Wnt10b protects cardiomyocytes against doxorubicin-induced cell death via MAPK modulation.
Doxorubicin, an anthracycline chemotherapeutic known to incur heart damage, decreases heart function in up to 11% of patients. Recent investigations have implicated the Wnt signaling cascade as a key modulator of cardiac tissue repair after myocardial infarction. Wnt upregulation in murine models resulted in stimulation of angiogenesis and suppression of fibrosis after ischemic insult. However, the molecular mechanisms of Wnt in mitigating doxorubicin-induced cardiac insult require further investigation. Identifying cardioprotective mechanisms of Wnt is imperative to reducing debilitating cardiovascular adverse events in oncologic patients undergoing treatment. Exposing human cardiomyocyte AC16 cells to varying concentrations of Wnt10b and DOX, we observed key metrics of cell viability. To assess the viability and apoptotic rates, we utilized MTT and TUNEL assays. We quantified cell and mitochondrial membrane stability via LDH release and JC-1 staining. To investigate how Wnt10b mitigates doxorubicin-induced apoptosis, we introduced pharmacologic inhibitors of key enzymes involved in apoptosis: FR180204 and SB203580, ERK1/2 and p38 inhibitors. Further, we quantified apoptotic executor enzymes, caspase 3/7, via immunofluorescence. AC16 cells exposed solely to doxorubicin were shrunken with distorted morphology. Cardioprotective effects of Wnt10b were demonstrated via a reduction in apoptosis, from 70.1% to 50.1%. LDH release was also reduced between doxorubicin and combination groups from 2.27-fold to 1.56-fold relative to the healthy AC16 control group. Mitochondrial membrane stability was increased from 0.67-fold in the doxorubicin group to 5.73 in co-treated groups relative to control. Apoptotic protein expression was stifled by Wnt10b, with caspase3/7 expression reduced from 2.4- to 1.3-fold, and both a 20% decrease in p38 and 40% increase in ERK1/2 activity. Our data with the AC16 cell model demonstrates that Wnt10b provides defense mechanisms against doxorubicin-induced cardiotoxicity and apoptosis. Further, we explain a mechanism of this beneficial effect involving the mitochondria through simultaneous suppression of pro-apoptotic p38 and anti-apoptotic ERK1/2 activities.


Extra-vascular findings in patients undergoing magnetic resonance angiography of the abdomen, pelvis and lower extremities: A retrospective study of 352 patients.
Background The aim of this study was to assess the prevalence and clinical significance of extra-vascular findings in patients undergoing magnetic resonance angiography of the abdomen, pelvis and lower extremities. Materials and methods Three hundred fifty-two patients underwent abdominal, pelvic and lower extremity 1.5 T magnetic resonance angiography. Clinically relevant vascular and extra-vascular findings were identified. Relevant vascular findings were classified as stenosis, occlusion, aneurysm, sclerosis, dissection or vasculitis. Relevant extra-vascular findings were categorized as 'safe' (Group A), intermediate - requiring additional investigation - (Group B) and malignant/endangering - requiring change of therapy (Group C). Results A total of 2152 clinically relevant vascular findings was identified (6.1/patient). The most frequent vascular finding was femoral artery stenosis (10.6%). Four hundred fifty-one extra-vascular findings were observed (1.3/patient) and classified into Group A (78%), Group B (19.5%) and Group C findings (2.4%). The most frequent malignant findings were lung cancer, lymphoma, osteosarcoma, hepatocellular carcinoma and renal cell carcinoma (7/352 patients). Conclusions Extravascular findings are frequently encountered in magnetic resonance angiography performed for vascular indications. Clinically relevant findings are seen in a substantial part of patients and should prompt further diagnostic work-up.


Antebrachium fractures: rush pin fixation today in the light of late results.
A study was undertaken to clarify the usefulness of the Rush pin intramedullary semirigid nailing technique in the treatment of 88 antebrachium fractures in 48 consecutive adult patients during the years 1966 through 1977. Of the patients 45 were followed for an average of 7.6 years (range, 2-14 years). The clinical results (antebrachium and wrist movements) were good in 78% of the cases with few complications. Union was delayed in five cases. There were no cases of wound infection, nonunion, or bone atrophy. The method was suitable for almost all types of fracture, even in elderly patients. Severe comminuted fractures with a shortening tendency on the radius require a special technique to prevent ulnar variance. The low degree of operative trauma may contribute to the excellent results obtained with the Rush technique.


The association of physical activity, cognitive processes and automobile driving ability in older adults: A review of the literature.
As the number of older adults in the United States grows, the number of automobile drivers over the age of 65 will also increase. Several cognitive processes necessary for automobile driving are vulnerable to age-related decline. These include declines in executive function, working memory, attention, and speed of information processing. The benefits of physical activity on physical, psychological and particular cognitive processes are well-documented; however few studies have explored the relationship between physical activity and driving ability in older adults or examined if cognitive processes mediate (or moderate) the effect of physical activity on driving ability. The purpose of this paper is to review the existing literature regarding physical activity, cognition and automobile driving. Recommendations for further research and utility of the findings to nursing and the health care team are provided.


Bioavailability of N-acetylprocainamide from mixed diet in rats.
The purpose of this study was to determine the bioavailability of N-Acetylprocainamide (NAPA) from mixed diet in rats. Six groups of 8 male Charles River CD rats received NAPA-HCl as follows: Group I, an intravenous dose (mean 21 mg) of 14C-labelled drug. Group II, in a solution given by oral gavage with and without feed (50 mg) in a two-way crossover fashion. Groups III-VI, incorporated in diet (42-68 mg). Urine and feces were collected for 48 hours and assayed for NAPA and procainamide by a specific HPLC method. On the average, 73% of the drug was eliminated unchanged in urine. Only a small percentage (3-4%) of the intact drug was recovered in feces after intravenous or oral administration. There were no detectable levels of procainamide in urine and feces. The absolute bioavailability of NAPA from oral solution with and without feed was 87 and 90%, respectively, and from the mixed diet was 84-92%. There was no statistically significant difference between the bioavailability of NAPA from solution in fasted and fed rats or from NAPA-mixed diet, indicating that the absorption of the drug in rats was not affected by food. The relative bioavailability of the drug from mixed diet ranged from 94-103%.


Severe autonomic dysreflexia induced cardiac arrest under isoflurane anesthesia in a patient with lower thoracic spine injury.
We present a case of severe autonomic dysreflexia (AD) progressing to cardiac arrest and death under isoflurane anesthesia. Though AD in chronic cervical spine injury is a common entity, occurrence of such an event in the stage of flaccid paralysis in lower dorsal spinal cord injury is rare, especially under general anesthesia. Manipulation of urinary bladder catheter under light plane of isoflurane anesthesia might be the precipitating factor. Increasing concentration of isoflurane failed to abort the episode or might have aggravated it. High level of suspicion and vigilance is necessary to prevent, diagnose and treat such a condition.


Factors Related to Axial Length Elongation in Myopic Children Who Received 0.05% Atropine Treatment.
Purpose: To evaluate the longitudinal changes of axial length (AL) and factors associated with AL growth in myopic children receiving 0.05% atropine. Methods: This single-center retrospective study included children aged 4-13 years with myopia of at least -0.5 diopters (D) treated with 0.05% atropine eye drops from November 2016 to May 2021. Predictive factors for AL change were evaluated using linear mixed models. Results: Among 109 patients (218 eyes), 58 (53.2%) were male and the mean age at treatment was 8.5 ± 2.0 years. At baseline measurement, the mean spherical equivalent was -4.05 ± 2.34 diopters (D), and AL was 25.00 ± 0.97 mm. The mean follow-up duration was 25.4 (12-58) months, and the mean AL elongation was 0.23 ± 0.17 mm/year during the follow-up periods. AL shortening of ≥0.05 mm at subsequent visit occurred in 18 patients (26 eyes). The mean AL change in the group without initial AL shortening was statistically larger than that in the group with initial AL shortening (0.26 ± 0.16 mm/year vs. 0.02 ± 0.17 mm/year, P < 0.001). In linear mixed model, the age at atropine treatment and initial AL shortening were significantly associated with respect to AL growth (beta coefficient: -0.032 and -0.122, respectively, P < 0.001 for both). Conclusions: Our study found that older age and initial AL shortening are predictors of favorable response after 0.05% atropine treatment. Children with AL shortening at initial subsequent visit may be associated with good long-term response, and younger children may require higher concentration of atropine for optimal response.


Characterization of nucleobase-amino acid stacking interactions utilized by a DNA repair enzyme.
The present work characterizes the gas-phase stacking interactions between four aromatic amino acid residues (histidine, phenylalanine, tyrosine, and tryptophan) and adenine or 3-methyladenine due to the proposed utilization of these interactions by enzymes that repair DNA alkylation damage. The MP2 potential energy surfaces of the stacked dimers are considered as a function of four variables (vertical displacement, angle of rotation, horizontal displacement, and tilt angle) using a variety of basis sets. It is found that the maximum stacking interaction energy decreases with the amino acid according to TRP > TYR approximately HIS > PHE for both nucleobases. However, the magnitude of the stacking interaction significantly increases upon alkylation (by 50-115%). Comparison of the stacking energies calculated using our surface scans to those estimated from experimental crystal structures indicates that the stacking interactions within the active site of 3-methyladenine DNA glycosylase can account for 65-75% of the maximum possible stacking interaction between the relevant molecules. The decrease in stacking in the crystal structure arises due to significant differences in the relative orientations of the nucleobase and amino acid. Nevertheless, alkylation is found to significantly increase the stacking energy when the crystal structure geometries are considered. Our calculations provide computational support for suggestions that alkylation enhances the stacking interactions within the active site of DNA repair enzymes, and they give a measure of the magnitude of this enhancement. Our results suggest that alkylation likely plays a more important role in substrate identification and removal than the nature of the aromatic amino acid that interacts with the substrate via stacking interactions.


Microcarriers for animal cell culture: a brief review of theory and practice.
Microcarrier beads for animal cell culture are considered in relation to aspects of cell adhesion and growth. Some "critical parameters" for a successful microcarrier are discussed, comparing currently available materials. The properties most critical for a successful microcarrier were closely fulfilled by the microcarrier CytodexTM 1 which has been used for the successful cultivation of more than 60 different cell types. Cytodex 1 has been used for the culture of primary cells, normal diploid cell strains and established or transformed cell lines in culture volumes ranging from a few millilitres to over 100 litres.


Identification and Validation of Gene Expression Patterns in Cystitis Glandularis Patients and Controls.
Our aim was to investigate differences in gene expression in bladder tissues between cystitis glandularis (CG) patients and healthy controls. Subsequent RNA was isolated from urinary bladder samples from CG patients and healthy controls, followed by RNA sequencing analysis. There were 4263 differentially expressed genes in urinary bladder between CG patients and controls, and 8 genes were verified with real-time PCR, Western blot, and enzyme-linked immunosorbent assay (ELISA) analysis. Gene set enrichment analysis (GSEA) revealed that 25 signaling pathways were upregulated in CG patients, and 17 signaling pathways were found upregulated in healthy controls. The mRNA expression levels of the indicated genes, including CCND1, CCNA1, EGFR, AR, CX3CL1, CXCL6, and CXCL1, were significantly increased in urinary bladder from CG and bladder cancer (BC) patients compared with healthy controls, while TP53 was decreased. CX3CL1, CXCL6, and CXCL1 concentrations in peripheral blood from CG and BC patients were significantly increased compared with healthy controls. The protein expression levels of CCND1, EGFR, and AR were significantly increased in urinary bladder from CG and BC patients compared with healthy controls. In conclusion, the gene expression profile of CG patients has established a foundation to study the gene mechanism of CG and BC progression.


Managing fever in children: a national survey of parents' knowledge and practices in France.
Identifying targets to improve parental practices for managing fever in children is the first step to reducing the overloaded healthcare system related to this common symptom. We aimed to study parents' knowledge and practices and their determinants in managing fever symptoms in children in France as compared with current recommendations. We conducted an observational national study between 2007 and 2008 of French general practitioners, primary care pediatricians and pharmacists. These healthcare professionals (HPs) were asked to include 5 consecutive patients from 1 month to 12 years old with fever for up to 48 hr who were accompanied by a family member. Parents completed a questionnaire about their knowledge of fever in children and their attitudes about the current fever episode. We used a multilevel logistic regression model to assess the joint effects of patient- and HP-level variables. In all, 1,534 HPs (participation rate 13%) included 6,596 children. Parental concordance with current recommendations for temperature measurement methods, the threshold for defining fever, and physical (oral hydration, undressing, room temperature) and drug treatment was 89%, 61%, 15%, and 23%, respectively. Multivariate multi-level analyses revealed a significant HP effect. In general, high concordance with recommendations was associated with high educational level of parents and the HP consulted being a pediatrician. In France, parents' knowledge and practices related to managing fever symptoms in children frequently differ from recommendations. Targeted health education interventions are needed to effectively manage fever symptoms in children.


[B17-D-leucine]insulin and [B17-norleucine]insulin: synthesis and biological properties.
The chemical synthesis of two porcine insulin analogues is described. Leucine in position B17 of the native molecule was substituted by its D-enantiomer and by L-norleucine, respectively. Both B-chain derivatives were synthesized by fragment condensation and purified as di-S-sulphonates by gel filtration followed by ion exchange chromatography on SP-Sephadex at pH3. Combination with native sulphhydryl A-chain yielded [DLeuB17]insulin and [NleB17]insulin. Both insulin analogues were isolated by gel filtration followed by ion exchange chromatography on CM-cellulose at pH 4.0. Biological activities of the analogues were determined relative to native pork insulin: 1) glucose oxidation in rat epididymal adipocytes was 6% for [DLeuB17]insulin and 16% for [NleB17]insulin, 2) receptor-binding affinity tested with cultured human fibroblasts and with rat adipocytes was 3% for [DLeuB17]insulin and 26% for [NleB17]insulin, and 3) thymidine incorporation into DNA of human fibroblasts was 35% for [DLeuB17]insulin and 100% for [NleB17]insulin.


[Histamine poisoning following consumption of fried fish].
Cases of food poisoning after consumption of fried fish in marinades are often caused by increased content of histamine. From 1973 to 1988 28 outbreaks in groups of persons with symptoms of histamine poisoning were analysed in the district of Dresden (GDR). The content of histamine most commonly exceeded the tolerance limit of 300 mg/kg fried fish.


Concept of experimental preparation for treating dentin hypersensitivity.
Dentinal hypersensitivity (DH) is a diagnostic and therapeutic problem that is now appearing more frequently in modern dentistry. The aim of this work was to elaborate formulation of a new, original desensitizing preparation with prolonged action based on the knowledge of similar commercializations and to compare their performance in vitro. The analyses were performed with the aid of NMR spectroscopy. The experimental and commercial preparations were examined in vitro after thermocycling on human teeth by optical microscopy. The presence of the material on tooth tissue, its ability to penetrate into the tooth structure and its layer thickness were subjected to statistical analysis. A detailed knowledge on composition of commercial material was achieved from spectroscopic measurements. A new adhesive monomer was synthesized and incorporated into an experimental desensitizing formulation. The new monomer appeared to have comparable performance to the commercial one when regarding the affinity to tooth tissue and resistance to thermocycling. The experimental formulation comprising a new adhesive monomer seems to be promising and could be applied in dental practice providing that biocompatibility is satisfactory.


Retention of virulence in a viable but nonculturable Edwardsiella tarda isolate.
Edwardsiella tarda is pathogen of fish and other animals. The aim of this study was to investigate the viable but nonculturable (VBNC) state and virulence retention of this bacterium. Edwardsiella tarda CW7 was cultured in sterilized aged seawater at 4 degrees C. Total cell counts remained constant throughout the 28-day period by acridine orange direct counting, while plate counts declined to undetectable levels (<0.1 CFU/ml) within 28 days by plate counting. The direct viable counts, on the other hand, declined to ca. 10(9) CFU/ml active cells and remained fairly constant at this level by direct viable counting. These results indicated that a large population of cells existed in a viable but nonculturable state. VBNC E. tarda CW7 could resuscitate in experimental chick embryos and in the presence of nutrition with a temperature upshift. The resuscitative times were 6 days and 8 days, respectively. The morphological changes of VBNC, normal, and resuscitative E. tarda CW7 cells were studied with a scanning electron microscope. The results showed that when the cells entered into the VBNC state, they gradually changed in shape from short rods to coccoid and decreased in size, but the resuscitative cells did not show any obvious differences from the normal cells. The VBNC and the resuscitative E. tarda CW7 cells were intraperitoneally inoculated into turbot separately, and the fish inoculated with the resuscitative cells died within 7 days, which suggested that VBNC E. tarda CW7 might retain pathogenicity.


Educational outcomes of a new curriculum on interproximal oral prophylaxis for dental students.
The aim of this study was to evaluate the effectiveness of a preclinical oral prophylaxis education program by examining the effectiveness of the teaching module on changes to the students' attitudes towards their individual hygiene behaviors with interdental brushes (IDBs). As being part of a new didactic program on oral interproximal prophylaxis, all preclinical third-year students (n = 96) enrolled in the 2014/15 academic year received theoretical, preclinical, and clinical lessons on interproximal prophylaxis. The evaluation of educational outcomes was linked to observed changes in students' hygiene behaviors using interdental brushes. Knowledge, skills, attitudes, satisfaction, competence and performance were also explored. The evaluation interviews were recorded at each recall, i.e., 1 week, 1 month, 3 months and 1 year after baseline. Motivation to use IDBs is clearly related to the perception of the effectiveness of the brushes and the perception of bleeding reduction. At one week, 89.6% of subjects reported using IDBs. Individual use decreased significantly from one week to one month (-26%, p = 0.006) while a non-significant upward trend occurred between one month and three months. Among students reporting usage of IDBs at 1 year (20.8%), only 2.0% used IDBs daily. Most students would recommend IDBs to other people at the beginning (69.8%). However, this share dropped to 50% at 3 months. IDB-users prescribed more than non-users. The implementation of a module on interdental hygiene practices in the oral health program is strongly recommended. However, corrective measures should be considered regarding the organization and frequency of recall periods in order to improve the performance of the curriculum.


Reference intervals for eight measurands of the blood count in a large population based study.
The blood count is widely used in clinical practice. Well defined reference intervals for each measurand are essential for correct clinical interpretation of results. Most previous studies have not been population-based. We therefore calculated reference intervals for several hematological measurands from a sample of the general adult population of Northeastern Germany. We used data from 2967 healthy individuals recruited for the population-based Study of Health in Pomerania (SHIP). Reference intervals were calculated according to the guidelines of the Clinical and Laboratory Standards Institute (CLSI) using the bootstrap method for the age range from 20 to 79 years and, in addition, stratified according to age and gender with both bootstrap and quantile regression procedures. Reference ranges for erythrocytes, hemoglobin and hematocrit increased with age in women but decreased in men. Our reference intervals were lower than those previously published for erythrocytes, hemoglobin, hematocrit and leukocytes but higher for Mean Corpuscular Volume (MCV) and Mean Corpuscular Hemoglobin (MCH). Different laboratory methods and study populations may lead to disparity in results.


Evaluation of urinary N-acetyl cysteinyl allyl isothiocyanate as a biomarker for intake and bioactivity of Brussels sprouts.
Isothiocyanates (ITC), glucosinolate hydrolysis products from Brussels sprouts (BS) and other cruciferous vegetables, are considered to protect the body from cancer by induction of detoxification enzymes such as quinone reductase (QR). Urinary N-acetyl-cysteine (NAC) conjugates of ITC have been proposed as biomarkers of crucifer intake. Here we asked if dietary intake and induction of detoxification enzymes are dose-related to urinary NAC conjugate appearance. Male F344 rats (4/group) received an AIN 76B-40 diet containing 0, 10 or 20% freeze-dried BS for 6 days. A human subject ingested 500 g BS. Urinary AITC-NAC was identified in human and rat urine. Ten and 20% BS diets caused a 1.4- and 2.3-fold induction of QR in the pancreas, a 1.5- and 2.5-fold induction in liver and a 3.1- and 3.6-fold induction in colonic epithelium, respectively. Liver and pancreatic QR induction was dose-related, whereas induction of QR in colon was less different between the two doses. Excretion of the conjugate was dose-related only on day 1, and unrelated to dose after day 2. These results suggest that urinary NAC-AITC is a qualitative biomarker for ingestion and bioactivity of BS, but that it may not be dose-related when rats are fed continuously for 2 or more days.


Xiaoaiping injection as adjunct therapy for patients with advanced esophageal carcinoma: A protocol for a systematic review and meta-analysis.
Esophageal carcinoma (EC) is one of the worst malignant digestive neoplasms with a strong tendency of invasion and metastasis. Despite the improvement of diagnostic and therapeutic methods in the past decades, the prognosis of EC remains unsatisfactory. Xiaoaiping injection (XAPI), a famous traditional Chinese herbal medicine, has been widely applied as a promising adjunctive drug for EC. However, the exact effects and safety of XAPI have yet to be systematically investigated. We aimed to summarize the efficacy and safety of XAPI for the treatment of advanced EC through the meta-analysis, in order to provide scientific reference for the design of future clinical trials. Relevant randomized controlled trials (RCTs) were searched from Cochrane Library, PubMed, Google Scholar, Web of Science, Excerpt Medica Database, Medline, China National Knowledge Infrastructure, Chinese Biomedical Literature Database, China Scientific Journal Database and Wanfang Database. Papers in English or Chinese published from January 2000 to May 2020 will be included without any restrictions.Study selection and data extraction will be performed independently by 2 investigators. The clinical outcomes including overall response rate, complete response rate, overall survival, Disease-free survival, quality of life, immune function and adverse events, were systematically evaluated. Review Manager 5.3 and Stata 14.0 were used for data analysis, and the quality of the studies was also evaluated. The results of this study will be published in a peer-reviewed journal, and provide more evidence-based guidance in clinical practice. Our study will draw an objective conclusion of the effects of XAPI combined with conventional treatment for advanced EC and provide a helpful evidence for clinicians to formulate the best postoperative adjuvant treatment strategy for EC patients. INPLASY202050094.


[Mnemonic performance in patients following surgery to treat an aneurysm affecting the anterior circulation of the brain].
Patients submitted to surgery to treat a brain aneurysm, who have suffered a subarachnoid haemorrhage, sometimes present cognitive disorders that can affect their social, familial, academic or occupational relationships. Memory disorders are frequent, although other cognitive functions may also be affected. The purpose of this research work was to study performance in logical verbal memory and visual-constructional memory in subjects following a surgical intervention (at least a year ago) to treat an aneurysm in the territory of the anterior circulation of the brain. We also wanted to analyse whether the location of the aneurysm in the brain had any effect on memory performance. We examined a sample of 24 adult subjects of both sexes, with no previous history of cognitive or psychiatric disorders, who had undergone surgical treatment of brain aneurysms in the middle cerebral, anterior communicating and posterior communicating arteries. Neuropsychological tests were performed to assess the general cognitive status, as well as logical verbal and visual-constructional memory. 79% of the patients present a general cognitive status within the range of what could be considered to be normal. In logical verbal memory, 92% present performances within the limits of the expected range of values and 83% did the same in visual-constructional memory. Depending on the location of the aneurysm, significant differences were only found in the delayed evocation of logical verbal material. A year after the intervention, most of the patients present a pattern of normality in the general cognitive status, and in logical verbal and visual-constructional memory. Yet, in spite of the good neurological resolution, alterations to memory are still to be found, although less frequently. The anatomical location of the aneurysm in the brain affects performance in tasks involving delayed logical verbal memory.


Time course of proteolytic, cytokine, and myostatin gene expression after acute exercise in human skeletal muscle.
The aim of this study was to examine the time course induction of select proteolytic [muscle ring finger-1 (MuRF-1), atrogin-1, forkhead box 3A (FOXO3A), calpain-1, calpain-2], myostatin, and cytokine (IL -6, -8, -15, and TNF-alpha) mRNA after an acute bout of resistance (RE) or run (RUN) exercise. Six experienced RE (25 +/- 4 yr, 74 +/- 14 kg, 1.71 +/- 0.11 m) and RUN (25 +/- 4 yr, 72 +/- 5 kg, 1.81 +/- 0.07 m) subjects had muscle biopsies from the vastus lateralis (RE) or gastrocnemius (RUN) before, immediately after, and 1, 2, 4, 8, 12, and 24 h postexercise. RE increased (P < 0.05) mRNA expression of MuRF-1 early (3.5-fold, 1-4 h), followed by a decrease in atrogin-1 (3.3-fold) and FOXO3A (1.7-fold) 8-12 h postexercise. Myostatin mRNA decreased (6.3-fold; P < 0.05) from 1 to 24 h postexercise, whereas IL-6, IL-8, and TNF-alpha mRNA were elevated 2-12 h. RUN increased (P < 0.05) MuRF-1 (3.6-fold), atrogin-1 (1.6-fold), and FOXO3A (1.9-fold) 1-4 h postexercise. Myostatin was suppressed (3.6-fold; P < 0.05) 8-12 h post-RUN. The cytokines exhibited a biphasic response, with immediate elevation (P < 0.05) of IL-6, IL-8, and TNF-alpha, followed by a second elevation (P < 0.05) 2-24 h postexercise. In general, the timing of the gene induction indicated early elevation of proteolytic genes, followed by prolonged elevation of cytokines and suppression of myostatin. These data provide basic information for the timing of human muscle biopsy samples for gene expression studies involving exercise. Furthermore, this information suggests a greater induction of proteolytic genes following RUN compared with RE.


The Family Adaptability and Cohesion Scale III in a Norwegian sample.
Olson's Family Adaptability and Cohesion Scales (FACES III) and Beavers' Self-report Family Inventory (SFI) were administered to 177 young Norwegian adults. Three questions were raised: (1) do the two-factor structure and curvilinear hypothesis of Olson's model of family functioning find support cross-culturally; (2) does curvilinearity depend on whether families of origin or procreation are described; and (3) does the data analytic technique dictate the results. In 1985, in their manual, Olson and his associates proposed the use of Distance from Center (DFC) scores to test the curvilinear hypothesis, a procedure that presupposes orthogonality between the dimensions of Cohesion and Adaptability, which was not found in several other samples nor in the present study. Using DFC scores, the curvilinear hypothesis received moderate support only when families of origin were described. A polynomic regression analysis gave clear evidence, however, of a linear relationship between the FACES dimensions and SFI Health Scores for both families of origin and families of procreation. The findings suggest that respondents do not have an implicit bipolar model of cohesion and adaptability.


Role of Lactobacilli and Lactoferrin in the Mucosal Cervicovaginal Defense.
The innate defense system of the female mucosal genital tract involves a close and complex interaction among the healthy vaginal microbiota, different cells, and various proteins that protect the host from pathogens. Vaginal lactobacilli and lactoferrin represent two essential actors in the vaginal environment. Lactobacilli represent the dominant bacterial species able to prevent facultative and obligate anaerobes outnumber in vaginal microbiota maintaining healthy microbial homeostasis. Several mechanisms underlie the protection exerted by lactobacilli: competition for nutrients and tissue adherence, reduction of the vaginal pH, modulation of immunity, and production of bioactive compounds. Among bioactive factors of cervicovaginal mucosa, lactoferrin, an iron-binding cationic glycoprotein, is a multifunctional glycoprotein with antibacterial, antifungal, antiviral, and antiparasitic activities, recently emerging as an important modulator of inflammation. Lactobacilli and lactoferrin are largely under the influence of female hormones and of paracrine production of various cytokines. Lactoferrin is strongly increased in lower genital tract mucosal fluid of women affected by Neisseria gonorrheae, Chlamydia trachomatis, and Trichomonas vaginalis infections promoting both innate and adaptive immune responses. In vaginal dysbiosis characterized by low amounts of vaginal lactobacilli and increased levels of endogenous anaerobic bacteria, the increase in lactoferrin could act as an immune modulator assuming the role normally played by the healthy microbiota in vaginal mucosa. Then lactoferrin and lactobacilli may be considered as biomarkers of altered microbial homeostasis at vaginal level. Considering the shortage of effective treatments to counteract recurrent and/or antibiotic-resistant bacterial infections, the intravaginal administration of lactobacilli and lactoferrin could be a novel efficient therapeutic strategy and a valuable tool to restore mucosal immune homeostasis.


Randomized Controlled Trial of Slow Versus Rapid Enteral Feeding Advancements on the Clinical Outcomes in Very Low Birth Weight Neonates.
Starting and advancement of feeding in very low birth weight (VLBW) infants are big challenges for the neonatal practitioners. Wide variations in volume of feed advancement have observed in earlier trials both in slow and rapid advancement groups. Volume advancement in slow advancement groups have ranged from 10ml/kg/day to 23ml/kg/day and in rapid advancement groups have ranged from 15ml/kg/day to 45ml/kg/day in earlier different studies. This randomized controlled trial was conducted in neonatal intensive care unit (NICU) of Bangabandhu Sheikh Mujib Medical University (BSMMU) from April 2013 to July 2014 to evaluate the effects of slow versus rapid rates of feeding advancements on the clinical outcomes in very low birth weight infants. A total 95 infants were enrolled into two strata according to their birth weight. Infants of each stratum were randomly allocated to either slow or rapid advancement group during initiation of feeding. After gut priming over five days, feeding was advanced daily 10ml/kg in slow and 15ml/kg in rapid advancement group for 1000 - <1250gm weighing infants. For 1250 - <1500gm weighing infants, feeding was advanced daily 15ml/kg in slow and 20ml/kg in rapid advancement group. The primary outcome variable was time taken to achieve full enteral feed. Total 82 infants completed the trial. Demographically both groups were same. Infants in the rapid feeding advancement group achieved full enteral feedings before the slow advancement group, had significantly fewer days of parenteral nutrition and regained birth weight earlier. There were no statistical differences in episodes of feed interruption, number of infants with apnea, feed intolerance or diagnosis of sepsis. Rapid enteral feeding advancements were well tolerated by very low birth weight infants.


An early marker for neurological deficits after perinatal brain lesions.
In normal awake infants, fidgety movements are seen from the age of 6 weeks to 20 weeks. The aim of the study was to test the predictive value of absent or abnormal spontaneous movements in young infants for the later development of neurological deficits. In a collaborative study involving five hospitals we collected data on the normal and abnormal quality of fidgety movements of 130 infants and compared it with assessments of neurological development done longitudinally until the age of 2 years. On the basis of ultrasound scans infants were classified as at low-risk or at high-risk of neurological deficits. Infants were videoed for 1 h every week from birth to discharge and then for 15 min every 3 to 4 weeks; quality of general movements was assessed. Repeated neurological assessments were also done until 24 months of corrected age. 67 (96%) of 70 infants with normal fidgety movements had a normal neurological outcome. Abnormal quality or total absence of fidgety movements was followed by neurological abnormalities in 57 (95%) of the 60 infants (49 had cerebral palsy and eight had developmental retardation or minor neurological signs). Specificity and sensitivity of fidgety movement assessment were higher (96% and 95%, respectively) than of ultrasound imaging of the infants' brain (83% and 80%, respectively). Our technique of assessing spontaneous motor activity can identify and distinguish between those infants who require early intervention for neurological abnormalities and those who do not. Our technique is simple, non-intrusive, reliable, quick, and can be done on very young infants.


Workplace bullying and violence in health sector in Saudi Arabia.
Workplace bullying violence (BV), with psychological and physical impacts, is increasing globally. However, studies from Saudi Arabia investigating which specialties are most exposed, and linking them with other factors, such as sociodemographic conditions, are scarce. This study aimed to estimate the prevalence of workplace BV over a 12-month period and determine the circumstances related to the event, consequences for the attacker, and targeted personnel among all healthcare providers in the Kingdom of Saudi Arabia (KSA). This analytical cross-sectional study included all health providers registered with the Saudi Commission for Health Specialties who worked for more than 1 year in the healthcare sector (governmental or private) in the KSA until May 2019. In total, 7398 healthcare workers were electively enrolled in the study; 51.3% were men, and 48.7% were women, with a mean age of 40 ± 8.62 years. They were mostly (60%) non-Saudi. Overall, 26.6% encountered BV. Those who worked in the private sector, in shifts, especially evening shifts, were significantly more exposed. Furthermore, pharmacists had the highest prevalence of workplace violence. The prevalence of BV is moderately high; however, it is a serious issue faced by healthcare workers, especially those working night shifts. Pharmacists were more likely to experience bullying. This demonstrates that more support, specific strategies, and policies are required to reduce the occurrence of workplace BV, protect healthcare providers, and prevent attacks. Underreporting these situations may give an incorrect indication of the magnitude of the problem; thus, more education and further studies in the KSA are needed.


Effects of liquid DL-2-hydroxy-4-methylthio butanoic acid on growth performance and immune responses in broiler chickens.
An experiment was conducted to determine the effects of different doses of liquid dl-2-hydroxy-4-methylthio butanoic acid (LMA) on growth performance and immune response in broiler chickens. In an arrangement with 4 graded levels of LMA to meet 80, 100, 120, and 140% of methionine requirements of broilers recommended by Chinese feeding standards for chickens, 256 one-day-old Arbor Acres male broiler chickens were randomly divided into 4 treatments with 8 replicates of 8 birds each. Growth performance, cellular immunity, and humoral immunity were determined. Results from increasing LMA levels were as follows. There were no significant differences (P > 0.05) in body weight gain and feed intake among the treatments, but the ratio of feed to gain was linearly decreased and significantly greatest (P < 0.05) in the group fed at 80% of methionine requirement. Serum globulin levels on d 21 and 42 were linearly increased significantly (P < 0.05); phagocytosis of neutral red of peripheral blood lymphocyte was quadratic and was lowest in the deficient group (P < 0.05). The proliferation of peripheral blood lymphocytes in response to lipopolysaccharide was quadratically influenced, and that of the 120% group on d 21 and the 100% group on d 42 was significantly greater than in the other groups (P < 0.05). Antibody titers to Newcastle disease virus on d 4 after the first inoculation of the vaccine were quadratically increased, anti-bovine serum albumin antibody production on d 13 after the second immunization was quadratic, and antibody titers were greatest in the groups fed at 100 or 120% of methionine requirement. In conclusion, methionine deficiency resulted in decreased feed utilization and decreased humoral and nonspecific immuno-competence of broiler chickens. The use of LMA to correct a methionine deficiency corrected these problems.


Could the new dairy policy affect milk allocation to infants in Kenya? A best-worst scaling approach.
Milk is an important food item in the diet of Kenyans, especially infants. During the last two decades, the dairy sector in Kenya has witnessed important growth in production and improvements in milk quality. The informal marketing channel still prevails, and the Kenya Dairy Board, the regulator of the dairy sector, is currently introducing new regulations to increase registration and licensing of smallholder producers and dairy business operators, improve product hygiene and quality, and safeguard the health of consumers. These new regulations encompass, among others, the requirement to pasteurize milk before it is sold and adopt traceability processes and quality tests; most of these will probably result in higher milk prices at retail level. Using the best-worst scaling approach in this study, we analyzed the potential effects of milk price increase on household milk purchase and allocation to infants (6-48 months of age). The results indicate that an increase in milk price will decrease milk allocation to and intake by children. Households will replace the lost infant milk intake by fruits or porridge that might not be of equivalent nutritional value to milk. Any reforms to policies and regulatory systems aimed at streamlining the dairy sector should account for impacts on milk prices, responsiveness of consumers to price variations and infant nutrition. We recommend that regulatory and development agencies consider interventions that do not increase price for consumers and facilitate access to affordable and safe milk for children and entire households.


Optimal Entanglement Certification from Moments of the Partial Transpose.
For the certification and benchmarking of medium-size quantum devices, efficient methods to characterize entanglement are needed. In this context, it has been shown that locally randomized measurements on a multiparticle quantum system can be used to obtain valuable information on the so-called moments of the partially transposed quantum state. This allows one to infer some separability properties of a state, but how to use the given information in an optimal and systematic manner has yet to be determined. We propose two general entanglement detection methods based on the moments of the partially transposed density matrix. The first method is based on the Hankel matrices and provides a family of entanglement criteria, of which the lowest order reduces to the known p_{3}-positive-partial-transpose criterion proposed in A. Elben et al. [Phys. Rev. Lett. 125, 200501 (2020)PRLTAO0031-900710.1103/PhysRevLett.125.200501]. The second method is optimal and gives necessary and sufficient conditions for entanglement based on some moments of the partially transposed density matrix.


A randomized study of fever prophylaxis and the immunogenicity of routine pediatric vaccinations.
Prophylactic antipyretic use during pediatric vaccination is common. This study assessed whether paracetamol or ibuprofen prophylaxis interfere with immune responses to the 13-valent pneumococcal conjugate vaccine (PCV13) given concomitantly with the combined DTaP/HBV/IPV/Hib vaccine. Subjects received prophylactic paracetamol or ibuprofen at 0, 6-8, and 12-16 h after vaccination, or 6-8 and 12-16 h after vaccination at 2, 3, 4, and 12months of age. At 5 and 13months, immune responses were evaluated versus responses in controls who received no prophylaxis. After the infant series, paracetamol recipients had lower levels of circulating serotype-specific pneumococcal anticapsular immunoglobulin G than controls, reaching significance (P<0.0125) for 5 serotypes (serotypes 3, 4, 5, 6B, and 23F) when paracetamol was started at vaccination. Opsonophagocytic activity assay (OPA) results were similar between groups. Ibuprofen did not affect pneumococcal responses, but significantly (P<0.0125) reduced antibody responses to pertussis filamentous hemagglutinin and tetanus antigens after the infant series when started at vaccination. No differences were observed for any group after the toddler dose. Prophylactic antipyretics affect immune responses to vaccines; these effects vary depending on the vaccine, antipyretic agent, and time of administration. In infants, paracetamol may interfere with immune responses to pneumococcal antigens, and ibuprofen may reduce responses to pertussis and tetanus antigens. The use of antipyretics for fever prophylaxis during infant vaccination merits careful consideration. ClinicalTrials.gov identifier: NCT01392378https://clinicaltrials.gov/ct2/show/NCT01392378?term=NCT01392378&rank=1.


HIV-risk reduction intervention for juvenile offenders on probation: The PHAT Life group randomized controlled trial.
Juvenile offenders report high rates of sexual risk taking, increasing the possibility of HIV. This 2-arm group randomized controlled trial tested the efficacy of PHAT Life, a sexual risk reduction program, compared with a time-matched health promotion program for youth on probation. Male and female 13- to 17-year-olds (M = 16.08; SD = 1.09) recently arrested and placed on probation at an Evening Reporting Center were eligible for the study. Youth were 66% male, and 90% African American. Teens self-reported their sexual behavior (condom use, number of sexual partners) at baseline and 6 months. Retention was 85%. Youth were randomized to PHAT Life (n = 163) or a health promotion program (n = 147). Among youth reporting the highest risk at baseline (a composite measure of multiple partners and inconsistent condom use), those who received PHAT Life were over 4 times more likely than the control group to report a lower level of risk (i.e., no sex or one partner plus consistent condom use) by 6 months, OR = 4.28 with 95% CI [1.37, 13.38], SE = 0.58, p = .01. Among sexually active teens who reported sexual debut before 12-years-old, those who received PHAT Life reported significantly fewer sexual partners at 6-months than controls, partial eta squared = .32, p = .002. Findings support PHAT Life's efficacy to reduce sexual risk for juvenile offenders on probation. Future research should examine how best to disseminate PHAT Life to ensure that it is self-sustaining within the juvenile justice system. (PsycINFO Database Record


Persistence of double-stranded RNA in insect hemolymph as a potential determiner of RNA interference success: evidence from Manduca sexta and Blattella germanica.
RNA interference (RNAi) is a specific gene silencing mechanism mediated by double-stranded RNA (dsRNA), which has been harnessed as a useful reverse genetics tool in insects. Unfortunately, however, this technology has been limited by the variable sensitivity of insect species to RNAi. We propose that rapid degradation of dsRNA in insect hemolymph could impede gene silencing by RNAi and experimentally investigate the dynamics of dsRNA persistence in two insects, the tobacco hornworm, Manduca sexta, a species in which experimental difficulty has been experienced with RNAi protocols and the German cockroach, Blattella germanica, which is known to be highly susceptible to experimental RNAi. An ex vivo assay revealed that dsRNA was rapidly degraded by an enzyme in M. sexta hemolymph plasma, whilst dsRNA persisted much longer in B. germanica plasma. A quantitative reverse transcription PCR-based assay revealed that dsRNA, accordingly, disappeared rapidly from M. sexta hemolymph in vivo. The M. sexta dsRNAse is inactivated by exposure to high temperature and is inhibited by EDTA. These findings lead us to propose that the rate of persistence of dsRNA in insect hemolymph (mediated by the action of one or more nucleases) could be an important factor in determining the susceptibility of insect species to RNAi.


Action of Phytochemicals on Insulin Signaling Pathways Accelerating Glucose Transporter (GLUT4) Protein Translocation.
Diabetes is associated with obesity, generally accompanied by a chronic state of oxidative stress and redox imbalances which are implicated in the progression of micro- and macro-complications like heart disease, stroke, dementia, cancer, kidney failure and blindness. All these complications rise primarily due to consistent high blood glucose levels. Insulin and glucagon help to maintain the homeostasis of glucose and lipids through signaling cascades. Pancreatic hormones stimulate translocation of the glucose transporter isoform 4 (GLUT4) from an intracellular location to the cell surface and facilitate the rapid insulin-dependent storage of glucose in muscle and fat cells. Malfunction in glucose uptake mechanisms, primarily contribute to insulin resistance in type 2 diabetes. Plant secondary metabolites, commonly known as phytochemicals, are reported to have great benefits in the management of type 2 diabetes. The role of phytochemicals and their action on insulin signaling pathways through stimulation of GLUT4 translocation is crucial to understand the pathogenesis of this disease in the management process. This review will summarize the effects of phytochemicals and their action on insulin signaling pathways accelerating GLUT4 translocation based on the current literature.


A rigorous dynamical-systems-based analysis of the self-stabilizing influence of muscles.
In this paper, dynamical systems analysis and optimization tools are used to investigate the local dynamic stability of periodic task-related motions of simple models of the lower-body musculoskeletal apparatus and to seek parameter values guaranteeing their stability. Several muscle models incorporating various active and passive elements are included and the notion of self-stabilization of the rigid-body dynamics through the imposition of musclelike actuation is investigated. It is found that self-stabilization depends both on muscle architecture and configuration as well as the properties of the reference motion. Additionally, antagonistic muscles (flexor-extensor muscle couples) are shown to enable stable motions over larger ranges in parameter space and that even the simplest neuronal feedback mechanism can stabilize the repetitive motions. The work provides a review of the necessary concepts of stability and a commentary on existing incorrect results that have appeared in literature on muscle self-stabilization.


Acute myocardial infarction during pregnancy.
We describe the case of a 27-year-old primigravida with an unremarkable medical history and no risk factors for coronary artery disease. At 28 weeks she received tocolytic therapy, first with ritodrine, subsequently with nifedipine for preterm labour. In addition she developed an uncomplicated non-Q wave anterolateral myocardial infarction. A coronary angiography performed 2 days after the acute event was normal. The further course was uneventful with a spontaneous vaginal delivery at 40 weeks. We reviewed the literature concerning the incidence of acute myocardial infarction during pregnancy, its physiologic backgrounds and the possible association with use of tocolytic therapy, sympathomimetic agents in particular. The impact of pregnancy on maternal haemodynamics is generally underestimated, which makes an early diagnosis often difficult. Future research has to define the specific role of currently available treatment options, including cardiac catheterization and more recently developed pharmacologic interventions. Obviously, foetal considerations will greatly influence the selection of different approaches.


Mass spectrometric study of variation in kinin peptide profiles in nasal fluids and plasma of adult healthy individuals.
The kallikrein-kinin system is assumed to have a multifunctional role in health and disease, but its in vivo role in humans currently remains unclear owing to the divergence of plasma kinin level data published ranging from the low picomolar to high nanomolar range, even in healthy volunteers. Moreover, existing data are often restricted on reporting levels of single kinins, thus neglecting the distinct effects of active kinins on bradykinin (BK) receptors considering diverse metabolic pathways. A well-characterized and comprehensively evaluated healthy cohort is imperative for a better understanding of the biological variability of kinin profiles to enable reliable differentiation concerning disease-specific kinin profiles. To study biological levels and variability of kinin profiles comprehensively, 28 healthy adult volunteers were enrolled. Nasal lavage fluid and plasma were sampled in customized protease inhibitor prespiked tubes using standardized protocols, proven to limit inter-day and interindividual variability significantly. Nine kinins were quantitatively assessed using validated LC-MS/MS platforms: kallidin (KD), Hyp4-KD, KD1-9, BK, Hyp3-BK, BK1-8, BK1-7, BK1-5, and BK2-9. Kinin concentrations in nasal epithelial lining fluid were estimated by correlation using urea. Circulating plasma kinin levels were confirmed in the very low picomolar range with levels below 4.2 pM for BK and even lower levels for the other kinins. Endogenous kinin levels in nasal epithelial lining fluids were substantially higher, including median levels of 80.0 pM for KD and 139.1 pM for BK. Hydroxylated BK levels were higher than mean BK concentrations (Hyp3-BK/BK = 1.6), but hydroxylated KD levels were substantially lower than KD (Hyp4-KD/KD = 0.37). No gender-specific differences on endogenous kinin levels were found. This well-characterized healthy cohort enables investigation of the potential of kinins as biomarkers and would provide a valid control group to study alterations of kinin profiles in diseases, such as angioedema, sepsis, stroke, Alzheimer's disease, and COVID-19.


Actinic lichen planus in a Japanese man: first case in the East Asian population.
Actinic lichen planus (ALP) is a rare variant of lichen planus in which lichen planus develops on the light-exposed areas of the skin. ALP is reported to occur in the African, Middle Eastern,and Indian populations, with very few cases reported in Caucasians. Here, we report a case of ALP in a Japanese man; to the best of our knowledge, this is the first reported occurrence of ALP in the East Asian population. A 52-year-old Japanese man developed recurrent painful annular erythema on the face and hands. Histopathological examination of his skin biopsy revealed lichenoid-type infiltrates of lymphocytes and histiocytes. We established a diagnosis of ALP on the basis of the distribution of eruptions only on the sunlight-exposed areas and histological findings. Oral administration of systemic steroids proved effective in improving his condition. Lichen planus is known to be induced by an irritant (Koebner phenomenon);we believe that our patient is genetically susceptible to sunlight exposure and that sunlight acted as an irritant stimulating the development of ALP.


The Obesity Paradox Is Not Observed in Critically Ill Patients on Early Enteral Nutrition.
To investigate the association between body mass index and mortality in a large, ICU population and determine if the relationship is observed among a subgroup of patients ordered early enteral nutrition. Retrospective cohort study within a national clinical mixed ICU database of patients admitted between January 1, 2008, and June 30, 2015. Initial ICU admissions among patients monitored by tele-ICU programs and recorded in the Philips eICU Research Institute database. A total of 1,042,710 adult patient stays with ICU length of stay more than 24 hours, of which 74,771 were ordered enteral nutrition within the first 48 hours. None. Patient stays from 409 ICUs were included. The average age, Acute Physiology and Chronic Health Evaluation IV score, and hospital mortality were 63.6 years, 56.7, and 9.0%, respectively. Hospital mortality among body mass index categories was estimated by multivariable modified Poisson regression models. Compared with the body mass index category 25.0-29.9 kg/m, hospital mortality was higher among underweight (body mass index, < 18.5; relative risk, 1.35; 95% CI, 1.32-1.39), normal weight (body mass index, 18.5-24.9; relative risk, 1.10; 95% CI, 1.09-1.12), and the extremely obese (body mass index, ≥ 50.0; relative risk, 1.10; 95% CI, 1.05-1.15). However, the risk was not statistically different from patients with body mass index 30.0-49.9 kg/m. Among patients ordered early enteral nutrition, the risk of mortality in the body mass index category 25.0-29.9 kg/m was not statistically different from those in the normal weight or extremely obese groups. A survival advantage for overweight and obese patients was observed in this large cohort of critically ill patients. However, among those ordered early enteral nutrition, the survival disadvantage for body mass index categories less than 25.0 kg/m was minimal or unobservable when compared with higher body mass index categories.


Further experience in treating patients with hepatocellular carcinoma in Uganda.
One hundred and thirty nine patients with histologically proven hepatocellular carcinoma (HC) were admitted to the Uganda Cancer Institute for treatment. The patients were considerably younger and seemed to have more advanced disease than HC patients in Europe and in North America. Of the 99 evaluable patients, 50 received Adriamycin intravenously; of these, 44% responded, with 10% achieving complete responses. Intraarterial Adriamycin tended to increase the response rate to 75%, but this may be merely a reflection of patient selection. Combination of Adriamycin with other drugs (dichloromethotrexate, 5-azacytidine, Rezoxane and cyclophosphamide) did not enhance its therapeutic effectiveness. The alphafetoprotein response curves observed when Adriamycin was combined with dichloromethotrexate suggested possible antagonisms between the two drugs. Hepatic artery ligation (HAL) is a good and simple palliative procedure with response rates similar to i.v. Adriamycin. However, the administration of Adriamycin after HAL tended to improve on response rates and survival. The toxicities observed were mainly myelosuppression, gastrointestinal disturbance, alopecia, and hyperpigmentation of the skin and mucous membranes.


New insights into the Jahn-Teller effect through ab initio quantum-mechanical/molecular-mechanical molecular dynamics simulations of CuII in water.
The CuII hydration shell structure has been studied by means of classical molecular dynamics (MD) simulations including three-body corrections and hybrid quantum-mechanical/molecular-mechanical (QM/MM) molecular dynamics (MD) simulations at the Hartree-Fock level. The copper(II) ion is found to be six-fold coordinated and [Cu(H2O)6]2+ exhibits a distorted octahedral structure. The QM/MM MD approach reproduces correctly the experimentally observed Jahn-Teller effect but exhibits faster inversions (< 200 fs) and a more complex behaviour than expected from experimental data. The dynamic Jahn-Teller effect causes the high lability of [Cu(H2O)6]2+ with a ligand-exchange rate constant some orders or magnitude higher than its neighbouring ions NiII and ZnII. Nevertheless, no first-shell water exchange occurred during a 30-ps simulation. The structure of the hydrated ion is discussed in terms of radial distribution functions, coordination numbers, and various angular distributions and the dynamical properties as librational and vibrational motions and reorientational times were evaluated, which lead to detailed information about the first hydration shell. Second-shell water-exchange processes could be observed within the simulation time scale and yielded a mean ligand residence time of approximelty 20 ps.


Intracranial lymphomas in simian retrovirus-positive Macaca fascicularis.
Two young adult Macaca fascicularis each had unilateral mydriasis and ptosis. Both animals were euthanatized, monkey No. I for progressive neurologic signs and monkey No. 2 because of a positive intradermal tuberculin test. At necropsy, each animal had a single intracranial mass on the ventral surface of the midbrain, surrounding the oculomotor nerve. Histologically, both masses were immunoblastic lymphomas. Immunohistochemical staining revealed the neoplasms to be of B-cell origin. Simian retrovirus (SRV) was isolated from both monkeys, but simian immunodeficiency virus was not found. Both animals lacked antibody to SRV. Both animals had antibodies to Epstein-Barr-like virus (EBV), but EBV antigens were not found by immunohistochemistry. Polymerase chain reaction analysis for integrated EBV DNA was unproductive. One of the animals (monkey No. 2) had a pulmonary infection with Mycobacterium avium, suggesting that immunosuppression was present. These cases represent a unique and previously undescribed type of solitary lymphoma in SRV-infected macaques.


Treatment of diabetic peripheral neuropathy with engineered mesenchymal stromal cell-derived exosomes enriched with microRNA-146a provide amplified therapeutic efficacy.
Diabetic peripheral neuropathy (DPN) is one of the most prevalent chronic complications of diabetes mellitus with no effective treatment. We recently demonstrated that mesenchymal stromal cell (MSC)-derived exosomes (exo-naïve) alleviate neurovascular dysfunction and improve functional recovery. MicroRNA (miRNA), one of the exosomal cargos, downregulates inflammation-related genes, resulting in suppression of pro-inflammatory gene activation. In the present study, we developed engineered MSC-exosomes loaded with miR-146a (exo-146a) and compared the therapeutic effects of exo-146a with exo-naïve in diabetic (db/db) mice with DPN. Exo-146a possesses a high loading capacity, robust ability to accumulate in peripheral nerve tissues upon systemic administration, and evokes substantially enhanced therapeutic efficacy on neurological recovery compared with exo-naïve. Treatment of DPN in diabetic mice with exo-146a for two weeks significantly increased and decreased nerve conduction velocity, and thermal and mechanical stimuli threshold, respectively, whereas it took four weeks of exo-naive treatment to achieve these improvements. Compared with exo-naïve, exo-146a significantly suppressed the peripheral blood inflammatory monocytes and the activation of endothelial cells via inhibiting Toll-like receptor (TLR)-4/NF-κB signaling pathway. These data provide a proof-of-concept about both the feasibility and efficacy of the exosome-based gene therapy for DPN. The translation of this approach to the clinic has the potential to improve the prospects for people who suffer from DPN.


Integration of silicon nanocrystals and erbium ring cavities for a silicon pumped Er:SiO2 laser.
In this work we present a novel two-stage approach to achieve electrically pumped lasing on a CMOS compatible material platform in the telecom region. The proposed design consists of an electrically pumped silicon nanocrystal (Si-nc) light source acting as an optical pump for an Erbium doped silicate (Er:SiO2) lasing cavity. The integrated design, based on concentric disks of Si-nc and Er:SiO2, provides a means of coupling the Si-nc pump signal to the Er ions without requiring overlap of the Er based lasing mode with the Si-nc material. We present an electromagnetic analysis of the pump and lasing modes in the proposed configuration. We also present fabrication and characterization of Si-nc and Er:SiO2 microdisks as components of the integrated design.


BATHYMETRIC PATTERNS OF BODY SIZE IN DEEP-SEA GASTROPODS.
The shift to smaller body size in marine invertebrates at the deep-sea threshold and size-depth clines within the deep-sea ecosystem are global biogeographic phenomena that remain poorly understood. We present the first standardized measurements of larval and adult size among ecologically and phylogenetically similar species across a broad and continuous depth range, using the largest family of deep-sea gastropods (the Turridae). Size at all life stages increases significantly with depth from the upper bathyal region to the abyssal plain. These consistent clines may result from selection favoring larger size at greater depths because of its metabolic and competitive advantages. The unusually small size of deep-sea mollusks, in general, may represent an independent evolutionary process that favors invasion by inshore taxa composed of small organisms.


Rapid development of feature binding in visual short-term memory.
The binding of object identity (color) and location in visual short-term memory (VSTM) was examined in 6.5- to 12.5-month-old infants (N= 144). Although we previously found that by age 6.5 months, infants can represent both color and location in VSTM, in the present study we observed that 6.5-month-old infants could not remember trivially simple color-location combinations across a 300-ms delay. However, 7.5-month-old infants could bind color and location as effectively as 12.5-month-old infants. Control conditions confirmed that the failure of 6.5-month-old infants was not a result of perceptual or attentional limitations. This rapid development of VSTM binding between 6.5 and 7.5 months occurs during a period of rapid increase in VSTM storage capacity and just after a period of dramatic neuroanatomical changes in parietal cortex. Thus, the ability to bind features and the ability to store multiple objects may both depend on a process that is mediated by posterior parietal cortex and is perhaps related to focused attention.


Predictors of dropout in psychodynamic psychotherapy of borderline personality disorder.
This study aimed to identify patient factors that predict early dropout from psychodynamic psychotherapy for borderline personality disorder (BPD). Thirty-six BPD patients began an open-ended course of twice per week psychodynamic psychotherapy that was defined in a treatment manual and supervised. Dropout rates were 31% and 36% at 3 and 6 months of therapy, respectively. Survival analysis techniques demonstrated that age and hostility ratings predicted early dropout, with continuers more likely to be older and expressing lower levels of hostility than dropouts. Many variables hypothesized to predict dropout failed to do so. Both the positive and negative findings are discussed relative to the literature.


Needle anxiety in children with type 1 diabetes and their mothers.
To report the prevalence of fear, distress, pain, and level of cooperation with insulin injections and blood glucose fingersticks in children with newly diagnosed diabetes and their mothers, and the association with diabetes control. Forty-six subjects (23 children and mother pairs) completed the Perceptions of Insulin Shots and Fingersticks Survey at diagnosis and 6 to 9 months later. Standard descriptive statistics, Fisher's exact tests, and Spearman correlation coefficients were used to analyze the data. Scores were analyzed for associations with age and hemoglobin A1c as a marker of diabetes control. More young children as compared to older subjects reported fear and pain with injections and fingersticks. A high percentage of mothers reported high fear and distress with needles at diagnosis. Although most improve, 13.6% of mothers continued to report high fear and distress 6 to 9 months later. Mothers' continued report of high distress correlated with the poor cooperation of children, which correlated with poorer diabetes control. Nurses should incorporate assessment and intervention for needle anxiety in children and parents at diagnosis of diabetes through informal interview or formal survey. Nurses can effectively incorporate coping strategies into their teaching of parents and children to administer injections and fingersticks.


Intervention to Reduce Stigma and Improve Knowledge of HPV and Cervical Cancer in Nigeria: A Community-Based Assessment.
We compared the effectiveness of an educational intervention at reducing stigma and improving knowledge of human papillomavirus (HPV) and cervical cancer among Nigerian men and women. We used a pre-/posttest design to deliver 2 educational interventions to 266 adults. Low knowledge was observed at baseline, which improved significantly post-intervention with no difference between groups. No significant changes were observed between groups in 5 out the 6 stigma domains. Health education was effective in improving knowledge. However, the lack of positive change in stigma shows urgent need for HPV and cervical cancer stigma reduction interventions.


Appendiceal Diverticulitis - A Case Report.
Appendiceal diverticulitis is a very rare cause for pain in the right iliac fossa. Whether it is simptomatic or discovered randomly during an appendectomy or barium enema, understanding its clinical evolution is important for having a good management. In this report we present the case of a 50 year old female who underwent an open appendectomy during which we discovered appendiceal diverticulitis.


Mitochondrial Extrusion through the cytoplasmic vacuoles during cell death.
Under various conditions, noxious stimuli damage mitochondria, resulting in mitochondrial fragmentation; however, the mechanisms by which fragmented mitochondria are eliminated from the cells remain largely unknown. Here we show that cytoplasmic vacuoles originating from the plasma membrane engulfed fragmented mitochondria and subsequently extruded them into the extracellular spaces in undergoing acute tumor necrosis factor alpha-induced cell death in a caspase-dependent fashion. Notably, upon fusion of the membrane encapsulating mitochondria to the plasma membrane, naked mitochondria were released into the extracellular spaces in an exocytotic manner. Mitochondrial extrusion was specific to tumor necrosis factor alpha-induced cell death, because a genotoxic stress-inducing agent such as cisplatin did not elicit mitochondrial extrusion. Moreover, intact actin and tubulin cytoskeletons were required for mitochondrial extrusion as well as membrane blebbing. Furthermore, fragmented mitochondria were engulfed by cytoplasmic vacuoles and extruded from hepatocytes of mice injected with anti-Fas antibody, suggesting that mitochondrial extrusion can be observed in vivo under pathological conditions. Mitochondria are eliminated during erythrocyte maturation under physiological conditions, and anti-mitochondrial antibody is detected in some autoimmune diseases. Thus, elucidating the mechanism underlying mitochondrial extrusion will open a novel avenue leading to better understanding of various diseases caused by mitochondrial malfunction as well as mitochondrial biology.


Alpha-1-antitrypsin deficiency in children: clinical characteristics and diagnosis.
Alpha-1-antitrypsin deficiency (AATD) is a relatively rare and clinically very heterogeneous autosomal recessive disorder. Presentation of clinical characteristics of AATD in the first months after birth, as well as the significance of testing brothers and sisters for its presence. Objectives of the study were analyzed on a sample of eight children (four male and four female, aged 63 months (mean 14.81 ± 23.96 months; range 1-63 months) with AATD confirmed based on its low serum value and pathological phenotype. RESULTS Of the total of eight patients, six manifested cholestasis syndrome (three male and three female, mean age 2.25 ± 1.37 months; range 1-4.5 months), while two patients, a 3.5-year-old girl and a 5.25-year-old boy, were without symptoms and clinical-laboratory signs of the disease, disclosed during family testing. Serum alpha-1-antitrypsin level rated 0.30-0.66 g/L (0.37 ± 0.12), among which seven were with ZZ phenotype 0.30-0.39 (0.33 ± 0.04), and in a boy with FZ the phenotype was disclosed on family screening, 0.66 g/L. In the group of patients with cholestasis syndrome (serum GTT 444.80 ± 203.15 U/L; range 201-676 U/L), three had mild to moderate hepatomegaly, one had longitudinal growth delay (< P3; -10.50%) and two had icterus with conjugated hyperbilirubinemia (92 and 109 μmol/L) and prolonged prothrombin time (PT 14.8 and 17 sec). All children with cholestasis syndrome also had hypertransaminasemia (ALT 80.83 ± 33 U/L; range 37-124 U/L and AST 116.67 ± 62.82 U/L; range 58-230 U/L). Cholestasis syndrome represents a basic manifestation of AATD in the first months after birth, while early testing of brothers and sisters enables early disclosure and adequate treatment of the subclinical forms of the disease.


The effect of wheat bran particle size on laxation and colonic fermentation.
Due to perceived inferior fecal bulking ability, finely ground wheat bran is not recommended for treatment of colonic disorders, despite possible short chain fatty acid generation with potential benefits for colonic mucosal health. We therefore tested the effects of very fine particle size wheat bran on colonic function. Two studies, each with three phases, were undertaken in healthy subjects in a randomized crossover design. In one study (metabolic, n=23) subjects took three diets containing either an additional 19 g/d dietary fiber with mean particle size (MPS) 50 microm or 758 microm in bread or a control low fiber bread. In the other study where the supplement was provided as a breakfast cereal (ad libitum, n=24) the respective wheat bran MPS were 692 microm and 1158 microm and the control was low fiber. Fecal collections were obtained during the last week of each diet. In the metabolic study, fecal short chain fatty acids were measured and 12-hour breath gas collections obtained. In both studies, wheat bran supplements significantly increased fecal bulk compared to the control (p<0.004), with no significant differences between brans of different particle size and no differences in fecal water content. However, higher fecal butyrate concentrations (p<0.007), butyrate output and breath CH4 levels (p=0.025) were seen on the low MPS wheat bran compared to the other two treatments, suggesting increased bacterial fermentation. Fine MPS wheat bran is an effective fecal bulking agent and may have added advantages if increased butyrate concentrations promote colonic mucosal integrity.


Human gene therapy: down the slippery slope?
The strength of a slippery slope argument is a matter of some dispute. Some see it as a reasonable argument pointing out what probably or inevitably follows from adopting some practice, others see it as essentially a fallacious argument. However, there seems to be a tendency emerging to say that in many cases, the argument is not actually fallacious, although it may be unsubstantiated. I shall not try to settle this general discussion, but merely seek to assess the strength of the slippery slope argument applied to human gene therapy. The structure of my argument will be the following. First, I shall distinguish between three different versions of the slippery slope argument; two logical versions and an empirical one. Next, I will address human gene therapy in terms of each of the three versions, partly relying on slippery slope arguments against this practice that have already surfaced in the literature. I shall argue that neither version pulls through. The logical versions fail primarily because relevant distinctions can be made between different uses of gene therapy, contrary to what the proponents of the arguments claim. The empirical version fails because there seems to be no evidence supporting the claim that we shall in fact slide down the slope if we engage in gene therapy, and because if we accepted the conclusion that we should not allow gene therapy on the basis of the empirical argument, we should have to make very far-reaching and undesirable modifications in health care in general, in order to be consistent. Or at least so I shall argue.


Study of a position-sensitive scintillator neutron detector prototype based on 6LiF/ZnS scintillator and silicon photomultiplier arrays readout.
Due to the shortage of the 3He gas and its rapidly increasing price, scintillator detectors, the advantages of which are high spatial resolution and capability of detection in real time, become widely used in many neutron instruments. In this work, a position-sensitive neutron detector consisting of a 6LiF/ZnS scintillation screen and a silicon photomultiplier array linked to a capacitive network to detect the positions of incident neutrons, is constructed and tested. To evaluate the detector performance, a series of neutron beam experiments with the detector prototype were performed in the BL20 at the China Spallation Neutron Source. The spatial resolution was measured, and the energy-selective neutron imaging and Bragg edge measurements of a 316L stainless steel sample were performed. A sub-millimeter spatial resolution could be obtained for the detector prototype under study. The detector with such a high spatial resolution is promising for applications in neutron scattering experimental installations, especially for neutron single-crystal diffractometers.


Gametophyte Development Needs Mitochondrial Coproporphyrinogen III Oxidase Function.
Tetrapyrrole biosynthesis is one of the most essential metabolic pathways in almost all organisms. Coproporphyrinogen III oxidase (CPO) catalyzes the conversion of coproporphyrinogen III into protoporphyrinogen IX in this pathway. Here, we report that mutation in the Arabidopsis (Arabidopsis thaliana) CPO-coding gene At5g63290 (AtHEMN1) adversely affects silique length, ovule number, and seed set. Athemn1 mutant alleles were transmitted via both male and female gametes, but homozygous mutants were never recovered. Plants carrying Athemn1 mutant alleles showed defects in gametophyte development, including nonviable pollen and embryo sacs with unfused polar nuclei. Improper differentiation of the central cell led to defects in endosperm development. Consequently, embryo development was arrested at the globular stage. The mutant phenotype was completely rescued by transgenic expression of AtHEMN1 Promoter and transcript analyses indicated that AtHEMN1 is expressed mainly in floral tissues and developing seeds. AtHEMN1-green fluorescent protein fusion protein was found targeted to mitochondria. Loss of AtHEMN1 function increased coproporphyrinogen III level and reduced protoporphyrinogen IX level, suggesting the impairment of tetrapyrrole biosynthesis. Blockage of tetrapyrrole biosynthesis in the AtHEMN1 mutant led to increased reactive oxygen species (ROS) accumulation in anthers and embryo sacs, as evidenced by nitroblue tetrazolium staining. Our results suggest that the accumulated ROS disrupts mitochondrial function by altering their membrane polarity in floral tissues. This study highlights the role of mitochondrial ROS homeostasis in gametophyte and seed development and sheds new light on tetrapyrrole/heme biosynthesis in plant mitochondria.


Bilateral radiation therapy followed by methotrexate-based chemotherapy for primary vitreoretinal lymphoma.
Primary vitreoretinal lymphoma (PVRL) is a subset of primary CNS lymphoma that presents as isolated ocular disease without brain involvement. Although ocular radiotherapy (RT) is an effective treatment for PVRL, the optimal treatment is uncertain. PVRL may later involve the brain in 56%-85% of patients. We report on 12 PVRL patients treated with a combination of bilateral RT and a systemic chemotherapy (CT) regimen containing high-dose methotrexate (M). Ten received RT (30-40 Gy) followed by CT, one received RT, and one was treated with intravitreal M; all achieved a complete response (CR). Three patients had tumor recurrence in the brain and received CT and one patient relapsed in the eye with a second recurrence in the brain. Three patients achieved CR-2 remain alive and one died of dementia. One died from recurrent CNS disease. With a median follow of 68 months (range, 17-154 months), median progression-free and overall survival have not been reached. Bilateral RT followed by M-based CT is an effective treatment for reducing CNS progression and prolonging survival.


[Clinical Study to Determine the Dose Intensity of BEP Chemotherapy for Ovarian Malignant Germ Cell Tumors].
A standard regimen for ovarian malignant germ cell tumors is bleomycin, etoposide, cisplatin(BEP)chemotherapy. Adherence to a treatment schedule of every 21 days has been reported to be important. However, the incidence of febrile neutropenia( FN)and the optimaluse of granulocyte-colony stimulating factor(G-CSF)are unclear because of the low incidence of ovarian malignant germ cell tumors. We experienced 2 cases of ovarian malignant germ cell tumors that received BEP therapy after fertility-conserving surgery. In 1 case, we delayed drug administration in the first cycle because of FN. However, in order to maintain dose intensity(DI), we performed chemotherapy every 21 days by shortening the rest period. Myelosuppression may be severe in the first cycle of BEP therapy; however, it may be possible to adhere to the treatment schedule by using primary prophylactic administration of G-CSF.


[Relationship between OX40/4-1 BB (CD134/CD137) costimulatory molecules expression on T lymphocytes and stimulating and blocking autoantibodies to the TSH-receptor in children with Graves' disease].
CD134 (OX-40) and CD137 (4-1 BB) are glycoprotein molecules provides the potent costimulatory signal for T cells activation and proliferation (to Th1 and Th2 subpopulation) via interactions with their ligands CD134L/CD137L molecule, present on the surface of Ag-presenting cells (APC). The present study was performed to elucidate the relationship between CD134/CD137 molecules and stimulating (TSAb) or blocking (TBAb) antibodies to the TSH-receptor in Graves' disease. The aim of the study was to estimate the expression of OX-40 and 4-1 BB molecules on peripheral blood cells in patients with Graves' disease (GD) (n=28, mean age 16.3 years), in patients with nontoxic nodular goiter (NTNG) (n=28, mean age 15.8 years) in comparison with sex- and age-matched healthy control subjects (n=28, mean age 15.9 years). The expression of the costimulatory molecules on mononuclear cells were analyzed by the three-color flow cytometry using a Coulter EPICS XL cytometer. Detection of stimulating and blocking antibodies to the TSH-receptor using JPO9 CHO cells in unfractionated serum were measured by a highly sensitive commercial radioimmuno assay. In untreated Graves' patients we observed a significant increase of CD134+ (p<0.001, p<0.01, p<0.04) and CD137+ (p<0.04, p<0.035, p<0.01) T lymphocytes in comparison to the healthy control subjects, non-toxic nodular goiter patients and euthyroid Graves' patients. After 6-12 months of methimazole therapy, the percentages of these cells in peripheral blood of hyperthyroid patients returned to the normal values. The analysis of CD3+ T lymphocytes co-expressing CD134 and CD137 antigens on peripheral blood revealed an increased percentages of OX-40/CD137 positive cells in patients with Graves' disease (p<0.025) compared to the controls, while CD134L (OX-40L) molecules were detected in some hyperthyroid patients on activated monocytes. In addition, 75% of children with untreated hyperthyroidism had positive TSAbs, whereas TBAbs were measured in 3 out of 7 TSAb negative patients with Graves' disease. In untreated Graves' patients a correlation between percentage of CD134+ T cells and serum level of stimulating (p<0.025) and blocking (p<0.04) antibodies to the TSH-receptor was found, while no such correlation was detected in relation to CD137+ T cells. We conclude that the changes of the expression of costimulatory molecules on peripheral blood mononuclear cells could be an important marker of activity of autoimmune process in children and adolescents with Graves' disease and that their levels are modulated by thyrostatic treatment.


[Effects of Cu and As on germination and seedling growth of crops].
A solution-culture experiment was carried out to explore effects of Cu and As on the germination and seedling growth of crops. The results showed that Cu or As pollution could reduce the activities of protease and diastase, inhibit the seedling growth and the respiration rate of germinating seed of soybean. The inhibition was strengthened with the increase in the concentrations of Cu and As. However, the activity of POD was increased with the concentrations of Cu and As in the exposed solution.


An ultrastructural review of collagen gels, a model system for cell-matrix, cell-basement membrane and cell-cell interactions.
Collagen gels, prepared from rat tail tendon, have been shown to be a useful system for the provision of a more physiologically relevant culture milieu than the rigid inert substratum of tissue culture plastic. The gel is penetrable by cells, but this depends on their origin, either mesenchymal or epithelial, normal or tumour derived. Furthermore, endothelial cells form a basement membrane on the gel surface from which they can be removed with detergent, providing a cell secreted substratum for testing the invasive ability of tumour derived cell lines. Various interactions between the cell and gel occur depending on cell type. Normal fibroblasts plated within the gel will stress and contract the matrix if the gel is freed and allowed to float in the culture medium. The fibroblasts also migrate to the surface and encapsulate the entire gel. Normal lymphocytes rapidly migrate into the gel and continue to move through the gel in a random manner, demonstrating gross changes in surface morphology. Studies are in progress to monitor the behaviour of leukaemic lymphocytes within the gels. Collagen gels will also support in vitro haemopoiesis, providing a useful environment for the positive selection of stromal cells. As an in vitro model for invasion and metastasis the plating of melanoma cells onto a monolayer of endothelium on the gels allows investigation of the interactions between the normal cells which form a barrier to circulating tumour cells and the tumour cells themselves.


Largely reduced grid densities in a vibrational self-consistent field treatment do not significantly impact the resultingwavenumbers.
Especially for larger molecules relevant to life sciences, vibrational self-consistent field (VSCF) calculations can become unmanageably demanding even when only first and second order potential coupling terms are considered. This paper investigates to what extent the grid density of the VSCF's underlying potential energy surface can be reduced without sacrificing accuracy of the resulting wavenumbers. Including single-mode and pair contributions, a reduction to eight points per mode did not introduce a significant deviation but improved the computational efficiency by a factor of four. A mean unsigned deviation of 1.3% from the experiment could be maintained for the fifteen molecules under investigation and the approach was found to be applicable to rigid, semi-rigid and soft vibrational problems likewise. Deprotonated phosphoserine, stabilized by two intramolecular hydrogen bonds, was investigated as an exemplary application.


Use of Alkali-Activated Slag as an Environment-Friendly Agent for High-Performance Stabilized Soil.
Discharged slag not only occupies a large amount of land for disposal, but also causes serious environmental pollution. The use of alkali-activated slag (AAS) instead of cement as a soil-stabilization agent is beneficial for industrial waste disposal and energy conservation, which complies with the concept of green and low-carbon sustainable development in the construction industry. In this study, the compressive strength, water permeability coefficient, chloride migration coefficient and sulfate resistance of alkali-activated slag-stabilized soil (AASS) were evaluated, and compared with those of cement-stabilized soil (CSS). The hydrated crystalline phases and microscopic pore structures were analyzed by X-ray diffraction, electrochemical impedance spectroscopy (EIS) and mercury intrusion porosimetry (MIP) tests, respectively. The results indicate that, compared with CSS, AASS exhibits a higher compressive strength, lower water permeability, chloride migration coefficient and better resistance to sulfate attack, with the optimum dosage higher than 10 wt.%. The results of the MIP analysis show that the addition of AAS reduces the porosity by 6.47%. The combined use of soil and AAS proves to be a viable and sustainable method of waste utilization and carbon emission reduction in the construction industry, which provides a practical path towards carbon peaking and carbon neutrality.


Anomalously weak solar convection.
Convection in the solar interior is thought to comprise structures on a spectrum of scales. This conclusion emerges from phenomenological studies and numerical simulations, though neither covers the proper range of dynamical parameters of solar convection. Here, we analyze observations of the wavefield in the solar photosphere using techniques of time-distance helioseismology to image flows in the solar interior. We downsample and synthesize 900 billion wavefield observations to produce 3 billion cross-correlations, which we average and fit, measuring 5 million wave travel times. Using these travel times, we deduce the underlying flow systems and study their statistics to bound convective velocity magnitudes in the solar interior, as a function of depth and spherical-harmonic degree ℓ. Within the wavenumber band ℓ < 60, convective velocities are 20-100 times weaker than current theoretical estimates. This constraint suggests the prevalence of a different paradigm of turbulence from that predicted by existing models, prompting the question: what mechanism transports the heat flux of a solar luminosity outwards? Advection is dominated by Coriolis forces for wavenumbers ℓ < 60, with Rossby numbers smaller than approximately 10(-2) at r/R([symbol: see text]) = 0.96, suggesting that the Sun may be a much faster rotator than previously thought, and that large-scale convection may be quasi-geostrophic. The fact that isorotation contours in the Sun are not coaligned with the axis of rotation suggests the presence of a latitudinal entropy gradient.


The electroencephalographic pattern during electroconvulsive therapy: V. Observations on the origins of phase III delta energy and the mechanism of action of ECT.
The generation of the spike-wave activity of Phase III of ECT seizures is attributed to the recurrence of synchronized, prolonged periods of intense inhibitory current flow (hyperpolarization), and associated rebound spike bursts, produced by the inhibitory circuit relationships and intrinsic electrophysiological properties of thalamic neurons. An anatomical and neurophysiological model of the development of generalized, synchronous 3-Hz spike-wave seizure activity is proposed which outlines the origin, maintenance, slowing, and termination of this fundamental seizure rhythm. Phase III inhibitory current flow (delta energy) and/or spike bursts may bring about therapeutic benefit by initiating a chain of agonist-independent and agonist-dependent events which results in long-term augmentation of serotonergic and noradrenergic neurotransmission and diminution of cholinergic neurotransmission in the forebrain. A specific anatomical and functional model of the mechanism of action of ECT is proposed, in which: (1) adrenergic and cholinergic pathways in the forebrain are assumed to be massively stimulated during ECT seizures, whereas serotonergic pathways are assumed to be inhibited during these seizures; (2) the beneficial effects of ECT are considered to be more dependent upon ECT-induced changes in 5-HT neurotransmission than upon alteration of noradrenergic function; (3) these beneficial effects involve up-regulation of 5-HT2 and down-regulation of M1- and M2-muscarinic receptor densities by both agonist-independent and agonist-dependent mechanisms, coupled with functional augmentation of noradrenergic neurotransmission; and (4) these effects may be brought about by Phase III inhibitory current flow- and/or spike burst-induced alteration of the function of second-messenger generator systems.


Stepped care for depression is easy to recommend, but harder to implement: results of an explorative study within primary care in the Netherlands.
Depression is a common mental disorder with a high burden of disease which is mainly treated in primary care. It is unclear to what extent stepped care principles are applied in routine primary care. The first aim of this explorative study was to examine the gap between routine primary depression care and optimal care, as formulated in the depression guidelines. The second aim was to explore the facilitators and barriers that affect the provision of optimal care. Optimal care was operationalised by indicators covering the entire continuum of depression care: from prevention to chronic depression. Routine care was investigated by interviewing general practitioners (GPs) individually and together with other mental health care providers about the depression care they delivered collaboratively. Qualitative analysis of transcripts was performed using thematic coding. Additionally, the GPs completed a self-report questionnaire. Six GPs and 22 other (mostly primary) mental health care providers participated. The GPs and their primary care colleagues embraced a general stepped care approach. They offered psycho-education and counselling to mildly depressed patients. When the treatment effects were not satisfactory or patients were more severely depressed, the GPs offered, or referred to, psychotherapy or pharmacotherapy. Patients with a complex and severe depressive disorder were directly referred to specialised mental health care. However, GPs relied on their clinical judgment and rarely used instruments to assess and monitor the severity of depressive symptoms. Structured, evidence based interventions such as self-management and e-health were rarely offered to patients with depressive symptoms. Specific psychological interventions for relapse prevention or for chronically depressed patients were not available. A wide range of influencing factors for the provision of optimal depression care were put forward. Close collaboration with other mental health care professionals was considered an important factor for improvement by nearly all GPs. The management of depression in primary care seems in line with stepped care principles, although it can be improved by applying more elements of a stepped care approach. Collaboration between GPs and mental health care providers in primary care and secondary care should be enhanced.


A clinical study of colchicine in childhood asthma.
A double-blind, randomized, crossover study was done to determine the efficacy of colchicine in 30 atopic children with moderately severe asthma. A constant dose of sustained-release theophylline and salbutamol by inhalation, as needed, was administered to all patients. Compared to placebo, colchicine, 0.5 mg twice daily, significantly reduced morning tightness and nocturnal asthma score. There was, however, no significant difference between colchicine and placebo for cough, daytime asthma, or daily combined symptom scores for each patient. Colchicine did not significantly decrease beta-2 agonist inhaler use when compared with placebo. Similarly, there was no statistically significant difference between placebo and colchicine therapy as far as pulmonary function tests and peak flow reversibility were concerned. Thus, colchicine administered for 4 weeks demonstrated insufficient antiasthma activity. Colchicine-induced clinical improvement that was reported in a previous study may be due to selection of patients with mild asthma symptoms. However, our group, comprised of moderately severe asthmatic patients, did not show a satisfactory clinical response.


Children of more empowered women are less likely to be left without vaccination in low- and middle-income countries: A global analysis of 50 DHS surveys.
To help provide a global understanding of the role of gender-related barriers to vaccination, we have used a broad measure of women's empowerment and explored its association with the prevalence of zero-dose children aged 12-23 months across many low- and middle-income countries, using data from standardized national household surveys. We used data from Demographic and Health Surveys (DHS) of 50 countries with information on both women's empowerment and child immunisation. Zero-dose was operationally defined as the proportion of children who failed to receive any doses of the diphtheria, pertussis, and tetanus containing vaccines (DPT). We measured women's empowerment using the SWPER Global, an individual-level indicator estimated for women aged 15-49 years who are married or in union and with three domains: social independence, decision-making and attitude towards violence. We estimated two summary measures of inequality, the slope index of inequality (SII) and the concentration index (CIX). Results were presented for individual and pooled countries. In the country-level (ecological) analyses we found that the higher the proportion of women with high empowerment, the lower the zero-dose prevalence. In the individual level analyses, overall, children with highly-empowered mothers presented lower prevalence of zero-dose than those with less-empowered mothers. The social independence domain presented more consistent associations with zero-dose. In 42 countries, the lowest zero-dose prevalence was found in the high empowerment groups, with the slope index of inequality showing significant results in 28 countries. When we pooled all countries using a multilevel Poisson model, children from mothers in the low and medium levels of the social independence domain had respectively 3.3 (95% confidence interval (CI) = 2.3, 4.7) and 1.8 (95% CI = 1.5, 2.1) times higher prevalence of zero-dose compared to those in the high level. Our country-level and individual-level analyses support the importance of women's empowerment for child vaccination, especially in countries with weaker routine immunisation programs.