Long-term outcomes of transposed femoral vein arteriovenous fistula for abandoned upper extremity dialysis access.
The number and longevity of patients with end-stage renal disease requiring dialysis access have continued to increase, leading to challenging situations, including exhausted upper extremity access and severe central venous stenosis. This has led to an increase in the use of alternative access sites, including the lower extremities. The transposed femoral vein arteriovenous fistula for dialysis access is a previously described alternative, although limited data are available on its long-term patency. Patients treated with a transposed femoral vein fistula were retrospectively reviewed. A transposed femoral vein fistula was created by harvesting the femoral vein and transposing it to the distal superficial femoral artery at the level of the adductor canal. The demographic information, perioperative characteristics, complications, and long-term outcomes were recorded and analyzed. A total of 21 patients had undergone transposed femoral vein fistula for dialysis access after an average of 5.3 ± 2.8 failed dialysis access procedures and a duration of 6.1 ± 4.9 years from the initiation of dialysis. The average age at the procedure was 53.5 ± 12.8 years. Ten patients (47.6%) had a history of diabetes mellitus and nine (42.9%) had a history of coronary artery disease. Technical success was achieved in 100% of cases, and 16 patients (76.2%) were discharged with anticoagulation therapy. The primary patency at 1, 3, and 5 years was 93%, 74%, and 74%, respectively. The secondary patency at 1, 3, and 5 years was 100%, 89%, and 89%, respectively. Two patients had compartment syndrome requiring fasciotomy, and six patients experienced wound complications. Transposed femoral vein fistula for dialysis access is a viable alternative for patients with an exhausted upper extremity access, with good long-term patency.


Relationship between diurnal blood pressure and renal histopathological changes in white coat hypertension.
Multiple epidemiological studies have clearly demonstrated the macrovascular risks associated with white coat hypertension (WCH) or sustained hypertension (SH). In patients with WCH, there is no literature available on renal histopathological changes and that on blood pressure pattern and native kidney outcome is scant. We aimed to clarify the relationship between blood pressure variables and pathological features of kidney biopsies in living kidney donors with WCH. This cross-sectional study included living kidney donors with WCH (n = 10) and SH (n = 10), and 20 healthy kidney donors with similar demographic features (control group). Kidney allograft biopsy samples were obtained during transplantation and chronic glomerular, vascular and tubulointertitial changes were semiquantitatively scored according to the Banff classification. The mean age of the 20 hypertensive subjects (Group 1) and controls (Group 2) was 59.3 ± 8.5 versus 59.6 ± 7.6 years and almost half were female. There was no difference in renal function parameters between the groups; however, kidney histopathology in Group 1 was worse than Group 2 with a chronicity index of 2.80 ± 1.67 versus 1.75 ± 1.16 (p = 0.02). There was no difference between histopathological scores of patients with WCH or SH (chronicity index: 2.60 ± 1.43 vs. 2.70 ± 1.70, p = 0.88). Night-to-day mean arterial pressure (MAP) ratio was significantly associated with chronicity index in patients with WCH. Moreover, WCH patients with non-dipper hypertensive pattern had a worse chronicity index. Significant histopathological alterations in the kidney were observed in patients with WCH and SH, and were accentuated in WCH patients with non-dipper blood pressure pattern.


Varicella disciform stromal keratitis.
We treated five patients, aged 26, 4, 6, 13, and 7 years, who developed disciform stromal keratitis one, four, four, eight, and ten weeks, respectively, after the onset of the acute vesicular exanthema. Serologic testing confirmed recent varicella and excluded other infectious causes in two cases. After initial improvement with a topical corticosteroid, three patients developed recurrent corneal inflammation resembling zoster keratitis. These cases and previous reports indicate that varicella-zoster virus is a cause of disciform stromal keratitis that may occur and recur several weeks or months after the primary skin rash has resolved.


Fatigue, weight gain, and altered sexuality in patients with breast cancer: exploration of a symptom cluster.
To identify the symptom cluster of fatigue, weight gain, and altered sexuality caused by treatment for breast cancer. Published research and literature review articles. Fatigue, weight gain, and altered sexuality commonly occur after breast cancer chemotherapy. Each symptom has a significant impact on quality of life; however, viewing them as a symptom cluster magnifies their impact. These symptoms have yet to be studied as a cluster. Exercise appears to be an intervention common to each that may be effective in reducing the severity of these treatment side effects. Nurses should view symptoms caused by breast cancer treatment holistically, keeping in mind that a reciprocal relationship often exists among symptoms. Identification of symptom clusters with empirically derived interventions may enhance quality of care and quality of life for patients.


Development of a MOF-based SPE method combined with GC-MS for simultaneous determination of alachlor, acetochlor and pretilachlor in field soil.
In this work, a rapid, highly selective, reusable and effective method was developed for simultaneous determination of alachlor, acetochlor and pretilachlor in field soil by GC-MS coupled with MIL-101 based SPE. Main factors affecting the SPE by using MIL-101 were optimized. Moreover, by comparing with the other commercial materials such as C18, PSA and Florisil, the MIL-101(Cr) exhibited excellent adsorption performance, which aimed at amide herbicides. On the other hand, method validation displayed excellent method performance, achieving good linearities with r2 ≥ 0.9921, limits of detection between 0.25-0.45 μg kg-1, enrichment factors ≥ 89, matrix effect in the range of ± 20%, recoveries between 86.3% and 102.4%, and RSD lower than 4.38%. The developed method was successfully applied to the determination of amide herbicides in soil taken from the wheat, corn and soybean field at different depths, where the concentration of alachlor, acetochlor and pretilachlor were in the range of 0.62-8.04 μg kg-1. It was demonstrated that the more depth of soil, the lower of three amide herbicides. This finding could be proposed a novel method to detect the amide herbicides in the agriculture and food industry.


Expression of cancer testis antigens in thymic epithelial tumors.
Cancer testis antigens (CTAs) are detected in cancer cells but not in healthy normal tissues, with the exception of gametogenic tissues. However, to our knowledge, expression of the antigens in thymic epithelial tumors has not been examined yet. We examined the immunohistochemical expression of five CTAs (MAGE-A, NY-ESO-1, MAGE-C1, SAGE and GAGE7) in 192 cases of thymic epithelial tumor. The CTAs were variably expressed in the thymic epithelial tumors. Type B component of type AB thymomas, type B1/B2/B3 thymomas, and thymic carcinomas showed a generally positive correlation between the malignancy grades and positive expression rates in four CTAs other than MAGE-C1. In thymic squamous cell carcinomas (SqCCs), four antigens except for MAGE-C1 showed high expression rates ranging from 23.1% to 43.6%. In the prognostic analysis, a positive expression of SAGE (P = 0.0485) and GAGE7 (P = 0.0289) were associated with a shorter overall survival in type B2/B3 thymomas, respectively. In thymic SqCC, a positive MAGE-A expression was significantly associated with an increased level of programmed death ligand in tumor-infiltrating lymphocytes (P = 0.0181). We showed (i) a frequent CTA expression, (ii) a general correlation of CTA expression with tumor malignancy grades and (iii) a prognostic impact in some of the CTAs.


The Use of Intraoperative Digital Radiography Alignment Software to Assess Implant Placement in Total Hip Arthroplasty.
Total hip arthroplasty (THA) is a highly successful surgery with growing rates of utilization in the USA, but surgical outliers leading to postoperative complications remain a concern. There is need for a standard system of accurate, predictable intraoperative evaluation to decrease component positioning outliers. Many current intraoperative imaging systems have shown promise, but there are drawbacks that have led to slow adoption. Digital radiography, in conjunction with Radlink™ technology, is a potential solution to this problem. This review summarizes the clinical application and scientific literature regarding the use of Radlink™ in THA. Traditional surgeon-directed component placement can result in surgical outliers. This is especially true not only among low-volume arthroplasty surgeons, but can also occur with experienced, high-volume surgeons. Digital radiography allows for more precise and accurate placement of the acetabular cup in a targeted range in an effort to improve THA outcomes. Intraoperative images are obtained quickly, and they are accurate when compared to postoperative images. Additionally, the use of Radlink™ results in a significant decrease in leg length and femoral offset outliers. The adoption of Radlink™ technology in THA can significantly decrease surgical outliers, especially errors in acetabular cup placement, leg length, and femoral offset. Digital radiography avoids many of the previous aversions to intraoperative imaging as it produces a fast, reliable image with little radiation exposure and minimal interruption to workflow. There is the potential for Radlink™ use to provide superior patient outcomes, as a decrease in surgical outliers can minimize implant malpositioning with resultant need for revision THAs. Radlink™ may also provide benefit in analyzing other parameters, such as component sizing.


Impact of fluoroscopic injection location on immediate and delayed pain relief in patients with greater trochanteric pain syndrome.
The purpose of this study was to assess whether fluoroscopically guided corticosteroid injections into the extrabursal tissues, trochanteric (subgluteus maximus) bursa, or subgluteus medius bursa provide better immediate and short-term pain relief. All fluoroscopically guided corticosteroid injections performed over a 67-month period for greater trochanteric pain syndrome were retrospectively reviewed. Procedural images were reviewed by two musculoskeletal radiologists to determine the dominant injection site based on final needle positioning and contrast spread pattern, with discrepancies resolved by consensus. Statistical analysis of the association between pain score reduction and dominant injection site was performed. One hundred forty injections in 121 patients met the inclusion criteria. The immediate and 1-week post-injection pain reduction was statistically significant for trochanteric bursa, subgluteus medius bursa, and non-bursal injections. However, there was no statistically significant difference in the degree of pain reduction between the groups. There was statistically significant increase in the 1-week post-injection mean pain score compared with immediate post-injection mean pain score in the subgluteus medius bursa and non-bursal injection groups (p < 0.01) but not in the trochanteric bursa group. Fluoroscopy is frequently chosen over blind injection or ultrasound guidance for trochanteric steroid injections in patients with a high body mass index. Our results indicate that fluoroscopically guided steroid injections into the trochanteric bursa and subgluteus medius bursa significantly reduced immediate and 1-week post-injection pain scores, as do non-bursal injections. Steroid injection into the subgluteus medius bursa and non-bursal sites may be less effective in maintaining pain reduction at 1-week post-injection.


Thiamine mediated reversal of left ventricular dysfunction in patients with alcoholic cardiomyopathy.
This study aimed to evaluate the effect of thiamine supplementation on left ventricular (LV) systolic function in patients of alcoholic cardiomyopathy(ACM) presenting with acute heart failure(HF). 11 newly diagnosed patients were included. They were treated with 3 days of intravenous(IV) therapy with thiamine followed by oral supplementation. LVEF was 30% at baseline which improved by 45% and 53% along with reduction in LV dimensions over 3 and 6 months respectively. The study suggests the benefit of thiamine supplementation on LVEF in ACM patients with HF.


The complete genome sequence of Stellaria aquatica virus A, a new member of the genus Alphacarmovirus, family Tombusviridae.
A new member of the genus Alphacarmovirus was detected in Stellaria aquatica using high-throughput RNA sequencing analysis. The complete genome sequence of this new virus isolate, tentatively named "Stellaria aquatica virus A" (StAV-A), comprises 4,017 nucleotides with five predicted open reading frames (ORFs) and has a typical alphacarmovirus genome organization. Pairwise comparison of StAV-A with selected members of family Tombusviridae showed 44-58%, 32-64%, and 19-49% sequence identity for the overall nucleotide sequence, polymerase, and coat protein, respectively. Phylogenetic analysis of polymerase sequences places StAV-A alongside other members of the genus Alphacarmovirus in the family Tombusviridae.


Mutation-rate determinations based on electrophoretic analysis of laboratory mice.
Rate calculations are described for germinal mutations detected by an electrophoretic system as applied to mice in a series of recent experiments. The utility of the electrophoretic system is examined from several comparative viewpoints. The electrophoretic approach has a number of features to recommend it for future applications concerned with genetic hazard assessment. Its advantages include sensitivity, versatility, cost effectiveness and relevance to humans.


The regulation of cadherin-mediated adhesion by tyrosine phosphorylation/dephosphorylation of beta-catenin.
The formation of stable cell-cell adhesions by type I cadherins depends on the association of their cytoplasmic domain with beta-catenin, and of beta-catenin with alpha-catenin. The binding of beta-catenin to these partners is regulated by phosphorylation of at least three critical tyrosine residues. Each of these residues is targeted by one or more specific kinases: Y142 by Fyn, Fer and cMet; Y489 by Abl; and Y654 by Src and the epidermal growth factor receptor. Developmental and physiological signals have been identified that initiate the specific phosphorylation and dephosphorylation of these residues, regulating cadherin function during neurite outgrowth, permeability of airway epithelium and synapse remodeling, and possibly initiating epithelial cell migration during development and metastasis.


Hydrochemical analysis to evaluate the seawater ingress in a small coral island of India.
The sustainable development of the limited groundwater resources in the tropical island requires a thorough understanding of detail hydrogeological regime including the hydrochemical behavior of groundwater. Detail analysis of chemical data of groundwater helps in assessing the different groundwater zone affected by formation as well as sea water. Groundwater and saline water interaction is better understood using groundwater major ion chemistry over an island aquifer. Multivariate methods to analyze the geochemical data are used to understand geochemical evolution of groundwater. The methods are successfully used to group the data to evaluate influence of various environs in the study area. Various classification methods such as piper, correlation method, and salinity hazard measurements are also employed to critical study of geochemical characteristics of groundwater to identify vulnerable parts of the aquifer. These approaches have been used to successfully evaluate the aquifer zones of a tiny island off the west coast of India. The most part of island is found to be safe for drinking, however some parts of island are identified that are affected by sea water ingress and dissolution of formation minerals. The analysis has successfully leaded to identification of that part of aquifer on the island which needs immediate attention for restoration and avoids further deterioration.


High levels of soluble intercellular adhesion molecule-1, insulin resistance and saturated fatty acids are associated with endothelial dysfunction in healthy adolescents.
Atherosclerosis begins and progresses during childhood and adolescence. Endothelial dysfunction is one of the earliest abnormalities that can be detected in the development of atherosclerosis. As the determinants of endothelial function in childhood are unknown, we investigated the influence of cardiovascular risk factors on endothelial function in a cohort of healthy adolescents. A total of 257 adolescents (age: 14.5 + or - 1.0 years, 138 girls) participated in this study. Endothelial function was measured as reactive hyperemic index (RHI) using a fingertip peripheral arterial tonometry device. Blood samples were collected for analysis of lipids, insulin, glucose, fatty acid composition of plasma phospholipids, and markers of inflammation and endothelial function. There was no gender difference in RHI. Boys had higher plasma level of vascular cellular adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), P-selectin and monocyte chemoattractant protein-1, and lower level of insulin, total cholesterol, high-density lipoprotein-cholesterol (HDL), low-density lipoprotein-cholesterol (LDL), ApoA1, ApoB, and docosahexaenoic acid of plasma phospholipids than girls. There was no gender difference regarding triacylglycerol, triacylglycerol/HDL, LDL/HDL and ApoB/ApoA. The RHI was inversely associated with plasma ICAM-1 (p=0.0003), HOMA index for insulin resistance (HOMA-IR, p=0.001) and saturated fatty acids of plasma phospholipids (SFA, p=0.001). The associations remained significant after adjusting for age, height, BMI-z-score, sex, blood pressure, HDL and smoking. In healthy adolescents impaired endothelial function is significantly associated with high level of soluble ICAM-1, HOMA-IR and SFA.


Diverse virological, histopathological and prognostic implications of seroconversion from hepatitis B e antigen to anti-HBe in chronic hepatitis B virus infection.
The evolutions of serum hepatitis B virus (HBV)-DNA, liver histology and intrahepatic expressions of HBV antigens were longitudinally investigated in 24 serum HBeAg+/HBV-DNA+ chronic hepatitis B patients who subsequently seroconverted to anti-HBe. After HBeAg conversion, serum HBV-DNA still persisted in 10 patients, and liver HBcAg in 7 of them. Of the 24 patients, 3 subgroups with diverse prognoses were identified. Ten patients progressed from chronic active hepatitis to cirrhosis, and in 7 of them HBV-DNA and/or HBcAg persisted. Eight patients with undetectable HBV-DNA and HBcAg recovered. In the remaining 6 patients, chronic liver diseases persisted; in 3 of them, HBV-DNA and in one HBcAg. These findings indicate that continued viral replication is present in a significant number of patients after HBeAg seroconversion in Taiwan, and is responsible for disease progression. In addition to HBcAg and HBV-DNA, the severity of underlying liver histology, when HBeAg seroconversion occurred, was critical for the outcome of the disease. Another remarkable finding was that clusters of ground-glass hepatocytes, well correlated with the marginal expression of HBsAg, were demonstrated in 14 of 16 biopsies with serum anti-HBe+/HBV-DNA-, but found in only 4 of 44 biopsies with positive serum HBV-DNA, indicating a strong association of the expressions of liver histology and hepatocyte HBsAg with the status of viral replication.


Effects of rhamnolipid on the cellulase and xylanase in hydrolysis of wheat straw.
The effects of biosurfactant rhamnolipid (RL) and chemical surfactant Triton X-100 on the production of cellulases and xylanase from Penicillium expansum (P. expansum) in untreated, acid- and alkali-pretreated wheat straw submerged fermentations were studied, and the influences on the activity and stability of Cellulase R-10 were also investigated. The results showed that RL and Triton X-100 enhanced the activities of cellulases and xylanase to different extents and the stimulatory effects of RL were superior to those of Triton X-100. During the peak enzyme production phase, RL (60 RE mg/l) increased cellulases activities by 25.5-102.9%, in which the raise of the same enzyme in acid-pretreated straw broths was the most. It was found that the reducing sugars by hydrolyzing wheat straw with Cellulase R-100 were not visibly increased after adding RL. However, it distinctly protected Cellulase R-10 from degradation or inactivation, keeping the reducing sugars yield at about 17%.


Insights on next-generation manufacturing of smart devices using text analytics.
With the mass expansion in technological user-friendly products, there is an increasing demand for smart devices, resulting in a highly competitive novel market. To ensure sustainable success, these products must remain robust and be perceived positively by customers. With the development of Web 2.0, individuals are able to make knowledgeable purchasing decisions, specifically with the availability of millions of online customer reviews. Companies manufacturing smart devices can utilize this unstructured data to analyze the customers' perceptions of their products and identify potential improvements. To the best of our knowledge, this paper is the first to propose next-generation manufacturing insights for companies producing smart devices by determining the current strengths, weaknesses, opportunities, and threats (SWOT) of these gadgets using text analytics. A three-stage methodology is utilized, consisting of bigram and trigram examination, topic identification, and SWOT analysis. After online review extraction, comments for each smart device are separated into positive, neutral, and negative categories, based on the customer ratings. Text analytic tools are then used to determine the most frequently occurring bigrams and trigrams to provide topics for conducting the SWOT analysis. Using the SWOT technique results, numerous next-generation smart device manufacturing recommendations are presented.


[Levofloxacin-based triple therapy for first-line Helicobacter pylori eradication treatment: a multi-central, randomized, controlled clinical study].
To compare efficacy and tolerability of 7-day standard triple therapy versus 7-day levofloxacin-based triple therapy in first-line treatment for Helicobacter pylori (H. pylori) infection. Three hundred consecutive H.pylori positive patients were randomized to receive: clarithromycin, amoxicillin, lansoprazole (Group A: n = 150); or amoxicillin, levofloxacin, lansoprazole (Group B: n = 150). H. pylori status was rechecked by (13)C-urea breath test 4 weeks after the end of therapy. The eradication rates in intention to treat (ITT) and per protocol (PP) analyses were: Group A, 74.5% (111/149) and 78.2% (111/142); and Group B, 82.4% (122/148) and 83.0%(122/147). Although the eradication rate achieved with levofloxacin-based triple therapy was higher than that with standard therapies in either ITT or PP analysis, but no significantly difference was found between the two triple therapies. The incidence of side effects was similar among groups. A 7-day levofloxacin-based triple therapy can achieve higher H.pylori eradication rate than standard regimen. The levofloxacin-based regimen can be one effective therapy for the first-line anti-H.pylori treatment.


Effect of clinical finishing procedures on amalgam microstructure.
Spherical amalgam specimens were burnished, burnished-polished, polished (wet), or polished (dry). The amalgams were sectioned normal to the prepared surface, elemental analyses were made at a series of depths from the surface with the electron microprobe and the phase fractions were calculated. Significant variations in phase distributions exist within 100 micrometers of the surface.


Cellulitis with compartment syndrome as a complication of varicella zoster infection.
Varicella zoster infection (chickenpox) is a common and usually benign self limiting disease of childhood in non-vaccinated populations. Although varicella usually goes along with mild to moderate illness in immunocompetent patients, serious complications can arise. Varicella is highly infectious, with attack rates in susceptible individuals ranging from 61% to 100%. This case describes a rare but life threatening complication of varicella zoster infection in a child. High morbidity in non-vaccinated populations that led to rare cases of severe complications became a significant health burden all over the world. This aspect must be considered in the discussion about the importance and benefit of a population wide varicella vaccination programme as it was added to the childhood immunization schedule in Germany in 2004. The case described here might have been avoided by vaccination.


Bone marrow-derived fibroblast migration via periostin causes irreversible arthrogenic contracture after joint immobilization.
Joint contracture causes distressing permanent mobility disorder due to trauma, arthritis, and aging, with no effective treatment available. A principal and irreversible cause of joint contracture has been regarded as the development of joint capsule fibrosis. However, the molecular mechanisms underlying contracture remain unclear. We established a mouse model of knee joint contracture, revealing that fibrosis in joint capsules causes irreversible contracture. RNA-sequencing of contracture capsules demonstrated a marked enrichment of the genes involved in the extracellular region, particularly periostin (Postn). Three-dimensional magnetic resonance imaging and immunohistological analysis of contracture patients revealed posterior joint capsule thickening with abundant type I collagen (Col1a2) and POSTN in humans. Col1a2-GFPTG ; Postn-/- mice and chimeric mice with Col1a2-GFPTG ; tdTomatoTG bone marrow showed fibrosis in joint capsules caused by bone marrow-derived fibroblasts, and POSTN promoted the migration of bone marrow-derived fibroblasts, contributing to fibrosis and contracture. Conversely, POSTN-neutralizing antibody attenuated contracture exacerbation. Our findings identified POSTN as a key inducer of fibroblast migration that exacerbates capsule fibrosis, providing a potential therapeutic strategy for joint contracture.


Insulin-like Growth Factor-1 Influences Prostate Cancer Cell Growth and Invasion through an Integrin α3, α5, αV, and β1 Dependent Mechanism.
Insulin-like growth factor-1 (IGF-1)-related signaling is associated with prostate cancer progression. Links were explored between IGF-1 and expression of integrin adhesion receptors to evaluate relevance for growth and migration. Androgen-resistant PC3 and DU145 and androgen-sensitive LNCaP and VCaP prostate cancer cells were stimulated with IGF-1 and tumor growth (all cell lines), adhesion and chemotaxis (PC3, DU145) were determined. Evaluation of Akt/mTOR-related proteins, focal adhesion kinase (FAK) and integrin α and β subtype expression followed. Akt knock-down was used to investigate its influence on integrin expression, while FAK blockade served to evaluate its influence on mTOR signaling. Integrin knock-down served to investigate its influence on tumor growth and chemotaxis. Stimulation with IGF-1 activated growth in PC3, DU145, and VCaP cells, and altered adhesion and chemotactic properties of DU145 and PC3 cells. This was associated with time-dependent alterations of the integrins α3, α5, αV, and β1, FAK phosphorylation and Akt/mTOR signaling. Integrin blockade or integrin knock-down in DU145 and PC3 cells altered tumor growth, adhesion, and chemotaxis. Akt knock-down (DU145 cells) cancelled the effect of IGF-1 on α3, α5, and αV integrins, whereas FAK blockade cancelled the effect of IGF-1 on mTOR signaling (DU145 cells). Prostate cancer growth and invasion are thus controlled by a fine-tuned network between IGF-1 driven integrin-FAK signaling and the Akt-mTOR pathway. Concerted targeting of integrin subtypes along with Akt-mTOR signaling could, therefore, open options to prevent progressive dissemination of prostate cancer.


A guide to systems-level immunomics.
The immune system is highly complex and distributed throughout an organism, with hundreds to thousands of cell states existing in parallel with diverse molecular pathways interacting in a highly dynamic and coordinated fashion. Although the characterization of individual genes and molecules is of the utmost importance for understanding immune-system function, high-throughput, high-resolution omics technologies combined with sophisticated computational modeling and machine-learning approaches are creating opportunities to complement standard immunological methods with new insights into immune-system dynamics. Like systems immunology itself, immunology researchers must take advantage of these technologies and form their own diverse networks, connecting with researchers from other disciplines. This Review is an introduction and 'how-to guide' for immunologists with no particular experience in the field of omics but with the intention to learn about and apply these systems-level approaches, and for immunologists who want to make the most of interdisciplinary networks.


[Suitability of MEDLINE for the study of the Spanish scientific production in biomedicine and medical sciences. A comparative appraisal with the Science Citation Index].
MedLine (ML) database in CD-ROM, one of the most popular sources for bibliographic citations and abstracts of medical-biomedical literature, is also being widely used as a bibliometric tool. The usefulness of MedLine for bibliometric purposes needs to be evaluated. A database (BDML) of the Spanish publications in medical-biomedical journals has been derived from ML in the period 1990-1994 searching for SPAIN or ESPANA in the author address (AD) and/or in the country of publication (CP) fields. Retrieved documents correspond to original and review articles. The journals were assigned to SCI categories and impact factors according to the Journal Citation Reports (1990 and 1994 issues). BDML contents were compared with the documents indexed in SCI-SSCI databases (1990-1993) as reported (Camí J et al. Med Clin [Barc] 1997; 109: 481-496). Spanish production in medical and biomedical publications indexed in BDML amounts to 27,452 documents in 1,639 journals or 19,915 documents in the 1,339 journals listed in JCR. This represents 3,983 articles and reviews in SCI journals per year on average. Similar calculation for the Spanish articles and reviews indexed in SCI-SSCI databases (1990-93) gives a rate of 3,727 documents/year. Coverage of biomedical literature in ML is much lower than in SCI + SSCI (11,729 and 15,723 documents respectively) although the differences can be lowered taking into account that SCI documents include case reports and letters to the Editor which can not be retrieved from ML searchs in the AD field. On the contrary, more Spanish articles in medical disciplines were retrieved from ML (15,723) than SCI + SSCI databases (7,858). ML indexes more Spanish medical journals than SCI (36 journals and 11,400 articles in ML90-94 against 12 journals and 1,622 documents in SCI90-93). The results validate the usefulness of MedLine for bibliometric studies in medical sciences.


Successful endoscopic transection of a partially obstructing antral diaphragm.
A 14-yr-old girl presented with long-standing symptoms of partial gastric outlet obstruction due to an antral mucosal diaphragm that had a central aperture of 4-5 mm. The literature of this congenital malformation is reviewed with respect to diagnostic criteria and feasibility of endoscopic transection. The procedure and outcome of this first successful endoscopic transection of a partially obstructing antral diaphragm are reported.


Loss of legumain induces premature senescence and mediates aging-related renal fibrosis.
Aging is an independent risk factor for acute kidney injury and subsequent chronic kidney diseases, while the underlying mechanism is still elusive. Here, we found that renal tubules highly express a conserved lysosomal endopeptidase, legumain, which is significantly downregulated with the growing of age. Tubule-specific legumain-knockout mice exhibit spontaneous renal interstitial fibrosis from the 3rd month. In the tubule-specific legumain-knockout mice and the cultured legumain-knockdown HK-2 cells, legumain deficiency induces the activation of tubular senescence and thus increases the secretion of profibrotic senescence-associated cytokines, which in turn accelerates the activation of fibroblasts. Blockage of senescence mitigates the fibrotic lesion caused by legumain deficiency. Mechanistically, we found that silencing down of legumain leads to the elevated lysosome pH value, enlargement of lysosome size, and increase of lysosomal voltage dependent membrane channel proteins. Either legumain downregulation or aging alone induces the activation of nuclear transcription factors EB (TFEB) while it fails to further upregulate in the elderly legumain-knockdown tubules, accompanied with impaired mitophagy and increased mitochondrial ROS (mtROS) accumulation. Therapeutically, supplementation of exosomal legumain ameliorated fibronectin and collagen I production in an in vitro coculture system of tubular cells and fibroblasts. Altogether, our data demonstrate that loss of legumain in combined with aging dysregulates lysosomal homeostasis, although either aging or legumain deficiency alone induces lysosome adaptation via stimulating lysosomal biogenesis. Consequently, impaired mitophagy leads to mtROS accumulation and therefore activates tubular senescence and boosts the interstitial fibrosis.


Seducing astrocytes to the dark side.
After injury and in disease of the central nervous system (CNS), local cells called astrocytes respond with diverse molecular changes whose functional consequences are incompletely understood. A combined genomic and experimental analysis shows that classically-activated microglia, which are innate immune cells resident in CNS neural tissue, release molecules that drive astrocytes into a neurotoxic state, raising important questions about potential adaptive and maladaptive functions of such a mechanism.


Neurocognitive performance in family-based and case-control studies of schizophrenia.
Neurocognitive deficits in schizophrenia (SZ) are established and the Consortium on the Genetics of Schizophrenia (COGS) investigated such measures as endophenotypes in family-based (COGS-1) and case-control (COGS-2) studies. By requiring family participation, family-based sampling may result in samples that vary demographically and perform better on neurocognitive measures. The Penn computerized neurocognitive battery (CNB) evaluates accuracy and speed of performance for several domains and was administered across sites in COGS-1 and COGS-2. Most tests were included in both studies. COGS-1 included 328 patients with SZ and 497 healthy comparison subjects (HCS) and COGS-2 included 1195 patients and 1009 HCS. Demographically, COGS-1 participants were younger, more educated, with more educated parents and higher estimated IQ compared to COGS-2 participants. After controlling for demographics, the two samples produced very similar performance profiles compared to their respective controls. As expected, performance was better and with smaller effect sizes compared to controls in COGS-1 relative to COGS-2. Better performance was most pronounced for spatial processing while emotion identification had large effect sizes for both accuracy and speed in both samples. Performance was positively correlated with functioning and negatively with negative and positive symptoms in both samples, but correlations were attenuated in COGS-2, especially with positive symptoms. Patients ascertained through family-based design have more favorable demographics and better performance on some neurocognitive domains. Thus, studies that use case-control ascertainment may tap into populations with more severe forms of illness that are exposed to less favorable factors compared to those ascertained with family-based designs.


Current applications and future perspective of CRISPR/Cas9 gene editing in cancer.
Clustered regularly interspaced short palindromic repeats (CRISPR) system provides adaptive immunity against plasmids and phages in prokaryotes. This system inspires the development of a powerful genome engineering tool, the CRISPR/CRISPR-associated nuclease 9 (CRISPR/Cas9) genome editing system. Due to its high efficiency and precision, the CRISPR/Cas9 technique has been employed to explore the functions of cancer-related genes, establish tumor-bearing animal models and probe drug targets, vastly increasing our understanding of cancer genomics. Here, we review current status of CRISPR/Cas9 gene editing technology in oncological research. We first explain the basic principles of CRISPR/Cas9 gene editing and introduce several new CRISPR-based gene editing modes. We next detail the rapid progress of CRISPR screening in revealing tumorigenesis, metastasis, and drug resistance mechanisms. In addition, we introduce CRISPR/Cas9 system delivery vectors and finally demonstrate the potential of CRISPR/Cas9 engineering to enhance the effect of adoptive T cell therapy (ACT) and reduce adverse reactions.


Effects of topical 5-aminosalicylic acid and prednisolone on prostaglandin E2 and leukotriene B4 levels determined by equilibrium in vivo dialysis of rectum in relapsing ulcerative colitis.
To determine the influence of inflammation and topical treatment with 5-aminosalicylic acid or prednisolone on arachidonic acid metabolism in vivo, we carried out a double-blind controlled study on the release of prostaglandin E2 and leukotriene B4 to the rectal lumen in 24 consecutive patients with proven distally located ulcerative colitis. Before and at days 15 and 29 a dialysis bag was placed in the emptied rectum for 4 h prior to assessing clinical, endoscopic, and histologic disease activity. A single enema was given daily at bedtime (1 g 5-aminosalicylic acid or 25 mg prednisolone) until complete remission or for a maximum of 4 wk. Clinical and endoscopic remission was obtained in 16 (7 on 5-aminosalicylic acid) and 11 (3 on 5-aminosalicylic acid) patients, respectively. Luminal concentrations of prostaglandin E2 and leukotriene B4 were positively correlated to disease activity and significantly decreased among the prednisolone-treated patients. In both treatment groups a decrease toward normal levels occurred in patients responding to therapy. In retrospect, the pretreatment prostaglandin E2 and leukotriene B4 levels were significantly higher in patients not responding to therapy than in those improving during treatment. In conclusion, luminal prostaglandin E2 and leukotriene B4 levels may prove more useful predictors of the outcome of treatment in relapsing ulcerative colitis than clinical indices of disease activity.


Characteristics and possible function of endoglin, a TGF-beta binding protein.
Endoglin was recently described as a major TGF-beta binding protein on endothelial cells. In this review we summarize the experimental data on this molecule, discuss some of our own findings, and speculate on its function.


Inhibition of Toxoplasma gondii by 1,2,4-triazole-based compounds: marked improvement in selectivity relative to the standard therapy pyrimethamine and sulfadiazine.
A safer treatment for toxoplasmosis would be achieved by improving the selectivity profile of novel chemotherapeutics compared to the standard therapy pyrimethamine (PYR) and sulfadiazine (SDZ). We previously reported on the identification of the compounds with imidazole-thiosemicarbazide scaffold as potent and selective anti-Toxoplasma gondii (T. gondii) agents. In our current research, we report on the optimisation of this chemical scaffold leading to the discovery cyclic analogue 20 b with s-triazole core structure. This compound displayed prominent CC30 to IC50 selectivity index (SI) of 70.72, making it 160-fold more selective than SDZ, 11-fold more selective than PYR, and 4-fold more selective than trimethoprim (TRI). Additionally, this compound possesses prerequisite drug-like anti-Toxoplasma properties to advance into preclinical development; it showed ability to cross the BBB, did not induce genotoxic and haemolytic changes in human cells, and as well as it was characterised by low cellular toxicity.


The effect of the plasminogen activator inhibitor-1 4G/5G polymorphism on the thrombotic risk.
Plasminogen activator inhibitor (PAI-1), is the central component of the fibrinolytic system. A deletion/insertion (4G/5G) polymorphism in the promoter region of the PAI-1 gene has been correlated with levels of plasma PAI-1. The 4G allele is associated with higher levels of PAI-1, and might increase the risk for intravascular thrombosis. However, the contribution of this genetic variant to the risk for thrombosis, both arterial and venous, has not been clearly established. A broad spectrum of findings regarding the effect of the 4G allele on thrombotic risk in different target organs has been reported. Our aim is to summarize the variable influence of this polymorphism on thrombotic events in different tissues or organs and explain the underlying mechanisms accounting for these differences.


[N.Yu. Piatnitsre «Mental signs of predisposition to functional mental disorders» Book I. Evolution of concepts from Th. Willis to E. Kraepelin. Moscow: RUSAYNS, 2020.202 S .; Book II. Evolution of concepts from E. Kraepelin to E. Kretschmer. Moscow: RUSAYNS, 2020.304 p .; Book III. Evolution of concepts from E. Kretschmer to P.B. Gannushkin. Moscow: RUSAYNS, 2021.388 p.]
N.Yu. Piatnitsre «Mental signs of predisposition to functional mental disorders» Book I. Evolution of concepts from Th. Willis to E. Kraepelin. Moscow: RUSAYNS, 2020.202 S .; Book II. Evolution of concepts from E. Kraepelin to E. Kretschmer. Moscow: RUSAYNS, 2020.304 p .; Book III. Evolution of concepts from E. Kretschmer to P.B. Gannushkin. Moscow: RUSAYNS, 2021.388 p.


[Clinical application of fast protein liquid chromatography (FPLC) system].
FPLC system is a high-performance liquid chromatography system, designed specifically for separation of proteins, peptides and polynucleotides. Many kinds of column have been prepared, including Mono Q, Mono S, Mono P, Superose, etc. for ion exchange chromatography, chromatofocussing, gel filtration, hydrophobic chromatography, reversed phase chromatography and affinity chromatography. It is a fast and simple system for separation of proteins in various body fluids, particularly plasma, urine and cerebrospinal fluid.


Categorizing "frequent visitors" in the psychiatric emergency room: a semistructured interview study.
Nurses can become demoralized and hostile toward frequent visitors in psychiatric emergency rooms because of the number of visits. The aim of this study was to develop more knowledge about the ways in which nurses categorize frequent visitors. Eleven nurses were interviewed, and their categorizing practices were examined from a social constructionist perspective. The results showed that the nurses did not categorize frequent visitors as particularly unlikeable or difficult to treat. Like other visitors, they could be categorized as difficult if they obstructed a smooth flow of successful referrals through the emergency room and/or there was poor rapport with the nurses.


Fistulotomy and primary sphincteroplasty for anal fistula: long-term data on continence and patient satisfaction.
The aim of this study was to evaluate the safety and long-term efficacy of fistulotomy and primary sphincteroplasty (FIPS). Secondary endpoints were its impact on postoperative continence status and patients' satisfaction. A retrospective study was conducted on patients with cryptoglandular anal fistula (AF) who had FIPS between June 2006 and May 2017. Patients were evaluated with standardized telephone interviews and clinical/instrumental assessment. Main outcome measures included fistula healing rate, continence status, and patient satisfaction. Incontinence was defined as an inability to hold either gas, liquid, or solid stools, as well as postdefecation soiling, and was measured by the Cleveland Clinic fecal incontinence score. Patient satisfaction was evaluated by an 11-point numeric rating scale. There were 203 patients (139 males; mean age: 48.7 years) who had FIPS. The overall healing rate was 93% (188 patients) with a mean follow-up period of 56 ± 31 months. Half of the total cohort (51%) had a complex fistula. Preoperatively, 8 (4%) patients complained of postdefecation soiling and 2 (1%) of gas incontinence. Postoperatively, 26 (13%) patients had continence impairment (de novo n = 24), mainly consisting of postdefecation soiling (10%). In univariate analysis, patients with recurrent (RR 6.153 95% CI 2.097-18.048; p = 0.002) or complex (RR 3.005 95% CI 1.203-7.506; p = 0.012) AF and those with secondary tracts (RR 8.190 95% CI 2.188-30.654; p = 0.004) or previous set on drainage (RR 5.286 95% CI 2.235-12.503; p = 0.0001) were at higher risk of incontinence. In multivariate analysis, no significant predictors were found, although fistula complexity approached statistical significance (RR 5.464 95% CI 0.944-31.623; p = 0.050). The mean patient satisfaction numeric rating scale was 9.3 ± 1.6. Lower satisfaction rates were found in patients with transphincteric (p = 0.011) or complex (p = 0.0001) AF, with secondary tracts (p = 0.041) or previous seton drainage (p = 0.008), and in those with postoperative continence impairment (p = 0.0001). Postoperative onset of incontinence was the only significant factor in multivariate analysis (p = 0.0001). FIPS should be considered a valid therapeutic option for selected AF. However, the risk of postoperative minor fecal incontinence exists, and should be discussed during preoperative patient counselling.


1 year follow Up results of "ARTIM HF TRIAL" (angiotensin receptor neprilysin inhibitor effect on TEI index & left ventricular mass in heart failure).
Sacubitril/Valsartan (ARNI) has now class 1 recommendation for treatment of heart failure with reduced ejection fraction (HFrEF). It has been shown to reduce cardiovascular morbidity & mortality in Heart failure with reduced ejection fraction (HFrEF) and significant improvement in all echocardiographic parameters besides TEI index. Tei index is a marker of inflammation, myocardial cell metabolism and its contractile function has not been evaluated as a distinctive entity so we took up this study to evaluate the effects of ARNI on the LV functions using two dimensional (2D)ECHO parameters in Indian population and to assess TEI index for myocardial function. 256 patients with class II, III or IV HF and EF<40% were enrolled. 171(66.8%) were males and 85(33.2%) were females. Patients were evaluated at baseline, 6 and 12 months for LVEF, LV mass &,LVMPI. Drug was discontinued in 2 patients due to angioedema, in 5 patients due to acute kidney injury and in 2 patients due to hypotension. LV mass measurement done by linear echocardiographic method and Flow Doppler method used for TEI index calculation. Baseline parameters in 247 patients were mean EF = 26.33 ± 6.28%, mean LV mass = 270.84 ± 68.94 gm, mean Tei Index = 0.852 ± 0.22. ARNI use was associated with an average gradual increase in EF, from a mean baseline of 26.33 ± 6.28% to 33.88 ± 7.73%(p = 0.000001) after 1 year of treatment. There was a significant progressive reduction of 57.97 g/m2 in mean LV mass index after 1 year of treatment (p = 0.000001).TEI index showed significant reduction from baseline mean 0.85 ± 0.22 to 0.70 ± 0.12(p = 0.000001)after 1 year of treatment. Use of ARNI as additive adjunct to standard care of treatment resulted in significant progressive decline in LV mass and increase in TEI index.


Role of Immunoglobulin M and A Antibodies in the Neutralization of Severe Acute Respiratory Syndrome Coronavirus 2.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected millions of people globally. Virus infection requires the receptor-binding domain (RBD) of the spike protein. Although studies have demonstrated anti-spike and -RBD antibodies to be protective in animal models, and convalescent plasma as a promising therapeutic option, little is known about immunoglobulin isotypes capable of blocking infection. We studied spike- and RBD-specific immunoglobulin isotypes in convalescent and acute plasma/serum samples using a multiplex bead assay. We also determined virus neutralization activities in plasma and serum samples, and purified immunoglobulin fractions using a vesicular stomatitis pseudovirus assay. Spike- and RBD-specific immunoglobulin (Ig) M, IgG1, and IgA1 were produced by all or nearly all subjects at variable levels and detected early after infection. All samples displayed neutralizing activity. Regression analyses revealed that IgM and IgG1 contributed most to neutralization, consistent with IgM and IgG fractions' neutralization potency. IgA also exhibited neutralizing activity, but with lower potency. IgG, IgM, and IgA are critical components of convalescent plasma used for treatment of coronavirus disease 2019 (COVID-19).


Healthcare professionals' information need related to antiseizure medication use in breastfeeding patients with epilepsy. Retrospective analysis of enquiries to Norwegian medicines information and pharmacovigilance centers.
Safety information of antiseizure medication (ASM) during breastfeeding is scarce and conflicting. We aimed to identify characteristic traits of safety concerns among healthcare professionals by reviewing enquiries to the Norwegian Regional Medicines Information and Pharmacovigilance Centres (RELIS). Enquiries related to breastfeeding, epilepsy, and ASM identified by their ATC-numbers were retrieved from the RELIS database of question-and-answer pairs (QAPs) by combining indexed and Boolean database searches and manual inspection. 112 QAPs were analyzed retrospectively using descriptive statistics. Hospital-employed physicians and nurses were puzzled by ambiguous or conflicting drug information advice and called for general information about the compatibility of an ASM with breastfeeding, mainly related to lamotrigine and levetiracetam. Other enquiries were related to co-medication with other drugs, mainly antidepressants. Half of the enquiries were posed after birth, 12 of these motivated by suspected adverse events in the infants. Healthcare professionals with acknowledged high competence in the topic were uncertain about the prevailing safety information of ASM during breastfeeding. The fear to harm the infant may lead to the decision not to recommend breastfeeding. Future information strategies should aim to reach these professions, and support their information need on this topic.


Nucleocytoplasmic shuttling of valosin-containing protein (VCP/p97) regulated by its N domain and C-terminal region.
Valosin-containing protein (VCP or p97), a member of the AAA family (ATPases associated with diverse cellular activities), plays a key role in many important cellular activities. A genetic deficiency of VCP can cause inclusion body myopathy associated with Paget's disease of bone and frontotemporal dementia (IBMPFD). Previous studies showed that the VCP N domain is essential for the regulation of nuclear entry of VCP. Here we report that IBMPFD mutations, which are mainly located in the N domain, suppress the nuclear entry of VCP. Moreover, the peptide sequence G780AGPSQ in the C-terminal region regulates the retention of VCP in the nucleus. A mutant lacking this sequence can increase the nuclear distribution of IBMPFD VCP, suggesting that this sequence is a potential molecular target for correcting the deficient nucleocytoplasmic shuttling of IBMPFD VCP proteins.


A case of tension pneumothorax mimicking spontaneous rupture of the diaphragm.
A 40 year old asthmatic presented with acute respiratory distress. Chest radiograph appeared to show loops of bowel within the thorax and a diagnosis of spontaneous/effort rupture of the diaphragm was made. Emergency laparotomy revealed an intact diaphragm and chest drain was inserted relieving a tension pneumothorax.


Effects of schedule of reinforcement on over-selectivity.
Stimulus over-selectivity refers to behavior being controlled by one element of the environment at the expense of other equally salient aspects of the environment. Four experiments trained and tested non-clinical participants on a two-component trial-and-error discrimination task to explore the effects of different training regimes on over-selectivity. Experiments 1 and 2 revealed no differentiation between partial reinforcement (PR) and continuous reinforcement (CRF) on over-selectivity. Experiments 3 and 4 both found that a change in reinforcement (from CRF to PR in Experiment 3, and from PR to CRF in Experiment 4) did not reduce levels of over-selectivity, but rather continuing training with the same contingency (either CRF or PR) did reduce over-selectivity. The results support assumptions made by the comparator hypothesis, extending the growing body of literature explaining over-selectivity as a post-acquisition, rather than attention, failure.


Isoniazid completion rates for latent tuberculosis infection among college students managed by a community pharmacist.
The authors' objective was to document 9-month and previously recommended 6-month treatment completion rates for latent tuberculosis infection (LTBI) in a pharmacist-managed LTBI clinic in a community pharmacy on a college campus, and to describe patient characteristics. Participants were university students diagnosed with LTBI. The authors conducted a retrospective review of pharmacy records from 2000 to 2006. Main outcome measures included 6-month and 9-month LTBI treatment completion rates, total isoniazid (INH) tablets taken, characteristics of completers versus noncompleters, average time to treatment completion, and reported adverse drug events. The 9-month completion rate was 59%, and the 6-month completion rate was 67%. Among those not completing treatment, 15.2% experienced fatigue and 2.2% experienced a rash (p=.04 and p=.03, respectively). LTBI clinics are a unique niche for community pharmacies and can provide individualized patient care to ensure LTBI treatment adherence, monitoring for disease progression, and safety of INH.


Histocompatibility in Italian couples with recurrent spontaneous abortions of unknown origin and with normal fertility.
We investigated HLA antigen and haplotype frequencies in 47 couples with primary recurrent abortions of unknown origin, in 65 fertile couples, and in a control panel of 98 males and 92 females. A significant increase of HLA-B17 was found in abortion couples in comparison with fertile couples. No difference between abortion and control fertile couples was observed regarding HLA sharing.


Animal cognition: crows spontaneously solve a metatool task.
A recent study found that tool-manufacturing New Caledonian crows spontaneously solved a metatool task in which the birds used a tool to obtain a second, longer tool that could then be used to obtain food that was otherwise out of reach.


Colophonium and Compositae mix as markers of fragrance allergy: cross-reactivity between fragrance terpenes, colophonium and compositae plant extracts.
The aim of this study was to assess the strength of any association between sensitization to 'new' fragrance compounds and sensitization to Compositae, fragrance mix, Myroxylon pereirae resin and colophonium, respectively. Consecutive eczema patients were tested with a series of essential oils and selected fragrance compounds and another series of oxidized terpenes in connection with European multicentre fragrance projects. Contact allergy to either series was frequently detected, in 5% of 318 and 4.6% of 262 persons tested, and both had a statistically significant association with Compositae, colophonium and fragrance mix sensitization. The individual results indicated that simultaneously occurring positive reactions to essential oils, colophonium and Compositae were based on cross-reactivity rather than concomitant sensitization. Thus, all patients with positive reaction to the rare fragrance sensitizer beta-caryophyllene had positive colophonium reactions, and cross-reactivity between essential oils and Compositae was related to the Compositae plant extracts of the Compositae mix and not the pure sesquiterpene lactones of the standard series. The implication is that Compositae mix and colophonium may be markers of fragrance allergy, which is important to know when assessing the relevance of positive reactions to Compositae plant extracts and colophonium.


Identifying high-density areas of oysters using species distribution modeling: Lessons for conservation of the native Ostrea edulis and management of the invasive Magallana (Crassostrea) gigas in Sweden.
Understanding spatial patterns of the distribution of adult native oyster, Ostrea edulis, and the invasive Magallana (Crassostrea) gigas is important for management of these populations. The aim of this study was to use ensemble SDM's to (a) identify and predict conservation hotspots, (b) assess the current level of protection for O. edulis, and (c) quantify the amount of overlap between the two species where interactions with M. gigas are most likely. Skagerrak, Sweden. We used data collected by video at depths from 0.5 to 10 m in 436 sites. Models of occurrence and densities >1 m-2 were fitted and assessed using ensemble methods ("biomod2" package). Models of high-density hotspots were used to predict, map, and quantify areal extent of the species in order to assess the degree of overlap with protected areas and the potential for interactions between the two species. Both species were widely distributed in the region. Observations of high-density habitats, mainly occurring at depths of ≈3 and 0.5 m for O. edulis and M. gigas, respectively, were found in 4% and 2% of the sites. Models provided useful predictions for both species (AUC = 0.85-0.99; sensitivity = 0.74-1.0; specificity = 0.72-0.97). High-density areas occupy roughly 15 km2 each with substantial overlap between species. 50% of these are protected only by fisheries regulations, 44% are found in Natura 2000 reserves and 6% of the predicted O. edulis enjoys protection in a national park. Data collection by video in combination with SDM's provides a realistic approach for large-scale quantification of spatial patterns of marine population and habitats. O. edulis and M. gigas are common in the area, but a large proportion of the most valuable O. edulis habitats are not found in protected areas. The overlap between species suggests that efforts to manage the invasive M. gigas need to be integrated with management actions to conserve the native O. edulis.


Detecting motion changes with peripheral vision: On the superiority of fixating over smooth-pursuit tracking.
Detecting motion changes is a fundamental prerequisite for solving tasks in sports and in everyday life. It is known that peripheral vision is used to detect these changes and that saccades impair detection performance. However, comparatively little is known about the role of smooth-pursuit eye-movements (SPEMs) during these tasks. Therefore, we compared peripheral motion-change detection during SPEM and fixation at eccentricities up to 18°, simulating the perceptual demands of real-life situations. Based on expert gaze behavior in sports, we predicted that motion detection should be better during fixation than SPEM. In a series of three experiments, we consistently found that detection rates and response times were impaired during SPEM compared to fixation, particularly at 18° eccentricity. With an invisible pursuit object and targets moving ahead rather than behind the pursued object, performance differences in response times declined, whereas differences in detection rates interestingly remained unmoved. We argue that retinal image motion and attentional demands are reasons for SPEM impairments.


Erratum: In vitro activity of anti-rheumatic drugs on release of pro-inflammatory cytokines from oral cells in interaction with microorganisms.
[This corrects the article DOI: 10.3389/froh.2022.960732.].


Antifungal effects of ZnO, TiO2 and ZnO-TiO2 nanostructures on Aspergillus flavus.
This study aimed to synthesis ZnO, TiO2, and ZnO-TiO2 (ratio weight of 1/1 for Zn/Ti) nanoparticles using zinc acetate and titanium isopropoxide through the sol-gel method. Physicochemical and morphological characterization and antifungal properties evaluation like minimum inhibition concentration (MIC) and minimum fungicide concentration (MFC) of nanopowders were investigated against A.flavus in vitro. All synthesized nanoparticles (50 μg/ml) showed fungal growth inhibition, while ZnO-TiO2 showed higher antifungal activity against A. flavus than pure TiO2 and ZnO. TiO2 and ZnO-TiO2 (300 μg/ml) inhibited 100% of spur production. Pure ZnO and TiO2 showed pyramidal and spherical shapes, respectively, whereas ZnO-TiO2 nanopowders illustrated both spherical and pyramidal shapes with grown particles on the surface. Based on our findings, a low concentration (150 μg/ml) of ZnO-TiO2 showed higher ROS production and oxidative stress induction, thus the fungicide effect as compared to alone TiO2 and ZnO. In conclusion, ZnO-TiO2 nanostructure can be utilized as a useful antifungal compound, but more studies need to be performed to understand the antifungal mechanism of the nanoparticles rather than ROS inducing apoptosis.


A double-blind clinical trial of mianserin versus amitriptyline: differentiation by adverse symptomatology.
A 6-week double-blind comparison of mianserin, a new antidepressant, and amitriptyline allowed us to explore the problem of demonstrating main effect differences in drug/drug trials when the focus is primarily only upon efficacy or upon common adverse symptomatology. Statistical analyses of standard psychiatric rating scales revealed no significant treatment differences, while both treatment groups exhibited significant parallel improvement across time. Examination of treatment emergent symptoms indicated that, while it evoked fewer anticholinergic symptoms than amitriptyline, mianserin exhibited a different profile of adverse symptomatology. The usefulness of a measure of the benefit/risk ratio was described as a means of clarifying drug/drug comparisons.


The unspoken grief of multiple stillbirths in rural Pakistan: an interpretative phenomenological study.
Pakistan has the highest rate of stillbirth (30.6 stillbirths per 1000 total births) as compared to other South Asian countries. The psychological impact of stillbirths on bereaved women is well documented; however, there is a dearth of literature on lived experiences of women with multiple stillbirths in Pakistan. The purpose of this research is to understand the lived experiences of women who had multiple stillbirths in Thatta, Pakistan. An interpretative phenomenological study was conducted in district Thatta with eight women who experienced more than one stillbirth. A semi-structured in-depth interview guide was used for data collection. The data were analyzed by using thematic analysis approach. The results of this study show that experiencing multiple stillbirths has a devastating impact on women's mental and social wellbeing. The women who experienced multiple stillbirths are stigmatized as "child-killer" or cursed or being punished by God. They are avoided in social gatherings within the families and community, because of these social pressures these women seek spiritual and religious treatment, and struggle to conceive again to deliver a live baby. It was observed that the psycho-social and medical needs of these bereaved women remain unaddressed not only by the healthcare system but also by the society at large. The physical, social and mental well-being of women who experience multiple stillbirth are at stake. These women are being considered social outcast. Health care providers including physicians, lady health workers, and traditional birth attendants should be trained on provision of psychosocial support along with the routine care that they provide in communities and health facilities. The health care providers should also inform the bereaved women about the biomedical causes of stillbirths that would be helpful to mitigate the stigma associated with stillbirths. Moreover, the health care providers should also counsel family members especially in-laws of these sorrowful women about the biomedical causes of stillbirths that would also be helpful to mitigate the stigma associated with stillbirths.


Method of approximations for the convection-dominated anomalous diffusion equation in a rectangular plate using high-resolution compact discretization.
The present method describes the high-resolution compact discretization method for the numerical solution of the nonlinear fractal convection-diffusion model on a rectangular plate by employing the Hausdorff distance metric. Estimation of anomalous diffusion is formulated by averaging forward and backward mesh stencils. The higher-order fractional derivatives are appropriately approximated on a minimum mesh stencil and subsequently considered for designing a numerical method that falls in the scope of expanded accuracy. Compact discretization is an efficient technique for partial differential equations; however, studies that apply high-resolution scheme for fractional-order systems are still uninvestigated. A second and fourth-order numerical method for the fractional-order convection-dominated anomalous diffusion equation in two dimensions is constructed for practical applications. Convergence of high-order method is obtained for the nonlinear partial differential equations employing Hausdorff fractal distance metric. The numerical simulations with fractal Graetz-Nusselt equation, fractal Poisson equation, fractal Schrödinger equation, and anomalous diffusion equations with variable and constant coefficients are considered to illustrate the utility of the numerical method in the context of local fractional partial differential equations.•The paper demonstrates a computational method for the fractal convection-diffusion model on a rectangular plate.•Two numerical methods of order two and four for the mildly nonlinear fractional-order convection-dominated anomalous diffusion equations are proposed.•The high-resolution scheme is computationally efficient and makes use of minimal data storage.Method name: High-order method for 2D convection-dominated anomalous diffusion equation, Graetz-Nusselt equation, Poisson equation, and Schrödinger equation in fractal media.


Development of a dot immunoblot method for differentiation of animals infected with foot-and-mouth disease virus from vaccinated animals using non-structural proteins expressed prokaryotically.
Five non-structural proteins (NSPs) of foot-and-mouth disease virus (FMDV) were expressed in E. coli to develop a dot immunoblot (dot blot) assay for the differentiation of FMDV infected animals from vaccinated animals (DIVA). The five NSPs were 3A (24 kDa), 3B (15 kDa), major B-cell epitope regions of 2C (23 kDa), partial 3D (44 kDa) and 3ABC (59 kDa). The criteria for the dot blot were determined and are described as follows: a test sample is considered positive if four or more NSPs demonstrate staining densities equal to or higher than those of their appropriate controls; a sample is considered negative if two or more antigens demonstrate densities below their negative control. A specificity of 100% was observed based on testing of sera from clinical healthy animals with or without vaccination; the sensitivity of the dot blot was 96.1% and 65.8% for testing of samples from infected cattle and swine, respectively, at an early stage of the infection. Meanwhile, high rates of concordance were observed between the dot blot and the PrioCHECK® FMDV-NS test. The dot blot has the potential to act as a confirmatory method for DIVA by 3ABC-ELISA.


Influence of temperature on the output of a mechanical coupler.
This research determined the influence of temperature on the output of two Bruel and Kjaer 4930 mechanical couplers using a Radioear B-71, B-72, and a Pracitronic KH 70 bone vibrator. When the temperature of the mechanical couplers was varied from 17 degrees C (62.6 degrees F) to 29 degrees C (84.2 degrees F) in steps of 3 degrees C (5.4 degrees F) and the bone vibrators had a constant temperature, the output of each mechanical coupler systematically decreased as its temperature increased for each bone vibrator type. The largest output differences for both couplers and each vibrator occurred at 4000 Hz. The average of these differences across the couplers and vibrators was 6.6 dB higher at 17 degrees C than at 29 degrees C which dB/3.6 degrees F). When the temperature of the bone vibrators was 17 and 29 degrees C and the mechanical couplers were maintained at a constant temperature, there were little or no differences in the output of the mechanical couplers. The temperature of a mechanical coupler rather than that of the bone vibrator is a critical variable in bone conduction calibration. Mechanical coupler temperature-dependent output coefficients were determined for use in bone conduction calibration from 250 to 4000 Hz for all three bone vibrator types and at 6000 and 8000 Hz for the KH 70.


Vesico-ureteric reflux: using mouse models to understand a common congenital urinary tract defect.
Vesico-ureteric reflux (VUR) is a common congenital urinary tract defect in which urine flows retrogradely from the bladder to the kidneys because of an abnormally formed uretero-vesical junction. It is associated with recurrent urinary tract infections, renal hypo/dysplasia, reflux nephropathy, hypertension, and end-stage renal disease. In humans, VUR is genetically and phenotypically heterogeneous, encompassing diverse renal and urinary tract phenotypes. To understand the significance of these phenotypes, we and others have used the mouse as a model organism and this has led to the identification of new candidate genes. Through careful phenotypic analysis of these models, a new understanding of the genetics and biology of VUR is now underway.


Corneal collagen as a potential therapeutic target in dry eye disease.
Dry eye disease (DED) is a major cause of ocular discomfort, inflammation and dysfunction worldwide. Tear film instability in DED both causes and is exacerbated by disruption of the corneal epithelium. This tandem leads to a cycle of inflammation at the corneal surface involving immune cell dysregulation and increased chemokines and cytokines, which activate mitogen-activated protein kinases in the epithelium and elevates matrix metalloproteinases (MMPs). We review evidence suggesting that corneal collagen might be highly susceptible in DED to MMP-induced disruption, digestion, and thinning. We also summarize that collagen is far from inert and contains binding sites that serve as ligands for multiple inflammatory and immune regulators. Fragmented collagen not only challenges these receptor-ligand binding relationships, but also can promote recruitment and motility of pro-inflammatory immune cells. Current physician-directed therapies for DED focus on reducing inflammation, but do not directly ameliorate the underlying corneal damage that could exacerbate surface inflammation. We argue that an important gap in practice is lack of a direct therapeutic reparative for damaged corneal collagen, which is slow to heal, and likely amplifies sight-threatening inflammation. Healing fragmented collagen in the cornea may represent a more effective means to interrupt the "vicious cycle" of inflammation in DED and other conditions that damages, sometimes irreversibly, the ocular surface.


Effect of pH on transport of Pb2+, Mn2+, Zn2+ and Ni2+ through lateritic soil: column experiments and transport modeling.
This study investigated the effects of pH on the transport of Pb2+, Mn2+, Zn2+ and Ni2+ through lateritic soil columns. Model results by fitting the symmetric breakthrough curves (BTCs) of bromide (Br-) with CXTFIT model suggested that physical non-equilibrium processes were absent in the columns. The heavy metal BTCs were, however, asymmetrical and exhibited a tailing phenomenon, indicating the presence of chemical non-equilibrium processes in the columns. The retardation factors of Pb2+ were the largest of the four metal ions at both pH 4.0 (33.3) and pH 5.0 (35.4). The use of Langmuir isotherm parameters from batch studies with HYDRUS-1D did not predict the BTCs well. Rather the two-site model (TSM) described the heavy metal BTCs better than the equilibrium linear/nonlinear Langmuir model. The fraction of instantaneous sorption sites (f) of all four metal ions on the lateritic soil was consistently about 30%-44% of the total sorption sites.


An isoimmune response to human sperm clathrin in an infertile woman with systemic lupus erythematosus.
We have employed a proteomic approach to study the immune response to human sperm in an infertile female patient suffering from systemic lupus erythematosus (SLE). Human sperm antigenic extracts were resolved by means of two-dimensional electrophoresis and electroblotted onto nitrocellulose membranes. The membranes were incubated with serum from the SLE patient. Sperm antigens that were reactive to polyclonal antibodies were next visualized on X-ray film, using the enhanced chemiluminescence (ECL). Three spots corresponding to the positions of sperm immunoreactive antigens on a nitrocellulose membrane were localized in a silver stained gel and subjected to mass spectrometry. A database search of the sequences recognized by the analyzed SLE serum revealed its homology to the clathrin heavy chain (CHC). Further analysis revealed that anti-CHC antibody reacted with multiple sperm antigenic determinants, resolved by either one- or two-dimensional electrophoresis. When studied by immunofluorescence, we demonstrated anti-CHC antibody reactivity with the sperm tail tip (corresponding to the sperm agglutination pattern), also with the principal piece and with cytoplasmic droplets around the sperm midpiece. Live sperm clearly exhibited reactivity with the midpiece. This study demonstrates clathrin heavy chain on human sperm using serum of an infertile individual with a concomitant autoimmune disease.


Frailty and pre-frailty in cardiac surgery: a systematic review and meta-analysis of 66,448 patients.
The burden of frailty on cardiac surgical outcomes is incompletely understood. Here we perform a systematic review and meta-analysis of studies comparing frail versus pre-frail versus non-frail patients following cardiac surgery. We searched MEDLINE and EMBASE databases until July 2018 for studies comparing cardiac surgery outcomes in "frail", "pre-frail" and "non-frail" patients. Data was extracted in duplicate. Primary outcome was operative mortality. There were 19 observational studies with 66,448 patients. Frail patients were more likely female (risk ratio [RR]1.7; 95%CI:1.5-1.9), older (mean difference: 2.4; 95%CI:1.3-3.5 years older) with greater comorbidities and higher STS-PROM. Frailty (RR2.35; 95%CI:1.57-3.51; p < 0.0001) and pre-frailty (RR2.03; 95%CI:1.52-2.70; p < 0.00001) were associated with increased operative mortality compared with non-frail patients. Frailty was also associated with greater risk of prolonged hospital stay (RR1.83; 95%CI:1.61-2.08; p < 0.0001) and intermediate care facility discharge (RR2.71; 95%CI:1.45-5.05; p = 0.002). Frail (Hazard Ratio [HR]3.27; 95%CI:1.93-5.55; p < 0.0001) and pre-frail patients (HR2.30; 95%CI:1.29-4.09; p = 0.005) had worse mid-term mortality (median follow-up 1 years [range 0.5-4 years]). After adjustment for baseline imbalances, frailty was still associated with greater operative mortality (odds ratio [OR]1.97; 95%CI:1.51-2.57; p < 0.00001), intermediate care facility discharge (OR4.61; 95%CI:2.78-7.66; p < 0.00001) and midterm mortality (HR1.37; 95%CI:1.03-1.83; p = 0.03). In patients undergoing cardiac surgery, frailty and pre-frailty were associated with 2-fold and 1.5-fold greater adjusted operative mortality, respectively, greater adjusted perioperative complications and frailty was associated with almost 5-fold risk of non-home discharge. Burden of frailty and pre-frailty on cardiac surgical outcomes.


Structural and physiochemical characterization of rhamnolipids produced by Acinetobacter calcoaceticus, Enterobacter asburiae and Pseudomonas aeruginosa in single strain and mixed cultures.
Rhamnolipids are naturally occurring biosurfactants with a wide range of potential commercial applications. As naturally derived products they present an ecological alternative to synthetic surfactants. The majority of described rhamnolipid productions are single strain Pseudomonas spp. cultivations. Here we report rhamnolipids producing bacteria Acinetobacter calcoaceticus, Enterobacter asburiae and Pseudomonas aeruginosa that were cultivated separately and as mixed populations. The ratio and composition of rhamnolipid congeners was determined by tandem mass spectrometry with negative electrospray ionization. Mono-rhamnolipid and di-rhamnolipid homologues containing one or two saturated or monounsaturated 3-hydroxy fatty acids were found in all strains. Physiochemical characterization of rhamnolipids was evaluated by the critical micelle concentration determination, the emulsification test, oil displacement test and phenanthrene solubilization. Critical micelle concentrations of rhamnolipids produced by both single strain and mixed cultures were found to be very low (10-63 mg/l) and to correspond with saturated/unsaturated fatty acid content of rhamnolipid homologues. The rhamnolipids produced by all strains effectively emulsified crude petroleum in comparison with synthetic surfactants Tween 80 and sodium dodecyl sulfate (SDS). Good performance of phenanthrene solubilization was exhibited by rhamnolipids from E. asburiae. The single strain and co-cultures cultivations were proposed as a possible way to produce rhamnolipid mixtures with a specific composition and different physiochemical properties, which could be exploited in bioremediation of various hydrophobic contaminants.


Genetic activity of the human carcinogen sulphur mustard towards Salmonella and the mouse bone marrow.
Sulphur mustard is clearly mutagenic to the repair-proficient (uvrB+) strain G46 of S. typhimurium. It is also a micronucleus-inducing agent to the mouse bone marrow. These data strengthen the database indicating that most human carcinogens are genotoxic.


Making new out of old: recycling and modification of an ancient protein translocation system during eukaryotic evolution. Mechanistic comparison and phylogenetic analysis of ERAD, SELMA and the peroxisomal importomer.
At first glance the three eukaryotic protein translocation machineries--the ER-associated degradation (ERAD) transport apparatus of the endoplasmic reticulum, the peroxisomal importomer and SELMA, the pre-protein translocator of complex plastids--appear quite different. However, mechanistic comparisons and phylogenetic analyses presented here suggest that all three translocation machineries share a common ancestral origin, which highlights the recycling of pre-existing components as an effective evolutionary driving force. Editor's suggested further reading in BioEssays ERAD ubiquitin ligases Abstract.


Use it or not: An agro-ecological perspective to flooded riparian land along the Three Gorges Reservoir.
The extensive flooded land associated with the Three Gorges Reservoir, poses a great social and environmental challenge, yet it is a potential valuable land and sociological resource for resolving human-land conflicts in the surrounding communities. Controversies arose over use or non-use of such land among local communities and authorities; and different management strategies were adopted. We compared two representative ecosystems, Wuyang Bay in small-scale agricultural use through opportunistic farming, and Baijiaxi Bay in a state of natural succession, and learned the challenges-cum-opportunities regarding sustainability through an agro-ecological perspective. We integrated the plant diversity, water quality improvement, market production services and people's attitudes to obtain a holistic evaluation of the socio-ecological and economic benefits delivered by two bays. Significant differences were found: Wuyang Bay performed much better than Baijiaxi Bay in terms of plant diversity maintenance and people's acceptance. Regarding the concerns about impacts on reservoir water, Wuyang Bay has lower TN, and NH4-N concentrations than Baijiaxi Bay. This may be because of the decomposition of a large amount of naturally grown-drowned vegetation in Baijiaxi Bay. Emergy analysis showed that the economic efficiency of Wuyang Bay is better than other similar systems given its limited growing season. However, this is at the expense of the environment through chemical fertilisers and pesticides seeping into the reservoir waters. Strictly speaking, Wuyang Bay cannot be counted as a sustainable agro-ecosystem although it hints at many practical merits, such as integrating natural landscape elements in fields, and employing multiple crops in spatial and temporal patterns. Our study offers new insights into the impacts of world's largest reservoir construction on the livelihoods of nearby communities on a small scale and the possible solutions. With the use-or-not contradiction, the government should offer appropriate policies and technical support to incentivise farmers to a more sustainable, multi-functional living landscape.


Immunotherapy Beats Chemo for Bladder Cancer.
Patients with advanced urothelial carcinoma live 3 months longer, on average, when given pembrolizumab as a second-line treatment instead of chemotherapy. The finding is based on data from the first phase III trial to test an immunotherapeutic in these patients, which could lead to another label indication for the PD-1 inhibitor.


Sequence analysis of new variants of porcine epidemic diarrhea virus in Luzon, Philippines, in 2017.
Porcine epidemic diarrhea virus (PEDV) is a coronavirus that causes emaciation and watery diarrhea in pigs. First identified in Europe in 1977, it eventually spread to Asia and North America, causing deadly outbreaks in neonatal piglets. In the Philippines, PEDV has caused several recorded outbreaks since 2005. However, DNA sequencing studies of local PEDV strains remain few and are limited to gene and gene fragment sequencing. Therefore, to provide updated sequence information about recent PEDV strains in the country, we performed reverse transcription PCR and sequencing of PEDV from swab samples collected from swine farms in the Philippines in 2017. Here, we report the first published whole genome sequence of PEDV from the Philippines as well as CO-26K equivalent (COE) domain sequences of strains from three provinces in Luzon where PEDV was detected in 2017. Sequence analysis suggested that PEDV from both the classical (genotype 1) and pandemic (genotype 2) groups are present in the Philippines, with possible East Asian and North American origins.


Continuing professional development needs of nursing and allied health professionals with responsibility for prescribing.
Continuing professional development (CPD) for non-medical prescribers is recognised as being pivotal in maintaining up -to -date knowledge and skills influencing prescribing competence. This study was, therefore, designed to ascertain the aspirations, priorities and preferred mode of CPD for non-medical prescribers. Qualitative data were derived from semi-structured in-depth interviews and a focus group given by 16 allied health professionals working in primary and secondary care settings. A topic guide was used to cover clinical decision-making (including difficult decisions), legal aspects of prescribing and diagnostic issues. A content analysis of the verbatim transcripts enabled four key emerging themes to be identified, thus offering a basis for developing a greater understanding of the CPD needs of non-medical prescribers. The four key emerging themes identified are the following: Theme 1: "Personal anxiety undermining confidence to prescribe", Theme 2: "External barriers and other factors that exacerbate anxiety", Theme 3: "Need for support identified through coping strategies", and Theme 4: "Preferred mode or style of learning". The findings suggest that anxiety and lack of confidence in non-medical prescribing pose a significant challenge for CPD. Strategies that are most likely to improve prescribing confidence are through a blended learning approach. Local higher education and workplace employer collaboration is an appropriate step forward to achieve this.


Subjective and functional outcome after revision surgery in carpal tunnel syndrome.
In spite of carpal tunnel release's prevalent good postoperative results, the number of revision surgeries needed should not be underestimated. In this study, subjective and functional results after carpal tunnel revision surgery were determined. Thirty-eight patients were examined approximately 2 years after their revision surgery of the carpal tunnel release. The subjective outcome of the patients was assessed using two different questionnaires (Amadio and DASH). A clinical examination was undertaken on selected patients who had persistent complaints. The clinical assessment analyzed grip strength, thumb opposition, pulp-to-pulp-pinch, key-pinch, hook-grip, Moberg-Pickup-test, two-point-discrimination, Phalen-test, and the Hoffmann-Tinel-sign. The subjective assessment showed that after the revision surgery, patients experienced load induced pain that occurred during daytime. However, the revision was able to improve the impaired sensibility. The functional outcome showed a persistent lack of strength when performing daily activities. The clinical assessment of the patients with relevant complaints confirmed the subjective outcome. The revision surgery can improve the impaired sensibility, particularly, paresthesia nocturna. The persistent weakness of the hand can only partly be improved. In spite of remaining complaints, revision surgery can yield satisfactory results for the patients.


Transactional relations between maternal anxiety and toddler anxiety risk through toddler-solicited comforting behavior.
Transactional developmental and anxiety theories suggest that mothers and toddlers may influence each other's anxiety development across early childhood. Further, toddlers' successful solicitations of comfort during uncertain, yet manageable, situations, may be a behavioral mechanism by which mothers and toddlers impact each other over time. To test these ideas, the current study employed a longitudinal design to investigate bidirectional relations between maternal anxiety and toddler anxiety risk (observed inhibited temperament and mother-perceived anxiety, analyzed separately), through the mediating role of toddler-solicited maternal comforting behavior, across toddlerhood. Mothers (n = 174; 93.6% European American) and their toddlers (42.4% female; 83.7% European American) participated in laboratory assessments at child ages 1, 2, and 3 years. Mothers self-reported anxiety symptoms. Toddler anxiety risk was observed in the laboratory as inhibited temperament and reported by mothers. Solicited comforting interactions were observed across standardized laboratory tasks. Direct and indirect bidirectional effects were tested simultaneously in two longitudinal path models. Toddler anxiety risk, but not maternal anxiety, predicted solicited comforting behavior, and solicited comforting behavior predicted maternal anxiety. No convincing evidence for parent-directed effects on toddler anxiety risk emerged. Results support continued emphasis on child-elicited effects in child and parent anxiety development in early childhood.


Efficacy of CPET Combined with Systematic Education of Cardiac Rehabilitation After PCI: A Real-World Evaluation in ACS Patients.
There are scarce real-world data on the long-term efficacy and safety of cardiopulmonary exercise testing (CPET) combined with the systematic education of cardiac rehabilitation (CR) approach for patients post-coronary stenting, which is, therefore, the subject of this study. Data collected between 1 April 2015 and 20 May 2017 from 11,345 patients in the rehabilitation center database at our hospital were retrospectively analyzed. Five hundred thirty-six patients with incomplete information, or unable to cooperate with telephone follow-up, were excluded; 4001 patients received the combined CR approach; and 6808 patients received only routine post-procedure education (controls). Of these, 2805 CR participants (CR group) were matched 1:1 to controls (control group) using propensity scores. The main outcome was quality of life in Seattle Angina Questionnaire (SAQ) scores. SAQ was measured in hospital and at follow-up; meanwhile, volume/type of habitual exercise, major adverse cardiovascular event (MACE), and its components of target vessel revascularization, myocardial infarction, and cardiac death were recorded and analyzed. At median 583 (range 184-963) day follow-up, compared with controls, the CR group showed fewer patients not engaging in physical exercise (22 vs. 956, p < 0.05); more cumulative exercise time (h/week) (8.22 ± 6.17 h vs. 3.00 ± 1.65 h, p < 0.05); higher SAQ scores (physical limitation, 69.59 ± 10.96 vs. 57.49 ± 7.19; anginal stability, 80.50 ± 18.21 vs. 58.82 ± 11.95; anginal frequency, 78.58 ± 11.07 vs. 67.14 ± 22.41; treatment satisfaction, 82.33 ± 13.21 vs. 56.84 ± 21.61; quality of life, 68.69 ± 18.33 vs. 60.26 ± 17.13, all p < 0.01), but a similar MACE rate (log-rank p = 0.621). Compared with only routine post-procedure education, CR combining at least one-time CPET with a systematic cardiac education program before discharge improved engagement in physical activity and quality of life for patients after percutaneous coronary intervention (PCI) without increasing clinical adverse events.


Distribution evaluation of tacrolimus in the ascitic fluid of liver transplant recipients with liver cirrhosis by a sensitive ultra-performance liquid chromatography-tandem mass spectrometry method.
Tacrolimus has a narrow therapeutic index and large individual differences in pharmacokinetics. The distribution of tacrolimus in ascitic fluid and its influence on whole-blood tacrolimus were unclear. In this study, a sensitive ultra-performance liquid chromatography-tandem mass spectrometry method was established and validated for the quantification of tacrolimus in the ascitic fluid of liver transplant recipients. Chromatographic separation was achieved on an Agilent ZORBAX Eclipse Plus Phenyl-Hexyl column (2.1 × 100 mm, 3.5 μm). Mass spectrometry was performed in multiple reaction monitoring conditions of transitions m/z 821.4→768.5 for tacrolimus. The concentrations of tacrolimus in the ascitic fluid range from 0.2 to 3.0 ng/mL, accounting for 1.19-31.87% of whole-blood tacrolimus concentrations. A linear mixed model showed a statistically significant positive correlation between the steady-state trough blood concentration of tacrolimus and the corresponding amount of tacrolimus excreted in the ascitic fluid for 24 consecutive hours, especially after normalization by daily dose per unit body weight. These data suggested that the distribution of tacrolimus in the ascitic fluid has great individual differences. The whole-blood tacrolimus concentration, dose per unit body weight, and other confounding factors may contribute to the excretion of tacrolimus in ascitic fluid, but the influence of tacrolimus excretion in drained ascitic fluid on the whole-blood tacrolimus concentration is negligible.


Mom Expo: Bridging the Gap Between Local Women and Perinatal Resources.
The purpose of this project was to describe the implementation of a perinatal health fair intended to connect local women to holistic resources. Researchers used participatory strategies to develop the health fair with local women and perinatal educators. Researchers evaluated the health fair using pragmatic measures based on the (Reach, Effectiveness, Adoption, Implementation, Maintenance) framework. Forty-two attendees were reached and 23 educators hosted booths and educational sessions. Feedback indicated strong enthusiasm for future similar events. Nearly three quarters of the time spent implementing the health fair was devoted to building relationships within the community. Overall, this project provides practical and empirical information to inform the planning, implementation, and evaluation of perinatal health fairs that establish meaningful connection between local women, perinatal educators, and health researchers.


Quantitative coronary arteriographic methods in the interventional catheterization laboratory: an update and perspective.
Recent research advances in the area of quantitative coronary arteriography are described with respect to their potential role in assessing the effects of interventional therapy and monitoring the restenosis process. Specific areas emphasized are the importance of quantitative arteriography and absolute measures of arterial dimension in monitoring restenosis, the development of a computerized method for measuring lesion roughness, the potential role of measuring stenosis flow reserve based on component analysis principles, limitations of direct measures of myocardial flow reserve using a digital angiographic method and cautionary notes about clinical applications of videodensitometry. The current use of radiography and quantitative measures in limiting arterial injury are briefly reviewed. Finally, a perspective is put forth on the need to develop complementary roles for endovascular echocardiography and angioscopy with existing radiographic imaging technology.


Conservative management of a chronic recurrent flexor hallucis longus stenosing tenosynovitis in a pre-professional ballet dancer: a case report.
To describe the successful conservative management of a chronic recurrent flexor hallucis longus (FHL) stenosing tenosynovitis. A 20-year-old female pre-professional ballet dancer presented with medial ankle and mid-foot pain of 7.5 months duration. Pain was constant but exacerbated with training and assuming the en pointe and demi-pointe dance positions. Plantar flexion of the great toe was pain provoking. Triggering of the great toe and audible and palpable crepitus were noted with active and passive great toe range of motion. A diagnosis of a chronic recurrent FHL stenosing tenosynovitis was made based on the history and physical exam. Soft tissue and joint mobilization and manipulation, laser therapy, kinesiology tape application and rehabilitative exercise was used over 4 months. The patient reported an 8-point decrease in her numeric pain rating scale score and a 15-point improvement in her Lower Extremity Functional Scale score.


Genetic background influences cortical bone response to ovariectomy.
Peak bone mass is genetically determined, but little is known about the heritability of bone loss. Inbred mice were ovariectomized at 16 weeks of age and killed at three time-points after surgery. We found that the variation in estrogen deficit-related cortical bone loss is genetically determined. Variability in adult bone morphology and composition among three inbred mouse strains-A/J, C57BL/6J (B6), and C3H/HeJ (C3H)-suggests that they gain bone in different ways during growth. In this study, we tested the hypothesis that these strains would also lose bone differently after estrogen deprivation. Female A/J, B6, and C3H mice (N = 70/strain) were either ovariectomized (OVX) or sham-operated at 16 weeks of age and killed at 4, 8, and 16 weeks after surgery. Cortical bone histomorphometry was performed on right femoral mid-diaphyseal cross-sections. Mechanical properties were determined by loading left femoral mid-diaphyses to failure in four-point bending. Both OVX-A/J and OVX-B6 mice showed a 7-8% decrease in cortical area and width because of an 8-10% marrow expansion at 16 weeks after OVX. This bone loss did not affect mechanical properties in OVX-A/J femurs, but maximum load and stiffness in OVX-B6 decreased slightly (9%) at 4 and 8 weeks, and markedly (14-19%) at 16 weeks after OVX. In contrast, OVX-C3H showed a significant decrease in cortical area and width (6-7%) at 4 weeks after OVX and a slight decrease in the subperiosteal area (4%) at 8 weeks after OVX, although marrow area remained unchanged. Surprisingly, intracortical resorption spaces, which were present in sham-C3H mice, were greatly increased (+195%) in OVX-C3H mice at 8 weeks after OVX. Bone strength and stiffness in OVX-C3H mice decreased markedly (12-14%) at 4 weeks but slightly (8-10%) at 8 weeks after OVX. All indices except intracortical pore area in OVX-C3H mice returned to sham levels at 16 weeks after OVX. The magnitude, timing, and location of cortical bone loss after OVX varied significantly among A/J, B6, and C3H mice. The subsequent changes in mechanical properties after OVX depended on the variable bone patterns as well as the size and shape of the adult bone. Our results suggest that patterns of estrogen deficit-associated cortical bone loss are genetically determined.


Synthesis and characterization of Fe doped CeO2 nanoparticles for pigmented ultraviolet filter applications.
Iron doped CeO2 nanoparticles with doping concentrations between 0 and 30 mol% were synthesized by the co-precipitation method for potential application as a pigmented ultraviolet filtration material. Each sample was calcined in air and in argon. The iron solubility limit in the CeO2 lattice was found to be between 10 and 20 mol%. Raman spectroscopy results revealed that both iron doping and argon calcination increase the concentration of oxygen vacancies in the CeO2 lattice. Iron doping causes a blue-shift of the absorbance spectrum, which can be linked to the decreased crystallite size, as obtained by XRD peak broadening using the Scherrer formula. The undoped samples showed weak ferromagnetic behaviour whereas the doped samples were all paramagnetic.