Microscale Spatiotemporal Variation and Generation Mechanisms of Reactive Oxygen Species in the Rhizosphere of Ryegrass: Coupled Biotic-Abiotic Processes.
Reactive oxygen species (ROS) play key roles in soil biogeochemical processes, yet the occurrence and accumulation of ROS in the rhizosphere are poorly documented. Herein, we first developed a ROS-trapping membrane to in situ determine ROS in the ryegrass rhizosphere and then quantified the temporal and spatial variations of representative ROS (i.e., O2•─, H2O2, and •OH). Fluorescence imaging clearly visualized the production of ROS in the rhizosphere. Both O2•─ and H2O2 content increased first and then declined throughout the life cycle of ryegrass, while •OH concentration decreased continuously. Spatially, ROS contents remained at a relatively high level at 0-5 mm and then descended with increasing distance. The concentrations of ROS in different soils followed the order of black soil > latosol soil > yellow-brown soil > tier soil ∼ red soil. Analysis of soil properties suggested that both biotic factors (microbial community) and abiotic factors (Fe(II) and water-soluble phenols) played critical roles in ROS production. The combined processes, including Fe(II) and water-soluble phenol-mediated electron transfer, microbial community-driven extracellular O2•─ release, and Fe(II)/Fe(III) cycling, may be responsible for ROS production. These findings provide insights into ROS-associated rhizosphere effects and inspiration for the phytoremediation of pollutants and element cycling.


Single percutaneous access for endoscopic extraction of lithiasis after intestinocystoplasty.
Bladder-stone formation is a common problem following augmentation cystoplasty. Urological management is controversial. We describe a minimally invasive technique using electrohydraulic vesicolithotripsy via a single percutaneous access. Between 1998 and 2004, 10 percutaneous extractions of bladder calculi were performed in seven patients with bladder augmentation. Prior bladder enlargement was performed for neuropathic bladder dysfunction in four cases and bladder exstrophy in three cases. The procedure involved percutaneous placement of a 10- or 12-mm laparoscopic trocar, after which the airtightness valve of the trocar was removed. A rigid nephroscope allowed direct visualization of calculi. Stones were fragmented with electrohydraulic lithotripsy when necessary. Removal of the fragments was by grasping forceps or basket. Vigorous, warmed-saline bladder irrigation eliminated residual fragments. The technique was successful in all cases, resulting in controlled bladder-stone-free status and no surgical complications. The only complication was hypothermia linked to prolonged operation time, inadequate warmed-saline irrigation and lack of waterproof sheets. Percutaneous vesicolithotripsy was highly successful and easy to perform, without being restricted by size and number of calculi. The continence mechanism of a reconstructed urethra or Mitrofanoff conduit should not be compromised. As recurrent stone formation is expected in children with augmented bladder, this technique appears to be suitable for bladder calculi removal during the long-term follow-up of multioperated patients.


Gender modulates the aging effects on different patterns of early repolarization.
Distinct patterns of early repolarization (ER) are associated with ventricular fibrillation and arrhythmic death. We evaluated whether gender modulated the aging effects on different ER patterns. We studied manifestations of ER in the anterior, inferior, and lateral leads on standard 12-lead electrocardiography from male (n = 1077) and female (n = 1170) individuals of young (≤44 years), middle-aged (45-64 years), and elderly (≥65 years) subjects. Among a total of 2247 individuals, 543 (24.2 %) subjects had ER and 417 (18.6 %) had single-location ER. Single-location ER occurred less in lateral leads than in anterior or inferior leads (2.1, 7.8, 8.6 %, respectively, p < 0.05). Subjects with inferior ER (n = 193) were older (61 ± 14, 49 ± 14, 54 ± 16 years, respectively, p < 0.05) than those with anterior (n = 176) or lateral (n = 48) ER. In males with ER, the elderly group (n = 22) had fewer instances of anterior ER (34, 59, 80 %, respectively, p < 0.05) than middle-aged (n = 76) or young (n = 59) groups. Elderly males (n = 37) and females (n = 48) had greater instances of inferior ER (57, 32, 19 %, p < 0.05; 86, 62, 46 %, respectively, p < 0.05) than middle-aged males (n = 41) and females (n = 41), and young males (n = 14) and females (n = 12), respectively. In conclusion, gender modulates the aging effects on the occurrences of anterior ER and inferior ER.


Efficacy and tolerability of ophthalmic epinastine: a randomized, double-masked, parallel-group, active- and vehicle-controlled environmental trial in patients with seasonal allergic conjunctivitis.
Epinastine hydrochloride is an antihistamine with mast cell-stabilizing and anti-inflammatory activity. The aim of this study was to assess the efficacy and tolerability of ophthalmic epinastine in patients with seasonal allergic conjunctivitis (SAC) exposed to environmental allergens. This randomized (age-stratified), double-masked, parallel-group, active- and vehicle-controlled, environmental, Phase III clinical trial was conducted at 6 ophthalmology clinics in the United States. Patients aged >or=9 years diagnosed with SAC and who had a positive reaction in a conjunctival allergen challenge were enrolled. Patients were randomly assigned in a 2:2:1 ratio to receive 1 drop/eye BID of epinastine hydrochloride 0.05% ophthalmic solution, levocabastine hydrochloride 0.05% ophthalmic suspension, or vehicle of epinastine, respectively, for 8 weeks. The primary end point was ocular itching, and secondary end points included ocular hyperemia, chemosis, ocular mucous discharge (all assessed on a 5-point scale), eyelid swelling (assessed on a 4-point scale), and tearing (present or absent). Efficacy analyses used assessments from the two 1-week periods with the highest pollen counts. For tolerability assessment slit-lamp biomicroscopy and visual acuity examinations were conducted at each study visit (weeks 0, 2, 4, 6, and 8). Two-hundred ninety-eight patients (159 females, 139 males; mean [SD] age, 32.7 [14.6] years [range, 9-71 years]) entered the study; 118 received epinastine, 118 received levocabastine, and 62 received vehicle. Epinastine-treated patients reported significantly less ocular itching than those receiving vehicle (P=0.045); scores for hyperemia were similar between these 2 groups. Ocular itching and hyperemia scores were similar between the epinastine and levocabastine groups. No clinically or statistically significant between-group differences were seen in slit-lamp biomicroscopy findings, changes in visual acuity from baseline, or the incidence of treatment-related adverse effects. In this study of patients with SAC, ophthalmic epinastine instilled twice daily was more effective than vehicle for the control of ocular itching and was similar in efficacy to levocabastine for control of ocular itching and hyperemia. Epinastine was well tolerated.


Deaths from injury in children and employment status in family: analysis of trends in class specific death rates.
To examine socioeconomic inequalities in rates of death from injury in children in England and Wales. Analysis of rates of death from injury in children by the eight class version of the National Statistics Socio-Economic Classification (NS-SEC) and by the registrar general's social classification. England and Wales during periods of four years around the 1981, 1991, and 2001 censuses. Children aged 0-15 years. Death rates from injury and poisoning. Rates of death from injury in children fell from 11.1 deaths (95% confidence interval 10.8 to 11.5 deaths) per 100,000 children per year around the 1981 census to 4.0 deaths (3.8 to 4.2 deaths) per 100,000 children per year around the 2001 census. Socioeconomic inequalities remain: the death rate from all external causes for children of parents classified as never having worked or as long term unemployed (NS-SEC 8) was 13.1 (10.3 to 16.5) times that for children in NS-SEC 1(higher managerial/professional occupations). For deaths as pedestrians the rate in NS-SEC 8 was 20.6 (10.6 to 39.9) times higher than in NS-SEC 1; for deaths as cyclists it was 27.5 (6.4 to 118.2) times higher; for deaths due to fires it was 37.7 (11.6 to 121.9) times higher; and for deaths of undetermined intent it was 32.6 (15.8 to 67.2) times higher. Overall rates of death from injury and poisoning in children have fallen in England and Wales over the past 20 years, except for rates in children in families in which no adult is in paid employment. Serious inequalities in injury death rates remain, particularly for pedestrians, cyclists, house fires, and deaths of undetermined intent.


Female choice and the MHC.
In animals, it is the female that typically selects a mating partner. This decision can occur before, during and after copulation. Here, recent evidence for the involvement of genes within the MHC in female choice is reviewed and the roles of MHC I and II antigens, various types of chemoreceptors, as well as MHC-encoded transcription factors, in securing an optimal genetic constitution of the offspring are discussed. Some particularly interesting and as yet unanswered questions are raised and some experiments that could provide deeper insight into the molecular mechanisms underlying female choice are suggested.


Gain-of-"endocytic' function in mutant p53 cancer cells.
Beyond its well-known canonical function as a tumor suppressor, p53 is also involved in numerous cellular processes through altered transcription under both normal and pathological conditions. The functional diversity of p53 outputs is complex and dependent on cell context. However, the underlying mechanisms responsible for this diversity remain largely unclear. The emerging evidence of p53 mutations involved in regulating endocytic trafficking and signaling, in tandem to promote malignancy (invasion, exosome biogenesis and immune evasion), sheds light on possible mechanisms behind the p53-driven complexity. The interrelated nature of endocytic trafficking and receptor signaling that form dynamic and adaptable feedback loops - either positive or negative - functions to modulate multiple cellular outputs. Biasing the tunable endocytic trafficking and receptor signaling network by mutant p53 expands the purview of p53, allowing its contribution to diverse and aggressive phenotypes. In this review, we explore recent studies in which the novel role of mutant p53 in altering endocytic trafficking to bias receptor signaling and drive transforming phenotypes is revealed. Understanding the complex crosstalk of mutant p53, endocytic trafficking and receptor signaling will allow the development of therapies to selectively target p53-altered endocytic processes.


Purification mechanism of microbial metabolism in kitchen-oil wastewater enhanced by cationic vacancies on γ-Al2O3.
The use of catalyst materials to mediate the enhancement of microbial degradation in wastewater is a new economic and energy saving breakthrough in water treatment technology. In this study, γ-Al2O3, which is commonly used as catalyst/carrier, is used as biological filler to treat kitchen-oil wastewater with low biodegradability, and the COD removal rate is about 50 %. It is found that the complexation of cationic vacancies on Al2O3 surface with extracellular polymeric substance (EPS) secreted by microorganisms in wastewater lead to the polarization of electron distribution on biofilm. The efficient degrading bacteria are enriched on reaction interface and obtain electrons to maintain electron dynamic balance by enhancing the transmembrane metabolism of pollutants. The aluminum vacancies on Al2O3 surface accelerate the microbial degradation of pollutants. The cationic vacancies in the structure of catalyst accelerate the acquisition of exogenous electrons by microorganisms without the addition of external energy, which provides a new idea for catalytic fillers to enhance wastewater degradation.


Single-lung transplantation in emphysematous patients.
We report six single-lung transplantations in emphysematous patients with end-stage disease. Compression of the graft or ventilation/perfusion imbalance were not observed. Rejection episodes were generally documented through transbronchial biopsies and the radiological changes related to acute infections or rejections were restricted to the transplanted lung. Three patients died from CMV pneumonia, status epilepticus and fibrosis of the graft following bronchography, respectively. The three remaining patients are well, with documented improvement of pulmonary function tests and arterial blood gases. Bronchial complications were observed in all patients and have in some cases required dilatation or insertion of a stent. Although requiring a longer follow up, single transplantation is feasible and beneficial in patients with end-stage emphysema.


Targeted manipulation of apoptotic pathways by using High Intensity Focused Ultrasound in cancer treatment.
Apoptosis, or programmed cell death, is a mechanism of cell death, which has been exploited for the treatment of cancers over the past few years. The understanding of apoptosis pathways (intrinsic and extrinsic) has led to discovery of treatment strategies which selectively target the cancer cells and spare the normal ones. This article reviews the current understanding of the apoptotic pathways which are utilized for targeting cancer cells using High Intensity Focused Ultrasound (HIFU).


Transcriptional inhibition of matrix metalloproteinase 9 (MMP-9) activity by a c-fos/estrogen receptor fusion protein is mediated by the proximal AP-1 site of the MMP-9 promoter and correlates with reduced tumor cell invasion.
Tumor cell invasion of basement membranes is one of the hallmarks of malignant transformation. Tumor cells secrete proteolytic enzymes known as matrix metalloproteinases (MMPs) which degrade extracellular matrix molecules. Increased expression of MMP-9 has been associated with acquisition of invasive phenotype in many tumors. However, multiple mechanisms for regulation of MMP-9 gene expression by tumor cell lines have been proposed. A number of transcription factor binding sites have been characterized in the upstream regulatory region of the MMP-9 gene, including those for AP-1. To determine how a specific AP-1 family member, c-fos, regulates MMP-9 promoter activity through these sites, we used an expression vector containing the c-fos coding region fused to the estrogen receptor (ER) ligand binding domain. This construct is activated upon binding estradiol. Stable expression of this construct in ER negative squamous cell carcinoma (SCC) lines produced an estradiol dependent decrease in the number of cells that migrated through a reconstituted basement membrane. This decreased invasiveness was accompanied by estradiol dependent downregulation of MMP-9 activity as determined by gelatin zymography. Estradiol also produced transcriptional downregulation of an MMP-9 promoter construct in cells transiently transfected with the c-fosER expression vector. This downregulation was mediated by the AP-1 site at -79 bp in the MMP-9 promoter. We concluded that the proximal AP-1 site mediated the transcriptional downregulation of the MMP-9 promoter by a conditionally activated c-fos fusion protein.


Chronic administration of a norepinephrine antagonist prevents and partially reverses escalation of cocaine self-administration.
Anxiety is a critical component of the development and maintenance of drug addiction; however, anti-anxiety medications such as benzodiazepines and beta-blockers (β-adrenergic receptor antagonists) are not used for the treatment of substance use disorder, except for the management of acute withdrawal syndrome. Preclinical studies have shown that beta-blockers may reduce stress-induced relapse; however, the effect of beta blockers on the escalation and maintenance of drug intake has not been tested. To address this issue, we chronically administered the β-adrenergic receptor antagonist propranolol during the escalation or maintenance of cocaine intake in a model of extended access (6 h) to cocaine self-administration (0.5 mg/kg). The behavioural specificity of propranolol was tested using a non-drug reward (saccharin). Daily administration of propranolol (15 mg/kg) prevented the development of escalation of cocaine self-administration and partially reversed self-administration after the establishment of escalation of intake. Moreover, propranolol dose-dependently decreased the motivation for cocaine tested under a progressive ratio schedule of reinforcement during the development of escalation and after maintenance. Finally, propranolol administration had no effect on the escalation and maintenance of saccharin self-administration. These results demonstrate that chronic treatment with propranolol provides therapeutic efficacy in reducing cocaine self-administration during the development and after the establishment of escalation of cocaine self-administration in an animal model relevant to cocaine use disorder. These results suggest that beta blockers should be further investigated as a target for medication development for the treatment of cocaine use disorder.


Parental age, family size, and offspring's risk of childhood and adult acute leukemia.
An association between childhood acute leukemia and advanced parental age was observed more than 50 years ago, and the association has been repeated in several, but not all, subsequent studies. In contrast to the many studies addressing childhood leukemia, few have included adult patients. In this register-based case-control study, we examined the association between parental age and incidence of acute leukemia in 2,660 childhood cases and 4,412 adult cases of acute leukemia, compared with 28,288 age-matched controls selected from a population-based register. Relative risks were estimated with conditional logistic regression. We found a small increased risk of childhood acute lymphoblastic leukemia with increasing paternal age (adjusted OR, 1.05 per 5-year increase in age). Risk estimates were similar for childhood acute myeloid leukemia (AML), whereas no association was found with adult leukemia. Meanwhile, we observed a decreased risk of adult AML with increasing number of siblings, both older and younger. The results support the idea of a prenatal etiology of leukemia but indicate that parental age effects are limited to childhood cases. This is the first large study on parental age and leukemia risk, which includes adult cases. The finding on family size and risk of adult AML needs to be validated in future studies.


A spontaneous giant pseudoaneurysm presenting with chronic headache in adolescent.
Intracranial pseudoaneurysms are rare vascular lesions, particularly in children and adolescents, and are characterized by the presence of organizing hematoma and fibrosis outside the true lumen, instead of true vascular elements. Most pseudoaneurysms result from an eminent insult, such as major trauma or grave infectious illness. Development of pseudoaneurysm without antecedent incident is rare. Furthermore, clinical manifestation with only a headache is also unusual in this age group. We now describe one patient who had a giant pseudoaneurysm arising at the distal middle cerebral artery. A 17-year-old boy complained of headache that had become apparent 3 years ago and intractable to medicine 3 months ago. Brain computed tomographic scan and lumbar cerebrospinal spinal fluid study revealed no trace of recent hemorrhage. However, digital subtraction angiography revealed a huge aneurysmal dilatation along the right M2 segment with the features of delayed filling and emptying of contrast agent. Surgical obliteration of the corresponding aneurysm with tandem clipping and aneurysmectomy rendered him free of headache thereafter. The actual cause and mechanisms of this case are not certain; nonetheless, we suggest that traumatic cause produced such a lesion, and minor repeated bleeding also elicited headache, albeit no evidence of recent major injury.


Elevated plasma activator inhibitor 1 is not related to insulin resistance and to gene polymorphism in healthy centenarians.
Previous studies demonstrated a relationship between the degree of insulin resistance and plasma plasminogen activator inhibitor type-1 (PAI-1) levels. We aim at investigating the relationship between the degree of insulin resistance and plasma PAI-1 levels in aged subjects (n=83) and in healthy centenarians (n=42). In all subjects the degree of insulin resistance was assessed by HOMA method. Our data demonstrated that healthy centenarians have higher plasma PAI-1 levels (73.1+/-13.9 vs 23.7+/-14.7 ng/ml, P<0.001) and lower degree of insulin resistance (1.4+/-0.5 vs 3.3+/-1.3, P<0.001) than aged subjects. In aged subjects plasma PAI-1 levels correlated with the degree of insulin resistance (r=0.61, P<0.001), fasting plasma triglycerides (r=0.74, P<0.001) and age (r=0.33, P<0.001). All such associations were lost in centenarians. Plasma PAI-1 Ag levels were also similar in aged subjects and centenarians even after categorization for PAI gene polymorphism. In multivariate analysis, a model made by age, sex, body mass index, fasting plasma triglycerides, HOMA and PAI-1 gene explained 65 and 50% of plasma PAI-1 level variations in aged subjects and centenarians, respectively. Nevertheless, HOMA (P<0.001) was significantly and independently associated with plasma PAI-1 levels only in aged subjects. In conclusion, our data demonstrates that in healthy centenarians, plasma PAI-1 were not associated with the degree of insulin resistance as in aged subjects. Frequency of PAI-1 genotype does not provide an explanation for such differences between aged subjects and centenarians.


Studies on the bioactive flavonoids isolated from Pithecellobium clypearia Benth.
One new flavonoid named (2R,3R)-7-O-galloylplumbocatechin A (1) and three known flavonoids, (-)-5,3',4',5'-tetrahydroxyflavan-7-gallate (2), (+)-3,5,3',4',5'-penta-hydroxyflavan-7-gallate (3), and (-)-7,4'-di-O-galloyltricetiflavan (4), were isolated from Pithecellobium clypearia Benth. Their structures were elucidated based on spectroscopic analysis, including homonuclear and heteronuclear correlation NMR (HSQC and HMBC) experiments. In vitro assays, compounds 1 and 2 showed moderate inhibitory effects against influenza H1N1 virus neuraminidase (NA). Compounds 1-4 were all found to inhibit the expression of proinflammatory cytokines IL-6 or MCP-1 induced by influenza H1N1 virus in human A549 lung carcinoma cells.


A Comparison of the Diagnostic Efficiency of Guided Fine Needle Aspiration Cytology Versus Conventional Fine Needle Aspiration Cytology of the Thyroid.
Fine needle aspiration cytology (FNAC) is possibly the most useful investigation for the thyroid. However, conventional FNAC (C-FNAC) is limited by a high rate of inadequate samples. Ultrasound guided FNAC (US-FNAC) has been proposed as an alternative. This study aims to estimate the measures of diagnostic accuracy of FNAC as well as to compare US-FNAC against C-FNAC. Patients who underwent FNAC at our for a period of 5 years were selected. This comprised of 237 C-FNAC cases and 173 US-FNAC cases. Out of these 410 cases, 129 cases had cyto-histological correlation. The proportion of inadequate samples, malignant cases as well as indeterminate cases were compared between US-FNAC and C-FNAC. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), likelihood ratios for positive and negative results and odds ratio were estimated for overall FNAC as well as US-FNAC and C-FNAC patients. US-FNAC has a significantly lower proportion of inadequate samples (0.58 vs. 15.19%), as well as a lower proportion of indeterminate samples (1.7 vs. 7.6%) and a higher proportion of malignant cases (6.4 vs. 2.1%). When the inadequate samples were excluded, the results for tests of diagnostic effectiveness for overall FNAC, US-FNAC and C-FNAC respectively ranged between 66.67 and 80% for sensitivity, between 86.05 and 100% for specificity, between 45.45 and 100% for PPV and between 97.37 and 98.7% for NPV. FNAC is a useful test for differentiating malignant from benign lesions. When inadequate samples are excluded, both US-FNAC and C-FNAC are accurate diagnostic tests. However, US-FNAC is a more useful test since it results in a lower number of inadequate samples. Also, US-FNAC results in a greater yield of malignancy and a lower percentage of indeterminates, possibly due to additional information received from ultrasound examination.


The Effects of Phonological Short Term Memory on Lexical and Grammatical Production Skills in Persian Children with Developmental Language Disorder.
The deficit in verbal working memory (vWM) skills has been frequently reported in children with developmental language disorder (DLD) and may contribute to their problems in language. This study aimed to compare the phonological short-term memory (pSTM) and linguistic skills between Persian-speaking children with DLD and typical language development (TLD) to explore the role that pSTM plays in lexical and grammatical problems of children with DLD. This study included 32 Persian-speaking children who were divided into two groups of DLD (n = 16) and TLD (n = 16) within the age range from 6 to 8 years. The Persian non-word repetition test was employed as the measure of pSTM. Lexical and grammatical indices were extracted from narrative generations. Independent-samples t test was used to analyze the group-related differences in vWM, lexical, and grammatical skills. Moreover, the one-way ANCOVA analysis by controlling for NWR was utilized as the covariate to investigate the effects of vWM on linguistic performances. According to the results, the children with DLD scored significantly lower on NWR task and all lexical and grammatical measures, compared to TLD children (P < 0.01, d > 1). The group-related differences disappeared after controlling for NWR (P > 0.05). The results show that Persian-speaking children with DLD experience significant difficulties in pSTM skills, which affect their lexical and grammatical performances.


Paenibacillus sinensis sp. nov., a nitrogen-fixing species isolated from plant rhizospheres.
Two strains HN-1T and 39 were isolated from rhizospheres of different plants grown in different regions of PR China. The two strains exhibited high nitrogenase activities and possessed almost identical 16S rRNA gene sequences. The average nucleotide identity (ANI) and digital DNA-DNA hybridization (dDDH) values between the two strains were 99.9 and 99.8%, respectively, suggesting that they belong to one species. Phylogenetic analysis based on the 16S rRNA gene sequence showed that strains HN-1T and 39 are the members of the genus Paenibacillus and both strains exhibited 99.5% similarity to Paenibacillus stellifer DSM 14472T and the both strains represented a separate lineage from all other Paenibacillus species. However, the ANI of type strain HN-1T with P. stellifer DSM 14472T was 90.69, which was below the recommended threshold value (< 95-96% ANI). The dDDH showed 42.1% relatedness between strain HN-1T and P. stellifer DSM 14472T, which was lower than the recommended threshold value (dDDH < 70%). The strain HN-1T contain anteiso-C15:0 as major fatty acids and MK-7 as predominant isoprenoid quinone. The major polar lipids were diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, four aminophospholipids and an unidentified glycolipid. Unlike the most closely related P. stellifer DSM 14472T, strain HN-1T or 39 was positive for catalase reaction. Distinct phenotypic and genomic characterisations from previously described taxa support the classification of strains HN-1T or 39 as representatives of a novel species of the genus Paenibacillus, for which the name Paenibacillus sinensis is proposed, with type strains HN-1T (=CGMCC 1.18902, JCM 34,620), and reference strain 39 (=CGMCC 1.18879, JCM 34,616), respectively.


Relationship of corporal punishment and antisocial behavior by neighborhood.
To examine the relationship of corporal punishment with children's behavior problems while accounting for neighborhood context and while using stronger statistical methods than previous literature in this area, and to examine whether different levels of corporal punishment have different effects in different neighborhood contexts. Longitudinal cohort study. General community. 1943 mother-child pairs from the National Longitudinal Survey of Youth. Internalizing and externalizing behavior problem scales of the Behavior Problems Index. Parental use of corporal punishment was associated with a 0.71 increase (P<.05) in children's externalizing behavior problems even when several parenting behaviors, neighborhood quality, and all time-invariant variables were accounted for. The association of corporal punishment and children's externalizing behavior problems was not dependent on neighborhood context. The research found no discernible relationship between corporal punishment and internalizing behavior problems.


Health-Related Quality of Life of HIV-Positive and HIV-Negative Pregnant Women in an Impoverished Area: Cross-sectional Study.
Liangshan prefecture of Sichuan province was an impoverished mountainous area in China, where the annual number of HIV-positive pregnant women accounted for approximately 10% of China's total population in the decades before 2020. In general, pregnant women living here are likely to be physically and mentally different from those in other places. This study aims to explore the health-related quality of life (HRQoL) of pregnant women living with HIV in an impoverished area. From December 2018 to January 2019, HIV-positive and HIV-negative parturients within 18 months after delivery were recruited in Liangshan Prefecture, Sichuan Province. Questionnaires were designed to collect their demographic data, while the EuroQol 5-Dimension, 3-Level questionnaire was used to measure their HRQoL when they were in the second trimester from 4 to 6 months of pregnancy, and their quantitative health scores were converted to corresponding healthy utility values by using the Chinese Utility Value Integral System (time trade-off coefficient). A total of 250 pregnant women (133 HIV-positive and 117 HIV-negative) were enrolled in the study. Among them, 55 (41.35%) and 75 (64.10%) of HIV-positive and HIV-negative pregnant women self-reported full health (healthy state 11111), respectively. The median health utility value of the 250 pregnant women was 0.961 (IQR -0.046 to 0.961), and those of the HIV-positive and HIV-negative pregnant women were 0.875 (0.424-0.961) and 0.961 (IQR -0.046 to 0.961), respectively. We observed a significant difference only in the dimension of anxiety or depression between the two groups (P=.002) and no significant difference in the distribution of health utility indices between the two groups in terms of maternal age, education level, occupation, annual household income, prenatal care visits, family size, and medical insurance category. Multivariate ordinal logistic regression analysis showed that age (odds ratio [OR] 0.62, P<.05) and prenatal care visit (OR 0.29, P<.01) were independent risk factors for health status. Most pregnant women self-reported satisfactory HRQoL in this impoverished mountainous area. HIV-negative pregnant women had an edge over HIV-positive pregnant women, and there were significant differences in anxiety or depression dimensions between the two groups.


Household costs associated with seeking malaria treatment during pregnancy: evidence from Burkina Faso and The Gambia.
Malaria in pregnancy remains a major health threat in sub-Saharan Africa to both expectant mothers and their unborn children. To date, there have been very few studies focused on the out of pocket costs associated with seeking treatment for malaria during pregnancy. A cross-sectional survey was undertaken in Burkina Faso and The Gambia to estimate the direct and indirect costs associated with outpatient consultations (OP) and inpatient admissions (IP). Direct costs were broken down into medical (admission fees, drug charges, and laboratory fees), and non-medical (transportation and food). Indirect costs reflected time lost due to illness. In total, 220 pregnant women in Burkina Faso and 263 in The Gambia were interviewed about their treatment seeking decisions, expenditure, time use and financial support associated with each malaria episode. In Burkina Faso 6.7% sought treatment elsewhere before their OP visits, and 27.1% before their IP visits. This compares to 1.3% for OP and 25.92% for IP in The Gambia. Once at the facility, the average direct costs (out of pocket) were 3.91US$ for an OP visit and 15.38US$ of an IP visit in Burkina Faso, and 0.80US$ for an OP visit and 9.19US$ for an IP visit in The Gambia. Inpatient direct costs were driven by drug costs (9.27US$) and transportation costs (2.72US$) in Burkina Faso and drug costs (3.44 US$) and food costs (3.44 US$) in The Gambia. Indirect costs of IP visits, valued as the opportunity cost of time lost due to the illness, were estimated at 11.85US$ in Burkina Faso and 4.07US$ in The Gambia. The difference across the two countries was mainly due to the longer time of hospitalization in Burkina Faso compared to The Gambia. In The Gambia, the vast majority of pregnant women reported receiving financial support from family members living abroad, most commonly siblings (65%). High malaria treatment costs are incurred by pregnant women in Burkina Faso and The Gambia. Beyond the medical costs of fees and drugs, costs in terms of transport, food and time are significant drivers. The role of remittances, particularly their effect on accessing health care, needs further investigation.


Effects of 5,7-dihydroxytryptamine lesions of the nucleus accumbens on rat intravenous morphine self-administration.
The role of serotonergic innervations of the nucleus accumbens in the processes maintaining intravenous morphine self-administration were assessed. Pairs of male rat littermates were implanted with intravenous jugular catheters and bilateral injection guide cannulae into the central medial nucleus accumbens, made physically dependent on morphine and then allowed to intravenously self-administer with continuous access. When stable baselines of drug intake were obtained (2-3 weeks), one of each pair received bilateral microinjections of vehicle and the other 5,7-dihydroxytryptamine (5,7-DHT) into the nucleus accumbens. Response independent infusions of morphine were delivered for 24 hours at the previous rate of self-injection and the animals were again allowed to self-administer while drug intake was monitored for thirteen days. The littermate pairs were then sacrificed by immersion in liquid nitrogen, the brains removed at -20 degrees C and frozen sections of the cannulae tract taken for histological assessment. The nucleus accumbens, anterior caudate nucleus and pyriform cortex were removed at -20 degrees C and biogenic monoamine content determined. The 5,7-DHT lesions resulted in a significant increase in drug intake and significantly decreased the content of serotonin (5-HT) and 5-hydroxyindoleacetic acid in the nucleus accumbens (-49% and -30%, respectively) and 5-HT in the anterior caudate nucleus (-14%) and pyriform cortex (-17%). Dose-effect relationships were assessed in four additional animals before and after similar bilateral 5,7-DHT lesions.(ABSTRACT TRUNCATED AT 250 WORDS)


Cardiac output and its distribution in peritonitis. (Septic) shock in the rat.
Cardiac output and its distribution were studied in rats made septic by an i.p. injection of live E. coli bacteria and in controls given an equivalent amount of saline. The E. coli injection was followed by signs of severe shock in eight of 12 rats. Control animals all survived with only minor changes in cardiac output and peripheral hemodynamics. Blood flow in shocked animals was characterized by a reduction of cardiac output, while myocardial and cerebral flows were not reduced. The intact circulation to the brain and to the heart in the shocked rats was at the expense of kidney, spleen, and skin blood flows.


Clinical study on empirical and diagnostic-driven (pre-emptive) therapy of voriconazole in severe aplastic anaemia patients with invasive fungal disease after intensive immunosuppressive therapy.
The aim of this study is to compare the curative effect of empirical with diagnostic-driven (pre-emptive) therapy of voriconazole in severe aplastic anaemia patients (SAAs) with invasive fungal disease (IFD) after intensive immunosuppressive therapy (IST). Patients undergoing voriconazole antifungal therapy were randomized to empirical therapy group and diagnostic-driven therapy group. Empirical therapy group accounted for 48.5% of all cases, and diagnostic-driven therapy group accounted for 51.5%. The morbidity of IFD (probable and proven cases) was slightly increased in diagnostic-driven therapy group compared with empirical therapy group (P > 0.05). The total effective rate was 62.1%. The effective rate in empirical therapy group was 78.1%, which was significantly increased compared with diagnostic-driven therapy group (47.1%) (P < 0.05). This value was especially significant in possible IFD cases (P < 0.05). The efficacy of possible IFD cases in empirical therapy group was the best (84%) followed by the probable and proven cases in empirical therapy group (57.1%). In diagnostic-driven therapy group, the efficacy of possible IFD cases was 50%, and the efficacy of probable and proven cases was only 37.5%. The difference was statistically significant (P < 0.05). Absolute neutrophil count (ANC) is the key anti-infection factor. The efficacy of patients whose ANC ˂ 0.1 × 109/L was 39.28%, which was significantly reduced compared with that of patients whose ANC ≥ 0.1 × 109/L (78.95%) (P < 0.05). This finding was especially obvious in diagnostic-driven therapy group. As empirical therapy is superior to diagnostic-driven therapy, we recommend that empirical therapy should be started for high-risk patients, and efforts should be made to definitively diagnose the disease.


Microfluidic generation of magnetic-fluorescent Janus microparticles for biomolecular detection.
Fluorescent magnetic multifunctional microparticles were fabricated by a facile droplet microfluidic strategy. Two sodium alginate streams, one doped with Fe3O4 nanoparticles (NPs) and the other with CdSe/ZnS quantum dots, were introduced into a flow-focusing channel as a type of parallel laminar flow to form droplets containing two distinct parts. Then, at the serpentine channel, the Ca(2+) in the oil phase diffused into the droplets, causing the solidification of the droplets. Thus, the Janus microparticles with excellent magnetic/fluorescent properties formed. The flow conditions were optimized and the effects of the flow rates on magnetic/fluorescent compositions were carefully investigated. Luminescent labeling and magnetic separation were simultaneously realized with the newly designed microparticles. Moreover, spatial separation between Fe3O4 NPs and QDs prevented the interference of QDs photoluminescence by the magnetic particles. The as-prepared fluorescent magnetic Janus particles were also successfully employed for DNA assay, which demonstrated the potential of the multifunctional microbeads in biological applications.


Peptide alpha-amidation: differential regulation by disulfiram and its metabolite, diethyldithiocarbamate.
The rate limiting step in the alpha-amidation of bioactive peptides is catalyzed by peptidylglycine-alpha-hydroxylating mono-oxygenase (PHM; EC 220.127.116.11). Sustained treatment with disulfiram (Antabuse), the disulfide dimer of diethyldithiocarbamate (DDC), inhibits PHM in vivo, causing tissue levels of alpha-amidated peptides to decrease. As a compensatory response, PHM protein is modified in such a way that its activity is increased when assayed under optimal conditions in a test tube. Because disulfiram is rapidly reduced to DDC in vivo, this investigation sought to determine if metabolic transformation plays a role in the effects of disulfiram treatment on alpha-amidation. While disulfiram treatment reduced concentrations of alpha-amidated peptides in the pituitary neurointermediate lobe and brain, DDC treatment did not, even at comparatively high doses. Both treatments increased the activity of PHM extracted from the neurointermediate pituitary and assayed under optimal copper conditions in vitro. Only disulfiram treatment elicited an increase in PHM activity extracted from cardiac atrium. It is concluded that the activity of PHM is regulated in a tissue specific fashion and that not all of the actions of disulfiram require its metabolism to DDC.


Chronic Akt activation accentuates aging-induced cardiac hypertrophy and myocardial contractile dysfunction: role of autophagy.
Aging is often accompanied with geometric and functional changes in the heart, although the underlying mechanisms remain unclear. Recent evidence has described a potential role of Akt and autophagy in aging-associated organ deterioration. This study was to examine the impact of cardiac-specific Akt activation on aging-induced cardiac geometric and functional changes and underlying mechanisms involved. Cardiac geometry, contractile and intracellular Ca(2+) properties were evaluated using echocardiography, edge-detection and fura-2 techniques. Level of insulin signaling and autophagy was evaluated by western blot. Our results revealed cardiac hypertrophy (enlarged chamber size, wall thickness, myocyte cross-sectional area), fibrosis, decreased cardiac contractility, prolonged relengthening along with compromised intracellular Ca(2+) release and clearance in aged (24-26 month-old) mice compared with young (3-4 month-old) mice, the effects of which were accentuated by chronic Akt activation. Aging enhanced Akt and mTOR phosphorylation while reducing that of PTEN, AMPK and ACC with a more pronounced response in Akt transgenic mice. GSK3β phosphorylation and eNOS levels were unaffected by aging or Akt overexpression. Levels of beclin-1, Atg5 and LC3-II-to-LC3-I ratio were decreased in aged hearts, the effect of which with the exception of Atg 5 was exacerbated by Akt overactivation. Levels of p62 were significantly enhanced in aged mice with a more pronounced increase in Akt mice. Neither aging nor Akt altered β-glucuronidase activity and cathepsin B although aging reduced LAMP1 level. In addition, rapamycin reduced aging-induced cardiomyocyte contractile and intracellular Ca(2+) dysfunction while Akt activation suppressed autophagy in young but not aged cardiomyocytes. In conclusion, our data suggest that Akt may accentuate aging-induced cardiac geometric and contractile defects through a loss of autophagic regulation.


Electrophysiological study with oxonol VI of passive NO3- transport by isolated plant root plasma membrane.
In contrast to animal cells, plant cells contain approximately 5-50 mM nitrate in cytosol and vacuole. The lack of specific spectroscopic probes, or suitable isotopes, impedes in vitro studies of NO3- transport. Reconstitution of root cell plasma membrane (PM) proteins in mixed soybean lipid:egg phosphatidylcholine allowed for the generation of large K+-valinomycin diffusion potentials (Em), monitored with the oxonol VI dye. Nevertheless, Em was restricted to approximately 130 mV by capacitor properties of biological membranes. This caused an increasing discrepancy at higher K+-Nernst potentials used for calibration. Therefore, Em was determined directly from the fluorescence of the dye free in buffer, bound at zero Em, and bound upon Em generation. Then, an electrophysiological analysis of the NO3--dependent dissipation rate of Em gave the net passive flux (JN) and the permeability coefficient to NO3- (PN). The plant root cell PM exhibited a strikingly large PN (higher than 10(-9) m s-1) at high Em (90-100 mV) and pH 6.5. At low Em (50-60 mV) and pH 7.4, PN decreased by 70-fold and became similar to that of the lipid bilayer. This agreed with the previous observation that 15 mM NO3- short-circuits the plant root PM H+-ATPase at its optimal pH of 6.5.


A dosimetric comparison of MammoSite and ClearPath high-dose-rate breast brachytherapy devices.
A new form of partial breast irradiation (PBI), ClearPath (CP) breast brachytherapy, has been introduced. We present our results of a dosimetric comparison of MammoSite (MS) and CP PBI. The dimensions of the CP device were reconstructed onto the MS planning CT scans for 15 previously treated patients. The mean %V(100), %V(150), %V(200) (percent of the PTV that received 100%, 150%, and 200% of the prescription dose, respectively), ipsilateral breast %V(50) (percent of the ipsilateral normal breast that received 50% of the prescription dose), ipsilateral lung %V(30) (percent of the ipsilateral lung that received 30% of the prescription dose), the heart %V(5) (percent of the heart that received 5% of the prescription dose), and the maximum skin point dose per fraction were then determined for each patient using the two methods of balloon-based PBI. The mean %V(100) was 96.5% vs. 96.5%, the mean %V(150) was 42.1% vs. 42.9% (p=ns), and the mean V(200) was 11.4% vs. 15.2% (p<.05) for the MS and CP methods, respectively. The mean ipsilateral breast %V(50) was 19.8% vs.18.0% (p<.05), the mean ipsilateral lung %V(30) was 3.7% vs. 2.8% (p<.05), the mean heart %V(5) was 57.0% vs. 54.3% (p<.05), and the maximum skin point dose per fraction was 312.2 and 273.6cGy (p<.05) for the MS and CP methods, respectively. The MS and CP methods of PBI offer comparable target volume coverage; however, the CP device achieves increased normal tissue sparing.


Interleukin-22 Inhibits Respiratory Syncytial Virus Production by Blocking Virus-Mediated Subversion of Cellular Autophagy.
Respiratory syncytial virus (RSV) infection can cause severe bronchiolitis in infants requiring hospitalization, whereas the elderly and immunocompromised are prone to RSV-induced pneumonia. RSV primarily infects lung epithelial cells. Given that no vaccine against RSV is currently available, we tested the ability of the epithelial-barrier protective cytokine interleukin-22 (IL-22) to control RSV production. When used in a therapeutic modality, IL-22 efficiently blunted RSV production from infected human airway and alveolar epithelial cells and IL-22 administration drastically reduced virus titer in the lungs of infected newborn mice. RSV infection resulted in increased expression of LC3B, a key component of the cellular autophagic machinery, and knockdown of LC3B ablated virus production. RSV subverted LC3B with evidence of co-localization and caused a significant reduction in autophagic flux, both reversed by IL-22 treatment. Our findings inform a previously unrecognized anti-viral effect of IL-22 that can be harnessed to prevent RSV-induced severe respiratory disease.


Iron and iron oxide nanoparticles are highly toxic to Culex quinquefasciatus with little non-target effects on larvivorous fishes.
The control of filariasis vectors has been enhanced in several areas, but there are main challenges, including increasing resistance to insecticides and lack of cheap and eco-friendly products. The toxicity of iron (Fe0) and iron oxide (Fe2O3) nanoparticles has been scarcely investigated yet. We studied the larvicidal and pupicidal activity of Fe0 and Fe2O3 nanoparticles against Culex quinquefasciatus. Fe0 and Fe2O3 nanoparticles produced by green (using a Ficus natalensis aqueous extract) and chemical nanosynthesis, respectively, were analyzed by UV-Vis spectrophotometry, FT-IR spectroscopy, XRD analysis, SEM, and EDX assays. In larvicidal and pupicidal experiments on Cx. quinquefasciatus, LC50 of Fe0 nanoparticles ranged from 20.9 (I instar larvae) to 43.7 ppm (pupae) and from 4.5 (I) to 22.1 ppm (pupae) for Fe2O3 nanoparticles synthesized chemically. Furthermore, the predation efficiency of the guppy fish, Poecilia reticulata, after a single treatment with sub-lethal doses of Fe0 and Fe2O3 nanoparticles was magnified. Overall, this work provides new insights about the toxicity of Fe0 and Fe2O3 nanoparticles against mosquito vectors; we suggested that green and chemical fabricated nano-iron may be considered to develop novel and effective pesticides.


Flow accumulation based method for the identification of erosion risk points in unpaved roads.
The unsuitable construction of unpaved roads has been causing problems related to the formation of erosive processes, sediments in watersheds, bogs, flooding, and holes. Presuming that the areas where flow accumulation intersects unpaved roads represent risk points, our objectives are (1) to develop a qualitative method based on the GIS software management tool (FlowAccRoad) for the identification of the intersection points between flow accumulation and roads and (2) to verify the discrepancy between the points of intersection produced by digital elevation models (DEM) accounting for different spatial resolutions. In the GIS environment, we used the Shuttle Radar Topography Mission (SRTM) and Goiania (GOI) digital elevation models for the modeling of flow accumulation and vectorization of the unpaved roads, both of which are based on the Bandeira Stream Watershed in Goiania, Goiás, Brazil. This highlights that 54 points of intersection between the flow accumulation and unpaved roads present problems related to erosive processes and quagmires, among others. The FlowAccRoad method identified the principal critical points observed in the field, using both the DEM of 30.4 m of spatial resolution (SRTM) and also of 4.8 m of spatial resolution (GOI). From the FlowAccRoad method, we observed that 91% of the risk points identified through the GOI DEM were located less than 20 m from valid points in the field by using GPS. Analyzing the SRTM DEM, only 45% of the critical risk points identified by the method were located less than 20 m from valid points in the field.


The animal experiment of a new optimised distraction implant.
Our aim was to evaluate the function of a new optimised distraction implant. Six dogs with alveolar bone defects had a total of 18 distraction, and 6 normal, implants inserted into edentulous mandibular ridges after osteotomy. Five days after insertion the distraction implants were activated at a rate of 1 mm/2 days to achieve a distraction height of 6mm. Radiographs were taken at 0, 1, 2, and 3 months after distraction. Two dogs were killed after 1, 2, and 3 months, respectively, and 12 distraction implants taken from the different time points were evaluated by microcomputed tomographic (MicroCT) scanning and histological examination. The other 6 distraction, and the 6 normal, implants were compared after osseointegration with a fatigue test. The results showed that all the distraction implants had successfully distracted the bone to the anticipated height. Radiographs showed that the density of the regenerated bone increased steadily during the consolidation period. MicroCT showed that the regenerated bone was comparable with the native bone 3 months after distraction. Both native and regenerated bone had osseointegrated histologically by 1 month and 3 months after distraction. The experiment successfully confirmed the usefulness and feasibility of this new distraction implant, and suggests interesting clinical uses.


An empirically derived short form of the Hypoglycaemia Fear Survey II.
To develop an empirically derived short version of the Hypoglycaemia Fear Survey II that still accurately measures fear of hypoglycaemia. Item response theory methods were used to generate an 11-item version of the Hypoglycaemia Fear Survey from a sample of 487 people with Type 1 or Type 2 diabetes mellitus. Subsequently, this scale was tested on a sample of 2718 people with Type 1 or insulin-treated Type 2 diabetes taking part in DIALOG, a large observational prospective study of hypoglycaemia in France. The short form of the Hypoglycaemia Fear Survey II matched the factor structure of the long form for respondents with both Type 1 and Type 2 diabetes, while maintaining adequate internal reliability on the total scale and all three subscales. The two forms were highly correlated on both the total scale and each subscale (Pearson's R > 0.89). The short form of the Hypoglycaemia Fear Survey II is an important first step in more efficiently measuring fear of hypoglycaemia. Future prospective studies are needed for further validity testing and exploring the survey's applicability to different populations.


The relationship between neurotrophic factors and CaMKII in the death and survival of retinal ganglion cells.
The scientific discourse relating to the causes and treatments for glaucoma are becoming reflective of the need to protect and preserve retinal neurons from degenerative changes, which result from the injurious environment associated with this disease. Knowledge, in particular, of the signal transduction pathways which affect death and survival of the retinal ganglion cells is critical to this discourse and to the development of a suitable neurotherapeutic strategy for this disease. The goal of this chapter is to review what is known of the chief suspects involved in initiating the cell death/survival pathways in these cells, and what still remains to be uncovered. The least controversial aspect of the subject relates to the potential role of neurotrophic factors in the protection of the retinal ganglion cells. On the other hand, the postulated triggers for signaling cell death in glaucoma remain controversial. Certainly, the restricted flow of neurotrophic factors has been cited as one possible trigger. However, the connections between glaucoma and other factors present in the retina, such as glutamate, long held to be a prospective culprit in retinal ganglion cell death are still being questioned. Whatever the outcome of this particular debate, it is clear that the downstream intersections between the cell death and survival pathways should provide important foci for future studies whose goal is to protect retinal neurons, situated as they are, in the stressful environment of a cell destroying disease. The evidence for CaMKII being one of these intersecting points is discussed.


Complex spatial organization and flagellin composition of flagellar propeller from marine magnetotactic ovoid strain MO-1.
Marine magnetotactic ovoid bacterium MO-1 is capable of swimming along the geomagnetic field lines by means of its two sheathed flagellar bundles at a speed up to 300 μm/s. In this study, by using electron microscopy, we showed that, in each bundle, six individual flagella were organized in hexagon with a seventh in the middle. We identified 12 flagellin paralogs and 2 putative flagellins in the genome of MO-1. Among them, 13 were tandemly located on an ~ 17-kb segment while the 14th was on a separated locus. Using reverse transcription PCR and quantitative PCR, we found that all the 14 flagellin or putative flagellin genes were transcribed and that 2 of them were more abundantly expressed than others. A nLC (nanoliquid chromatography)-ESI (electrospray ionization)-MS/MS (mass spectrometry/mass spectrometry) mass spectrometry analysis identified all the 12 flagellin proteins in three glycosylated polypeptide bands resolved by one-dimensional denaturing polyacrylamide gel electrophoresis and 10 of them in 21 spots obtained by means of two-dimensional electrophoresis of flagellar extracts. Most spots contained more than one flagellin, and eight of the ten identified flagellins existed in multiple isoforms. Taken together, these results show unprecedented complexity in the spatial organization and flagellin composition of the flagellar propeller. Such architecture is observed only for ovoid-coccoid, bilophotrichously flagellated magnetotactic bacteria living in marine sediments, suggesting a species and environmental specificity.


Pediatric chest CT radiation dose reduction: protocol refinement based on noise injection for pulmonary nodule detection accuracy.
To establish appropriate chest computed tomography (CT) acquisition protocols that balance radiation dose and diagnostic capability in pediatric bone marrow transplant patients by assessing the accuracy of pulmonary nodule detection at simulated lower-radiation acquisitions, chest CT images from bone marrow transplant patients were reviewed by four pediatric radiologists at artificially reduced CT dose levels (0%, 30%, and 60%). Average accuracy for nodule detection in 31 randomly selected cases was 0.87 at 0% dose reduction, 0.90 at 30% reduction, and 0.86 at 60% reduction. We observed no clinically relevant difference in acceptability of images or accuracy levels with tested dose reductions to 60%.


The fragmentation pathways of protonated glycine: a computational study.
Numerous studies have demonstrated that protonated aliphatic amino acids, [H2NCHRCO2H + H]+, fragment in the gas phase to form iminium ions, H2N=CHR+. Unfortunately none of these studies have probed the structure of the neutral(s) lost as well as the mechanism of fragmentation. Three main mechanisms have been previously proposed: (1) loss of the combined elements of H2O and CO; (2) loss of dihydroxycarbene (HO)2C: and (3) loss of formic acid, HC(=O)OH. Herein, ab initio and density functional theory calculations have been used to calculate the key reactants, transition states, and products of these and several other competing reaction channels in the fragmentation of protonated glycine. The loss of the combined elements of H2O and CO is thermodynamically and kinetically favored over the alternative formic acid or (HO)2C fragmentation processes.


Simple stochastic fingerprints towards mathematical modeling in biology and medicine 2. Unifying Markov model for drugs side effects.
Most of present mathematical models for biological activity consider just the molecular structure. In the present article we pretend extending the use of Markov chain models to define novel molecular descriptors, which consider in addition other parameters like target site or biological effect. Specifically, this mathematical model takes into consideration not only the molecular structure but the specific biological system the drug affects too. Herein, a general Markov model is developed that describes 19 different drugs side effects grouped in eight affected biological systems for 178 drugs, being 270 cases finally. The data was processed by linear discriminant analysis (LDA) classifying drugs according to their specific side effects, forward stepwise was fixed as strategy for variables selection. The average percentage of good classification and number of compounds used in the training/predicting sets were 100/95.8% for endocrine manifestations, (18 out of 18)/(13 out of 14); 90.5/92.3% for gastrointestinal manifestations, (38 out of 42)/(30 out of 32); 88.5/86.5% for systemic phenomena, (23 out of 26)/(17 out of 20); 81.8/77.3% for neurological manifestations, (27 out of 33)/(19 out of 25); 81.6/86.2% for dermal manifestations, (31 out of 38)/(25 out of 29); 78.4/85.1% for cardiovascular manifestation, (29 out of 37)/(24 out of 28); 77.1/75.7% for breathing manifestations, (27 out of 35)/(20 out of 26) and 75.6/75% for psychiatric manifestations, (31 out of 41)/(23 out of 31). Additionally a back-projection analysis (BPA) was carried out for two ulcerogenic drugs to prove in structural terms the physical interpretation of the models obtained. This article develops a mathematical model that encompasses a large number of drugs side effects grouped in specifics biological systems using stochastic absolute probabilities of interaction ((A)pi(k)(j)) by the first time.


Anti-Domain I β2-Glycoprotein I Antibodies and Activated Protein C Resistance Predict Thrombosis in Antiphospholipid Syndrome: TAC(I)T Study.
Antibodies binding to domain I of β2-glycoprotein I (aDI) and activated protein C (APC) resistance are associated with an increased risk of thrombosis in cross-sectional studies. The objective of this study was to assess their predictive value for future thromboembolic events in patients with antiphospholipid antibodies (aPL) or antiphospholipid syndrome. This prospective multicenter cohort study included consecutive patients with aPL or systemic lupus erythematosus. We followed 137 patients (43.5 ± 15.4 year old; 107 women) for a mean duration of 43.1 ± 20.7 months. We detected aDI IgG antibodies by ELISA in 21 patients. An APC sensitivity ratio (APCsr) was determined using a thrombin generation-based test. The APCsr was higher in patients with anti-domain I antibodies demonstrating APC resistance (0.75 ± 0.13 vs 0.48 ± 0.20, P < 0.0001). In univariate analysis, the hazard ratio (HR) for thrombosis over time was higher in patients with aDI IgG (3.31 [95% CI, 1.15-9.52]; P = 0.03) and patients with higher APC resistance (APCsr >95th percentile; HR, 6.07 [95% CI, 1.69-21.87]; P = 0.006). A sensitivity analysis showed an increased risk of higher aDI IgG levels up to HR 5.61 (95% CI, 1.93-16.31; P = 0.01). In multivariate analysis, aDI IgG (HR, 3.90 [95% CI, 1.33-11.46]; P = 0.01) and APC resistance (HR, 4.98 [95% CI, 1.36-18.28]; P = 0.02) remained significant predictors of thrombosis over time. Our study shows that novel tests for antibodies recognizing domain I of β2-glycoprotein I and functional tests identifying APC resistance are significant predictors of thrombosis over time and may be useful for risk stratification.


The reaction of bovine alpha-thrombin with tetranitromethane. Characterization of the modified protein.
Previous studies from several laboratories have shown that thrombin is inactivated by tetranitromethane with the formation of nitrotyrosine. The inactivation is characterized by an apparently greater loss of fibrinogen-clotting activity than activity toward synthetic ester substrates, suggesting that the residues modified by tetranitromethane are involved in the interaction of thrombin with fibrinogen. This study was designed 1) to determine the effect of solvent conditions on the rate of modification and the stoichiometry of the reaction of tetranitromethane with bovine alpha-thrombin; 2) to identify the residue(s) modified; and 3) to characterize the modified enzyme with respect to its interaction with peptide nitroanilide substrates and fibrinogen. The inactivation of thrombin by tetranitromethane proceeded more rapidly in 50 mM Tris, pH 8.0, than in 50 mM sodium phosphate, 100 mM NaCl, pH 8.0. Approximately 10% fibrinogen-clotting activity remained at maximal inactivation. A study of the effect of tetranitromethane concentration on the rate of inactivation suggested that the loss of activity was the result of the modification of 1 mol of tyrosine/mol of thrombin. A similar result was obtained from the analysis of the extent of inactivation as a function of the extent of protein modification. Structural analysis of the modified protein showed substantial modification at both Tyr71 and Tyr85. Enzyme kinetic studies were performed with the modified protein and a control thrombin with N2-tosylglycylprolylarginine p-nitroanilide. H-D-phenylalanylpipecolylarginine p-nitronailide, and purified bovine fibrinogen. With all three substrates, a substantial decrease in kcat was observed, whereas there was essentially no change in Km. These results suggest that, contrary to previous suggestions, the modification of Tyr71 and Tyr85 in thrombin does not influence the binding of substrates, but rather influences active site reactivity.


Elder-Friendly Emergency Department: Development and Validation of a Quality Assessment Tool.
To develop and validate a comprehensive quality assessment tool for emergency department (ED) geriatric care. Four-step study: (1) Content development of tool by a multidisciplinary panel, (2) survey of ED lead physicians and nurses, (3) development of subscales using principal component analysis and clinical judgment, (4) reliability and validity assessment. Province of Quebec, Canada. Lead ED nurses and physicians at 76 Quebec EDs who participated in a 2013/14 survey (66% of 116 adult nonpsychiatric EDs in the province). Geriatric care items (n = 62) grouped into seven preliminary content areas (screening and assessment, clinical protocols, discharge planning, staffing, physical environment, continuing education, quality assessment), lead nurse and physician perceptions of the quality of ED geriatric care, institutional prioritization of geriatric care, and ED type. Thirteen subscales were developed; most were associated with ED type and quality indicators. Thirteen subscales for geriatric ED services are proposed for evaluation in various ED settings.


A note on utilising binary features as ligand descriptors.
It is common in cheminformatics to represent the properties of a ligand as a string of 1's and 0's, with the intention of elucidating, inter alia, the relationship between the chemical structure of a ligand and its bioactivity. In this commentary we note that, where relevant but non-redundant features are binary, they inevitably lead to a classifier capable of capturing only a linear relationship between structural features and activity. If, instead, we were to use relevant but non-redundant real-valued features, the resulting predictive model would be capable of describing a non-linear structure-activity relationship. Hence, we suggest that real-valued features, where available, are to be preferred in this scenario.


FLAIR vascular hyperintensity with DWI for regional collateral flow and tissue fate in recanalized acute middle cerebral artery occlusion.
Fluid-attenuated inversion recovery (FLAIR) vascular hyperintensity (FVH) extent or FVH-DWI mismatch as a primary influencing factor of clinical outcome in acute ischemic stroke is controversial. This study elucidated the regional pathophysiology and tissue fate in four types of cortical territories classified by the initial FVH and DWI findings in patients with acute proximal middle cerebral artery (M1) occlusion successfully recanalized using mechanical thrombectomy. We retrospectively evaluated 35 patients successfully recanalized within 24 h of acute M1 occlusion onset between 2016 and 2019. Each Alberta stroke program early CT score area of M1-M6 were categorized as group A (DWI-, FVH-), B (DWI-, FVH+), C (DWI+, FVH+), or D (DWI+, FVH-). Territorial collateral status was graded on a 4-point scale by initial angiogram. Follow-up head computed tomography (CT) findings on days 2-9 were assessed for the territorial outcome. Overall, 210 cortical territories were identified; of these, 88 (41.9 %) were categorized into group A; 72 (34.3 %), group B; 37 (17.6 %), group C; and 13 (6.2 %), group D. The rate of territories with good collaterals (grade 2 or 3) significantly decreased in the order of groups as 78.3 %, 62.7 %, 27.6 %, and 0%, respectively (Ptrend <.001). Conversely, the rate of territories with any hypo- or hyper-density on follow-up CT significantly increased in the order of groups as 13.4 %, 23.1 %, 88.5 %, and 85.7 %, respectively (Ptrend <.001). Categorization of cortical areas based on the FVH and DWI findings can stratify territorial collateral status and tissue fate.


A combined CaMKII inhibition and mineralocorticoid receptor antagonism via eplerenone inhibits functional deterioration in chronic pressure overloaded mice.
In the diseased and remodelled heart, increased activity and expression of Ca2+/ calmodulin-dependent protein kinase II (CaMKII), an excess of fibrosis, and a decreased electrical coupling and cellular excitability leads to disturbed calcium homeostasis and tissue integrity. This subsequently leads to increased arrhythmia vulnerability and contractile dysfunction. Here, we investigated the combination of CaMKII inhibition (using genetically modified mice expressing the autocamtide-3-related-peptide (AC3I)) together with eplerenone treatment (AC3I-Epler) to prevent electrophysiological remodelling, fibrosis and subsequent functional deterioration in a mouse model of chronic pressure overload. We compared AC3I-Epler mice with mice only subjected to mineralocorticoid receptor (MR) antagonism (WT-Epler) and mice with only CaMKII inhibition (AC3I-No). Our data show that a combined CaMKII inhibition together with MR antagonism mitigates contractile deterioration as was manifested by a preservation of ejection fraction, fractional shortening, global longitudinal strain, peak strain and contractile synchronicity. Furthermore, patchy fibrosis formation was reduced, potentially via inhibition of pro-fibrotic TGF-β/SMAD3 signalling, which related to a better global contractile performance and a slightly depressed incidence of arrhythmias. Furthermore, the level of patchy fibrosis appeared significantly correlated to eplerenone dose. The addition of eplerenone to CaMKII inhibition potentiates the effects of CaMKII inhibition on pro-fibrotic pathways. As a result of the applied strategy, limiting patchy fibrosis adheres to a higher synchronicity of contraction and an overall better contractile performance which fits with a tempered arrhythmogenesis.


Cell migration in development and disease.
A recent meeting at the Max Delbrück Center in Berlin, Germany provided a forum to discuss the molecular mechanisms of cell migration in a broad range of contexts including chemotaxis, development, immunity, and cancer.


[Unusual evolution of a complex bile duct injury after a laparoscopic cholecystectomy].
Since the advent of laparoscopic surgery of cholelithiasis the incidence rate of bile duct injuries has increased significantly in the literature in relation to the operators' learning curve. Unknown injuries can have dramatic, immediate consequences and progress to bile peritonitis. Moreover surgical repair of external biliary fistula at the stage of bile duct dilatation requires biliodigestive anastomosis or liver resections "réglées".


Calcium events in smooth muscles and their interstitial cells; physiological roles of sparks.
The observation of spontaneous sporadic releases of packets of stored calcium made 20 years ago has opened up a number of new concepts in smooth muscle physiology: (1) the calcium release sites are ryanodine and inositol 1,4,5-trisphosphate (IP3) receptor channels which contribute to cell-wide increases in [Ca2+]i in response to cell depolarization, activation of IP3-generating receptors, or other stimuli; (2) changes in [Ca2+]i act back on the cell membrane to activate or modulate K+, Cl- and cation channel activity so affecting contraction, in arterial smooth muscle for example affecting blood pressure; (3) IP3 production is voltage dependent and is believed to contribute to pacemaker potentials and to refractory periods which control the rhythmical motility of many hollow organs. Most smooth muscle tissues contain interstitial cells (ICs) in addition to contractile smooth muscle cells (SMCs). The interactions of these internal mechanisms, and in turn the interactions of SMCs and ICs in various smooth muscle tissues, are major factors in determining the unique physiological profiles of individual smooth muscles.


Angiotensin II regulates the activity of mouse suprachiasmatic nuclei neurons.
Neuropeptide signaling plays key roles in coordinating cellular activity within the suprachiasmatic nuclei (SCN), site of the master circadian oscillator in mammals. The neuropeptide angiotensin II (ANGII) and its cognate receptor AT1, are both expressed by SCN cells, but unlike other SCN neurochemicals, very little is known about the cellular actions of ANGII within this circadian clock. We used multi-electrode, multiunit, extracellular electrophysiology, coupled with whole-cell voltage and current clamp techniques to investigate the actions of ANGII in mouse SCN slices. ANGII (0.001-10 microM) dose dependently stimulated and inhibited extracellularly recorded neuronal discharge in many SCN neurons ( approximately 60%). Both actions were blocked by pre-treatment with the AT1 receptor antagonist ZD7155 (0.03 microM), while suppressions but not activations were prevented by pre-treatment with the GABA A receptor antagonist bicuculline (20 microM). AT1 receptor blockade itself suppressed discharge in a subset ( approximately 30%) of SCN neurons, and this action was not blocked by bicuculline. In voltage-clamped SCN neurons (-70 mV), AT1 receptor activation dose-dependently enhanced the frequency of action potential-driven, GABA A receptor-mediated currents, but did not alter their responses to exogenously applied GABA. In current-clamped SCN neurons perfused with tetrodotoxin, ANGII induced a membrane depolarization with a concomitant decrease in input resistance. In conclusion we show that AT1 receptor activation by ANGII depolarizes SCN neurons and stimulates action potential firing, leading to increased GABA release in the mouse SCN. Additionally we provide the first evidence that endogenous AT1 receptor signaling tonically regulates the activities of some SCN neurons.


Geographic patterns in patient demographics and insulin use in 18 countries, a global perspective from the multinational observational study assessing insulin use: understanding the challenges associated with progression of therapy (MOSAIc).
Among patients with type 2 diabetes, insulin intensification to achieve glycemic targets occurs less often than clinically indicated. Barriers to intensification are not well understood. We present patients' baseline characteristics from MOSAIc, a study investigating patient-, physician-, and healthcare environment-based factors affecting insulin intensification and subsequent health outcomes. MOSAIc is a longitudinal, observational study following patients' diabetes care in 18 countries: United Arab Emirates (UAE), Argentina, Brazil, Canada, China, Germany, India, Israel, Italy, Japan, Mexico, Russia, Saudi Arabia, South Korea, Spain, Turkey, United Kingdom, United States. Eligible patients are age ≥ 18, have type 2 diabetes, and have used insulin for ≥ 3 months with/without other antidiabetic medications. Extensive baseline demographic, clinical, and psychosocial data are collected at baseline and regular intervals during the 24-month follow-up. We conducted descriptive analyses of baseline data. Four thousand three hundred forty one patients met eligibility criteria. Patients received their type 2 diabetes diagnosis 12 ± 8 years prior to baseline visit, yet patients in developing countries were younger than in developed countries (e.g., UAE, 55 ± 10; Germany = 70 ± 10). Saudi Arabians had the highest HbA1c values (9.0 ± 2.2) and Germany (7.5 ± 1.4) among the lowest. Most patients in 5 (28%) of the 18 countries did not use an oral antidiabetic drug. Over half of patients in fourteen (78 %) countries exclusively used basal insulin; most Indian and Chinese patients exclusively used mixed insulin. MOSAIc's baseline data highlight differences in patient characteristics across countries. These patterns, along with physician and healthcare environment differences, may contribute to the likelihood of insulin intensification and subsequent clinical outcomes.


Small-Molecule Inhibitor of 8-Oxoguanine DNA Glycosylase 1 Regulates Inflammatory Responses during Pseudomonas aeruginosa Infection.
The DNA repair enzyme 8-oxoguanine DNA glycosylase 1 (OGG1), which excises 8-oxo-7,8-dihydroguanine lesions induced in DNA by reactive oxygen species, has been linked to the pathogenesis of lung diseases associated with bacterial infections. A recently developed small molecule, SU0268, has demonstrated selective inhibition of OGG1 activity; however, its role in attenuating inflammatory responses has not been tested. In this study, we report that SU0268 has a favorable effect on bacterial infection both in mouse alveolar macrophages (MH-S cells) and in C57BL/6 wild-type mice by suppressing inflammatory responses, particularly promoting type I IFN responses. SU0268 inhibited proinflammatory responses during Pseudomonas aeruginosa (PA14) infection, which is mediated by the KRAS-ERK1-NF-κB signaling pathway. Furthermore, SU0268 induces the release of type I IFN by the mitochondrial DNA-cGAS-STING-IRF3-IFN-β axis, which decreases bacterial loads and halts disease progression. Collectively, our results demonstrate that the small-molecule inhibitor of OGG1 (SU0268) can attenuate excessive inflammation and improve mouse survival rates during PA14 infection. This strong anti-inflammatory feature may render the inhibitor as an alternative treatment for controlling severe inflammatory responses to bacterial infection.


Internal strains in healthy and degenerated lumbar intervertebral discs.
A biomechanical study investigating the intradiscal mechanics of human lumbar intervertebral discs (IVDs). To assess the relationship between nucleus pulposus migration and intradiscal strains as a function of degeneration. Intradiscal deformation studies have documented the nucleus pulposus migration capabilities during bending but without assessing subsequent intradiscal strains of the anulus fibrosus. Degenerated IVDs show higher anular laxity, hypermobility, and, perhaps, segmental instability. It is unknown if nucleus pulposus migration might be the cause of increased intradiscal anular strains and if such a phenomenon is modulated by IVD degeneration. Eighteen healthy and degenerated IVDs were subjected to compression, extension, flexion, and lateral bending. Craniocaudal radiographs at unloaded and loaded steps documented positions of wires placed within and beads glued to the external surface in the mid-transverse plane. Circumferential and radial strains from the anterior, lateral, and posterolateral regions during load were compared between healthy and degenerated IVDs. The nucleus pulposus migrated to the opposite side of bending regardless of bending direction and significantly more in degenerated IVDs. The highest nucleus pulposus migration was observed during lateral bending. Circumferential tensile strains were significantly higher in the posterolateral regions of degenerative IVDs during all loads. Degeneration significantly increased radial tensile and compressive strains during all bending loads. Increased nucleus pulposus migration in degenerated IVDs may result in increased shifting of the IVD pivot point during bending movements as well as intradiscal anular strains, particularly in the posterolateral anulus. This phenomenon may explain the segmental instability observed in degenerated segments as well as the associated anular tears present in the posterolateral region before IVD failure.


The isolation and the characterization of two polysaccharides from the branch bark of mulberry (Morus alba L.).
Two water-soluble polysaccharides termed MBBP-1 and MBBP-2 were isolated from the branches of the mulberry tree (Morus alba L.) using hot water extraction and purified on Anion-exchange DEAE52-cellulose and Sephadex G-100 column. MBBP-1 was shown to be composed of rhamnose, xylose, arabinose, mannose, glucose and galactose in the molar ratio of 4.53:2.49:4.38:4.67:17.85:5.88. MBBP-2 was composed of rhamnose, xylose, arabinose, mannose, glucose, galactose and galacturonic acid in the molar ratio of 26.85:13.8:3.14:4.4:6.1:3.19:4.9. Their structural characteristics were further investigated by FI-IR spectroscopy, Smith degradation, methylation analysis and NMR spectroscopy. Based on the data obtained, MBBP-1 had a backbone mainly consisting of (1 → 3)-linked glucose. MBBP-2 had a backbone mainly consisting of (1 → 3)-linked rhamnose and (1 → 2, 4)-linked xylose. Antioxidant assays indicated that antioxidant activities of MBBP-2 were significantly stronger than those of MBBP-1, and this was likely in relation to the different content of 8.2 % galacturonic acid in MBBP-2.


Characterization of changes in total body composition for patients with head and neck cancer undergoing chemoradiotherapy using dual-energy x-ray absorptiometry.
Patients with head and neck cancer experience significant weight loss secondary to concurrent chemoradiotherapy (CCRT). Using dual-energy X-ray absorptiometry (DEXA) scans, we characterize total body composition changes during and after CCRT in order to develop novel clinical care models that will improve the patient's quality of life (QOL). Sixty DEXA scans were obtained from 12 patients undergoing CCRT for locally advanced squamous cell head and neck cancer. DEXAs were performed at baseline, during treatment, completion of CCRT, and then 1 and 2 months posttreatment. Mean weight loss by treatment end was 9.5 kg (10.2%; p = .0002). On average, lean body mass (LBM) decreased 10.2% (p = .001), and fat body mass (FBM) decreased 11.1% (p = .001) during CCRT. LBM began to normalize after completion of treatment, whereas FBM continued to decline. Substantial loss of muscle and FBM occurs in patients undergoing CCRT for head and neck cancer. To prevent long-term disability and QOL decline after curative CCRT, clinical care interventions incorporating aggressive nutrition/exercise counseling are needed.


Acute lymphoblastic leukemia: an assessment of international incidence, survival, and disease burden.
Acute lymphoblastic leukemia (ALL) is a rare hematological malignancy. With the recent introduction of a classification system for hematopoietic and lymphoid neoplasms, more comprehensive assessment of ALL epidemiology is now possible. In this study, we describe recent international incidence of ALL and project the annual number of diagnoses to 2025. We also estimate relative survival and average potential years of life lost (AYLL) to assess the societal burden of ALL. Age-specific incidence data for ALL from select cancer registries in different geographies were obtained from the International Agency for Research on Cancer's Cancer Incidence in Five Continents Database. Country-specific age-standardized rates were calculated to allow for direct comparisons between countries. ALL-specific mortality and relative survival data were only available from the United States (US) National Cancer Institute's Surveillance, Epidemiology, and End Results program; mortality rates were estimated for other countries. The age-standardized incidence rate of ALL during 2003-2007 ranged from 1.08 to 2.12 per 100,000 person-years in selected countries. Incidence was generally higher in the Americas and Oceania and lower in Asia and Eastern Europe. In most countries, the incidence rate of ALL in children was approximately four times that in adults. Survival was particularly poor among adults. In selected countries, the estimated AYLL ranged from 30 to 48 years for all ages and from 23 to 39 years for adults. Although a rare disease, ALL presents a significant public health burden given poor survival outcomes among adults, AYLL, and its importance as the most common pediatric cancer.


Toward Universal Half-Saturation Coefficients: Describing Extant K(s) as a Function of Diffusion.
Observed (extant) K(s) is not a constant and it is strongly influenced by diffusion. This paper argues that diffusion can be used to describe bacterial kinetic effects that are sometimes attributed to "K-strategists" and, in fact, the physics of the system is the dominant mechanism affecting the apparent (extant) Ks--not intrinsic biological characteristics--in real water resource recovery facility systems. Four different biological processes have been modeled using the "porter-diffusion" model that was originally developed by Pasciak and Gavis (1974) for aquatic systems. The results demonstrate that diffusion is the dominant mechanism affecting K(s) in all four biological processes. Therefore, the authors argue that for treatment processes in which substrate concentrations are low, it is important to consider shifting to variable extant K(s) values or explicitly modeling the effects of diffusion.


Association between dinner timing and glucose metabolism in rural China: A large-scale cross-sectional study.
Meal timing is a major risk factor for metabolic disease. The aim of this study was to assess the relationship between dinner timing and glucose metabolism in the rural Chinese population. This cross-sectional study included 7701 participants from a Henan rural cohort study. Basic information was collected by in-person questionnaires. Multiple linear regression analysis was used to evaluate the relationship between dinner timing and fasting insulin (FINS), fasting plasma glucose (FPG), and homeostatic model assessment for insulin resistance (HOMA-IR). Restricted cubic spline was employed to investigate the dose-response relationship between dinner timing and FINS, FPG, and HOMA-IR. A generalized linear model was used to explore the interaction effect of age and dinner timing on FINS, FPG, and HOMA-IR. After adjusting for confounding factors, FINS concentration was reduced by 0.482 mmol/L (P < 0.001) for each hour delay in dinner timing. Furthermore, the HOMA-IR index decreased by 0.122 mmol/L for each hour delay. The results indicated a noticeable trend of decreasing values associated with later dinner timing (FINS: Poverall association < 0.001, Pnonlinear association = 0.144; HOMA-IR: Poverall association = 0.001, Pnonlinear association = 0.186). The interaction between age and dinner time significantly correlated with FINS and HOMA-IR (P < 0.05). This relationship was statistically significant before 69 y (P < 0.05). A significant association between dinner timing and glucose metabolism was observed in the rural Chinese population. Delayed dinner timing may be associated with lower fasting insulin. The negative effect of dinner timing on FINS and HOMA-IR was diminished with age.


Is smart carbon emission reduction justified in China? Evidence from national big data comprehensive pilot zones.
The intelligent revolution caused by new digital technologies has provided new impetus to reduce carbon emissions. However, the current research on new digital technologies and carbon emissions is still in its infancy and lacks empirical conclusions between them. Therefore, this paper studies the impact of new digital technologies on carbon emissions, identifies its mechanism, and analyzes the regional heterogeneity of its effects. This research treats the National Big Data Comprehensive Pilot Zones pilot in China as a quasi-natural experiment for the development of new digital technologies along with city-level data covering from 2011 to 2019 to conduct a staggered difference-in-difference (DID) model analysis. We find that new digital technologies significantly reduce carbon emissions. This conclusion is still valid after a series of robustness tests such as heterogeneity treatment effect analysis, ex-ante trend test, spillover effect test, and placebo test. Additionally, new digital technologies can reduce carbon emissions by promoting the transformation of industrial structure, improving the level of green technology innovation, and promoting industrial agglomeration. At the same time, the heterogeneity analysis shows that new digital technologies' carbon emission reduction effect is more evident in non-western regions, southern regions, and large cities. To expand the carbon emission reduction effect of new digital technologies, the government should promote the development and application of new digital technologies, and implement differentiated policies based on regional characteristics.


Calcium use during in-hospital pediatric cardiopulmonary resuscitation: a report from the National Registry of Cardiopulmonary Resuscitation.
Specific patterns of calcium use during in-hospital pediatric cardiopulmonary resuscitation have not been reported since publication of pediatric advanced life support guidelines by the American Heart Association in 2000 recommended that calcium use during cardiopulmonary resuscitation be limited to select circumstances. We hypothesized that calcium is used frequently during in-hospital pediatric cardiopulmonary resuscitation and that its use is associated with worse survival to hospital discharge. We reviewed 1477 consecutive pediatric cardiopulmonary resuscitation index events (for patients younger than 18 years) submitted to the National Registry of Cardiopulmonary Resuscitation from January 2000 through July 2004. The primary outcome was survival to hospital discharge. Secondary outcomes included survival of event and neurologic outcome. Multivariable logistic regression was performed to analyze the association between calcium use and outcomes. Calcium was used in 659 (45%) of 1477 events. Calcium was more likely to be used during cardiopulmonary resuscitation in the settings of pediatric facilities, ICUs, cardiac surgery, cardiopulmonary resuscitation duration of > or = 15 minutes, asystole, and concurrently with other advanced life support medications: epinephrine, vasopressin, sodium bicarbonate, and magnesium sulfate. The use of calcium during cardiopulmonary resuscitation adjusted for confounding factors was associated with decreased survival to discharge and was not associated with favorable neurologic outcome. Calcium is used frequently during in-hospital pediatric cardiopulmonary resuscitation. Although epidemiologic associations do not necessarily indicate causality, calcium use during cardiopulmonary resuscitation is associated with decreased survival to hospital discharge and unfavorable neurologic outcome.


Prediction of NK Cell Licensing Level in Selection of Hematopoietic Stem Cell Donor, Initial Results.
Natural killer (NK) cell licensing status depends on clonal expression of inhibitory killer cell immunoglobulin-like receptors (iKIR) and short term HLA environment. Licensed NK cells are more efficient in tumor killing than unlicensed NK cells. Cognate KIR-HLA pairs in hematopoietic stem cell transplant (HSCT) donor and recipient are decisive for the possible change in the NK cell licensing status after HSCT. We assessed clinical outcomes in 297 patients with lymphoproliferative or myeloproliferative malignancies, or myelodysplastic syndrome in a model with upward licensing, downward resetting, and unchanged licensing genetics status after T cell replate HSCT from unrelated donors. We found extremely low (0%) relapse/progression incidence (RI), and better (59%) event-free survival (EFS) in recipients with upward licensing status and highly increased RI (37.5%), and reduced EFS (8%) among patients with the downward resetting status of repopulated donor NK cells after HSCT, as compared with unchanged NK cell licensing (RI 23%, EFS 47%). These trends were confirmed in adjusted multivariable models (for RI p = 6.66E-09, OR = 1.47, 95% CI 1.29-1.66 and for EFS p = 3.79E-13, OR = 1.67, 95% CI 1.50-1.84). Differences in the incidence of acute graft versus host disease (GvHD 62, 69, and 47%) and chronic GvHD (24, 44, and 15%, respectively) in three groups were insignificant. It would be rationale the preferential selection of the donors with upward licensing over downward resetting inhibitory KIR:HLA constellation and inclusion of the KIR genotyping in the donor selection algorithm for malignant patients. Further studies using enlarged cohorts of patients with more homogenous diagnosis are essential to reliably verify these preliminary data.


Hepatitis Delta Virus Acts as an Immunogenic Adjuvant in Hepatitis B Virus-Infected Hepatocytes.
Hepatitis delta virus (HDV) requires hepatitis B virus (HBV) to complete its infection cycle and causes severe hepatitis, with limited therapeutic options. To determine the prospect of T cell therapy in HBV/HDV co-infection, we study the impact of HDV on viral antigen processing and presentation. Using in vitro models of HBV/HDV co-infection, we demonstrate that HDV boosts HBV epitope presentation, both in HBV/HDV co-infected and neighboring mono-HBV-infected cells through the upregulation of the antigen processing pathway mediated by IFN-β/λ. Liver biopsies of HBV/HDV patients confirm this upregulation. We then validate in vitro and in a HBV/HDV preclinical mouse model that HDV infection increases the anti-HBV efficacy of T cells with engineered T cell receptors. Thus, by unveiling the effect of HDV on HBV antigen presentation, we provide a framework to better understand HBV/HDV immune pathology, and advocate the utilization of engineered HBV-specific T cells as a potential treatment for HBV/HDV co-infection.


Bilateral deep anterior lamellar keratoplasty for the management of bilateral post-LASIK mycobacterial keratitis.
A 25-year-old Vietnamese man who had bilateral simultaneous laser in situ keratomileusis (LASIK) for moderate myopia developed bilateral Mycobacterium abscessus keratitis that was treated with intensive medical therapy, flap removal, superficial keratectomy, and, following disease progression, therapeutic deep anterior lamellar keratoplasty (DALK). To our knowledge, this is the first reported case of bilateral post-LASIK mycobacterial keratitis successfully treated with DALK.


Subfractionation of CsCl-purified H-1 parvovirus on metrizamide gradients.
The different density classes of H-l parvovirus, collected within 30 hr of infection of par-asynchronous cultures, following the standard CsCl purification step, have been shown to be heterogeneous. Rebanding of the denser form (HF, p = 1.46 g/cm3) and the less dense form (LF, p = 1.42 g/cm3) of infectious virus in the nonionic density generating solute, metrizamide, showed that both HF and LF virus bands were heterogeneous in density. The infectivity banded with isotopically labeled virus protein and DNA at 1.32 g/cm3 for both HF and LF virus. Amounts of protein and DNA which varied from preparation to preparation, but which were greater from the HF virus band, were distributed throughout the rest of the gradient, but predominated in a peak at a density of 1.2 g/cm3. The protein in this peak was without hemagglutinating activity but had the molecular weights and proportions of the H-l virion proteins (VPl, VP2', and VPZ). The DNA was of the same size as H-l DNA monomers and its proportion to the protein was similar to that of the infectious peak. The DNA was susceptible to micrococcal nuclease digestion. The nature of this noninfectious viral material thus seemed to be incompletely assembled virus. Radiolabeled H-l virus collected after 72 hr of infection formed a discrete single peak in both CsCl (p = 1.42 g/cm3), and metrizamide gradients (p = 1.32 g/cm3). There was no significant amount of the 1.20 g/cm3 viral protein-DNA complex in these mature preparations.


Estimations of the thermodynamic properties of halogenated benzenes as they relate to their environment mobility.
In this work, several simple new equations for predicting important environmental mobility properties, at T = 298.15 K, were derived for halogenated benzenes: standard Gibbs energy of hydration, aqueous solubility, octanol-water partition coefficients, and Henry's law constants. A discussion on our previous estimates of other related properties (standard Gibbs energy and vapor pressure of sublimation and of vaporization) and their relation with entropy of fusion is also presented. As we aimed to estimate these properties for any of the ca. 1500 halogenated benzenes that may exist theoretically, an equation for estimating the temperature of fusion was also derived, since some of the proposed predictive equations (solubility of solids and Gibbs energy of sublimation) require its knowledge. For the other estimated properties just the number of each halogen that replaces hydrogen atoms in the halogenated benzene is needed. It was found that the coefficients that multiply the number of halogen atoms in the predictive equations vary linearly with the volume of the halogen atom.


The changing epidemiology of syndactyly in Chinese newborns: a nationwide surveillance-based study.
Little is known about the epidemiologic features of syndactyly (SD) in Chinese newborns. Using 2007-2019 data from the Chinese Birth Defects Monitoring Network, we conducted a prevalence analysis on overall, isolated and associated syndactyly according to birth year, maternal age, maternal residence, geographic region and infant sex, with special interests in time trends, perinatal outcomes and clinical phenotypes. A total of 13,611 SD cases were identified among 24,157,719 births in the study period, yielding the prevalence of 5.63, 4.66 and 0.97 per 10,000 for overall, isolated, and associated SD, respectively. The prevalence of each type of SD exhibited an upward trend over the period. The prevalence of overall SD varied significantly by maternal residence (urban vs. rural, 6.69/10,000 vs. 4.35/10,000), maternal age (< 20 years, 5.43/10,000; 20-24 years, 5.03/10,000; 25-29 year, 5.65/10,000; 30-34 years, 6.07/10,000; ≥ 35 years, 5.76/10,000), geographic region (central, 5.07/10,000; east, 6.75/10,000; west, 5.12/10,000), and infant sex (male vs. female, 6.28/10,000 vs. 4.86/10,000). Newborns with associated SD were more likely to be born prematurely (29.2% vs. 10.6%) or with low birthweight (30.5% vs.9.8%) than those with isolated SD. The bilaterally, and unilaterally affected cases accounted for 18.4% and 76.7%, respectively. The feet were more frequently involved (64.3%) in those bilaterally affected cases, while right side preference (right vs left: 53.8% vs 46.2%) and upper limbs preference (hand vs foot: 50.8% vs 48.0%) were found in unilateral cases. The prevalence of syndactyly in China is on the rise and notably higher than that in other Asian and European countries, highlighting the importance of investigating the etiology, epidemiology, and clinical implications of this condition in the Chinese population.


[Malignant transformation of multiple gastric adenomatous polyps in a teenage girl: a case report].
A 14-year-old female was found to have gastric polyposis by gastroscopy and barium meal study. During operation, multiple polyps in different sizes were noted over the whole stomach, the largest one measured 6 x 6 x 4 cm. The pathological report was adenomatous polyps. After 4 years, the polyps finally transformed to multifocal gastric adenocarcinoma. The relationship between gastric polyps and gastric adenocarcinoma, and the management of gastric polyposis were discussed.