Dual specificity phosphatase (DUSP)-4 is induced by platelet-derived growth factor -BB in an Erk1/2-, STAT3- and p53-dependent manner.
Dual specificity phosphatase (DUSP) 4 has been described as a negative regulator of MAP kinase signaling, in particular for the ERK1/2 and JNK pathways. We found that DUSP4 expression was upregulated in response to prolonged platelet-derived growth factor (PDGF)-BB stimulation. The PDGF-BB-induced DUSP4 expression was dependent on ERK1/2, STAT3 and p53. We found that inhibition of ERK1/2 effectively reduced DUSP4 mRNA levels, whereas STAT3 was necessary for maintaining p53 expression. p53 has binding sites in the DUSP4 promoter and was found to promote DUSP4 expression.


Genetic and molecular analysis of the anthocyanin pigmentation pathway in Epimedium.
Flower color is an ideal trait for studying the molecular basis for phenotypic variations in natural populations of species. Epimedium (Berberidaceae) species exhibit a wide range of flower colors resulting from the varied accumulation of anthocyanins and other pigments in their spur-like petals and petaloid sepals. In this work, the anthocyanidins of eight different Epimedium species with different floral pigmentation phenotypes were analyzed using HPLC. Twelve genes involved in anthocyanin biosynthesis were cloned and sequenced, and their expression was quantified. The expression levels of the catalytic enzyme genes DFR and ANS were significantly decreased in four species showing loss of floral pigmentation. Complementation of EsF3'H and EsDFR in corresponding Arabidopsis mutants together with overexpression of EsF3'5'H in wild type Arabidopsis analysis revealed that these genes were functional at the protein level, based on the accumulation of anthocyanin pigments. These results strongly suggest that transcriptional regulatory changes determine the loss of anthocyanins to be convergent in the floral tissue of Epimedium species.


On the limitations in assessing stability of oxygen evolution catalysts using aqueous model electrochemical cells.
Recent research indicates a severe discrepancy between oxygen evolution reaction catalysts dissolution in aqueous model systems and membrane electrode assemblies. This questions the relevance of the widespread aqueous testing for real world application. In this study, we aim to determine the processes responsible for the dissolution discrepancy. Experimental parameters known to diverge in both systems are individually tested for their influence on dissolution of an Ir-based catalyst. Ir dissolution is studied in an aqueous model system, a scanning flow cell coupled to an inductively coupled plasma mass spectrometer. Real dissolution rates of the Ir OER catalyst in membrane electrode assemblies are measured with a specifically developed, dedicated setup. Overestimated acidity in the anode catalyst layer and stabilization over time in real devices are proposed as main contributors to the dissolution discrepancy. The results shown here lead to clear guidelines for anode electrocatalyst testing parameters to resemble realistic electrolyzer operating conditions.


Exploring the therapeutic role of creatine supplementation.
Creatine (Cr) plays a central role in energy provision through a reaction catalyzed by phosphorylcreatine kinase. Furthermore, this amine enhances both gene expression and satellite cell activation involved in hypertrophic response. Recent findings have indicated that Cr supplementation has a therapeutic role in several diseases characterized by atrophic conditions, weakness, and metabolic disturbances (i.e., in the muscle, bone, lung, and brain). Accordingly, there has been an evidence indicating that Cr supplementation is capable of attenuating the degenerative state in some muscle disorders (i.e., Duchenne and inflammatory myopathies), central nervous diseases (i.e., Parkinson's, Huntington's, and Alzheimer's), and bone and metabolic disturbances (i.e., osteoporosis and type II diabetes). In light of this, Cr supplementation could be used as a therapeutic tool for the elderly. The aim of this review is to summarize the main studies conducted in this field and to highlight the scientific and clinical perspectives of this promising therapeutic supplement.


Medicare Part D's effect on the under- and overuse of medications: a systematic review.
To evaluate the literature regarding the effect of Medicare Part D on the under- and overuse of specific medications and corresponding health outcomes. Systematic review. Medline search of the peer-reviewed literature from January 1, 2006, to October 8, 2010. Medicare beneficiaries who obtained drug insurance from the Part D program. The review evaluated changes in the use of specific drugs or drug classes after implementation of Part D, as described in original, peer-reviewed articles. Nineteen articles met inclusion criteria. Part D's implementation was associated with greater use of essential medications such as clopidogrel and statins, especially in beneficiaries who had been previously uninsured, but increases in inappropriate antibiotic use for the treatment of acute respiratory tract infections and increases in claims for the often overused proton pump inhibitor drug class were also observed. In the Part D transition period, dually eligible beneficiaries' drug use remained largely unchanged. When beneficiary cost sharing increased in the coverage gap, use of essential and overused medications declined. Increasing drug coverage led to greater use of underused essential medications and inappropriate, or overused, medications under Medicare Part D. Despite efforts to have it do so, the Part D benefit did not sufficiently discriminate between essential and nonessential medication use.


Heightened TLR7 Primes BCR-Activated Cells in Chronic Graft-Versus-Host Disease for Effector Functions.
Chronic graft-versus-host disease (cGVHD) is a debilitating, autoimmune-like syndrome that can occur after allogeneic hematopoietic stem cell transplantation. Constitutively activated B cells contribute to ongoing allo- and autoreactivity in patients with cGVHD. Excessive tissue damage that occurs following transplantation exposes B cells to nucleic acids in the extracellular environment. Recognition of endogenous nucleic acids within B cells can promote pathogenic B cell activation. Therefore, we hypothesized that cGVHD B cells aberrantly signal through RNA and DNA sensors such as Toll-Like Receptor 7 (TLR7) and TLR9. We found that B cells from patients and mice with cGVHD had higher expression of TLR7 than non-cGVHD B cells. Using ex vivo assays, we found that B cells from cGVHD patients also demonstrated increased IL-6 production following TLR7 stimulation with R848. Low-dose B cell receptor (BCR) stimulation augmented B cell responses to TLR7 activation. TLR7 hyperresponsiveness in cGVHD B cells correlated with increased expression and activation of the downstream transcription factor Interferon Regulatory Factor 5 (IRF5). Since RNA-containing immune complexes can activate B cells through TLR7, we used a protein microarray to identify RNA-containing antigen targets of potential pathological relevance in cGVHD. We found that many of the unique targets of active cGVHD IgG were nucleic acid (NA) binding proteins. This unbiased assay identified the autoantigen and known cGVHD target Ro-52, and we found that RNA was required for IgG binding to Ro-52. Herein, we find that BCR-activated B cells have aberrant TLR7 signaling responses that promote potential effector responses in cGVHD.


Undertriage of patients requiring direct admission to intensive care from the emergency department for medical conditions: impact on prognosis and associated factors.
To determine whether undertriage affects the outcome for patients requiring direct admission to the intensive care unit (ICU) from the emergency department due to a medical condition. To identify factors associated with undertriage. Retrospective review of patients treated in 2018 for medical emergencies requiring direct admission to the ICU from the emergency department. The cases were classified in 2 groups according to the assigned triage level. Underestimation was defined as a triage level of III or more. Independent variables were demographic and epidemiologic data and indicators of severity recorded in the emergency department. The main outcome was 30-day mortality. Secondary outcomes were in-hospital mortality, prolonged ICU stay, and prolonged hospital stay. We included 470 patients with a median age of 68 years (first-third quartile range, 57-78 years); 61.1% were men, and 151 (32.1%) were undertriaged. Factors directly related to undertriage according to odds ratios (ORs) were age (OR = 1.017; 95% CI, 1.003-1.032), Quick Sequential Organ Failure Assessment score of 0 or 1 (OR = 1.761; 95% CI, 1.038-2.988), ratio of oxygen saturation to fraction of inspired oxygen greater than 300 (OR = 2.447; 95% CI, 1.418-4.223), a diagnosis of infection (OR = 5.003, 95% CI 2.727-9.188) whether respiratory (OR = 3.993, 95% CI 1.919-8.310) or other (OR = 1.980, 95% CI, 1.036-3.785) versus a diagnosis of cardiovascular disease. Factors inversely related to undertriage were admission during the afternoon (OR = 0.512, 95% CI, 0.306-0.856) and ambulance transfer (OR = 0.373; 95% CI, 0.232-0.600). Ninety patients (19.1%) died within 30 days. Undertriage was not related to 30-day mortality or the other outcomes analyzed. Undertriage was not associated with a worse outcome in patients requiring direct admission to the ICU for a medical emergency. The factors we found to be associated with undertriage, such as patient age and time of day admitted, merit special attention given that these factors should not be affecting the triage process.


Direct immunoprecipitation of protein.
Many biochemical experiments depend on the measurement of the amount of an enzyme (or other protein) independently of any enzymatic activity it may have. When working with cell-free extracts or other complex mixtures this is not simple to do, and most procedures that have general application involve the use of antibodies. Two distinct strategies have been used to good effect. The amount of antibody bound can be made to reflect amount of antigen, as in an ELISA assay (ref. 1 and Vol. 1 of this series) or in a "Western blot" (ref. 2 and Chapters 28 and 29 in this volume). Alternatively, the antibody can be used effectively to purify the antigen protein. The method described here is of the latter sort and has advantages of simplicity and rapidity both over ELISA and blotting techniques, on the one hand, and indirect precipitation techniques on the other.


Optimized conditions for the supplementation of human-induced pluripotent stem cell cultures with a GSK-3 inhibitor during embryoid body formation with the aim of inducing differentiation into mesodermal and cardiac lineage.
We optimized the conditions for the differentiation of human induced pluripotent stem cells (hiPSCs) into mesoderm lineage-committed cells by supplementing the cultures with CHIR, a selective GSK-3 inhibitor, during embryoid body (EB) formation. In vitro treatment with 4 μM CHIR during the late 2 days of a 4-day suspension culture period was most effective at promoting mesodermal differentiation. The resulting EBs showed a significant increase in the expression levels of mesoderm-associated genes (WNT3A, T, DKK1, GATA4, FOXC1, and MESP1) and a maintenance of OCT3/4 and NANOG expressions. Upon subsequent differentiation into a cardiac cell lineage, these EBs were shown to generate contractile cardiomyocytes. When shortening the CHIR treatment period to 1 day, the resulting EBs showed reduced expression of mesoderm-associated genes in comparison to the 2-day CHIR treatment. In particular, the expression level of FOXC1 in the 1-day CHIR-treated EBs was much lower than that of the 2-day CHIR-treated EBs. When the treatment period with CHIR was extended to 4 days, the resulting EBs presented significantly reduced expression of WNT3A, OCT3/4, and NANOG upon CHIR concentrations above 4 μM. Similarly, when CHIR treatment was conducted after the formation of EBs, the effectiveness of the GSK-3 inhibitor was reduced compared to a treatment performed during EB formation. Our results indicate that spatiotemporal constraints associated with EB formation, i.e., three-dimensional structuration and cell development in EBs, should be taken into account when designing EB formation-based differentiation protocol involving CHIR treatment.


Long-term trends and predictors of smoking behaviors among men following first-ever ischemic stroke.
Continued smoking following stroke is associated with adverse outcomes including increased risk of mortality and secondary stroke. The aim of this study was to examine the long-term trends in smoking behaviors and factors associated with smoking relapse among men who survived their first-ever stroke. Data collection for this longitudinal study was conducted at baseline through face-to-face interviews and follow-up was completed every 3 months via telephone, beginning in 2010 and continuing through 2014. Cox proportional hazard regression models were used to identify predictors of smoking relapse behavior. At baseline, 372 male patients were recruited into the study. Totally, 155 (41.7%) of these patients stopped smoking for stroke, and 61 (39.3%) began smoking again within 57 months after discharge with an increasing trend in the number of cigarettes smoked per day. Exposure to environmental tobacco smoke at places outside of home and work (such as bars, restaurants) (HR, 2.34; 95% CI, 1.04-5.29, P=0.04), not having a spouse (HR, 0.12; 95% CI, 0.04-0.36; P=0.0002) and smoking at least 20 cigarettes per day before stroke (HR, 2.42; 95% CI, 1.14-5.14, P=0.02) were predictors of smoking relapse. It was concluded that environmental tobacco smoke is an important determinant of smoking relapse among men who survive their first stroke. Environmental tobacco smoke should be addressed by smoke-free policies in public places.


A comparison of the effects of fixed versus variable foreperiods on anticipatory cardiac deceleration prior to an exercise task in grade school children.
Children's heart rate responses in anticipation of a signalled exercise task were examined. The use of fixed (15 s) vs variable (10, 15 or 20 s) preparatory intervals (PI) was compared. The analysis across all subjects indicated that the children exhibited a stable deceleration immediately prior to the exercise task. A difference was found between the fixed and variable PI's. During the period immediately before the exercise task, those subjects receiving the variable PI exhibited a decrease across trials in the size of the anticipatory heart rate deceleration. The children receiving the fixed PI showed an increase across trials in the size of the deceleration.


On the psychoanalytic theory of instinctual drives. IV: Instinctual drives and the ego-id-superego model.
Freud's work on instinctual drives from 1916 to 1939 is reviewed and related to his earlier drive and structure propositions. A summary of the series of four papers on the evolution of Freud's drive theory is presented.


Several strains of Echinococcus granulosus infect livestock and humans in Argentina.
Mitochondrial cytochrome oxidase subunit 1 (CO1) sequencing, Southern blot of a repetitive DNA element and single strand conformation polymorphism of the 5' non-transcribed region of the cytosolic malate dehydrogenase (MDH) gene were used to determine the extent and distribution of Echinococcus granulosus genetic variation in Argentina. Five distinct strains of E. granulosus were shown to exist in the country. The common sheep, Tasmanian sheep, cattle and camel strains were identified in humans. Unlike the situation found in other countries, where the common sheep strain is the major source of human contamination, the Tasmanian sheep and camel strains produced a significant number of human infections in some regions of Argentina. This is the first report of cattle strain in humans in South America. Goats could be the natural intermediate host of the camel strain, which was not identified in humans from other regions so far. More than one genotype was identified in the same geographic area. These findings may have important consequences for human health and the control of hydatid disease. Within-strain differences were also observed, showing the potential of variation of E. granulosus.


Simple versus complex performance impairments at three blood glucose levels.
By using a visual reaction time paradigm, we sought to determine if disruption of relatively simple responding (finger tapping or letter recognition) or more complex responding (choice reaction time) would occur in response to blood glucose deviations. Glucose levels were maintained in 24 male diabetics to within 4% of the following targeted concentrations: 55 mg/dl (hypoglycemia), 110 mg/dl (euglycemia/control), and 300 mg/dl (hyperglycemia). The results indicate that simple motor and perceptual skills were not affected by blood glucose alterations, while more complex cognitive processing required significantly longer response latencies during hypoglycemia. Performance impairments occurred independently of disease duration and control, and without documented neuropathy, underscoring the sensitivity of some cognitive skills to acute glucose fluctuations.


Minimization of the amount of Kryptofix 222 - KHCO3 for applications to microscale 18F-radiolabeling.
Conversion of aqueous [18F]fluoride to reactive [18F]fluoride is an important first step in the radiosynthesis of 18F-labeled compounds by nucleophilic substitution. A versatile method for the rapid preparation of reactive [18F]fluoride by the combined use of an Oasis MAX cartridge and a methanolic solution of the Kryptofix 222-KHCO3 complex (K.222/KHCO3) was developed. The latter amount was optimized with the aim to keep it as low as possible while achieving recovery yields of [18F]fluoride comparable to those attained with the commonly used QMA cartridge. Thus, a 97% recovery yield was obtained with just 2µmol of K.222/KHCO3 methanolic solution (10mM, 200µL) within 7min. This result allowed in turn to optimize the microscale radiosynthesis of [18F]FDG. Moreover, the method was successfully applied to the 100µL-scale 18F-substitution reactions of several precursors.


The effects of surface inclination on gastrocnemius, soleus and tibialis anterior muscle activation during gait.
Inclined walking is associated with multiple musculoskeletal benefits and is considered a therapeutic exercise. Various patterns of increased and decreased muscle activation with inclined surfaces have been observed in normal muscles, with more focus on the proximal lower limb musculature. The aim of this study was to assess the differences in electromyographic activation of gastrocnemius, soleus, and tibialis anterior at various inclined surfaces during gait. Fourteen healthy male participants aged between 17-30 years walked at a self-selected speed at motor driven treadmill on 0, 2 and 4 degrees of inclination. EMG activity of the muscles was recorded using the Delsys Trigno surface EMG system. Results showed that muscular activation of tibialis anterior significantly decreased with increase in the level of inclination (p< 0.05). However, soleus, gastrocnemius medialis and gastrocnemius lateralis showed no significant differences (p> 0.05) in their muscular activation, and no noticeable trends were found. Furthermore, no significant difference was found between all the muscles at ground level and inclined level 2 and 4. These differences in activation patterns found in distal extremity can be useful for designing rehabilitation protocols in sports training and for patients with neurological and musculoskeletal pathologies.


Decoyinine Induced Resistance in Rice against Small Brown Planthopper Laodelphax striatellus.
Induced resistance against SBPH via microbial pesticides is considered as an eco-friendly and promising management approach. In this study, the induced resistance against SBPH in rice seedling by a new potential microbial pesticide, decoyinine (DCY), a secondary metabolite produced by Streptomyces hygroscopicus, was evaluated to investigate the effects of DCY on SBPH's biological and population parameters along with defense-related physiological and biochemical indices in rice against SBPH feeding. We found that DCY has potential to improve rice resistance and significantly reduced the fecundity of SBPH. Laboratory results revealed that DCY treated rice significantly changed SBPH's fecundity and population life table parameters. The concentrations of hydrogen peroxide (H2O2), soluble sugars and malondialdehyde (MDA) were significantly lower in DCY treated rice plants against SBPH infestation at 24, 48 and 96 hours post infestation (hpi), respectively. The concentrations of antioxidant enzymes, catalase (CAT) was significantly higher at 72 hpi, while super oxidase dismutase (SOD) and peroxidase (POD) concentrations were recorded higher at 96 hpi. The concentrations of synthases enzymes, phenyl alanine ammonia-lyase (PAL) was higher at 48 hpi, whereas polyphenol oxidase (PPO) concentration was maximum at 72 hpi against SBPH infestation. The results imply that DCY has unique properties to enhance rice resistance against SBPH by stimulating plant defensive responses. Microbial pesticides may be developed as an alternative to chemical pest control.


Antiseptic and antibiotic resistance in gram-negative bacteria causing urinary tract infection in spinal cord injured patients.
Fifty-seven isolates of Gram-negative bacterial species from urinary tract infections in spinal cord injured patients were tested for their sensitivity to chlorhexidine, cetrimide, glutaraldehyde, phenyl mercuric nitrate (PMN), a phenolic disinfectant (Hycolin) and a proprietary antiseptic containing a mixture of picloxydine, octylphenoxypolyethoxyethanol and benzalkonium chloride (Resiguard). None of the isolates were resistant to glutaraldehyde, Hycolin or PMN but a substantial percentage were resistant to chlorhexidine (44 per cent), cetrimide (26 per cent) and Resiguard (42 per cent). The resistant organisms were members of the genera Proteus, Providencia and Pseudomonas and they were also generally resistant to five, six or seven antibiotics. Significant correlations were observed between multiplicity of antibiotic resistance and the minimum inhibitory concentrations of the three cationic antiseptics. It is suggested that an antiseptic policy for the bladder management of spinal cord injured patients that relies on the extensive use of cationic agents might lead to the selection of a flora of notoriously drug-resistant species.


Molecular imaging of large vessel vasculitis.
Large vessel vasculitis (LVV) affects mainly large arteries with giant cell arteritis (GCA) and Takayasu arteritis (TAK) being the two most frequent forms. Clinical symptoms can be non-specific, including headache, fatigue, weight loss, and change in vision. Untreated, LVV may also lead to serious complications such as blindness, aortic aneurysm and dissection. Therefore, rapid recognition of the disease leading to accurate diagnosis and appropriate treatment is essential. FDG-PET/CT imaging has emerged as a sensitive marker of active vascular inflammation and its use in the management of LVV is now integrated in guidelines. In this article, we will discuss the role of FDG-PET/CT for the diagnosis of LVV and monitoring of therapy, as well as review technical and interpretation parameters.


Coronary artery intramural hematoma, a rare complication of percutaneous coronary intervention.
Coronary artery intramural hematoma is a rare complication of percutaneous coronary intervention which develops from intimal tear of coronary artery and propagates by blood accumulation along the medial surface of adjacent segment. Fifty-three-year-old male presented with nonexertional chest pain; he was referred after a positive stress test with+ moderate lateral wall ischemia. Coronary angiography showed 80% lesion in mid-left anterior descending artery (mLAD). Angiogram after angioplasty with 2.0 mm × 15 mm balloon and 3.0 mm × 15 mm drug-eluting-stent demonstrated a new stenotic lesion distal to stented mLAD segment. Subsequently, an overlapping 3.0 mm × 30 mm stent was placed with effective restoration of blood flow through LAD. During percutaneous coronary intervention (PCI), balloon predilatation can result in plaque fracture and stent deployment may cause intimal tear forming intramural hematoma which can lead to post-PCI myocardial infarction necessitating prompt detection by intravascular imaging with intravascular ultrasound and optical coherence tomography. Management is based on individual patient's characteristics and includes medical therapy, angiographic surveillance or repeat PCI.


A systematic scoping review of published qualitative research pertaining to the field of perioperative anesthesiology.
Qualitative research (QR) take advantage of a wide range of methods and theoretical frameworks to explore people's beliefs, perspectives, experiences, and behaviours and has been applied to many areas of healthcare. The aim of this review was to explore how QR has contributed to the field of perioperative anesthesiology. We performed a systematic scoping review of published QR studies pertaining to the field of perioperative anesthesiology in three databases (CINAHL, Pubmed, and Embase), published between January 2000 and June 2018. We extracted data regarding publication and researchers' characteristics, main study objectives, and methodological details. Descriptive statistics were generated for each data extraction category. A total of 107 articles fulfilled our inclusion criteria. We identified 13 main research topics addressed by the included studies. Topics such as "patient safety," "barriers to evidence-base medicine," "patient experiences under local/regional anesthesia," "training in practice," "experiences of care," and "implementation of changes in clinical practice" were commonly tackled. Others, such as "interprofessional communication", "work environment," and "patients'/healthcare professionals' interactions" were less common. Qualitative research was often poorly reported and methodological details were frequently missing. Qualitative research has been used to explore an array of issues in perioperative anesthesiology. Some areas may benefit from further primary research, such as interprofessional communication or patient-centred care, while other areas may deserve a detailed systematic knowledge synthesis. We identified suboptimal reporting of qualitative methods and their link to study findings. Increased attention to quality criteria and reporting standards in QR is called for.


Role of SiOx in rice-husk-derived anodes for Li-ion batteries.
The present study investigated the role of SiOx in a rice-husk-derived C/SiOx anode on the rate and cycling performance of a Li-ion battery. C/SiOx active materials with different SiOx contents (45, 24, and 5 mass%) were prepared from rice husk by heat treatment and immersion in NaOH solution. The C and SiOx specific capacities were 375 and 475 mAh g-1, respectively. A stable anodic operation was achieved by pre-lithiating the C/SiOx anode. Full-cells consisting of this anode and a Li(Ni0.5Co0.2Mn0.3)O2 cathode displayed high initial Coulombic efficiency (~ 85%) and high discharge specific capacity, indicating the maximum performance of the cathode (~ 150 mAh g-1). At increased current density, the higher the SiOx content, the higher the specific capacity retention, suggesting that the time response of the reversible reaction of SiOx with Li ions is faster than that of the C component. The full-cell with the highest SiOx content exhibited the largest decrease in cell specific capacity during the cycle test. The structural decay caused by the volume expansion of SiOx during Li-ion uptake and release degraded the cycling performance. Based on its high production yield and electrochemical benefits, degree of cycling performance degradation, and disadvantages of its removal, SiOx is preferably retained for Li-ion battery anode applications.


Traditional Indian medicine in China: The status quo of recognition, development and research.
Traditional Indian medicine is one of the oldest medical systems and remains popular worldwide. Traditional medicine systems in China and India have historical origins pertaining to mutual learning, reference, and development from medical theory to the drugs used. The exchange of traditional medicine between China and India began in the Qin and Han Dynasties (221 BC-220 AD), prospered in the Tang Dynasty (618-907 AD), and declined after the Song Dynasty (960-1279 AD). It was also directly related to the rise and fall of Buddhism. The traditional medicines of the two countries are highly complementary because of differences in geographical climate and the modernisation process of traditional medicine. This review aimed to understand the spread and development of traditional Indian medicine in China to further promote exchange and cooperation between China and India in the field of traditional medicine. We performed a systematic search of MEDLINE via PubMed, CNKI, Science Direct, Sci-Hub, and other databases using the terms 'traditional Indian medicine' or 'Indian medicine' or 'Ayurveda' or 'Yoga' or 'Unani', and limiting the search to articles published between 1958 and 2019. We analysed the sources, publication date, type, and topic of the retrieved articles/studies. Based on the results of research on traditional Indian medicine carried out by Chinese scholars, 518 academic papers and 60 classic works published in China and abroad were collected. The results showed the following. First, Chinese scholars have systematically investigated traditional Indian medicine including its composition, management, and education; the scale of medicinal and pharmaceutical plants; protective measures of intellectual property rights of traditional medicine; and international promotion of Yoga. Second, studies have examined the development status of traditional Indian medicine in China including the spread of Yoga in the country and the industrial scale of, education in, existing problems in, and clinical research on Yoga. In addition, Chinese scholars conducted research on and the translation of classic works and terms of Ayurveda, and studied the theory, treatment, and medicine thereof. Third, the historical exchange and trading status of traditional medicine between India and China have been discussed, including the exchange of traditional medicine between the two countries, effect of traditional Indian medicine on Chinese Buddhism, and minority medicine and trade in medicinal materials between the two countries. India attaches great importance to the management of, education in, and industry of traditional medicine, and has made various efforts to protect intellectual property rights. Indian Yoga is very popular in China, and Chinese scholars have conducted some clinical research thereon. However, regulatory systems and legislation for Yoga are lacking in China. At present, traditional Chinese medicine scholars have an enhanced understanding of the term Yoga and less knowledge of the terms Ayurveda, Siddha, Unani, and similar concepts. We suggest that Chinese scholars further study the classic works, basic theories, treatment of clinical diseases, medicinal materials, and prescriptions compounding traditional Indian medicine. The results of this study highlight directions for Chinese scholars to pursue in further studying traditional Indian medicine comprehensively, and will help promote exchange and cooperation between China and India in the field of traditional medicine.


Alpha interferon in human pregnancy.
The concentration of interferon-alpha was measured by a specific two-site immunoradiometric assay in a variety of fluids and tissues collected during human pregnancy. Maternal blood and blood and tissues from non-pregnant adults contained little or no interferon-alpha. Fetal blood, fetal organs, placenta, membranes, amniotic fluid and decidua all contained significant and roughly equivalent amounts ranging from 1.1 to 10 u/ml (or per g of tissue). These findings demonstrate that the fetus and its immediate surroundings are permeated with interferon. It is suggested that this may play a role in regulation of the maternal-fetal graft relation.


Tailoring Cognitive Behavioral Therapy for Trauma-Exposed Persons Living With HIV.
This Treatment Development Report describes the need for evidence-based psychosocial trauma-focused treatment for people living with comorbid posttraumatic stress disorder (PTSD) and HIV. Individuals with HIV have higher rates of exposure to traumatic events and PTSD than the general public, and they also experience additional consequences of PTSD on the management of their chronic disease (e.g., established link between PTSD symptoms and lack of adherence to antiretroviral therapy [ART]). We used the empirically-supported ADAPT-ITT approach to consider the initial steps in adapting evidence-based Cognitive Processing Therapy (CPT) for individuals with PTSD and HIV. This paper reviews a case example that involved various clinical issues that may arise when providing trauma-focused treatment for people living with HIV including HIV-stigma, disease management, and the need for making multicultural adaptations to psychotherapy. This case example illustrates how trauma-focused treatment may benefit from enhancement to address additional barriers that may arise over the course of PTSD treatment in this population. Feasibility of engaging and delivering a "full dose" of evidence-based PTSD treatment among individuals living with HIV is discussed. While evidence-based treatments can reduce PTSD symptom severity, issues related to chronic disease coping and HIV-related stigma management could be integrated to augment the efficacy of treatment for individuals with HIV. Adaptive intervention research targeting PTSD in persons living with HIV warrants further attention, especially given the association between PTSD and adherence to ART.


Effect of 13-NLE-motilin on gastric secretion, serum gastrin level and mucosal blood flow in dogs.
1. In dogs with gastric fistulas and vagally innervated fundic and antral pouches, 13-norleucine-motilin (13-nle-motilin), a synthetic analogue of motilin, infused intravenously in graded doses produced a dose-dependent increase in gastric acid and pepsin outputs. 2. The motilin-induced stimulation of gastric secretion occurred independently of antral pH and was not accompanied by any alteration in the serum gastrin level suggesting that motilin did not affect the release of gastrin. 3. When infused intravenously in a constant dose against a constant background stimulation with pentagastrin or histamine 13-nle-motilin inhibited both acid and pepsin secretion from the main stomach and fundic pouch. 4. The inhibitory effect of 13-nle-motilin was always associated with a marked reduction in mucosal blood flow but without any change in the ratio of aminopyrine concentration in the gastric juice and blood plasma indicating that this peptide primarily affected gastric secretion but did not limit the gastric mucosal microcirculation.


Long term follow-up and risk of breast cancer after a radial scar or complex sclerosing lesion has been identified in a benign open breast biopsy.
Radial scars (RS)/complex sclerosing lesions (CSL) are rare, benign breast lesions of unknown aetiology. Associations with breast cancer have been suggested particularly with larger lesions. This study aims to identify the risk of developing subsequent breast cancer after excision of a benign RS/CSL with respect to lesion size and compared to expected rates in the normal UK population. A prospective cohort analysis was performed on patients diagnosed with RS/CSL in benign, open breast biopsy specimens over a 20-year period. The rate of subsequent breast cancer development was compared to expected rates in the normal UK population. Subjects were divided into two groups according to lesion size and the rates of subsequent breast cancer compared. 149 women without proliferative breast disease were followed for an average of 68 months. Five women developed subsequent cancer, equating to a rate of 0.84% per year. This compares to 0.32% per year in the normal population (RR 2.6, 95% CI 0.86-6.0). There were two subsequent cancers in the RS group and three subsequent cancers in the CSL group, P = 0.64. The study finds no evidence to suggest that lesions greater than 10 mm (CSL) have any greater risk of developing cancer after excision than those below 10 mm (RS). Women treated for RS/CSL do not need any additional follow-up beyond routine mammographic breast screening. Additional surveillance should only be performed if there is associated pathology indicating an increased risk of subsequent malignancy.


ADHD, Religiosity, and Psychiatric Comorbidity in Adolescence and Adulthood.
Religiosity has been repeatedly proposed as protective in the development of depression, sociopathy and addictions. ADHD frequently co-occurs with these same conditions. Although ADHD symptoms may affect religious practice, religiosity in ADHD remains unexplored. Analyses examined data from >8000 subjects aged 12 to 34 in four waves of the Add Health Study. Relationships of religious variables with childhood ADHD symptoms were statistically evaluated. Observed correlations of ADHD symptoms to depression, delinquency, and substance use were tested for mediation and moderation by religiosity. ADHD symptoms correlated with lower levels of all religious variables at nearly all waves. In some analyses at Wave IV, prayer and attendance interacted with ADHD to predict worsened psychopathology. ADHD symptoms predicted lower engagement in religious life. In adulthood, some aspects of religiosity interacted with ADHD symptoms to predict worse outcomes. Further research should explore whether lower religiosity partially explains prevalent comorbidities in ADHD.


Determination of residual erythrocytes in rat tissue homogenates using commercially available anti-red blood cell sera.
A method to determine the residual erythrocyte content in rat tissue homogenates by means of radial immunodiffusion (Mancini et al., 1965) is described. The method makes use of commercially available antisera against rat erythrocytes. Tissues were homogenized after addition of digitonin and applied on Mancini plates. To measure within the linear part of the calibration curve, the tissue homogenates were diluted to concentrations between 0.062% and 2.5% wet weight content, depending on the type of tissue and on the degree of bleeding before the death of the animal. Recovery data of added blood as well as a comparison with results from organ distribution studies with 59Fe-labeled erythrocytes demonstrated that this simple method is sufficiently reliable and sensitive. The present procedure is to control experiments in which drug tissue levels (e.g., antibiotics) are to be determined and in which the drug content of residual blood is likely to bias the results to an unknown extent. It can be used as well in organ distribution studies of substances with a high affinity for erythrocytes (e.g., Pb; As in rats). It is possible to individually control the success of procedures without the use of isotopes--such as exsanguination or vascular perfusion--that are performed in order to reduce the blood content in the organs under consideration.


Mechanistic homeostasis of vitamin D metabolism in the kidney through reciprocal modulation of Cyp27b1 and Cyp24a1 expression.
Cyp27b1 and Cyp24a1 are reciprocally regulated in the kidney by the key hormones PTH, FGF23, and 1,25(OH)2D3. Our recent genomic studies in mice identified a complex kidney-specific enhancer module located within the introns of adjacent Mettl1 (M1) and Mettl21b (M21) genes that mediate basal and PTH induction of Cyp27b1 as well as suppression by FGF23 and 1,25(OH)2D3. Gross deletion of these segments in mice has severe consequences on skeletal health, and directly affects Cyp27b1 expression in the kidney. Deletion of both M1 and M21 submodules together fully eliminates basal Cyp27b1 expression in the kidney, leading to a systemic and skeletal phenotype similar to that of the Cyp27b1-KO mouse due to depletion of 1,25(OH)2D3 and high PTH. Cyp24a1 levels in the double KO mouse were low due to compensatory regulation by elevated PTH and reduced FGF23. However, expression of Cyp27b1 and retention of its regulation by inflammation (LPS) in the NRTCs remained unperturbed. Dietary normalization of calcium, phosphate, PTH, and FGF23 rescues this aberrant phenotype and normalizes the skeletal issues. Cyp24a1 is controlled by its own unique enhancers for 1,25(OH)2D3, FGF23, and PTH. We were also able to eliminate these activities in mice. Collectively, the hormone-mediated enhancer regulation of both Cyp27b1 and Cyp24a1 in the kidney is responsible for the circulating levels of 1,25(OH)2D3 in the blood which in turn primarily affects calcium and phosphate regulation. Importantly, we can now manipulate this system with our enhancer deletion animal models to study 1,25(OH)2D3 production in non-renal target cells and tissues not only in disease, where it is known to affect the immune system, but also in healthy individuals. Here we will review our studies that have defined a finely balanced homeostatic control mechanism employed by PTH and FGF23 with catastrophic toxicity protection from 1,25(OH)2D3 in the genomic regulation of vitamin D metabolism and its accompanied control of mineral maintenance.


Sonochemical preparation and characterization of Sm-doped GO/KSrPO4 nanocomposite photocatalyst for degradation of methylene blue dye.
The present work pertains to synthesis of Sm-doped GO/KSrPO4 (GO/KSrPO4 :Sm) nanocomposite using ultrasound-assisted method. Successful decoration of graphene oxide sheets with the KSrPO4 :Sm3+ phosphor was confirmed using analysis techniques including SEM, EDS, UV/visible spectrometry, XRD, and FTIR of the prepared GO/KSrPO4 :Sm nanocomposite. Further, photocatalytic activity of this nanocomposite material was studied by examining degradation of methylene blue (MB) dye from water. The effects of several parameters like concentration of Sm3+ in KSrPO4 :Sm3+ phosphor within the GO/KSrPO4 :Sm nanocomposite photocatalyst, photocatalyst loading, initial dye concentration, pH, and preparation method were evaluated. At a higher concentration of Sm3+ in the photocatalyst (1 mol.%), higher photocatalyst loading (1.5 mg/ml), lesser dye concentration (20 mg/L), and higher pH (11.4), the GO/KSrPO4 :Sm nanocomposite photocatalyst prepared using ultrasound-assisted method showed higher dye removal compared to other conditions. A maximum of 83.35% removal of MB dye was achieved by the use of ultrasonically prepared GO/KSrPO4 :Sm nanocomposite photocatalyst having a concentration of 1 mol.% of Sm3+ in the KSrPO4 :Sm3+ phosphor at a loading of 1.5 mg/ml, initial dye concentration of 20 mg/L, and a pH of 11.4. Rate constant for MB dye degradation using the GO/KSrPO4:Sm nanocomposite photocatalyst synthesized by ultrasonic-assisted method was found to be 0.0053 min-1 . PRACTITIONER POINTS: GO/KSrPO4 :Sm nanocomposite photocatalyst prepared by ultrasonic-assisted method. Higher Sm3+ doping in nanocomposite with the use of ultrasound assisted method showed better performance of photocatalyst. A maximum removal of 83.35% of methylene blue dye was achieved.


Effect of tongue-strengthening exercises on tongue strength and swallowing-related parameters in chronic radiation-associated dysphagia.
Radiation-associated dysphagia (RAD) is highly prevalent in head and neck cancer (HNC) patients, with insufficient tongue strength (TS) as a characteristic of this disabling complication. The effects of tongue-strengthening exercises (TSE) on TS, swallowing, and quality of life (QoL) have not been studied in this population. A prospective phase 2 study using an 8 weeks during TSE protocol was carried out in 15 patients with chronic RAD. Outcome parameters were maximal isometric pressure (MIP), TS during swallowing (Pswal), swallowing function, and QoL. All parameters were evaluated at baseline, after 4 and 8 weeks of training, and 4 weeks after the last training session. MIP increased significantly, without detraining effects. Pswal did not increase significantly, but relevant effect sizes were measured. Swallowing function ameliorated, but did not result in increased functional oral intake, self-reported outcome or QoL. TSE in patients with RAD results in increased strength and swallowing function.


Exploring inequalities in life expectancy and lifespan variation by race/ethnicity and urbanicity in the United States: 1990 to 2019.
Investigating trends in life expectancy and lifespan variation can highlight disproportionate mortality burdens among population subgroups. We examined inequalities in life expectancy and lifespan variation by race/ethnicity and by urbanicity in the US from 1990 to 2019. Using vital registration data for 322.0 million people in 3,141 counties from the National Center for Health Statistics, we obtained life expectancy at birth and lifespan variation for 16 race/ethnicity-gender-urbanicity combinations in six 5-year periods (1990-1994 to 2015-2019). Race/ethnicity was categorized as Hispanic, and non-Hispanic White, Black, and Asian/Pacific Islander. Urbanicity was categorized as metropolitan vs nonmetropolitan areas, or in six further detailed categorizations. Life expectancy and lifespan variation (coefficient of variation) were computed using life tables. In 2015-2019, residents in metropolitan areas had higher life expectancies than their nonmetropolitan counterparts (79.6 years compared to 77.0 years). The widest inequality in life expectancy occurred between Asian/Pacific Islander women and Black men, with a 17.7-year gap for residents in metropolitan areas and a 16.9-year gap for residents in nonmetropolitan areas. Nonmetropolitan areas had greater dispersion around average age at death. Black individuals had the highest lifespan variations in both metropolitan and nonmetropolitan areas. Until the mid-2010s, life expectancy increased while lifespan variation decreased; however, recent trends show stagnation in life expectancy and increases in lifespan variation. Metropolitan-nonmetropolitan inequalities in both life expectancy and lifespan variation widened over time. Despite previous improvements in longevity, life expectancy is now stagnating while lifespan variation is increasing. Our results highlight that early-life deaths (i.e., young- and middle-age mortality) disproportionately affect Black individuals, who not only live the shortest lifespans but also have the most variability with respect to age at death.


Global patterns and edaphic-climatic controls of soil carbon decomposition kinetics predicted from incubation experiments.
Knowledge about global patterns of the decomposition kinetics of distinct soil organic matter (SOM) pools is crucial to robust estimates of land-atmosphere carbon fluxes under climate change. However, the current Earth system models often adopt globally-consistent reference SOM decomposition rates (kref), ignoring effects from edaphic-climate heterogeneity. Here, we compile a comprehensive set of edaphic-climatic and SOM decomposition data from published incubation experiments and employ machine-learning techniques to develop models capable of predicting the expected sizes and kref of multiple SOM pools (fast, slow, and passive). We show that soil texture dominates the turnover of the fast pools, whereas pH predominantly regulates passive SOM decomposition. This suggests that pH-sensitive bacterial decomposers might have larger effects on stable SOM decomposition than previously believed. Using these predictive models, we provide a 1-km resolution global-scale dataset of the sizes and kref of these SOM pools, which may improve global biogeochemical model parameterization and predictions.


Microvascular and structural analysis of the retina and choroid in heart failure patients with reduced ejection fraction.
This cross-sectional study was designed to assess alterations of choroidal and retinal microvasculature in patients with Heart Failure with Reduced Ejection Fraction (HFrEF) and compare them with a normal age and sex-matched population. Fifty-two eyes of 26 patients with HFrEF (left ventricular ejection fraction [LVEF] < 40%) and 64 eyes of 32 healthy individuals were considered as the patient and the control groups, respectively. We found no statistically significant differences in age-adjusted mean central macular thickness (CMT), superficial or deep retinal capillary plexus vascular densities, and choriocapillaris flow (CC flow) density between the HFrEF group and the normal controls, with the exception of the parafoveal mean superficial capillary plexus vascular density (P = 0.023), which remained statistically significant after adjusting for age (P = 0.034). The patients with HFrEF had a significantly lower subfoveal choroidal thickness (SFCT) than the normal subjects (264 ± 82 vs 313 ± 72; P = 0.009), and the difference was still statistically significant after age adjustment (P = 0.026). Although choroidal vascularity index (CVI) was lower in the HFrEF group than in the control group, the difference was not statistically significant before and after age adjustment (73.45 ± 6.67 vs 75.77 ± 5.92; P = 0.118 and P = 0.096, respectively). In conclusion, in patients with HFrEF, we observed a reduction in parafoveal retinal VD in the superficial capillary plexus, as well as SFCT, but no significant change in CVI, CMT, or CC flow density.


Functional and phenotypic analysis of basophils allows determining distinct subtypes in patients with chronic urticaria.
Chronic urticaria (CU) is a frequent skin disease characterized by relapsing appearance of pruritic hives. While clinical symptoms are due to the release of histamine by cutaneous mast cells, the underlying pathophysiology is still unknown. However, previous studies indicate that basophils might be of relevance. Besides, the occurrence of autoantibodies against IgE or its receptor, FcεRI, and the therapeutic efficacy of anti-IgE antibodies imply that IgE-mediated mechanisms also play an important role in CU. Reactivity of CU patients' peripheral blood basophils (n=60) to specific anti-FcεRI and IgE-independent fMLP stimulation was determined by basophil activation test in comparison with patients suffering from IgE-mediated allergic rhinitis (n=10) and healthy controls (n=10). In addition, immunoglobulin receptor (FcεRI, FcγRII) expression and surface bound antibodies (IgE, IgG) were quantified on basophils. Furthermore, the autoreactive capacity of CU sera was evaluated and urticaria-related symptoms were assessed by both UCT and CU-Q2 oL. Stimulating CU patients' basophils via FcεRI, we identified three distinct immunologic phenotypes. One subgroup of patients' basophils reacted to FcεRI stimulation, whereas the others had anti-FcεRI nonreactive basophils. Among the latter, a subgroup with pronounced basopenia was identified. Of note, this group was characterized by augmented serum-induced basophil activation, increased levels of autoantibodies against thyroid peroxidase, and also exhibited the strongest disease impact on their quality of life. Patients with CU can be categorized into three immunologic subgroups based on their basophil reactivity and frequency. These phenotypes are associated with different clinical characteristics, pointing to basophils as important players in CU pathophysiology.


Hydrometrocolpos, postaxial polydactyly, congenital heart disease, and anomalies of the gastrointestinal and genitourinary tracts: a rare autosomal recessive syndrome.
Nine cases with the hydrometrocolpospolydactyly syndrome (4 males, 5 females) from four unrelated families are presented. Leading symptoms of this rare disorder were hydrocolpos and postaxial polydactyly. Three affected girls had urinary hydrocolpos without vaginal septum or imperforate hymen, one had partial vaginal atresia, and one had no hydrometrocolpos. Glandular hypospadias and prominent scrotal raphe are added to the spectrum of malformations in this disorder in males. The literature is reviewed and problems in genetic counseling in this autosomal recessive disorder are discussed.


The accuracy of tibial intramedullary alignment devices in total knee arthroplasty.
The accuracy of a tibial medullary alignment device is assessed radiographically in 30 varus and 30 valgus knees undergoing total knee arthroplasty. The results suggest that although the device is reliable and accurate for varus knees, it may lead to malalignment of up to 5 degrees in valgus knees. Overall neutral alignment was achieved in 83% of the varus knees and 37% of the valgus knees. Tibial bowing was the main source of error and was present in 66% of the valgus knees, with mean of 3 degrees. Preoperative long films or cross-checking with external alignment devices is recommended to assure neutral alignment in genu valgus deformity.


In vitro immunocompetence of two compounds isolated from Polygala tenuifolia and development of resistance against grass carp reovirus (GCRV) and Dactylogyrus intermedius in respective host.
The present study was undertaken to isolate some compounds from methanol extract of Polygala tenuifolia and evaluate their immunostimulatory properties and antiviral activity using grass carp Ctenopharyngodon idella kidney (CIK) cells and GCRV. By applying insecticidal bioassay-guided, chromatography techniques and successive recrystallization, two purified compounds were obtained. The changes of expression of selected immune genes (Mx1, IL-1β, TNFα, MyD88 and IgM) in C. idella kidney cell lines were evaluated after exposure to these isolated compounds. The results showed that compound 1 and 2 up-regulated to varying degrees of Mx1, IL-1β, TNFα, and MyD88 in C. idella kidney cells. WST-8 kit assay verified the two compounds has no toxic effects on CIK cell, and furthermore, have in vitro antivirus activity. Especially, that there is keeping 79% cell viability when exposure to compound 2 (100 mg L(-1)). According to in vivo insecticidal assays against Dactylogyrus intermedius, compound 2 exhibited higher efficacy than compound 1, which was found to be 87.2% effective at the concentrations of 5 mg L(-1) and safe to goldfish (Carassius auratus). Besides, the purified compounds were identified by spectral data as: (1) 1,5-Anhydro-D-glucitol and (2) 3,4,5-trimethoxy cinnamic acid. Overall, the results indicate that bath administration of these compounds modulates the immune related genes in C. idella kidney cells and to some extent, eliminate the virus and parasitic infections.


Pimavanserin for psychosis in Parkinson's disease dementia: Subgroup analysis of the HARMONY Trial.
Pimavanserin is FDA-approved to treat Parkinson's disease (PD) psychosis. We analyzed the effect of pimavanserin on psychosis in the PD dementia (PDD) subgroup from the phase 3 HARMONY trial. This subgroup analysis included PDD patients enrolled in an international, multicenter, randomized discontinuation study of pimavanserin for dementia-related psychosis. PDD patients with moderate-to-severe psychosis, age 50-90 years, received pimavanserin 34 mg/day for 12 weeks (open-label period). Those with a sustained psychosis response to pimavanserin at weeks 8 and 12 were randomized during the double-blind period to continue pimavanserin or receive placebo. Primary efficacy endpoint was time to psychosis relapse as measured by the SAPS-H + D and CGI-I. Safety was assessed, as were effects on motor symptoms and cognitive abilities using the ESRS-A and MMSE. 392 patients were enrolled in HARMONY (mean age: 72.6 years; 38.8 % female): 59 had PDD; 49/59 remained on pimavanserin during the open-label period (safety analysis set), and 36/49 were randomized to pimavanserin (n = 16) or placebo (n = 20) in the double-blind phase (intent-to-treat analysis set). Risk of psychosis relapse was lower with pimavanserin 34 mg compared with placebo in the double-blind phase (HR = 0.052; 95 % CI 0.016-0.166; 1-sided nominal p < 0.001). During the open-label period, 46.9 % experienced a treatment-emergent adverse event; event incidence was similar across arms in the double-blind period. Pimavanserin did not adversely affect motor or cognitive function in either treatment phase. Pimavanserin significantly reduced risk of psychosis relapse in patients with PDD, was well tolerated, and did not worsen motor or cognitive function.


Optimal Allocation of Proton Therapy Slots in Combined Proton-Photon Radiation Therapy.
Proton therapy is a limited resource that is not available to all patients who may benefit from it. We investigated combined proton-photon treatments, in which some fractions are delivered with protons and the remaining fractions with photons, as an approach to maximize the benefit of limited proton therapy resources at a population level. To quantify differences in normal-tissue complication probability (NTCP) between protons and photons, we considered a cohort of 45 patients with head and neck cancer for whom intensity modulated radiation therapy and intensity modulated proton therapy plans were previously created, in combination with NTCP models for xerostomia and dysphagia considered in the Netherlands for proton patient selection. Assuming limited availability of proton slots, we developed methods to optimally assign proton fractions in combined proton-photon treatments to minimize the average NTCP on a population level. The combined treatments were compared with patient selection strategies in which patients are assigned to single-modality proton or photon treatments. There is a benefit of combined proton-photon treatments compared with patient selection, owing to the nonlinearity of NTCP functions; that is, the initial proton fractions are the most beneficial, whereas additional proton fractions have a decreasing benefit when a flatter part of the NTCP curve is reached. This effect was small for the patient cohort and NTCP models considered, but it may be larger if dose-response relationships are better known. In addition, when proton slots are limited, patient selection methods face a trade-off between leaving slots unused and blocking slots for future patients who may have a larger benefit. Combined proton-photon treatments with flexible proton slot assignment provide a method to make optimal use of all available resources. Combined proton-photon treatments allow for better use of limited proton therapy resources. The benefit over patient selection schemes depends on the NTCP models and the dose differences between protons and photons.


Increased mortality after post-stroke epilepsy following primary intracerebral hemorrhage.
This study aimed to determine whether post-stroke epilepsy (PSE) predicts mortality, and to describe the most prominent causes of death (COD) in a long-term follow-up after primary intracerebral hemorrhage (ICH). We followed 3-month survivors of a population-based cohort of primary ICH patients in Northern Ostrobothnia, Finland, for a median of 8.8 years. Mortality and CODs were compared between those who developed PSE and those who did not. PSE was defined according to the ILAE guidelines. CODs were extracted from death certificates (Statistics Finland). Of 961 patients, 611 survived for 3 months. 409 (66.9%) had died by the end of the follow-up. Pneumonia was the only COD that was significantly more common among the patients with PSE (56% vs. 37% of deaths). In the multivariable models, PSE (hazard ratio [HR] 1.41, 95% confidence interval [CI] 1.06-1.87), age (HR 1.07, 95% CI 1.06-1.08), male sex (HR 1.35, 95% CI 1.09-1.67), dependency at 3 months (HR 1.52, 95% CI 1.24-1.88), non-subcortical ICH location (subcortical location HR 0.78, 95% CI 0.61-0.99), diabetes (HR 1.43, 95% CI 1.07-1.90) and cancer (HR 1.45, 95% CI 1.06-1.98) predicted death in the long-term follow-up. PSE independently predicted higher late morality of ICH in our cohort. Pneumonia-related deaths were more common among the patients with PSE.


Factors to preserve CpG-rich sequences in methylated CpG islands.
Mammalian CpG islands (CGIs) normally escape DNA methylation in all adult tissues and developmental stages. However, in our previous study we unexpectedly identified many methylated CGIs in human peripheral blood leukocytes. Methylated CpG dinucleotides convert to TpG dinucleotides through deaminization of their cytosine bases more frequently than hypomethylated CpG dinucleotides. Therefore, we wondered how methylated CGIs in germline or non-germline cells maintain their CpG-rich sequences. It is known that events such as germline hypomethylation, CpG selection, biased gene conversion (BGC), and frequent CpG fixation can contribute to the maintenance of CpG-rich sequences in methylated CGIs in germline or non-germline cells. However, it has not been investigated which of the processes maintain CpG-rich sequences of methylated CGIs in each genomic position. In this study, we comprehensively examined the contribution of the processes described above to the maintenance of CpG-rich sequences in methylated CGIs in germline and non-germline cells which were classified by genomic positions. Approximately 60-80% of CGIs with high methylation in H1 cell line (H1-HM) in all the genomic positions showed a low average CpG→TpG/CpA substitution rate. In contrast, fewer than half the numbers of CGIs with H1-HM in all the genomic positions showed a low average CpG→TpG/CpA substitution rate and low levels of methylation in sperm cells (SPM-LM). Furthermore, a small fraction of CGIs with a low average CpG→TpG/CpA substitution rate and high levels of methylation in sperm cells (SPM-HM) showed CpG selection. On the other hand, independent of the positions in genes, most CGIs with SPM-HM showed a slightly higher average TpG/CpA→CpG substitution rate compared with those with SPM-LM. Relatively high numbers (approximately 60-80%) of CGIs with H1-HM in all the genomic positions preserve their CpG-rich sequences by a low CpG→TpG/CpA substitution rate caused mainly by their SPM-LM, and for those with SPM-HM partly by CpG selection and TpG/CpA→CpG fixation. BGC has little contribution to the maintenance of CpG-rich sequences of CGIs with SPM-HM which were classified by genomic positions.


Sizes and rates of elongation of replicons in the frog embryo.
DNA fiber autoradiography has shown an increase in size of replicons during early development of the frog embryo. Replicons of endoderm cells were considerably larger than those of dorsal ectoderm and mesoderm cells in tailbud embryos. Late replicating DNA in partially synchronized tailbuds has a more rapid rate of replicon elongation than does early replicating DNA.


Independent risk factors for adverse events associated with propofol-based pediatric sedation performed by anesthesiologists in the radiology suite: a prospective observational study.
This study aimed to identify the types and frequencies of adverse events, as well as the risk factors for respiratory complications related to pediatric sedation. This single-center, prospective, observational study was conducted in a radiology suite at a tertiary university hospital for 2 years. Patients aged under 18 years, who underwent sedation solely by anesthesiologists for computed tomography or magnetic resonance imaging scans, were eligible for inclusion. Univariate and multivariate logistic regression analyses were carried out to identify the risk factors of adverse events, including respiratory complications, related to the propofol-based sedation. We further performed a sensitivity test with 1-to-5 propensity score matching analysis to assess the robustness of our findings. Among 2569 children, 3.9% experienced respiratory problems related to the sedation. After 1-to-5 propensity matching analysis, cardiac and neurologic comorbidities, crying before sedation, a history of snoring or upper respiratory infection, and prolonged duration of sedation were independently associated with the occurrence of adverse respiratory events.Conclusions: Our protocol for pediatric sedation demonstrates a high success rate and low likelihood of fatal complications, but proactive management prior to propofol-based sedation is critical to prevent adverse respiratory events in children. What is Known: • Propofol-based pediatric sedation is associated with adverse events necessarily even though performed by professional anesthesiologists solely. What is New: • Cardiac and neurologic comorbidities, crying before sedation, a history of snoring or upper respiratory infection, and prolonged duration of sedation were independently associated with the occurrence of respiratory adverse events. • Proactive management prior to sedation is critical to preventing adverse respiratory events for pediatrics.


Use of Electronic Cigarettes to Aid Long-Term Smoking Cessation in the United States: Prospective Evidence From the PATH Cohort Study.
Electronic cigarettes (e-cigarettes) are the preferred smoking-cessation aid in the United States; however, there is little evidence regarding long-term effectiveness among those who use them. We used the Population Assessment of Tobacco and Health Study to compare long-term abstinence between matched US smokers who tried to quit with and without use of e-cigarettes as a cessation aid. We identified a nationally representative cohort of 2,535 adult US smokers in 2014-2015 (baseline assessment), who, in 2015-2016 (exposure assessment), reported a past-year attempt to quit and the cessation aids used, and reported smoking status in 2016-2017 (outcome assessment; self-reported ≥12 months continuous abstinence). We used propensity-score methods to match each e-cigarette user with similar nonusers. Among US smokers who used e-cigarettes to help quit, 12.9% (95% confidence interval (CI): 9.1%, 16.7%) successfully attained long-term abstinence. However, there was no difference compared with matched non-e-cigarette users (cigarette abstinence difference: 2%; 95% CI: -3%, 7%). Furthermore, fewer e-cigarette users were abstinent from nicotine products in the long term (nicotine abstinence difference: -4%; 95% CI: -7%, -1%); approximately two-thirds of e-cigarette users who successfully quit smoking continued to use e-cigarettes. These results suggest e-cigarettes may not be an effective cessation aid for adult smokers and, instead, may contribute to continuing nicotine dependence.


Changes in views on aging in later adulthood: the role of cardiovascular events.
A number of longitudinal studies have pointed to the long-term impact of different views on aging (VoA) on health in later life, whereas the reverse relationship has rarely been examined. Serious cardiovascular events such as myocardial infarction or stroke are life-threatening events which might in turn lead to changes in VoA. The present longitudinal study examined the effect of a cardiovascular event (CVE) on VoA over a three-year period using pooled data from three waves of the German Ageing Survey (2008, 2011, 2014, age range: 40-95 years). In order to account for alternative explanations for changes in VoA, individuals without CVE (n = 200) were matched to individuals who experienced a CVE (n = 202) using a propensity score matching procedure. Compared to individuals without CVE, individuals who experienced a CVE showed adverse changes in three VoA indicators (self-perceptions of aging as associated with physical losses/with ongoing development; subjective age). These results suggest that CVE can in fact change how individuals view their own aging. According to previous studies, this can lead to future health changes and thus become a health-related downward spiral. Health promotion programs could, therefore, profit by adding specific VoA interventions for individuals who experienced a CVE.


Comparison of HER2 amplification status among breast cancer subgroups offers new insights in pathways of breast cancer progression.
Although the prognostic and predictive significance of human epidermal growth factor receptor 2 (HER2) in invasive breast cancer is well established, its role in ductal carcinoma in situ (DCIS) remains unclear. Reports on combined evaluation of both HER2 protein expression and HER2 amplification status in pure DCIS and DCIS adjacent to invasive ductal carcinoma (i.e., admixed DCIS) are scarce. In this study, immunohistochemistry and fluorescence in situ hybridization (FISH) were used to assess HER2 status in 72 cases of pure DCIS, 73 cases of DCIS admixed with invasive ductal carcinoma (IDC), and 60 cases of pure IDC. HER2 copy number-based amplification was present in 49% of pure DCIS, 16% of admixed DCIS, 18% of admixed IDC, and 8% of pure IDC. Amplified pure DCIS with clusters of HER2 signals showed a significantly lower HER2 copy number than amplified admixed DCIS with clusters. Whereas pure DCIS and admixed DCIS presented significant differences, the in situ and invasive component of admixed tumors showed striking similarities regarding mean HER2 and chromosome 17 centromere (CEP17) copy number, grade, and estrogen and progesterone receptor expression. The discrepant prevalence of HER2 amplification among breast cancer subgroups indirectly suggests that HER2 may not play a crucial role in the transition of in situ to invasive breast cancer. The similarities in HER2 amplification status between the in situ and invasive component of admixed tumors hint at a common biological pathway for both components. Our data support the theory that pure DCIS, pure IDC, and admixed lesions have a common progenitor, but can progress as separate lineages.


Composite endpoints.
Studies often combine several events, for example, death or myocardial infarction or stroke, into a single study outcome. This is called a composite endpoint. Composite endpoints make doing trials easier by reducing the sample size or follow-up period required to demonstrate the effectiveness of an intervention. However, interpreting the results of composite endpoints can be confusing. To avoid misleading conclusions about the effectiveness of an intervention, it is important for readers of studies reporting a composite endpoint to ascertain that the clinical importance, the frequency of events, and the effect of the intervention on each component of the composite endpoint are similar.


Haemopoietic long-term bone marrow cultures from adult mice show osteogenic capacity in vitro on 3-dimensional collagen sponges.
Adult murine bone marrow cells, cultured under conditions for long-term haemopoietic marrow cultures, produce bone matrix proteins and mineralized tissue in vitro, but only after the adherent stromal cells were loaded on a 3-dimensional collagen sponge. Provided more than 8 x 10(6) cells are loaded, mineralization as measured by 85Sr uptake from the culture medium, occurred in this 3-dimensional configuration (3-D) within 6 days. In contrast if undisrupted marrow fragments (containing more than 10(7) cells) are placed directly on a collagen sponge, then it requires more than 10 days before significant mineralization can similarly be detected. The 2-dimensional (2-D) long-term marrow culture system allows prior expansion of the stromal cells and some differentiation in an osteogenic direction within the adherent stromal layer. This is suggested by the presence of type I collagen and alkaline phosphatase positive cells. However; synthesis of osteonectin and a bone specific protein, osteocalcin, as well as calcification are only observed in 3-D cultures. Electron microscopy demonstrated hydroxyapatite mineral on collagen fibres, osteoblast-like cells, fibroblasts, cells which accumulated lipids, and macrophages which were retained on the collagen matrices. Irradiation of confluent long-term bone marrow cultures, prior to their loading on the collagen sponge showed that haemopoietic stem cells are not necessary for the mineralization.


EZH2-Deficient T-cell Acute Lymphoblastic Leukemia Is Sensitized to CHK1 Inhibition through Enhanced Replication Stress.
Loss-of-function mutations of EZH2, the enzymatic component of PRC2, have been associated with poor outcome and chemotherapy resistance in T-cell acute lymphoblastic leukemia (T-ALL). Using isogenic T-ALL cells, with and without CRISPR/Cas9-induced EZH2-inactivating mutations, we performed a cell-based synthetic lethal drug screen. EZH2-deficient cells exhibited increased sensitivity to structurally diverse inhibitors of CHK1, an interaction that could be validated genetically. Furthermore, small-molecule inhibition of CHK1 had efficacy in delaying tumor progression in isogenic EZH2-deficient, but not EZH2 wild-type, T-ALL cells in vivo, as well as in a primary cell model of PRC2-mutant ALL. Mechanistically, EZH2 deficiency resulted in a gene-expression signature of immature T-ALL cells, marked transcriptional upregulation of MYCN, increased replication stress, and enhanced dependency on CHK1 for cell survival. Finally, we demonstrate this phenotype is mediated through derepression of a distal PRC2-regulated MYCN enhancer. In conclusion, we highlight a novel and clinically exploitable pathway in high-risk EZH2-mutated T-ALL. SIGNIFICANCE: Loss-of-function mutations of PRC2 genes are associated with chemotherapy resistance in T-ALL, yet no specific therapy for this aggressive subtype is currently clinically available. Our work demonstrates that loss of EZH2 activity leads to MYCN-driven replication stress, resulting in increased sensitivity to CHK1 inhibition, a finding with immediate clinical relevance.This article is highlighted in the In This Issue feature, p. 890.


Cold-induced adaptive thermogenesis in lean and obese.
On entering a cold environment, people react by increasing insulation and energy expenditure (EE). However, large interindividual differences exist in the relative contribution of each mechanism. Short-term studies revealed that obese subjects increase EE (i.e., adaptive thermogenesis) less than lean subjects, which might have implications for the predisposition to obesity. In this study, we validate the differences in adaptive thermogenesis between lean and obese upon midterm mild cold exposure. Therefore, 10 lean and 10 obese subjects were exposed for 48 h to mild cold (16 degrees C) in a respiration chamber. The preceding 36 h they stayed in the same chamber at a neutral temperature (22 degrees C) for the baseline measurements. EE, physical activity, skin temperature, and core temperature have been measured for the last 24 h of both parts. Mean daytime EE increased significantly in the lean subjects (P < 0.01), but not in the obese. Physical activity decreased significantly in the lean (P < 0.01) and the obese (P < 0.001) subjects. The change in EE was related to the change in physical activity in both groups (respectively R(2) = 0.673, P < 0.01 and R(2) = 0.454, P < 0.05). Upon mild cold exposure, lean subjects decreased proximal skin temperature less, but distal skin temperature more than obese. In conclusion, the interindividual differences in cold-induced thermogenesis were related to changes in physical activity in both lean and obese, pointing at the existence of individual variation in physical activity to compensate for cold-induced thermogenesis. Furthermore, although a large part of the lean subjects counteracted the cold by increasing EE, most obese subjects changed temperature distribution, and therefore, increased insulation.


Erratum to "Nanotechnology in Wound Healing; Semisolid Dosage Forms Containing Curcumin-Ampicillin Solid Lipid Nanoparticles, in Vitro, Ex Vivo and in Vivo Characteristics".
[This corrects the article DOI: 10.15171/apb.2018.046.].


Characterization of Prochloraz Resistance in Fusarium fujikuroi from Heilongjiang Province in China.
Prochloraz is widely used to control rice bakanae disease caused by Fusarium fujikuroi. The current study was aimed at monitoring the development of F. fujikuroi resistance to prochloraz in the Heilongjiang Province and analyzing the fitness of F. fujikuroi strains with different resistance levels. The results indicated that most of the 89 F. fujikuroi strains collected from the Heilongjiang Province were resistant to prochloraz, with resistance frequency reaching 92.1%. To assess the field resistance risk of prochloraz, 21 F. fujikuroi strains with different resistance levels were selected to investigate their biological characteristics and assess their fitness. Mycelial growth, sporulation, and germination rates were significantly different among the tested strains. However, when grouped into two subpopulations, no significant difference was tested between prochloraz-resistant and prochloraz-sensitive strains. Pathogenicity assays revealed that the disease severity index of prochloraz-resistant strains was higher than that of prochloraz-sensitive strains. Cross-resistance assays showed no cross-resistance between prochloraz and five other fungicides, namely phenamacril, ipconazole, tebuconazole, carbendazim, and fluopyram. Ffcyp51A gene overexpression was observed in the prochloraz-resistant F. fujikuroi strains after exposure to prochloraz. Collectively, these results indicated that F. fujikuroi resistance against prochloraz was severe. Furthermore, prochloraz-resistant strains were highly fit and could potentially become a dominant population in rice fields, consequently resulting in yield loss.


Artifacts in the measurement of skin temperature under infant radiant warmers.
All skin temperature probes measure, to some extent, operative temperature as well as skin temperature, and thus artifactually measure a temperature different from true skin temperature. To assess the magnitude and direction of these artifacts in the measurement of surface temperature in radiant warmers designed for human infants, the artifactual deviation of measured surface temperatures from mean surface temperature was determined under a short-wavelength warmer and a long-wavelength radiant warmer, using a copper ball as an experimental model. The measurements were made using both a disk-shaped thermistor and a tubular thermistor. All measurements were made near the top of the hemisphere of the ball facing the heating element of the warmer. In all cases, the average artifact was negative. That is, even on the surface of the ball near the radiant heat source, the surface temperature probes recorded an artifactually low temperature. In the analogous clinical setting, a somewhat larger negative artifact would be expected.


Restorative proctocolectomy for ulcerative colitis: impact on lipid metabolism and adipose tissue and serum fatty acids.
The aim of this prospective study was to evaluate the changes of the metabolism of circulating and storage lipids in patients with ulcerative colitis after restorative proctocolectomy. Fifteen consecutive patients and 15 sex- and age-matched healthy controls were enrolled. Disease activity, diet, inflammatory parameters, plasma lipoprotein concentrations, and fatty acids (FA) of serum phospholipids and of the subcutaneous adipose tissue were assessed at colectomy and at ileostomy closure. In ulcerative colitis patients, total cholesterol and docosahexaenoic acid were lower than in healthy subjects (p < 0.01 and p < 0.05). The median interval between colectomy and ileostomy closure was 6 (range 2-9) months. During that interval, the inflammatory parameters improved, high-density lipoproteins (HDL) cholesterol increased (p < 0.01), and low-density (LDL) cholesterol decreased (p = 0.01). At ileostomy closure, serum arachidonic acid levels were increased (p = 0.04), whereas serum oleic acid level was decreased (p = 0.02). In this interval, no significant alteration, either in serum n-3 FA precursors or in the FA of subcutaneous adipose tissue, was observed. The increase of serum arachidonic acid after colectomy might suggest a lower utilization for inflammatory process. The reduction of LDL cholesterol is an index of malabsorption probably due to the accelerated transit and to the exclusion of the terminal ileum caused by the covering ileostomy.


Biomonitoring equivalents for 2,2',4,4',5-pentabromodiphenylether (PBDE-99).
Biomonitoring Equivalents (BEs) are defined as the concentration or range of concentrations of a chemical or its metabolite in a biological medium (blood, urine, or other medium) that is consistent with an existing health-based exposure guideline such as a reference dose (RfD) or tolerable daily intake (TDI). BE values can be used as a screening tool for the evaluation of population-based biomonitoring data in the context of existing risk assessments. This study reviews health based risk assessments and exposure guidance values for 2,2',4,4',5-pentabromodiphenylether (PBDE-99) from Health Canada and the United States Environmental Protection Agency (US EPA). Toxicokinetic data from laboratory animals and humans are reviewed. A BE value corresponding to the US EPA RfD is derived here for PBDE-99 based on the assumption of chronic steady-state exposure, distribution into body lipids, and a previously-estimated first-order half-life of elimination of 1040days. The steady-state lipid-adjusted BE(RfD) is 520ng/g lipid. Sources of uncertainty relating to the underlying toxicokinetic and toxicologic database for PBDE-99 and the simultaneous exposure to multiple PBDE congeners are discussed. The BE(RfD) value may be used as a screening tool for evaluation of population biomonitoring data for PBDE-99 in the context of the existing US EPA risk assessment and can assist in prioritization of the potential need for additional risk assessment efforts for PBDE-99 relative to other chemicals.


Trends and age-related characteristics of substance use in the hospitalized homeless population.
We aimed to examine trends and characteristics of substance use (opioid, cocaine, marijuana, and heroin) among hospitalized homeless patients in comparison with other hospitalized patients in 3 states.This was a cross-sectional study, based on the 2007 to 2015 State Inpatient Data of Arizona, Florida, and Washington (n = 32,162,939). Use of opioid, cocaine, marijuana, heroin, respectively, was identified by the International Classification of Diseases, 9th Revision. Multi-level multivariable regressions were performed to estimate relative risk (RR) and 95% confidence intervals (CI). Dependent variables were the use of substances (opioid, cocaine, marijuana, and heroin), respectively. The main independent variable was homeless status. The subgroup analysis by age group was also conducted.Homeless patients were associated with more use of opioid (RR [CI]), 1.23 [1.20-1.26], cocaine 2.55 [2.50-2.60], marijuana 1.43 [1.40-1.46], and heroin 1.57 [1.29-1.91] compared to other hospitalized patients. All hospitalized patients including those who were homeless increased substance use except the use of cocaine (RR [CI]), 0.57 [0.55-0.58] for other patients and 0.60 [0.50-0.74] for homeless patients. In all age subgroups, homeless patients 60 years old or older were more likely to be hospitalized with all 4 types of substance use, especially, cocaine (RR [CI]), 6.33 [5.81-6.90] and heroin 5.86 [2.08-16.52] in comparison with other hospitalized patients.Homeless status is associated with high risks of substance use among hospitalized patients. Homeless elderly are particularly vulnerable to use of hard drugs including cocaine and heroin during the opioid epidemics.


Effects of flaxseed on blood pressure, body mass index, and total cholesterol in hypertensive patients: A randomized clinical trial.
Given the antioxidant properties of flaxseed and its biologically active ingredients, this study was conducted to determine the effects of flaxseed supplementation on body mass index (BMI), blood pressure, and total cholesterol levels in patients with hypertension. In this triple-blind clinical trial, 112 patients, with an age range of 35 to 70 years, were randomized to 2 groups receiving 10 g (n = 45) and 30 g (n = 45) of flaxseed supplementation and 1 group receiving placebo (n = 45) for 12 weeks by stratified block randomization. They were evaluated in terms of systolic (SBP) and diastolic blood pressure (DBP), BMI, and total serum cholesterol. Physical activity was measured using the International Physical Activity Questionnaire-Short Form (IPAQ-SF) and food intake was assessed using the Food Frequency Questionnaire (FFQ). The data were analyzed with SPSS, version 22, using the chi-square, Kruskal-Wallis, repeated measures analysis, ANOVA, and ANCOVA tests. The interaction effects among the study groups and time on the mean SBP (p = 0.001), DBP (p = 0.001), total cholesterol level (p = 0.032), and BMI (p < 0.001) were significant. During the study, the 30-g group achieved the best results, so that a 13.38-unit decrease in SBP was observed compared to a 1.72 unit increase in the placebo group and a 5.6-unit decrease in DBP was measured compared to a 2.39 unit increase in the placebo group. BMI decreased by 0.86 units compared to 0.06 units in the placebo group. Total cholesterol also decreased by 20.4 units compared to 11.86 units in the placebo group. The results of this study showed that flaxseed can be effective in reducing blood pressure, total cholesterol, and body mass index in hypertensive patients in a twelve-week period.


Overexpression of UDP-glucuronosyltransferase and cytochrome P450 enzymes confers resistance to sulfoxaflor in field populations of the aphid, Myzus persicae.
The green peach aphid, Myzus persicae, is a highly damaging, globally distributed crop pest that has evolved multiple resistance to numerous insecticides. It is thus imperative that insecticides that are not strongly compromised by pre-existing resistance are carefully managed to maximise their effective life span. Sulfoxaflor is a sulfoximine insecticide that retains efficacy against M. persicae clones that exhibit resistance to older insecticides. In the current study we monitored the efficacy of sulfoxaflor against M. persicae populations collected in Western Australia, following reports of control failures in this region. We identified clones with low (4-23-fold across multiple independent bioassay experiments), but significant, levels of resistance to sulfoxaflor compared with a reference susceptible clone. Furthermore, we demonstrate that sulfoxaflor resistance can persist after many months of culturing in the laboratory in the absence of insecticide exposure. Resistance was not conferred by known mechanisms of resistance to neonicotinoid insecticides, that act on the same target-site as sulfoxaflor, i.e. the R81T mutation or overexpresssion of the P450 gene CYP6CY3. Rather, transcriptome profiling of multiple resistant and susceptible clones identified the P450 CYP380C40 and the UDP-glucuronosyltransferase UGT344P2 as highly overexpressed (21-76-fold and 6-33-fold respectively) in the resistant clones. Transgenic expression of these genes demonstrated that they confer, low, but significant, levels of resistance to sulfoxaflor in vivo. Taken together, our data reveal the presence of low-level resistance to sulfoxaflor in M. persicae populations in Australia and uncover two novel mechanisms conferring resistance to this compound. The findings and tools generated in this study provide a platform for the development of strategies that aim to slow, prevent or overcome the evolution of more potent resistance to sulfoxaflor.


Exogenous Lipoid Pneumonia in Laryngectomy Patients: Radiological Findings.
Exogenous lipoid pneumonia (ELP) is a rare (incidence 1.0%-2.5%), often under-diagnosed disease, caused by the aspiration and accumulation of exogenous lipids within the pulmonary alveoli. Various cases have been described due to inhalation of lubricants via the nasal passages and oropharynx, aspiration of mineral oils in laxatives in patients with eating disorders, application of lip gloss, occupational exposure to liquid paraffin or mineral oils ("fire-eaters", industrial use in washing of machinery, automobile workshops, plastic paints, etc.) and application of Vaseline during the insertion of nasogastric tubes and in the care of tracheotomy patients. ELP usually presents radiologically as areas of low-attenuation peribronchial consolidation and ground glass opacities, with a predominantly bibasal distribution. We present 5 cases of long-standing laryngectomy patients diagnosed with ELP who admitted using Vaseline in their tracheal stoma care.


Effectiveness of cognitive-behavioral therapy on perceived stress among patients undergoing percutaneous coronary intervention: A randomized controlled trial.
This study aimed to determine the effectiveness of cognitive-behavioral therapy on perceived stress of patients undergoing percutaneous coronary intervention (PCI). This was a randomized clinical trial in which the patients under coronary intervention were allocated to two groups, intervention and control by using block randomization. The experiment group received eight sessions of cognitive-behavioral therapy. The patients' perceived stress was measured before, immediately, and 1-month post ntervention. The results showed the perceived stress scores changed significantly in the intervention group compared with the control group immediately and 1 month after the intervention. Therefore, the perceived stress level significantly reduced in the patients of the intervention group (p < 0.001). Cognitive-behavioral therapy significantly reduced perceived stress in patients undergoing PCI.


Phylogenetic affiliation and determination of bioactive compounds of bacterial population associated with organs of mud crab, Scylla olivacea.
Mud crab belongs to the genus Scylla is an economically valuable and preferred species for costal aquaculture in Asian countries, including India. In recent years, there has been a tremendous expansion of Scylla farming, which has led to increasing research on its habit and habitats. However, there has been no study undertaken to understand the role of the bacterial population associated with the different organs of the mud crab, Scylla olivacea. In total, 43 isolates were recovered from four selected parts of the crab (carapace, n = 18; abdomen n = 11; leg, n = 8; and hand, n = 6), and the 16S rRNA gene was used to identify the bacterial isolates. The antimicrobial potential along with the detection of modular polyketide synthase (PKSI), cytochrome P450 hydroxylase (CYP) and non-ribosomal peptide synthetase (NRPS) gene clusters were investigated to show a relationship among the biosynthetic genes with their useful aspects. Additionally, the potential three strains (BPS_CRB12, BPS_CRB14 and BPS_CRB41), which showed significant antimicrobial activities, also showed the presence of twenty volatile compounds (VOCs) using GC-MS analysis. We conclude that the strain Aneurinibacillus aneurinilyticus BPS_CRB41 could be source for the production of bioactive compounds.


Deployment and testing of an automated medical equipment service communication and documentation system at a rural hospital in Kenya.
The Medical Equipment Network Documentation System (MENDS) provides a simple communication network for equipment servicing from failure to restoration. It is a text messaging-based platform, designed to use existing technologies in place in low- and middle-income settings. The system gathers and relays information about equipment service requests and reports and automatically saves them to an online database. MENDS was deployed at a high volume, rural, charity medical facility in Kijabe, Kenya for a 3-mo pilot test. The results show MENDS more than tripled documentation and enhanced ease and speed of communication. Comprehensive data provided by MENDS created more accurate measures of equipment performance, which can be used to decrease the time that equipment is out of service and improve the efficiency of repairs, equipment quality and procurement.


Trisomy 21 as a sole acquired abnormality in an adult Omani patient with CD7- and CD9-positive acute myeloid leukemia.
We describe a case of acute myeloid leukemia (AML) in which trisomy 21 was the sole acquired cytogenetic abnormality. The immunophenotype showed positivity for CD7 and CD9 along with CD13, CD33, and CD34. The chromosomal analysis of bone marrow showed 47,XY +21 in all the metaphases analyzed. The constitutional karyotype was normal. The patient was an adult and did not have any features of Down's syndrome. The bone marrow morphology was AML-M2 as per the French-American-British (FAB) criteria. A final diagnosis of CD7- and CD9-positive AML-M2 was established with trisomy 21 as a sole cytogenetic abnormality. The patient responded remarkably well to chemotherapy and achieved complete clinical remission. This is the first case of CD7- and CD9-positive AML with trisomy 21 as a sole abnormality. A putative role for the co-expression of abnormal lymphoid markers in achieving quick remission is discussed.


Impact of bariatric surgery on circulating PCSK9 levels as a marker of cardiovascular disease risk: a meta-analysis.
This systematic review and meta-analysis focuses on PCSK9 changes in obese patients following bariatric surgery. A systematic literature search in four databases was performed. Comprehensive Meta-Analysis (CMA) V2 software used to conduct the meta-analysis. Studies were evaluated regarding heterogeneity in design, populations under investigation, and treatment duration using a random-effects model and the generic inverse variance weighting approach. A random-effect meta-regression approach was used to investigate the association with the estimated effect size. The results of the meta-analysis on 4 trials including 260 individuals demonstrated a remarkable decline of PCSK9 after bariatric surgery (WMD = -57.34 ng/ml, 95% CI: -87.97, -26.71, p < 0.001; I 2 = 96.25%). Consistently, a significant decrease of LDL-C after bariatric surgery (WMD = -22.57 mg/dl, 95% CI: -27.5, -17.574, p < 0.001; I 2 = 86.35%) was observed. PCSK9 is reduced significantly after bariatric surgery. The decrease of PCSK9 might be utilized as an independent surrogate marker of improvement of atherosclerotic cardiovascular disease risk after bariatric surgery.


Identification of a new vascular smooth muscle contracting polypeptide in Phoneutria nigriventer spider venom.
The fractionation of Phoneutria nigriventer spider venom by gel filtration (Sephadex G-10-120) followed by ion-exchange chromatography (microgranular CM-cellulose-52) resulted in sixteen fractions (CI to CXVI) from which CVII+VIII, CIX and CX+XI caused dose-dependent and short-lived contractions of both arterial and venous rabbit vessels. Fraction CX+XI was further purified by a reverse phase HPLC, and a contractile polypeptide (PNV2) was isolated. The amino terminal sequence of PNV2 (LAKRADICQPGKTSQRACET) indicated that it represents a pure polypeptide consisting of a single chain. Furthermore, the amino acid analysis of PNV2 revealed the presence of four disulfide bridges, a high content in Lys (14%), Glx (11%), and the absence of His. The global amino acid composition showed that this polypeptide is composed of 102 residues (Trp not included) with a calculated molecular weight of 12,114. Whether this peptide is responsible for the vascular alterations observed in Phoneutria envenomation, such as lung edema and priapism, remains to be further investigated.


Modulation of fear memory by retrieval and extinction: a clue for memory deconsolidation.
Memories are fragile and easily forgotten at first, but after a consolidation period of hours to weeks, are inscribed in our brains as stable traces, no longer vulnerable to conventional amnesic treatments. Retrieval of a memory renders it labile, akin to the early stages of consolidation. This phenomenon has been explored as memory reactivation, in the sense that the memory is temporarily 'deconsolidated', allowing a short time window for amnesic intervention. This window closes again after reconsolidation, which restores the stability of the memory. In contrast to this 'transient deconsolidation' and the short-spanned amnesic effects of consolidation blockers, some specific treatments can disrupt even consolidated memory, leading to apparent amnesia. We propose the term 'amnesic deconsolidation' to describe such processes that lead to disruption of consolidated memory and/or consolidated memory traces. We review studies of these 'amnesic deconsolidation' treatments that enhance memory extinction, alleviate relapse, and reverse learning-induced plasticity. The transient deconsolidation that memory retrieval induces and the amnesic deconsolidation that these regimes induce both seem to dislodge a component that stabilizes consolidated memory. Characterizing this component, at both molecular and network levels, will provide a key to developing clinical treatments for memory-related disorders and to defining the consolidated memory trace.


Upregulation of C4 characteristics does not consistently improve photosynthetic performance in intraspecific hybrids of a grass.
C4 photosynthesis is thought to have evolved via intermediate stages, with changes towards the C4 phenotype gradually enhancing photosynthetic performance. This hypothesis is widely supported by modelling studies, but experimental tests are missing. Mixing of C4 components to generate artificial intermediates can be achieved via crossing, and the grass Alloteropsis semialata represents an outstanding study system since it includes C4 and non-C4 populations. Here, we analyse F1 hybrids between C3 and C4 , and C3 +C4 and C4 genotypes to determine whether the acquisition of C4 characteristics increases photosynthetic performance. The hybrids have leaf anatomical characters and C4 gene expression profiles that are largely intermediate between those of their parents. Carbon isotope ratios are similarly intermediate, which suggests that a partial C4 cycle coexists with C3 carbon fixation in the hybrids. This partial C4 phenotype is associated with C4 -like photosynthetic efficiency in C3 +C4 × C4 , but not in C3 × C4 hybrids, which are overall less efficient than both parents. Our results support the hypothesis that the photosynthetic gains from the upregulation of C4 characteristics depend on coordinated changes in anatomy and biochemistry. The order of acquisition of C4 components is thus constrained, with C3 +C4 species providing an essential step for C4 evolution.


Bovine papillomavirus genome elicits skin tumours in transgenic mice.
Transmission of the bovine papillomavirus-1 (BPV-1) genome through the mouse germ line results in the heritable formation of fibropapillomas of the skin, a tissue-specific phenotype analogous to that observed in natural BPV-1 infection of cattle. Oncogenesis is slow, with tumours first arising at 8-9 months of age, usually in areas prone to wounding. Extrachromosomal BPV-1 DNA is detected in all tumours, whereas normal tissues show only integrated DNA.