lacunae formation as well as production of hCG, progesterone, oestrogen, basement membrane glycoprotein, and Type IV collagen. These cell types cultured from the chorionic villus and amniotic fluid provide a means for in vitro study of specific embryonic cell lineages.


Projecting demand for cardiac pacemakers.
A cardiac pacemaker implantation program involves substantial resources of money, facilities, and manpower. This paper presents a model for forecasting future numbers of implants, thus enabling the more efficient use of such resources. The model embraces both new implants and replacements, both short-term and long-term planning, and can be used with relevant data from any source.


Beta-adrenergic receptor changes in learned helplessness may depend on stress and test parameters.
Behavioral deficits following inescapable stress (learned helplessness) may serve as an animal model of depression. Previous studies using foot-shock stress to induce learned helplessness and a bar-press test for the stress-induced behavioral deficit have found increased beta-adrenergic receptor density in the hippocampus of learned helpless rats. We replicated these experiments using a tail-shock stress and the shuttle-box test. In our experiments, rats that developed learned helplessness after inescapable stress did not demonstrate any significant differences in beta-adrenergic receptor density or affinity in the frontal cortex, cerebellum, or hippocampus compared to the nonhelpless rats, nor to the tested control rats. These results suggest that beta-adrenergic receptor changes in learned helplessness may depend on the specific stress and test procedures used.


Direct and indirect effects in microcosm communities of protists.
Increased complexity in biological communities can increase the variety of interactions among species, but the relative strengths and long-term consequences of various direct and indirect interactions require further investigation. I studied interactions among four species of protists by monitoring their population dynamics when they were cultured either together or in seven different subset communities. Two protists were bacterivores (Chilomonas and Tetrahymena) and two were predators (Actinosphaerium and Euplotes). Actinosphaerium was omnivorous, and could eat both predatory Euplotes and bacterivores. Three indirect effects occurred among the four species of protists, including indirect facilitation of one predator by the other, apparent competition between bacterivores, and indirect facilitation of one bacterivore by the omnivorous predator. Community structure and invasibility depended on both direct and indirect effects; thus both can be mechanisms for assembly rules.


Socioeconomic Impact on Outcomes During the First Year of Life of Patients with Single Ventricle Heart Disease: An Analysis of the National Pediatric Cardiology Quality Improvement Collaborative Registry.
Socioeconomic status (SES) affects a range of health outcomes but has not been extensively explored in the single ventricle population. We investigate the impact of community-level deprivation on morbidity and mortality for infants with single ventricle heart disease in the first year of life. Retrospective cohort analysis of infants enrolled in the National Pediatric Cardiology Improvement Collaborative who underwent staged single ventricle palliation examining mortality and length of stay (LOS) using a community-level deprivation index (DI). 974 patients met inclusion criteria. Overall mortality was 20.5%, with 15.7% of deaths occurring between the first and second palliations. After adjusting for clinical risk factors, the DI was associated with death (log relative hazard [Formula: see text] = 8.92, p = 0.030) and death or transplant (log relative hazard [Formula: see text] = 8.62, p = 0.035) in a non-linear fashion, impacting those near the mean DI. Deprivation was associated with LOS following the first surgical palliation (S1P) (p = 0.031) and overall hospitalization during the first year of life (p = 0.018). For every 0.1 increase in the DI, LOS following S1P increased by 3.35 days (95% confidence interval 0.31-6.38) and total hospitalized days by 5.08 days (95% CI 0.88-9.27). Community deprivation is associated with mortality and LOS for patients with single ventricle congenital heart disease. While patients near the mean DI had a higher hazard of one year mortality compared to those at the extremes of the DI, LOS and DI were linearly associated, demonstrating the complex nature of SES factors.


Point-of-care (POC) devices by means of advanced MEMS.
Microelectromechanical systems (MEMS) have become an invaluable technology to advance the development of point-of-care (POC) devices for diagnostics and sample analyses. MEMS can transform sophisticated methods into compact and cost-effective microdevices that offer numerous advantages at many levels. Such devices include microchannels, microsensors, etc., that have been applied to various miniaturized POC products. Here we discuss some of the recent advances made in the use of MEMS devices for POC applications.


The prevalence and effects of treatments of rapidly progressive interstitial lung disease of dermatomyositis/polymyositis adults: A systematic review and meta-analysis.
Rapidly progressive interstitial lung disease (RP-ILD) clearly harms the prognoses of dermatomyositis/polymyositis (DM/PM) patients, however there is a dearth of numerical prevalence and therapy comparison in this field. Therefore, the purpose of this study was to determine the prevalence of RP-ILD in DM/PM patients and compare prognoses, including remission rate and survival data, between treatments. Studies with reports of RP-ILD in DM/PM patients and studies with definite remission and/or survival data of DM/PM-RP-ILD were included in the study. Data sources were Pubmed, Embase, and Cochrane Library without language restrictions. Two authors (WHL and WWQ) extracted independently the data. Estimates of the pooled effects were calculated using the Mantel-Haenszel technique (random effects). The prevalence meta-analysis included 18 papers with 6058 DM/PM patients, and 31 papers were analyzed for treatment effects, including remission rate, 6-month survival rate, 1-year survival rate, and 5-year survival rate. Database search yielded 1816 articles. In the DM/PM population, the combined prevalence of RP-ILD was 8.9% (95% CI, 5.8% to 12.1%). Patients with RP-ILD have a remission rate of 58.4% (95% CI, 47.3% to 69.4%), with biologic treatment with the highest remission rate, followed by triple therapy (defined as adding a third intravenous medication, including cyclophosphamide and immunoglobulin). Biologics therapy had the highest overall survival rate at six months (95% CI, 49.8% to 73.9%), followed by cDMARDs, plasma exchange, and triple therapy. The 1-year survival rate was 77.4% (95% CI, 66.7% to 88.1%), and triple therapy and cDMARDs had the best survival rates. The 5-year survival rate was 40.0% (95% CI, 10.0% to 69.9%). The prevalence of RP-ILD in DM/PM was approximately 8.9%, with a poor long-term prognosis. The use of biological agents appears to provide the best therapeutic outcomes, providing RP-ILD management with a novel evidence-based therapy. The use of strong immunosuppressive treatments may result in life-threatening side effects, thus clinicians must closely monitor the condition.


Determination of factors associated with perforation in patients with geriatric acute appendicitis.
Recognition and management of abdominal emergencies in geriatric patients are more complicated compared to the younger population. We aimed to investigate the demographic characteristics of geriatric patients diagnosed with acute appendicitis and to investigate the factors associated with perforation in the early stages in this study. After obtaining local ethical committee approval, patients 65 years and older who had appendectomy between January 2015 and December 2019 were included the study. Demographic data of the patients, physical examination findings, and laboratory results were analyzed. Patients were divided into two groups based on surgical reports: Perforated and simple appendicitis. During the study period, 72 patients were evaluated. In our study, 48.6% of the patients were male, and the median age was 71.5 years (IQR 25-75, 68-80). Perforated appendicitis was detected in 28% of the patients. We were determined that the vast majority of patients with perforated appendicitis were male; had more frequent chronic kidney disease and post-operative local complications; had increased leukocytes, neutrophils, blood urea nitrogen, creatinine, and total bilirubin; and had reduced albumin; and these differences were statistically significant (all values p<0.05). Multivariate analysis shows increased neutrophil count and male sex was significantly associated with perforated appendicitis (p=0.035 and p=0.01, respectively). Geriatric patients with chronic kidney disease can be at higher risk of perforated appendicitis due to inadequate abdominal physical examination results. In addition, male gender and an elevated neutrophil count are independent predictors of perforation.


Intra- and Perioperative Complications Associated with Endoscopic Spine Surgery: A Multi-Institutional Study.
To report on intra- and perioperative complications associated with working channel endoscopic spine surgery. This study is a retrospective chart review of a multi-institutional patient cohort operated on by surgeons within the Endoscopic Spine Study Group between May 2010 and June 2017. Our study cohort consists of a total of 553 consecutive cases with an average age of 57 years. The most common procedure was an endoscopic discectomy (n = 377, 68%) followed by foraminotomy (n = 156, 28.2%), unilateral laminotomy for bilateral decompression (n = 55, 9.9%), and lateral recess decompression (n = 29, 5.2%). Overall, the rate of intra- and perioperative complications was 2.7%. There were 3 durotomies (0.54%), 2 epidural hematomas (0.36%), 2 patients developed a complex pain disorder (0.36%), 4 recurrent disc herniations within 3 months (1.1%), 4 systemic complications (1.1%), and no wound infections. No risk factors were identified with regards to age, sex, approach, or number of segments. Endoscopic spine surgery is associated with a favorable rate of intra- and perioperative complications compared with reported rates of minimally invasive ortraditional open spine surgeries. Our report proposes safe and effective strategies for management of these complications.


Motility of rat ascites hepatoma cells, with reference to malignant characteristics in cancer metastasis.
The motility of four strains of rat ascites tumor cells in an agar medium was studied quantitatively by means of time lapse cinematography. The motility of these cells differed characteristically with each strain. Yoshida sarcoma and AH-66F cells showed active locomotion and partial movement markedly, while AH-130 and AH-100B cells made no locomotion and only a slight movement.


How does debt shape health outcomes for older Americans?
The deleterious effects that debt can have on health outcomes are well documented, yet comprehensive studies of the debt-health link for older adults remain limited even as their indebtedness has increased dramatically in recent decades. Additionally, the literature cannot explain the causal pathway linking poor health with debt. Using data from the Health and Retirement Study (1998-2016), we examine a range of physical and mental health measures and assess how they may be shaped by the amount and type of debt held by older adults. To address the likely endogeneity of debt and health, we employ marginal structural models, developed specifically as an identification strategy in the presence of possible endogeneity, alongside population-averaged models that allow us to compare outcomes for populations with and without debt without relying on unverifiable assumptions regarding the underlying population distribution as is the case with random- and fixed-effects models. Findings indicate that carrying any debt has a negative effect on a range of health outcomes for older adults, including objective and subjective physical and mental health. In addition, the more debt older adults carry, the more detrimental it is for their health. Finally, the type of debt matters: while secured debt has a limited, if any, negative impact on health outcomes, unsecured debt has a substantial negative impact on health. Policymakers should design policies that promote the prudent use of debt and discourage carrying large debt burdens, especially unsecured debt, into retirement as this would promote better health outcomes for older Americans.


Economic burden of adult patients with β-thalassaemia major in mainland China.
β-thalassaemia major poses a substantial economic burden, especially in adults. We aimed to estimate the economic burden of adult patients with β-thalassaemia major from a societal perspective using the real-world data. According to the clinical guideline, we also estimated the annual medical costs for patients with the same body weight and calculated the lifetime medical costs over 50 years in mainland China. This was a retrospective cross-sectional study. An online survey with snowball sampling covering seven provinces was conducted. We extracted patient demographics, caregiver demographics, disease and therapy information, caring burden, and costs for adult patients diagnosed with β-thalassaemia major and their primary caregivers. In the real world, we estimated the annual direct medical cost, direct nonmedical cost, and indirect cost. In addition, we calculated the annual direct medical cost and lifetime direct medical cost by weight with discounted and undiscounted rates according to the clinical guideline. Direct medical costs was the main driver of total cost, with blood transfusion and iron chelation therapy as the most expensive components of direct medical cost. In addition, adult patients with β-thalassaemia major weighing 56 kg were associated with an increase of $2,764 in the annual direct medical cost using the real-world data. The undiscounted and discounted (5% discount rate) total lifetime treatment costs were $518,871 and $163,441, respectively. Patients with β-thalassaemia major often encounter a substantial economic burden in mainland China. Efforts must be made to help policymakers develop effective strategies to reduce the burden and pevalence of thalassaemia.


Identification of serine protease as a major allergen of Curvularia lunata.
Several proteins from Curvularia lunata have been identified as important fungal allergens. It will be worthwhile to study the functional aspects of these allergens. The present study aimed at purifying a major allergen and determining its biological function. Concanavalin A and Superdex 75 were used to purify Cur l 1 major allergen from C. lunata. Cur l 1 activity was determined qualitatively and quantitatively. Serine protease inhibitors and specific substrate was used to determine the biological function of the protein. Concanavalin A-bound fraction showed five allergenic proteins, which on Superdex G-75 purification gave a homogenous Cur l 1 protein. Cur l 1 showed IgE reactivity with 80% of the C. lunata hypersensitive patient's sera indicating it to be a major allergen. It showed protease activity on different substrates. Cur l 1's amino terminal sequence, GLTQKSAPWGLGADTIVAVELDSY, showed homology with the alkaline serine protease precursor. Phenylmethylsulfonylfluoride, pefabloc, aprotinin and leupeptin inhibited 70-80% enzymatic activity of Cur l 1 and no inhibition was observed with ethylenediaminetetraacetic acid (EDTA). A dose-dependent hydrolysis of Nalpha-benzoyl-l-arginine ethyl ester-hydrochloride, a specific serine protease substrate was obtained with Cur l 1. A major glycoprotein allergen Cur l 1 was purified to homogeneity from C. lunata. Amino terminal sequence and biochemical assays identified it as a serine protease.


Efficient Inhibition of wear debris-induced inflammation by locally delivered siRNA.
Aseptic loosening is the most common long-term complication of total joint replacement, which is associated with the generation of wear debris. The purpose of this study was to investigate the inhibitory effect of small interfering RNA (siRNA) targeting tumor necrosis factor-alpha (TNF-alpha) on wear debris-induced inflammation. A local delivery of lentivirus-mediated TNF-alpha siRNA into the modified murine air pouch, which was stimulated by polymethylmethacrylate (PMMA) particles, resulted in significant blockage of TNF-alpha both in mRNA and protein levels for up to 4 weeks. In addition, significant down-regulation of interleukin-1 (IL-1) and interleukin-6 (IL-6) was observed in TNF-alpha siRNA-treated pouches. The safety profile of gene therapy was proven by Bioluminescent assay and quantitative fluorescent flux. Histological analysis revealed less inflammatory responses (thinner pouch membrane and decreased cellular infiltration) in TNF-alpha siRNA-treated pouches. These findings suggest that local delivery of TNF-alpha siRNA might be an excellent therapeutic candidate to inhibit particle-induced inflammation.


Up-regulation of tissue-type transglutaminase after traumatic brain injury.
Tissue-type transglutaminase (tTG, EC 188.8.131.52) has been implicated in various disease paradigms including neurodegenerative disease. In these studies, tTG induction after traumatic brain injury was studied using a rat cortical impact model. Using western blots, two forms of tTG protein expression were identified--an approximately 79-kDa primary form (tTG-L) and a less abundant approximately 70-kDa form (tTG-S). Both forms of tTG protein were elevated after injury. In ipsilateral cortex, peak induction of tTG-L protein [561% +/- 80% of control (n = 5)] was observed five days after injury, with expression remaining elevated after two weeks. Peak induction of tTG-S protein [302% +/- 81% of control (n = 5)] was observed three days after injury. Lesser tTG protein induction was observed in hippocampus. Northern blot analysis demonstrated two tTG transcripts in the ipsilateral cortex with peak induction of tTG-L mRNA three days after injury. However, tTG-S mRNA was not identified in control samples and only faintly detected in injured tissue. To facilitate analysis of low abundance transcripts in smaller tissue samples, a semiquantitative real-time PCR strategy was used. Semi-quantitative PCR analysis of tTG-L mRNA induction in ipsilateral cortex (peak after three days; 414% +/- 21% of control, n = 3) confirmed tTG-L mRNA induction determined by northern blot (410% of control).


Can convolutional neural networks identify external carotid artery calcifications?
We developed and evaluated the accuracy and reliability of a convolutional neural network (CNN) in detecting external carotid artery calcifications (ECACs) in cone-beam computed tomography scans. Using TensorFlow, we developed a program to identify calcification in 427 cone-beam computed tomography scans evaluated to determine the presence of ECACs. We compared the results to the findings of a human evaluator. Using an 80:20 training-to-validation ratio, we calculated the k-fold cross-validation accuracy of the initial dataset and extrapolated the F1 score and Matthews Correlation Coefficient. We calculated a k-fold cross-validation accuracy of 76%, with a recall and precision of 66% and 79%, respectively, and a combined F1 score of 0.72. We extrapolated a Matthews correlation coefficient of 0.53, showing a strong balance between confusion matrix categories. Our CNN model can reliably identify ECACs in cone-beam computed tomography scans.


The influence of traditional and new processing technologies on the structure and function of food polysaccharide.
Food processing is the method of transforming raw materials into food or food into other forms through physical or chemical technology and is an important means to extend the shelf life of food. The influence of processing technology on the structure and functional characteristics of polysaccharide was analyzed for the three aspects of dehydration processing technology, hot processing technology and new processing technology to provide reference for prolonging the shelf life of food and protecting its nutritional value.


Dechlorination of p,p'-DDTs coupled with sulfate reduction by novel sulfate-reducing bacterium Clostridium sp. BXM.
A novel non-dsrAB (without dissimilatory sulfite reductase genes) sulfate-reducing bacterium (SRB) Clostridium sp. BXM was isolated from a paddy soil. Incubation experiments were then performed to investigate the formation of reduced sulfur compounds (RSC) by Clostridium sp. BXM, and RSC-induced dechlorination of p,p'-DDT in culture medium and soil solution. The RSCs produced were 5.8 mM and 4.5 mM in 28 mM sulfate amended medium and soil solution respectively after 28-day cultivation. The p,p'-DDT dechlorination ratios were 74% and 45.8% for 5.8mM and 4.5 mM RSCs respectively at 6h. The metabolites of p,p'-DDT found in the two reaction systems were identified as p,p'-DDD and p,p'-DDE. The dechlorination pathways of p,p'-DDT to p,p'-DDD and p,p'-DDE were proposed, based on mass balance and dechlorination time-courses. The results indicated that RSC-induced natural dechlorination may play an important role in the fate of organochlorines.


The unfolded protein response in plants: a fundamental adaptive cellular response to internal and external stresses.
In eukaryotic cells, proteins that enter the secretory pathway are translated on membrane-bound ribosomes and translocated into the endoplasmic reticulum (ER), where they are subjected to chaperone-assisted folding, post-translational modification and assembly. During the evolution of the eukaryotic cell, a homeostatic mechanism was developed to maintain the functions of the ER in the face of various internal and external stresses. The most severe stresses imposed on eukaryotic cells can induce ER stress that can overwhelm the processing capacity of the ER, leading to the accumulation of unfolded proteins in the ER lumen. To cope with this accumulation of unfolded proteins, the unfolded protein response (UPR) is activated to alter transcriptional programs through inositol-requiring enzyme 1 (IRE1) and bZIP17/28 in plants. In addition to transcriptional induction of UPR genes, quality control (QC), translational attenuation, ER-associated degradation (ERAD) and ER stress-induced apoptosis are also conserved as fundamental adaptive cellular responses to ER stress in plants. This article is part of a Special Issue entitled: Translational Plant Proteomics.


[Immune functions of patients following lobectomy for lung cancers: a comparative study between video-assisted thoracoscopic surgery and posterolateral thoracotomy].
To compare acute inflammatory responses and immunosuppression to lobectomy in lung cancer patients with video-assisted thoracoscopic surgery (VATS) and posterolateral thoracotomy (PLT). A total of 103 patients who underwent either a VATS (n = 51) or a PLT (n = 52) lobectomy for early non-small cell lung cancers (NSCLC, stage I ) were recruited for this study. Blood samples of the participants were taken preoperatively and at 24 h and 72 h post-operatively for analyses of C-reactive protein (CRP), interleukin (IL)-6, IL-2 receptors (IL-2R), and serum amyloid A (SAA). Blood samples taken pre-operatively and at 2 d and 7 d post operations were also analyzed for total lymphocytes, NK cells, CD4+ T, and CD8+ T. Patients in the VATS group lost significantly less blood than those in the PLT group (P = 0.001). Patients in the PLT group had significantly higher serum SAA than those in the VATS group (P = 0. 006). Significant reduction of CD8+ T was found in the patients with PLT after operations (P < 0.01). Patients in the PLT group had significantly lower at CD8+ T 7 d post operations than those in the VATS group (P = 0.015). VATS pulmonary lobectomy is associated with reduced acute inflammatory responses and immunosuppression compared with the PLT approach.


Descending facilitation maintains long-term spontaneous neuropathic pain.
Neuropathic pain is frequently characterized by spontaneous pain (ie, pain at rest) and, in some cases, by cold- and touch-induced allodynia. Mechanisms underlying the chronicity of neuropathic pain are not well understood. Rats received spinal nerve ligation (SNL) and were monitored for tactile and thermal thresholds. While heat hypersensitivity returned to baseline levels within approximately 35 to 40 days, tactile hypersensitivity was still present at 580 days after SNL. Tactile hypersensitivity at post-SNL day 60 (D60) was reversed by microinjection of 1) lidocaine; 2) a cholecystokinin 2 receptor antagonist into the rostral ventromedial medulla; or 3) dorsolateral funiculus lesion. Rostral ventromedial medulla lidocaine at D60 or spinal ondansetron, a 5-hydroxytryptamine 3 antagonist, at post-SNL D42 produced conditioned place preference selectively in SNL-treated rats, suggesting long-lasting spontaneous pain. Touch-induced FOS was increased in the spinal dorsal horn of SNL rats at D60 and prevented by prior dorsolateral funiculus lesion, suggesting that long-lasting tactile hypersensitivity depends upon spinal sensitization, which is mediated in part by descending facilitation, in spite of resolution of heat hypersensitivity. These data suggest that spontaneous pain is present for an extended period of time and, consistent with likely actions of clinically effective drugs, is maintained by descending facilitation.


Predictive Accuracy of Frailty Tools for Adverse Outcomes in a Cohort of Adults 80 Years and Older: A Decision Curve Analysis.
To compare the predictive performance of 3 frailty identification tools for mortality, hospitalization, and functional decline in adults aged ≥80 years using risk reclassification statistics and decision curve analysis. Population-based, prospective cohort. BELFRAIL study, Belgium. 560 community-dwelling adults aged ≥80 years. Frailty by Cardiovascular Health Study (CHS) phenotype, Longitudinal Aging Study Amsterdam (LASA) markers, and Groeningen Frailty Indicator (GFI); mortality until 5.1 ± 0.25 years from baseline and hospitalization until 3.0 ± 0.25 years; and functional status assessed by activities of daily living at baseline and after 1.7 ± 0.21 years. Frailty prevalence was 7.3% by CHS phenotype, 21.6% by LASA markers, and 22% by GFI. Participants determined to be frail by each tool had a significantly higher risk for all-cause mortality and first hospitalization. For functional decline, only frail by GFI had a higher adjusted odds ratio. Harrell 's C-statistic for mortality and hospitalization and area under receiver operating characteristic curve for functional decline were similar for all tools and <0.70. Reclassification statistics showed improvement only by LASA markers for hospitalization and mortality. In decision curve analysis, all tools had higher net benefit than the 2 default strategies of "treat all" and "treat none" for mortality risk ≥20%, hospitalization risk ≥35%, and functional decline probability ≥10%, but their curves overlapped across all relevant risk thresholds for these outcomes. In a cohort of adults aged ≥80 years, 3 frailty tools based on different conceptualizations and assessment sources had comparable but unsatisfactory discrimination for predicting mortality, hospitalization, and functional decline. All showed clinical utility for predicting these outcomes over relevant risk thresholds, but none was significantly superior. Future research on frailty tools should include a focus on the specific group of adults aged ≥80 years, and the predictive accuracy for adverse outcomes of different tools needs a comprehensive assessment that includes decision curve analysis.


Cumulative influence of elastin peptides and plasminogen on matrix metalloproteinase activation and type I collagen invasion by HT-1080 fibrosarcoma cells.
HT-1080 fibrosarcoma cells express at their plasma membrane the elastin-binding protein (EBP). Occupancy of EBP by elastin fragments, tropoelastin or XGVAPG peptides was found to trigger procollagenase-1 (proMMP-1) overproduction by HT-1080 cells at the protein and enzyme levels. RT-PCR analysis indicated that elastin peptides did not modify the MMP-1 mRNA steady state levels, suggesting the involvement of a post-transcriptional mechanism. We previously reported that binding of elastin peptides to EBP induced other matrix metalloproteinases (MMP-2 and MT1-MMP) expression. Since those peptides were here found to also accelerate the secretion of urokinase from HT-1080 cells, culture medium was supplemented with plasminogen together with elastin peptides at aims to induce or potentiate MMPs activation cascades. In such conditions, plasmin activity was generated and exacerbate proMMP-1 and proMMP-2 activation. As a consequence, elastin peptides and plasminogen-treated HT-1080 cells displayed a significant type I collagen matrix invasive capacity.


Perceptions of Freshwater Algal Blooms, Causes and Health among New Brunswick Lakefront Property Owners.
Changes to water conditions due to eutrophication and climate change have resulted in the proliferation of algae blooms in freshwater and marine environments globally, including in Canadian lakes. We developed and administered an online survey to evaluate the awareness of these blooms and the perceptions of health risks in a sample of New Brunswick waterfront cottage and homeowners. The survey was distributed to lake and cottage associations in New Brunswick and was completed by 186 eligible respondents (18 years of age or older). Participants were asked about the water quality of their lake, awareness about algae blooms, sociodemographic and cottage characteristics, and to complete a self-rated measure of physical and mental health. While approximately 73% of participants reported that the quality of their lake water was good or very good, 41% indicated a concern about algae blooms. We found no differences in self-reported physical or mental health between those who were aware of algae blooms at their cottage and those who were not (p > 0.05). Participants expressed concerns about the impacts of algae blooms on the health of their pets, and wildlife. While climate change was the most frequently identified cause of algae blooms, there was substantial heterogeneity in the responses. In addition, the reporting of the presence and frequency of algae bloom varied between respondents who lived on the same lake. Taken together, the findings from our survey suggest that cottage owners in New Brunswick are aware and concerned about the impacts of algae blooms, however, there is a need to provide additional information to them about the occurrence and causes of these blooms.


Neighbourhood community life and health: A systematic review of reviews.
Neighbourhood community life has been widely recognized as an important determinant of population health. This systematic review of reviews provides an overview of the evidence for the ecological correlation between neighbourhood community life and population health. Nine databases were searched from 2008 to 2018 in order to identify systematic reviews of studies examining the association between neighbourhood community life and population health in urban neighbourhoods within the Organisation for Economic Co-operation and Development countries. Two reviewers completed selection and data extraction, then assessed the methodological quality of reviews using the Measurement Tool to Assess Systematic Reviews. We identified three high quality reviews and five of moderate quality. The reviews vary in quality of methodology, concepts, and measures. Most of the reviews examined the influence of social cohesion, social capital, and social interactions on health. Reviews found evidence supporting a consistently favourable correlation between social cohesion and physical activity, as well as a favourable trend in the relationship between social cohesion and healthy weight. They also found evidence of a favourable trend in the correlation between social capital and healthy weight. Reviews identified studies supporting a consistently favourable correlation between social interaction and depression. We identify evidence of a positive association between neighbourhood community life and several population health outcomes. Future research should define and conceptualize neighbourhood community life factors and health indicators to improve the comparison between studies and the process of evidence synthesis. This will also enable policy makers to take appropriate decisions.


A self-amplifying RNA vaccine against COVID-19 with long-term room-temperature stability.
mRNA vaccines were the first to be authorized for use against SARS-CoV-2 and have since demonstrated high efficacy against serious illness and death. However, limitations in these vaccines have been recognized due to their requirement for cold storage, short durability of protection, and lack of access in low-resource regions. We have developed an easily-manufactured, potent self-amplifying RNA (saRNA) vaccine against SARS-CoV-2 that is stable at room temperature. This saRNA vaccine is formulated with a nanostructured lipid carrier (NLC), providing stability, ease of manufacturing, and protection against degradation. In preclinical studies, this saRNA/NLC vaccine induced strong humoral immunity, as demonstrated by high pseudovirus neutralization titers to the Alpha, Beta, and Delta variants of concern and induction of bone marrow-resident antibody-secreting cells. Robust Th1-biased T-cell responses were also observed after prime or homologous prime-boost in mice. Notably, the saRNA/NLC platform demonstrated thermostability when stored lyophilized at room temperature for at least 6 months and at refrigerated temperatures for at least 10 months. Taken together, this saRNA delivered by NLC represents a potential improvement in RNA technology that could allow wider access to RNA vaccines for the current COVID-19 and future pandemics.


Construction of lacZ promoter probe vectors for use in Synechococcus: application to the identification of CO2-regulated promoters.
It was shown that the Escherichia coli lacZ gene could be expressed in the cyanobacterium Synechococcus R2 PCC7942 both as a plasmid-borne form and also integrated into the chromosome. A promoterless form of the lacZ gene was constructed and used as a reporter gene to make transcriptional fusions with cyanobacterial promoters using a shuttle vector system and also via a process of integration by homologous recombination. Synechococcus R2 promoter-lacZ gene fusions were then used to identify CO2-regulated promoters, by quantitatively assessing beta-galactosidase activity under high and low CO2 conditions using a fluorescence assay. Several promoters induced under low CO2 conditions were detected.


Culturally tailored postsecondary nutrition and health education curricula for indigenous populations.
In preparation for the initial offering of the University of Alaska Fairbanks (UAF), Interior-Aleutians Campus Rural Nutrition Services (RNS) program, a literature review was conducted to establish the need for the proposed program and to substantiate the methodology for delivering integrated, culturally tailored postsecondary education and extension to Alaska Natives and rural Alaskans. There was a striking absence of peer-reviewed journal articles describing culturally tailored postsecondary health curricula for indigenous populations. To complete and discuss a current (November 2012) literature review for culturally tailored postsecondary health curricula designed and delivered for indigenous populations. The author conducted an expanded online search that employed multiple configurations of key terms using Google and Google Scholar, as well as pertinent sources. The author located archived reports in person and contacted authors by email. The expanded search produced a modest amount of additional literature for review. A disappointing number of publications describing or evaluating culturally tailored postsecondary health curricula in mainstream institutions are available. Related resources on culturally tailored extension and resources for the development and delivery of culturally tailored nutrition and health curricula were identified. The present results demonstrate a significant absence of literature on the topic, which may or may not indicate the absence of sufficient culturally tailored postsecondary health curricula for indigenous populations. There are indications that culturally tailored postsecondary health curricula for indigenous populations have the potential to effectively address certain issues of health literacy and health disparities.


Adjuvant therapy following surgery in non-small cell lung cancer (NSCLC).
Non-small cell lung cancer (NSCLC) accounts for 80-90 % of cases of primary lung cancer. Although surgery is recommended as the primary treatment for early-stage NSCLC, the prognosis is unsatisfactory even when complete resection is achieved. Recent clinical trials have shown that postoperative adjuvant chemotherapy with cytotoxic agents, namely uracil-tegafur (UFT) for stage IA (>2 cm in diameter)-IB patients or cisplatin-based regimens for stage II-IIIA patients, improves the prognosis, and adjuvant chemotherapy is recommended as the "standard treatment of care." However, adjuvant chemotherapy provides only a modest 5-year survival benefit of 4 % and may sometimes be fatal. To improve the risk-benefit balance of adjuvant chemotherapy, targeting agents such as antibodies against vascular endothelial growth factor (VEGF) and tyrosine-kinase inhibitors of epidermal growth factor receptor (EGFR-TKIs) are being evaluated in ongoing adjuvant trials. Another promising approach may be the individualization of adjuvant chemotherapy based on biomarkers that may predict the prognosis or benefits associated with adjuvant chemotherapy. The current status and future perspectives of adjuvant chemotherapy for NSCLC are reviewed and discussed.


A meta-analysis of arable soil phosphorus pools response to manure application as influenced by manure types, soil properties, and climate.
Manure amendments to agricultural soils is an excellent opportunity for sustainable utilization of agricultural waste while providing multiple benefits to improve soil quality and increase the availability of nutrients to plants, including phosphorus (P). In this study, a meta-analysis of published data from 411 independent observations based on 133 peer-reviewed papers was performed for an in depth understanding of various factors affecting the transformation of soil P pools with manure application. Manure application increased all soil inorganic P (Pi) by 58.0%-282% and organic P (Po) by 65.0%-105%, while decreasing Po/total P (TP), compared to those in unamended soils. Manure types, soil TP, and manure application rates were the important factors that influenced soil P fractions. Elevation of soil labile Pi was more pronounced with compost application, while poultry and pig manure were more beneficial for promoting soil Pi fractions and stable Po contents compared with other manure types. The manure application rate had pronounced effect on increasing the stable Po fractions. The effects of manure application on increasing soil P fractions were greater in soils with lower TP contents as compared to that in high TP soils. Manure effects on enhancing soil labile Pi and moderately labile Pi were greater in acidic soil than that in neutral and alkaline soils. In addition, soil P fractions showed significant correlation with latitude and mean annual precipitation (MAP). By integrating the impacts of manure types, soil properties, and climate, this meta-analysis would help to develop the management of manure application in a specific region of agriculture as well as promote the interpretation of the interfering factors on the soil P fractions changes in the manure-amended soils.


Testing the Ability of Convolutional Neural Networks to Learn Radiomic Features.
Radiomics and deep learning have emerged as two distinct approaches to medical image analysis. However, their relative expressive power remains largely unknown. Theoretically, hand-crafted radiomic features represent a mere subset of features that neural networks can approximate, thus making deep learning a more powerful approach. On the other hand, automated learning of hand-crafted features may require a prohibitively large number of training samples. Here we directly test the ability of convolutional neural networks (CNNs) to learn and predict the intensity, shape, and texture properties of tumors as defined by standardized radiomic features. Conventional 2D and 3D CNN architectures with an increasing number of convolutional layers were trained to predict the values of 16 standardized radiomic features from real and synthetic PET images of tumors, and tested. In addition, several ImageNet-pretrained advanced networks were tested. A total of 4000 images were used for training, 500 for validation, and 500 for testing. Features quantifying size and intensity were predicted with high accuracy, while shape irregularity and heterogeneity features had very high prediction errors and generalized poorly. For example, mean normalized prediction error of tumor diameter with a 5-layer CNN was 4.23 ± 0.25, while the error for tumor sphericity was 15.64 ± 0.93. We additionally found that learning shape features required an order of magnitude more samples compared to intensity and size features. Our findings imply that CNNs trained to perform various image-based clinical tasks may generally under-utilize the shape and texture information that is more easily captured by radiomics. We speculate that to improve the CNN performance, shape and texture features can be computed explicitly and added as auxiliary variables to the networks, or supplied as synthetic inputs.


Evolving Genital Structures: A Deep Look at Network Co-option.
Novel body structures are often generated by the redeployment of ancestral components of the genome. In this issue of Developmental Cell, Glassford et al. (2015) present a thorough analysis of the co-option of a gene regulatory network in the origin of an evolutionary novelty.


[Acute chest syndrome as the inaugural sign of sickle cell anemia. A case report and review of the literature].
Acute chest syndrome is a frequent complication of sickle cell disease. This syndrome is characterized by recent infiltrate on chest X-ray with chest pain or fever or dyspnea. We report the case of a 26-year-old man in whom an acute chest syndrome with fat embolism was the inaugural sign of sickle cell disease. This report illustrates the frequency of potentially serious fat embolism in the acute chest syndrome and the importance of bronchoscopy and bronchoalveolar lavage (fatty macrophages) for determining the etiology of acute chest syndrome.


Successful sub-zero non-freezing preservation of rat lungs at -2 degrees C utilizing a new supercooling technology.
A lower temperature, namely below 0 degrees C, has been thought to be desirable for organ preservation because of the lower rate of metabolism; however, its benefits are still poorly understood. Supercooling is a non-freezing state of liquid below the freezing point, and the new development of a refrigerator for supercooling has now made it possible to preserve organs at sub-zero temperatures in a non-frozen state without cryoprotectants. Rat lungs were ventilated and perfused for 60 minutes in the 3 groups (n = 7 each): (1) the fresh group, in which the lungs were reperfused immediately after harvesting; (2) the 4 degrees C group, in which the lungs were stored after harvesting in ET-Kyoto solution at 4 degrees C for 17 hours before reperfusion; and (3) the supercooling group, in which lungs were preserved in ET-Kyoto solution at -2 degrees C for 17 hours. Ischemia-reperfusion injury was significantly attenuated in the supercooling group, with a decrease in the pulmonary artery pressure (p < 0.02) and weight gain (p < 0.001), and an increase in the tidal volume (p = 0.001) and arterial oxygen tension (p < 0.001) compared with the 4 degrees C group. In the supercooling group, most of these indicators were equivalent to the fresh lung, with less damage to the endothelial cells of the pulmonary arteries and higher levels of adenosine triphosphate than in the 4 degrees C group. Lungs stored using this new supercooling method of lung preservation showed better organ function than conventional storage at 4 degrees C.


Synthesis and antioxidant potential of novel synthetic benzophenone analogues.
Considering that oxidative stress is strongly implicated in the toxicity of chemotherapy, much effort is focused on the research of diverse antioxidants as protective agents. An efficient synthesis of three novel benzophenones containing 1,3-thiazol moiety (6a-c) is described. Their antioxidant power was evaluated in vitro and in three cell lines (the cancerous MCF7 and the non-cancerous hTERT-HME1 mammary cells, and the H9c2 cardiomyoblastic cells). One analogue 5-(2,5-dihydroxybenzoyl)-2(3H)-benzothiazolone (6c), displayed an important antioxidant activity, a low cytotoxicity, and could decrease reactive oxygen species production generated by tert-butyl hydroperoxide (tBHP) in all three cell lines. Interestingly, 6c was able to protect the non-cancerous cells against tBHP-induced death. Further studies are underway to determine its relevance as an adjuvant in oxidative stress inducing chemotherapy.


Comparison of effectiveness of cardiac resynchronization therapy in patients <70 versus > or =70 years of age.
In the present study, the effects of cardiac resynchronization therapy (CRT) in elderly patients were evaluated. The study included 170 consecutive patients whose clinical and echocardiographic improvements were evaluated after 6 months of follow-up. Survival was evaluated up to 2 years. The effects of CRT in elderly patients (age > or =70 years) were compared with those in younger patients (age <70 years).


Accumulation of Cd by three forage mulberry (Morus atropurpurea Roxb.) cultivars in heavy metal-polluted farmland: a field experiment.
A 3-year field experiment was conducted to evaluate the accumulation ability of 3 forage mulberry (Morus atropurpurea Roxb.) varieties (Guisangyou 62, Guisangyou 12, Yuesang 11) for Cadmium (Cd). The results showed that the shoot biomass of forage mulberry could reach to 64.51~69.58 t/ha in 2018. The total production of Guisangyou 12 was the highest among the tested 3 cultivars in each year. However, the biomass of the 3 varieties displayed without significant differences at every sampling time. In addition, the concentrations of Cd in the roots of the 3 mulberry cultivars were higher than those in the corresponding shoots in 2018. But in 2019, the Cd content in roots was near to that of shoots. The Cd concentrations in the roots of the forage mulberry showed Guisangyou 62 > Yuesang 11 > Guisangyou 12. And the Cd concentrations in shoots of all the 3 tested forage mulberry varieties were less than 1 mg/kg, meeting the hygienical standard for feeds (China). Though the 3 forage mulberry varieties were not hyperaccumulators for Cd, they could be used as alternative plants to make use of the Cd-polluted (< 1.0 mg/kg) paddy soils.


Increased Plasma Lipocalin-2 Levels in Patients with Myelin Oligodendrocyte Glycoprotein-IgG-Positive Optic Neuritis.
This study aimed to evaluate the correlation between plasma lipocalin-2 (LCN2) levels and myelin oligodendrocyte glycoprotein (MOG)-immunoglobulin G (IgG) seropositivity in patients with optic neuritis. Peripheral blood samples were collected from 19 patients with optic neuritis and 20 healthy controls. Plasma LCN2 and MOG-IgG levels were measured using enzyme-linked immunosorbent assay and a cell-based assay, respectively. The correlation between plasma LCN2 levels and MOG-IgG titers in patients with optic neuritis was analyzed. Receiver operating characteristic (ROC) curves were constructed to assess and compare the ability of plasma LCN2 and MOG-IgG levels for predicting optic neuritis recurrence. Patients with MOG-IgG-positive optic neuritis had significantly higher mean plasma LCN2 levels than controls and patients with MOG-IgG-negative optic neuritis (p = 0.037). Plasma LCN2 and MOG-IgG levels were significantly correlated in patients with optic neuritis (r = 0.553, p = 0.0141). There were no significant differences in the areas under the ROC curve (AUC) of plasma LCN2 (0.693, 95% confidence interval [CI] 0.443-0.880, p = 0.133) and MOG-IgG (0.641, 95% CI, 0.400-0.840, p = 0.298) levels (95% CI, -0.266-0.448, p = 0.618). Plasma LCN2 levels may aid differentiation of MOG-IgG-positive optic neuritis from MOG-IgG-negative optic neuritis.


A protocol of histone modification-based mechanistic study of acupuncture in patients with stable angina pectoris.
Angina pectoris (Angina) is a medical condition related to myocardial ischemia. Although acupuncture has been widely accepted as a clinical approach for angina, there is no sufficient evidence of its effectiveness against this syndrome, and its mechanisms have not yet been well elucidated. We develop this protocol to confirm the clinical efficacy of electro-acupuncture on stable angina pectoris by needling on acupoint Neiguan (PC6). Furthermore, we employ high-throughput sequencing technology to investigate the gene expression profiling and determine involvement of histone modifications in the regulation of genes after electro-acupuncture treatment. A randomized, controlled, double-blinded (assessor and patients) trial will be carried out. Sixty participants will be randomly assigned to two acupuncture treatment groups and one control group in a 1:1:1 ratio. Participants in acupuncture groups will receive 12 sessions of electro-acupuncture treatment across 4 weeks, followed by a 12-week randomization period. The acupuncture groups are divided into Neiguan (PC6) on Pericardium Meridian of Hand-jueyin or a non-acupoint. The primary clinical measure of effect is the frequency of angina attacks between these groups for four weeks after randomization. RNAs are extracted from peripheral neutrophils collected from all participants on day 0, day 30, and week 16, and are processed to RNA-Seq. We then investigate profiles of histone modifications by ChIP-Seq, for H3 Lysine 4 (H3K4me) and acetylation of H3 Lysine 27 (H3K27ac), in the presence or absence of acupuncture treatment. This study determines the efficacy and mechanisms of electro-acupuncture on stable angina pectoris. We focus on effectiveness of acupuncture on alleviating symptoms of myocardial ischemia and the gene regulation and the chromatin remodeling marks, including H3K4me1, H3K4me2, and H3K27ac, which could be key factors for regulating gene expressions caused by electro-acupuncture treatment at Neiguan. This is the first genome-wide study of electro-acupuncture treatment in angina patients, and will provide valuable information for future studies in the fields of acupuncture and its underlying mechanisms. Fourteen patients have been recruited since recruitment opened in November of 2012. This study is scheduled to end in November of 2014. ChiCTR-TRC-12002668.


Evaluation of initial dofetilide dosing recommendation based on actual body weight in overweight and obese patients.
The dofetilide label recommends using actual body weight (ABW) to calculate the Cockcroft-Gault creatinine clearance (CrCl) for the determination of the initial dose; however, few studies have attempted to evaluate this dosing recommendation in overweight and obese patients. We evaluated whether the current dofetilide dosing recommendation based on ABW is appropriate in overweight and obese patients. This is a retrospective cohort study conducted at two large academic medical centres in the United States on overweight and obese patients (body mass index ≥ 25 kg/m(2)) who were newly started on dofetilide based on ABW. Patients were categorized into (i) the different-dose group if their CrCl calculated based on the ideal body weight (IBW) resulted in a lower initial dofetilide dose compared with ABW-based CrCl and (ii) the same-dose group if they would have the same initial dose based on IBW and ABW. The primary outcome was dofetilide dose reduction or discontinuation due to prolongation of the corrected QT interval during the first 3 days of dofetilide therapy. Multivariable logistic regression analysis was performed to identify factors predicting the risk of primary outcome. Of the 132 patients included in the study, 29 (22·0%) were in the different-dose group and 40 (30·3%) had the primary outcome. The per cent of patients with the primary outcome was not statistically significantly different between the different-dose and same-dose groups (37·9% vs. 28·2%; P = 0·31). Diabetes mellitus was a significant predictor for the primary outcome (odds ratio 2·54; 95% confidence interval 1·05-6·15). Our study provides the evidence on the safety of the current dofetilide dosing recommendation in overweight and obese populations in clinical practice. Current ABW-based dofetilide dosing is reasonable in overweight and obese patients.


Impact of tumor size on the difficulty of laparoscopic left lateral sectionectomies.
Tumor size (TS) represents a critical parameter in the risk assessment of laparoscopic liver resections (LLR). Moreover, TS has been rarely related to the extent of liver resection. The aim of this study was to study the relationship between tumor size and difficulty of laparoscopic left lateral sectionectomy (L-LLS). The impact of TS cutoffs was investigated by stratifying tumor size at each 10 mm-interval. The optimal cutoffs were chosen taking into consideration the number of endpoints which show a statistically significant split around the cut-points of interest and the magnitude of relative risk after correction for multiple risk factors. A total of 1910 L-LLS were included. Overall, open conversion and intraoperative blood transfusion were 3.1 and 3.3%, respectively. The major morbidity rate was 2.7% and 90-days mortality 0.6%. Three optimal TS cutoffs were identified: 40-, 70-, and 100-mm. All the selected cutoffs showed a significant discriminative power for the prediction of open conversion, operative time, blood transfusion and need of Pringle maneuver. Moreover, 70- and 100-mm cutoffs were both discriminative for estimated blood loss and major complications. A stepwise increase in rates of open conversion rate (Z = 3.90, P < .001), operative time (Z = 3.84, P < .001), blood loss (Z = 6.50, P < .001), intraoperative blood transfusion rate (Z = 5.15, P < .001), Pringle maneuver use (Z = 6.48, P < .001), major morbidity(Z = 2.17, P = .030) and 30-days readmission (Z = 1.99, P = .047) was registered as the size increased. L-LLS for tumors of increasing size was associated with poorer intraoperative and early postoperative outcomes suggesting increasing difficulty of the procedure. We determined three optimal TS cutoffs (40-, 70- and 100-mm) to accurately stratify surgical difficulty after L-LLS.


Integrated chemiluminescence-based lab-on-chip for detection of life markers in extraterrestrial environments.
The detection of life markers is a high priority task in the exploration of the Solar System. Biochips performing in-situ multiplex immunoassays are a very promising approach alternative to gas chromatography coupled with mass spectrometry. As part of the PLEIADES project, we present the development of a chemiluminescence-based, highly integrated analytical platform for the detection of biomarkers outside of the Earth. The PLEIADES device goes beyond the current lab-on-chip approaches that still require bulky external instrumentation for their operation. It exploits an autonomous capillary force-driven microfluidic network, an array of thin-film hydrogenated amorphous silicon photosensors, and chemiluminescence bioassays to provide highly sensitive analyte detection in a very simple and compact configuration. Adenosine triphosphate was selected as the target life marker. Three bioassay formats have been developed, namely (a) a bioluminescence assay exploiting a luciferase mutant with enhanced thermal and pH stability and (b and c) binding assays exploiting antibodies or functional nucleic acids (aptamers) as biospecific recognition elements and peroxidase or DNAzymes as chemiluminescence reporters. Preliminary results, showing limits of detection in the nanomolar range, confirm the validity of the proposed approach.


Patient-specific processes for occipitocervical fixation using biomodelling and additive manufacturing.
This report describes a novel method for occipitocervical fixation using a patient-specific, 3D-printed implant and tools. A 79-year-old female presented with progressive neck pain due to a pathologic fracture of C1. DICOM data was used to 3D-print 1:1 scale biomodels of the occipitocervical spine for pre-operative planning, patient education, and intraoperative reference. The surgeon collaborated with engineers to design and 3D-print a titanium patient-specific implant (PSI) and a stereotactic drill guide for occipitocervical screw fixation. The surgical plan specified the occipitocervical "neutral" position, screw sizes, entry points, and trajectories. The PSI was pre-contoured to match the posterior occipitocervical bony spine and reproduce the planned occipitocervical "neutral" position. Stereotactic portholes for screw fixation were integrated into the PSI. The planned "neutral" position was achieved by intraoperatively matching the occipitocervical alignment to the PSI. Screw placement under fluoroscopy was simplified using the stereotactic drill guide. There were no intraoperative or postoperative complications. At 6-month follow up, our patient reported resolution of symptoms and demonstrated satisfactory occipitocervical alignment without evidence of implant dysfunction. Our experience demonstrates that preoperative planning can be combined with biomodelling and 3D-printing to develop patient-specific tools and implants that are viable for occipitocervical fixation surgery.


False-positive prostate cancer markers in a man with symptomatic urethral Chlamydia trachomatis infection.
Symptomatic male urethral Chlamydia trachomatis infection resulted in inflammation of the prostate, with associated increases in both prostate-specific (PSA) and prostate cancer-specific (PCA3) markers with prostate biopsies showing no evidence of malignancy.


A sex difference in the platelet count.
A study of the platelet counts of 868 blood donors aged 18-65 showed a higher mean count in women than in men, the difference in the premenopausal age groups being highly significant (P less than 0.001) and of the order of 40-70 x 10(9)/1. The mean counts of women taking a contraceptive pill did not differ significantly from those who were not.


Clinical review: Disorders of water homeostasis in neurosurgical patients.
Disorders of water balance are common in neurosurgical patients and usually manifest as hypo- or hypernatremia. They are most commonly seen after subarachnoid hemorrhage, traumatic brain injury, with intracranial tumors, and after pituitary surgery. We reviewed the experience of endocrine evaluation and management of disorders of salt and water balance in a large cohort of inpatients attending the national neurosciences referral centre in Dublin, Ireland, and compared this experience with findings from other studies. The study group included unselected neurosurgical patients admitted to our centre and requiring endocrine evaluation. We conducted investigations to determine the underlying mechanistic basis for disorders of salt and water balance in neurosurgical patients and treatment to restore normal metabolism. Morbidity and mortality associated with deranged salt and water balance were measured. The underlying pathophysiology of disordered water balance in neurosurgical patients is complex and varied and dictates the optimal therapeutic approach. A systematic and well-informed approach is needed to properly diagnose and manage disorders of salt and water balance in neurosurgical patients.


Evolving an integral ecology of mind.
A deliberation upon the possibility of generating a comprehensive view of 'mind as a whole' by integrating biology, psychology and sociology, and considering 'Mind' as a dynamical interplay between values existing over many levels and scales of complex systems. This view of mind as a coevolutionary whole is related to similar ecological viewpoints being developed in the fields of artificial life and multi-agent systems. A meta-model of mind is proposed which attempts to integrate the various existing views of mind from a time perspective, and positions the field in a way that we think augurs well for the potential of mind studies based upon modern complex systems science concepts.


Continuous positive airway pressure in preterm neonates: an update of current evidence and implications for developing countries.
Continuous Positive Airway Pressure (CPAP) is a cost-effective and minimal invasive respiratory support for the newborn. To review the evidence related to various aspects of CPAP usage and its applicability for developing countries. We conducted a literature search on PubMed, CENTRAL, and Cochrane Database of Systematic Reviews using the terms CPAP OR continuous positive airway pressure OR, non-invasive ventilation AND newborn OR neonate OR infant. We also searched the reference lists from the above articles and of review articles. Extracted manuscripts and reviews were analyzed and results related to various aspects of CPAP usage were summarized in narrative form. Early use of CPAP with early rescue surfactant (InSurE) is the ideal approach for management of respiratory distress syndrome in preterm and extremely preterm infants. Delivery room CPAP is feasible and reduces the need for surfactant and mechanical ventilation by nearly 50%. Prophylactic surfactant for extreme preterms should be discouraged. Heated humidified high flow nasal cannula is best utilized for post-extubation respiratory support. The search for ideal interface still continues and binasal prongs or nasal masks are the good contenders. Evidence on the ideal CPAP delivery is still inconclusive. CPAP, if used early and judiciously, is an effective intervention and need immediate scaling-up in resource-limited settings. Future research should focus on the ideal interface and the CPAP delivery methods.


How Effective Are Citizen Scientists at Contributing to Government Tree Health Public Engagement and Surveillance Needs-An Analysis of the UK Open Air Laboratories (OPAL) Survey Model.
The incidence of tree disease has been increasing in the UK in recent years as a result of a range of alien tree pests and pathogens new to the country. In the early 2010s government staff resources to monitor, identify and eradicate these pathogens were limited, so we tested the efficacy of "citizen scientists" to support these needs. The Open Air Laboratories (OPAL) is a successful citizen science programme launched in 2007, which at that time of launch involved over 650 thousand people in a range of environmental surveys. In 2012-2013, the Food and Environment Research Agency (Fera) and Forest Research staff worked with OPAL and its partners to launch a citizen science tree health survey in Great Britain and this was extended to cover Northern Ireland until it closed in 2019. Over 2800 surveys were completed including records on more than 4500 trees, the majority from urban areas. This paper discusses the results of the survey and their value for the assessment of tree health. It also considers the implications of engagement with the general public for the future of tree health surveillance. Recommendations are made for further development of the OPAL "model" and more generally for the role of citizen science in this important area.


[Peritrochanteric fractures treated with a lamina-plate with stay].
60 peritrochanteric fractures treated with a lamina-plate with stay were studied. Their socio-professional caracteristics were similar to the whole sample. The functionnal results and the Duke's score were lower than the other osteosyntheses methods, despite a low number of complications. These results could be explained by systematic early weight bearing for the patients. This causes pain which is not well endured by patients included in this study. These patients, in good general and intellectual health, are able to bear, and prefer, prolonged decubitus (without pain). But while early weight bearing is not a priority for this population, it remainds fundamental for the patients with low intellectual function, who most frequently present with this type of fracture.


Microplastics in agricultural soils on the coastal plain: Spatial characteristics, influencing factors and sources.
Farmland is a major sink for microplastics (MPs), but research on MPs in coastal plain soil, particularly their occurrence in agricultural areas with changing coastlines, is limited. Here, we investigated the distribution, influencing factors and sources of MPs in a typical agricultural county near the southeast coast of China considering different human activities and soil property changes. The average MP concentration in farmland soils was 314 items/kg, ranging from 70.2 to 851.3 items/kg. MPs increased first and then decreased from inland to the coast, and this trend was greatly affected by coastline expansion. Bulk density, clay and textile points of interest (POIs) are the major factors affecting MPs in farmland. Network analysis was used to divide the whole MP community into two modules, and the average similarity between each MP community and the other 25.5 MP communities was >0.5. Overall, the similarity of the MP community tended to decrease with increasing geographical distance (P < 0.01). In the soil environmental factors group, bulk density and clay affected the total MP abundance, accounting for 14.7 % and 9.4 % of MPs, respectively. After fitting 8 types of POIs and the total MP diversity integrated index (MDII) of farmland, washing POIs (R2 = 0.65, P < 0.01) displayed the greatest and most significant fit with MDII, followed by clothing POIs (R2 = 0.29, P < 0.01). The MDII-POI results showed that the major POI sources of soil MPs were clothing manufacturing and washing POIs. Unlike in urban areas, automobile service POIs, packaging POIs and textile POIs had no significant relationship with the MDII, which may be related to the population and economic development scale. The results emphasize the importance of investigating MP occurrence and sources in coastal agricultural areas to promote the effective management of MPs and plastic emissions in land-sea transition zones.


Prevalence of ADHD in nonpsychotic adult psychiatric care (ADPSYC): A multinational cross-sectional study in Europe.
Attention-deficit/hyperactivity disorder (ADHD) often persists into adulthood. This study was designed to estimate the prevalence of ADHD in adult psychiatric outpatients in several European countries. ADHD diagnosis was made using the Diagnostic Interview for ADHD in Adults, version 2.0 (DIVA), according to criteria of the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision (DSM-IV-TR) and 5th Edition (DSM-5). Of 5662 patients present/approached, 2284 (40.3 %) consented, of whom 1986 patients (87.0 %) completed the study. Based on the DIVA, and applying DSM-IV-TR or DSM-5 criteria, 15.8 % (95 % confidence interval [CI] 14.2 %-17.4 %) or 17.4 % (95 % CI 15.7 %-19.0 %) of patients were diagnosed with ADHD, respectively. The prevalence of ADHD was 15.3 % when counting as non-ADHD those patients who screened positive but did not complete the DIVA (DSM-5). Estimates from this study indicate that a relevant part of the psychiatric outpatient care population suffers from ADHD.


Base or nucleophile? DFT finally elucidates the origin of the selectivity between the competitive reactions triggered by MeLi or LDA on propanal.
The competition between basicity and nucleophilicity of two standard organolithium reagents was studied using DFT. Comparing the reactivity of solvated (MeLi)2 and (LDA)2 toward propanal finally explains why methyllithium adds onto the carbonyl while LDA deprotonates the α-position, in accord with experiment and Ireland's deprotonation TS.


Pat1 activates late steps in mRNA decay by multiple mechanisms.
Pat1 is a hub for mRNA metabolism, acting in pre-mRNA splicing, translation repression, and mRNA decay. A critical step in all 5'-3' mRNA decay pathways is removal of the 5' cap structure, which precedes and permits digestion of the RNA body by conserved exonucleases. During bulk 5'-3' decay, the Pat1/Lsm1-7 complex engages mRNA at the 3' end and promotes hydrolysis of the cap structure by Dcp1/Dcp2 at the 5' end through an unknown mechanism. We reconstitute Pat1 with 5' and 3' decay factors and show how it activates multiple steps in late mRNA decay. First, we find that Pat1 stabilizes binding of the Lsm1-7 complex to RNA using two conserved short-linear interaction motifs. Second, Pat1 directly activates decapping by binding elements in the disordered C-terminal extension of Dcp2, alleviating autoinhibition and promoting substrate binding. Our results uncover the molecular mechanism of how separate domains of Pat1 coordinate the assembly and activation of a decapping messenger ribonucleoprotein (mRNP) that promotes 5'-3' mRNA degradation.


Thoracoabdominal trauma in ski accidents.
Higher speed in ski sports has in recent years increased the number of thoracoabdominal injuries. Our restrospective study concerns 30 patients from the region of Chur, Switzerland, injured between 1965 and 1976. The patients were all male with an average age of 26 years. Details of the injuries, operations and treatment are given and a few typical cases are demonstrated.


Rapid test strips for analysis of mycotoxins in food and feed.
An overview is given on recent trends and applications of rapid immunodiagnostic tests for screening of food and feed for mycotoxins. Different test formats are discussed, and challenges in the development of lateral-flow devices for on-site determination of mycotoxins, with requirements such as being robust, fast, and cost-effective, are briefly elucidated.


Motor response of the human isolated colon to capsaicin and its relationship to release of vasoactive intestinal polypeptide.
The aim of this study was to obtain indirect evidence of the presence of capsaicin-sensitive afferents in the human colon by studying the motor response to capsaicin of longitudinal strips from the human isolated taenia coli in parallel to the ability of capsaicin or KCl to induce peptide release from the human superfused colon. Capsaicin (1 microM) evoked a relaxation of the taenia, approaching 60-80% of the response to isoprenaline. Tachykinins evoked contractions of the taenia, while calcitonin gene-related peptide induced a relaxation. Neither tachyphylaxis to calcitonin gene-related peptide nor preincubation with an anti-calcitonin gene-related peptide serum did block the response to capsaicin which was also unaffected by tetrodotoxin, apamin, naloxone or an anti-galanin serum. Vasoactive intestinal polypeptide produced a concentration-dependent tetrodotoxin-resistant relaxation which was shifted rightward in the presence of anti-vasoactive intestinal polypeptide serum. The anti-vasoactive intestinal polypeptide serum reduced the response to capsaicin and application of capsaicin prevented the ability of anti-vasoactive intestinal polypeptide serum to block exogenous vasoactive intestinal polypeptide. Capsaicin (1 microM) evoked a significant release of vasoactive intestinal polypeptide-like immunoreactivity from the superfused muscle but not mucosa of the human colon. A significant vasoactive intestinal polypeptide-like immunoreactivity release was also observed in response to KCl (80 mM). KCl but not capsaicin evoked a significant release of neurokinin A-like immunoreactivity from colonic muscle and mucosa. No significant release of either substance P-, neuropeptide Y-, galanin- or calcitonin gene-related peptide-like immunoreactivity was detected in response to capsaicin or KCl although detectable levels of each peptide were evident in tissue extracts.(ABSTRACT TRUNCATED AT 250 WORDS)


Perivascular nerves in the rat submandibular salivary gland.
Perivascular nerves in the rat submandibular salivary gland have been studied using a variety of histochemical procedures coupled with electron microscopy. Two principal nerve types, adrenergic and cholinergic, appear to predominate and are localized principally around arterioles. Venules are rarely innervated. The possibility that a non-adrenergic non-cholinergic nerve population might influence blood flow is discussed critically in the light of anatomical and physiological findings.


Human biomonitoring of heavy metals exposure in different age- and gender-groups based on fish consumption patterns in typical coastal cities of China.
The study aimed to investigate heavy metals (HMs) concentrations in human hair based on fish consumption patterns in Qingdao, Xiamen, and Zhoushan. The (HMs) concentrations were determined using acid digestion and an inductively coupled plasma mass spectrometer (ICP-MS, NexION 300X, PerkinElmer). The associated health risks were investigated using risk assessment models described by the United States Environmental Protection Agency (USEPA). The order of fish HMs concentration in Qingdao was Cd<Pb<As>Cr<Cu<Zn, while The in Zhoushan and Xiamen the order was Cd<Pb<Cr<Cu<As<Zn. The highest concentrations of HMs in fish were found in Zhoushan and lowest in Xiamen. Zn showed the highest values in fish, while Cd and Pb were the lowest. The Cr concentration in Scomberomorus niphonius collected in Qingdao exceeded the safety standards. The HMs in both male and female hair followed a descending order of Zn>Cu>Pb>Cr>As>Cd in all three study areas. The hair Zn concentration in 28 % of the studied population exceeded the safety standards. Overall, the hair HMs concentration was found to be high in middle-aged groups (19-45 and 45-59), and the hair HMs concentrations were high, especially in the case of females. A significant correlation was noticed between hair As (0.119; p < 0.05), Cr (0.231; p < 0.05),) and Cu (0.117; p < 0.05),) and fish consumption frequency. High Odd ratios (>2) were noticed for As, Cu and Zn in high fish-eating frequency. A significant non-carcinogenic risk was noticed in human Cr exposure (1.10E+00) in Xiamen, and the hazard index values indicated non-carcinogenic risk in Xiamen and Zhoushan. The carcinogenic risk for human As exposure (2.50E-05-7.09E-03) indicated a significant cancer risk.


KofamKOALA: KEGG Ortholog assignment based on profile HMM and adaptive score threshold.
KofamKOALA is a web server to assign KEGG Orthologs (KOs) to protein sequences by homology search against a database of profile hidden Markov models (KOfam) with pre-computed adaptive score thresholds. KofamKOALA is faster than existing KO assignment tools with its accuracy being comparable to the best performing tools. Function annotation by KofamKOALA helps linking genes to KEGG resources such as the KEGG pathway maps and facilitates molecular network reconstruction. KofamKOALA, KofamScan and KOfam are freely available from GenomeNet (https://www.genome.jp/tools/kofamkoala/). Supplementary data are available at Bioinformatics online.


Transcriptome analysis of common carp (Cyprinus carpio) provides insights into the ovarian maturation related genes and pathways in response to LHRH-A and dopamine inhibitors induction.
Luteinizing hormone-releasing hormone analog (LHRH-A) and dopamine inhibitors have been widely used to induce oocyte maturation and ovulation in domesticated fishes. Although this approach represents a reliable method for regulating fish reproduction, the underlying molecular mechanisms mediating LH action are largely unexplored. The objective of this study was to determine the transcriptional profile of gene programming in hormone-treated common carp. In the present study, female common carp were intraperitoneally injected with LHRH-A together with dopamine inhibitors, and control fish were injected with saline. Ovarian morphological changes were analysed by both light microscopy and scanning electron microscopy. Furthermore, gene expression profiling of the brain and ovarian tissues was performed by Illumina sequencing. Compared to the control carp, hormone treatment resulted in morphological changes including disappearance of nuclear membrane, breakdown of germinal vesicle (GVBD), and fusion of yolk globules, reflecting that hormones significantly promoted oocyte maturation. In comparison to control, we have identified 867 and 9,053 differentially expressed genes in the hormone-treated female brain and ovary, respectively. In the brain, most of the identified genes were significantly enriched in 18 KEGG pathways. In the ovarian tissue, the identified genes were significantly involved in 9 pathways. In the hormone-treated carp, genes were involved in calcium signalling pathway, cAMP signalling pathway, insulin secretion, and oxidative phosphorylation pathway, which showed obvious associations with ovarian maturation. The present study provides transcriptomic information for hormone-treated carp, which might be useful for studying the endocrine regulation and mechanisms of ovarian maturation in domesticated fishes.


[Interventional endovascular therapeutic modalities of giant intracranial aneurysm].
To treat 28 cases of intracranial giant aneurysms in the last 7 years and study the therapeutic methods and their effectiveness on this disease. The cases of giant aneurysms were divided into several groups. The advantages and disadvantages of the methods were compared. The main modality of endovascular therapy was to use balloon to occlude the parent artery. In the 16 cases treated by the proximal balloon occlusion, 13 were cured angiographically with complete obliteration of the aneurysmal sac and in 4 of them the aneurysms disappeared both on CT and MRI. No deterioration after operation was encountered with the exception of 2 deaths. Endovascular therapy can cure the intracranial aneurysms which were difficulty treated by direct open operation.


Deletion of arcA increased the production of acetyl-CoA-derived chemicals in recombinant Escherichia coli.
Acetyl-CoA is used to produce many valuable metabolites in Escherichia coli. However, acetate overflow is a major shortcoming. Knockout of the global regulator gene, arcA, may solve this problem. The arcA gene of E. coli BL21(DE3) was knocked out, and the production of phloroglucinol (PG) and 3-hydroxypropionate (3HP), both derived from acetyl-CoA, were used to evaluate its effect. The arcA mutants had higher cell yields and higher glucose utilization efficiencies than the corresponding control strains, and the productions of PG and 3HP were 0.92 g/l and 0.27 g/l, respectively; more than twice that of the control strains. Furthermore, arcA knockout also showed significant repression on formation of acetate, the major byproduct in fermentation. Acetate concentrations were decreased 69.4 % and 87 % by arcA knockout during the production of PG and 3HP, respectively. The arcA gene knockout is a solution to acetate overflow and may improve production of a wide range of acetyl-CoA-derived metabolites.


An iron-deficient diet prevents alcohol- or diethylnitrosamine-induced acute hepatotoxicity in mice by inhibiting ferroptosis.
The liver is easily injured by exogenous chemicals through reactive oxygen species (ROS), which lead to ferroptosis, a ROS-dependent programmed cell death characterized by iron accumulation and lipid peroxidation. However, whether iron restriction has a positive role in chemicals-induced liver injuries is unknown. The present study investigated the effects of an iron-deficient diet on liver injuries induced by alcohol or diethylnitrosamine (DEN). Mice were fed an iron-deficient diet for four weeks, then treated with three doses of alcohol (5 g/kg, 24 h interval, gavage) to mimic mild liver injury or five doses of DEN (50 mg/kg, 24 h interval, i. p.) to mimic severe liver failure. The results showed that mice were iron-deficient after four weeks of feeding. Interestingly, as evaluated by H&E staining of liver slices, liver/body weight ratio, serum ALT and AST, iron deficiency significantly alleviated liver injuries triggered by alcohol or DEN. The activities of alcohol dehydrogenase (ADH) and acetaldehyde dehydrogenase (ALDH), and the expression of CYP2E1 were increased by iron deficiency. Mechanistically, iron deficiency prevented the decrease of glutathione peroxidase 4 (GPX4), which eliminated malondialdehyde (MDA) by utilizing glutathione (GSH). In summary, alcohol- or DEN-induced liver injuries were mitigated by the iron-deficient diet by inhibiting ferroptosis, which might be a promising measure for preventing liver injuries induced by alcohol, DEN, or other exogenous chemicals.


Distribution of peripherally stained neurons by the colloidal iron histochemical method in albino rat cerebral cortex. A quantitative study.
A few stained neurons were demonstrated in several cortical areas by the Colloidal Iron method. The intense positive histochemical reaction was located surrounding the perikaryon and some neuronal branches. A quantitative study demonstrated that the largest percentage of stained neurons was found in III, IV and V layers of the visual and auditory cortex. The number of stained neurons in the auditory cortex was greater than in the visual cortex. Statistically significant differences (Student's t-test) were obtained between layers I, II, III and VI of both cortical areas. In other cortical areas studied there were no stained neurons (area insularis ventralis, area entorhinalis and area piriformis).