The role of blood lnc-ZFAS1 in acute ischemic stroke: correlation with neurological impairment, inflammation, and survival profiles.
Long non-coding RNA zinc finger antisense 1 (lnc-ZFAS1) has been reported to inhibit neuronal damage in acute ischemic stroke (AIS). However, the role of lnc-ZFAS1 in AIS patients remains unclear. Therefore, we assessed the relationship of lnc-ZFAS1 with neurological impairment, inflammation, and prognosis in AIS patients. Totally, 241 AIS patients and 120 controls were enrolled. lnc-ZFAS1 in peripheral blood mononuclear cells was evaluated using reverse transcription-quantitative polymerase chain reaction. Besides, a 3-year follow-up was conducted to assess recurrence-free survival (RFS) and overall survival (OS) in AIS patients. lnc-ZFAS1 was reduced in AIS patients compared to that in controls (Z = -10.693, p < 0.001). In AIS patients, lnc-ZFAS1 was negatively correlated with National Institutes of Health Stroke Scale score (rs = -0.335, p < 0.001), C-reactive protein (rs = -0.284, p < 0.001), tumor necrosis factor-alpha (rs = -0.293, p < 0.001), interleukin-1β (rs = -0.149, p = 0.021), and interleukin-6 (rs = -0.161, p = 0.012), but not underlying diseases (all p > 0.05). Besides, lnc-ZFAS1 was divided into high and low levels based on the median expression in AIS patients. Indeed, high lnc-ZFAS1 predicted better RFS (χ2 = 6.222, p = 0.013); the 1-year, 2-year, and 3-year RFS rates were 94.2%, 88.3%, and 85.5%, respectively, in patients with high lnc-ZFAS1, then 87.5%, 79.2%, and 71.6%, respectively, in those with low lnc-ZFAS1. However, lnc-ZFAS1 was not correlated with OS (χ2 = 1.404, p = 0.236); the 1-year, 2-year, and 3-year OS rates were 98.3%, 95.8%, and 94.0%, respectively, in patients with high lnc-ZFAS1, then 96.7%, 93.9%, and 89.6%, respectively, in those with low lnc-ZFAS1. Lower lnc-ZFAS1 expression is connected with increased neurological impairment and inflammation as well as worse RFS in AIS patients.


Interaction of atrial muscarinic receptors with three kinds of GTP-binding proteins.
Purified porcine atrial muscarinic acetylcholine receptors were reconstituted into lipid vesicles with three different G proteins (Gi, Go and Gn)1 purified from porcine cerebrum. All the G proteins interacted with the receptor as evidenced by GTP-sensitive high affinity binding with acetylcholine, and stimulation by acetylcholine of GTP gamma S binding and GTPase activities. The curves of displacement by acetylcholine of [3H]QNB binding were explained by assuming two sites with the same affinity for [3H]QNB but different affinities for acetylcholine. The proportion of the high affinity site increased from 3 to 7% up to 82 to 83% of total binding sites with increasing G protein concentration, and essentially the same results were obtained with the three G proteins. The GTPase activities of Gi, Go and Gn in the reconstituted vesicles were 2.7-, 1.7- and 1.6-times higher, respectively, in the presence of 1 mM acetylcholine than those in the presence of 10 microM atropine. An obvious enhancement by acetylcholine of the GTP gamma S binding was observed in the presence of 10 to 100 microM GDP, while the enhancement was minimal, if at all, in the absence of GDP. When the molar ratios of reconstituted Gi, Go and Gn to muscarinic receptors were 54, 84 and 107, respectively, the acetylcholine-induced increase in the [35S]GTP gamma S binding was as much as 12, 35 and 27 mol with Gi, Go and Gn, respectively, per mole of the receptor molecule, indicating that the muscarinic receptors interact with G proteins catalytically.(ABSTRACT TRUNCATED AT 250 WORDS)


Building medical ontologies by terminology extraction from texts: an experiment for the intensive care units.
In many medical fields, maintenance, comparison and aggregation of unambiguous terminologies go through formal specialized clinical terminologies: ontologies. We describe a methodology to build medical ontology from textual reports using a natural language processing tool, the SYNTEX software. The methodology is illustrated in the surgical intensive care medical domain. We have tested the possibility for an expert to build a sizeable ontology in a reasonable time. The quality of the ontology has been evaluated according to its capacity to cover the ICD-10 terminology in the field. Finally, the methodology itself is discussed.


Development of a framework identifying domains and elements of importance for arthritis rehabilitation.
Rehabilitation is effective and beneficial for patients with arthritis. The lack of a common structure for describing the content of rehabilitation makes it difficult to compare, transfer and implement research evidence into clinical practice. To develop a framework comprising domains and elements of importance when describing arthritis rehabilitation. On the basis of a systematic literature search and review, the framework was developed through a 9-step development process, including 5 Delphi consensus rounds within the Scandinavian Team Arthritis Register - European Team Initiative for Care Research (STAR-ETIC) collaboration, a group of clinicians, researchers and patients from northern Europe. Based on Donabedian's healthcare model, the Inter-national Classification of Function, Disability and Health, and a rehabilitation model by D. T. Wade, 4 domains (context, structure, process and outcome) were defined. Within each domain, the most important and relevant key elements for describing rehabilitation were selected. This framework contains 1 key element under context, 9 under structure, 3 under process, and 9 under outcome. The STAR-ETIC framework can be used to describe arthritis rehabilitation, by emphasizing key elements in 4 main domains. A common framework may facilitate comparisons of rehabilitation programmes across countries and different levels of care, and may improve the implementation of rehabilitation research in clinical practice.


Deconstructing the "July Effect" in Operative Outcomes: A National Study.
This study analyzes the relationship between hospital teaching status, failure to rescue, and time of year in select gastrointestinal operations. Procedure codes for laparoscopic cholecystectomy, colectomy, and pancreatectomy were queried from the Nationwide Inpatient Sample (2004-2011). Failure to rescue was defined as inpatient mortality when ≥1 complication. A total of 2,777,267 laparoscopic cholecystectomies, 2,519,903 colectomies, and 129,619 pancreatectomies were performed. Teaching hospitals had increased overall rates of failure to rescue compared to non-teaching hospitals, 10.0 vs. 9.5 % (p = 0.0187), particularly between May and August. There was greater inter-month variability in non-teaching hospitals amongst individual operations. On multivariable analysis, July was not predictive of increased odds of failure to rescue. Teaching status, hospital characteristics, and patient demographics were associated with increased odds of failure to rescue. Although teaching hospitals have a higher overall failure to rescue rate amongst the selected gastrointestinal operations, odds of failure to rescue are not increased in the month of July. Non-teaching hospitals tend to exhibit more monthly variation in failure to rescue rates, and hospital/patient demographics are predictive of failure to rescue. Further investigation targeted at identifying drivers of temporal variation is warranted to optimize patient outcomes.


Centrality of drug targets in protein networks.
In the pharmaceutical industry, competing for few validated drug targets there is a drive to identify new ways of therapeutic intervention. Here, we attempted to define guidelines to evaluate a target's 'fitness' based on its node characteristics within annotated protein functional networks to complement contingent therapeutic hypotheses. We observed that targets of approved, selective small molecule drugs exhibit high node centrality within protein networks relative to a broader set of investigational targets spanning various development stages. Targets of approved drugs also exhibit higher centrality than other proteins within their respective functional class. These findings expand on previous reports of drug targets' network centrality by suggesting some centrality metrics such as low topological coefficient as inherent characteristics of a 'good' target, relative to other exploratory targets and regardless of its functional class. These centrality metrics could thus be indicators of an individual protein's 'fitness' as potential drug target. Correlations between protein nodes' network centrality and number of associated publications underscored the possibility of knowledge bias as an inherent limitation to such predictions. Despite some entanglement with knowledge bias, like structure-oriented 'druggability' assessments of new protein targets, centrality metrics could assist early pharmaceutical discovery teams in evaluating potential targets with limited experimental proof of concept and help allocate resources for an effective drug discovery pipeline.


Catalytic combustion of carbon tetrachloride.
The catalytic combustion of carbon tetrachloride (CCl4) by metal oxide catalysts coated on the monolith support was investigated. The prepared catalysts were tested at temperatures between 300 and 800 degrees C and at varying gas hourly space velocity (GHSV) values with an excess air ratio of 3100%. The catalyst, whose composition was 18% Cr2O3, 2% Ce2O3 and 80% gamma-Al2O3, was found to almost completely oxidize CCl4. The operating conditions proposed are 5702 h(-1) for GHSV, 3100% excess air and a temperature slightly higher than 800 degrees C. The reaction rate expression was found to be independent of oxygen partial pressure but strongly dependent on CCl4 partial pressure.


To cut or not to cut? A prospective randomized controlled trial on short-term outcomes of the uncut Roux-en-Y reconstruction for gastric cancer.
Roux-en-Y (R-Y) anastomoses have been widely used in distal gastrectomy, while the incidence of Roux stasis syndrome remains common. Uncut R-Y anastomosis maintains the neuromuscular continuity, thus avoiding the ectopic pacemaker of the Roux limb and reducing the occurrence of Roux stasis. However, retrospective studies of Uncut R-Y anastomosis remain scarce and randomized controlled trials have not been reported. We conducted a randomized controlled trial to compare the surgical safety, nutritional status, and postoperative quality of life (QOL) between uncut and classic Roux-en-Y (R-Y) reconstruction patients. Patients with Stage I gastric cancer were randomly enrolled and underwent laparoscopic distal gastrectomy followed by uncut or classic R-Y reconstruction. Body mass index and blood test were used to evaluate the nutritional status. QOL was evaluated using European Organization for Research and Treatment of Cancer QOL Questionnaire (STO22) and laboratory examinations at postoperative month (POM) 3, 6, 9, and 12. Computed tomography scanning was used to evaluate the skeletal muscle index (SMI) at POM 6 and 12. Endoscopy was performed at POM 12. Operation time, blood loss, time to recovery, complication morbidities, and overall survival were similar between the two groups. Compared with the classic R-Y group, the uncut R-Y group displayed a significantly decreased QOL at POM 9, possibly due to loop recanalization, determined to be occupied 34.2% of the uncut R-Y group. Post-exclusion of recanalization, the QOL was still higher in the classic R-Y group than in the uncut R-Y group, despite their hemoglobin and total protein levels being better than those in the classic R-Y group. Preoperative pre-albumin level and impaired fasting glycemia significantly correlated with the postoperative recanalization. We found no significant benefit of uncut over classic R-Y reconstruction which challenges the superiority of the uncut R-Y reconstruction. ClinicalTrials.gov Identifier: NCT02644148.


Assessment of Fraction of Exhaled Nitric Oxide and Soluble Receptor for Advanced Glycation End Products Biomarkers for Jordanian Asthmatic Children.
Fraction of exhaled nitric oxide (FeNO) and soluble advanced glycation end-product receptor (sRAGE) are proposed as biomarkers of asthma, therefore we sought to assess their use in asthmatic children of Jordan. We conducted a case-control study at The University of Jordan Hospital. A total of 141 asthmatic children followed by respiratory pediatricians and 118 healthy children aged 4-18 years were recruited. FeNO was measured by NObreath device and serum sRAGE by ELISA that detect endogenously soluble isoform (esRAGE) and total soluble RAGE (sRAGE). sRAGE in asthmatic was half of the control (p <0.001). In addition, ratio of esRAGE/sRAGE was two-fold higher in asthmatic (p = <0.001). Neither FeNO nor esRAGE levels were significantly different between groups. FeNO and asthma control test (ACT) score were negatively correlated corrected for age and body mass index (BMI), (r = -0.180, p= 0.034). For the uncontrolled asthma group, esRAGE/sRAGE negatively correlated with ACT score (r = -.329, p = 0.038). Receiver operating curve (ROC) analysis revealed significant predictive value (PV) for sRAGE and esRAGE/sRAGE in asthma detection with area under the curve (AUC) of (0.751 ± 0.031) and (0.711±.033), consequently. However, no biomarker had a significant PV for lack of control. The current study supports utilizing sRAGE as a marker for asthma and present a potential therapeutic target. However, our results indicate that both FeNO and sRAGE have a limited role in the management of asthmatic children or assessment of asthma control.


Long-period gratings inscribed in photonic crystal fiber by symmetric CO(2) laser irradiation: erratum.
This erratum amends the wrongly cited NSF grant number in acknowledgment section in our publication.


Effect of early and late prenatal vitamin D and maternal asthma status on offspring asthma or recurrent wheeze.
Childhood asthma developmental programming is complex. Maternal asthma is a strong risk factor for childhood asthma, whereas vitamin D (VD) has emerged as a modifiable prenatal exposure. Our aim was to examine the combined effect of early and late prenatal VD status in during pregnancies in women with and without asthma on childhood asthma or recurrent wheeze development. We conducted a cohort study using prospectively collected data from the Vitamin D Antenatal Asthma Reduction Trial, a randomized, double-blinded, placebo-controlled VD supplementation trial in pregnant women at high risk of offspring asthma (N = 806 mother-offspring pairs). 25-Hydroxyvitamin-D (25(OH)D) level was measured in early and late pregnancy. Our main exposure was an ordered variable representing early and late prenatal VD sufficiency (25(OH)D level ≥ 30 ng/mL) status during pregnancy in women with and without asthma. The primary outcome was offspring with asthma or recurrent wheeze by age 3 years. We also examined the effect of prenatal VD level on early life asthma or recurrent wheeze progression to active asthma at age 6 years. Among mothers with asthma versus among mothers with early and late prenatal VD insufficiency, those with early or late VD sufficiency (adjusted odds ratio = 0.56; 95% CI = 0.31-1.00) or early and late VD sufficiency (adjusted odds ratio = 0.36; 95% CI = 0.15-0.81) had a lower risk of offspring with asthma or recurrent wheeze by age 3 years (Pfor trend = .008). This protective trend was reiterated in asthma or recurrent wheeze progression to active asthma from age 3 to 6 years (Pfor trend = .04). This study implies a protective role for VD sufficiency throughout pregnancy, particularly in attenuating the risk conferred by maternal asthma on childhood asthma or recurrent wheeze development.


A Bibliometric Analysis of Atopic Dermatitis Research over the Past Three Decades and Future Perspectives.
Atopic dermatitis (AD) has been increasing in prevalence over the past few decades; however, AD has never been analyzed using a bibliometric approach. We searched for AD studies in the dermatology and allergy category of the Web of Science and SCOPUS databases using the keywords "atopic dermatitis", "eczema", and "atopy". In total, 53,460 documents were retrieved. We analyzed annual publication trends and performed keyword and co-authorship network analyses. The annual number of AD publications has increased over the years. Asthma, food allergies, the skin barrier, IgE, and epidemiology have received extensive attention. The keywords 'allergic rhinitis', 'child(ren)', 'quality of life', and 'probiotics' have become more commonly used in recent years. AD research has been led by only a few countries, such as the USA, Germany, and the UK, and longstanding research topics such as asthma, allergy, and the immune system continue to be important. We suggest that global collaborations, research in developing countries, and research that is more holistic (thus exploring how genes, the immune system, the environment, and the microbiome together impact AD) are necessary.


Inflammation switches the differentiation program of Ly6Chi monocytes from antiinflammatory macrophages to inflammatory dendritic cells in the colon.
Dendritic cells (DCs) and macrophages (MPs) are important for immunological homeostasis in the colon. We found that F4/80(hi)CX3CR1(hi) (CD11b(+)CD103(-)) cells account for 80% of mouse colonic lamina propria MHC-II(hi) cells. Both CD11c(+) and CD11c(-) cells within this population were identified as MPs based on multiple criteria, including an MP transcriptome revealed by microarray analysis. These MPs constitutively released high levels of IL-10 at least partially in response to the microbiota via an MyD88-independent mechanism. In contrast, cells expressing low to intermediate levels of F4/80 and CX3CR1 were identified as DCs based on phenotypic and functional analysis and comprise three separate CD11c(hi) cell populations: CD103(+)CX3CR1(-)CD11b(-) DCs, CD103(+)CX3CR1(-)CD11b(+) DCs, and CD103(-)CX3CR1(int)CD11b(+) DCs. In noninflammatory conditions, Ly6C(hi) monocytes (MOs) differentiated primarily into CD11c(+) but not CD11c(-) MPs. In contrast, during colitis, Ly6C(hi) MOs massively invaded the colon and differentiated into proinflammatory CD103(-)CX3CR1(int)CD11b(+) DCs, which produced high levels of IL-12, IL-23, iNOS, and TNF. These findings demonstrate the dual capacity of Ly6C(hi) blood MOs to differentiate into either regulatory MPs or inflammatory DCs in the colon and that the balance of these immunologically antagonistic cell types is dictated by microenvironmental conditions.


A study of Epstein Barr virus receptor activity in cell free extracts of human lymphoblastoid cells.
Epstein Barr Virus (EBV) receptor activity in cell free extracts is operationally defined as one which causes a reduction in the effective concentration of the early antigen inducing particles of an EBV preparation when the latter is preincubated with the extract before infection. Such activity was detected in the surface extract of Raji cells and to a lesser extent in that of BJAB cells, both of which are B lymphoblastoid cells that are susceptible to infection with EBV. Receptor activity was not detected in similar extracts of P3HR-1 cells and human diploid fibroblasts neither of which are known to be susceptible to EBV infection. Receptor activity in the Raji cell extract was found to be associated with membranous structures. This may have rendered the activity resistant to treatment with trypsin and sonication. The activity was however abrogated if the extract was exposed to neutral detergent. Binding of receptor activity was observed when Raji cell extract was chromatographed on a column of immobilized EBV. Subsequent electrophoretic analysis showed however that this procedure did not result in an appreciable purification of the receptor activity. Neutral detergent treated extract was similarly chromatographed. The resulting eluates did not contain detectable receptor activity but were less heterogeneous in protein content as compared with that of the original extract. It is not certain at present if these EBV binding proteins are involved in the receptor activity of the extract.


Assessment of Clinical Response Following Atezolizumab and Bevacizumab Treatment in Patients With Neuroendocrine Tumors: A Nonrandomized Clinical Trial.
Therapies for patients with advanced well-differentiated neuroendocrine tumors (NETs) have expanded but remain inadequate, with patients dying of disease despite recent advances in NET therapy. While patients with other cancers have seen long-term disease control and tumor regression with the application of immunotherapies, initial prospective studies of single-agent programmed cell death 1 inhibitors in NET have been disappointing. To evaluate the response rate following treatment with the combination of the vascular endothelial growth factor inhibitor bevacizumab with the programmed cell death 1 ligand 1 inhibitor atezolizumab in patients with advanced NETs. This single-arm, open-label nonrandomized clinical study in patients with rare cancers included 40 patients with advanced, progressive grade 1 to 2 NETs (20 with pancreatic NETs [pNETs] and 20 with extrapancreatic NETs [epNETs]) treated at a tertiary care referral cancer center between March 31, 2017, and February 19, 2019. Data were analyzed from June to September 2021. Patients received intravenous bevacizumab and atezolizumab at standard doses every 3 weeks until progression, death, or withdrawal. The primary end point was objective radiographic response using Response Evaluation Criteria in Solid Tumors, version 1.1, with progression-free survival (PFS) as a key secondary end point. Following treatment of the 40 study patients with bevacizumab and atezolizumab, objective response was observed in 4 patients with pNETs (20%; 95% CI, 5.7%-43.7%) and 3 patients with epNETs (15%; 95% CI, 3.2%-37.9%). The PFS was 14.9 (95% CI, 4.4-32.0) months and 14.2 (95% CI, 10.2-19.6) months in these cohorts, respectively. In this nonrandomized clinical trial, findings suggest that clinical responses in patients with NET may follow treatment with the combination of bevacizumab and atezolizumab, with a PFS consistent with effective therapies. ClinicalTrials.gov Identifier: NCT03074513.


Female Bechstein's bats adjust their group decisions about communal roosts to the level of conflict of interests.
Most social animals depend on group decisions for coordination. Recent models suggest that the level of interindividual conflict strongly influences whether groups reach a consensus during decision making. However, few experimental studies have explored how wild animals make group decisions in situations with conflicting interests. Such experimental data are particularly lacking for animal societies with regular fission and fusion of subgroups. In this long-term study, we varied the level of conflict of interest among members of three wild Bechstein's bat (Myotis bechsteinii) colonies with high fission-fusion dynamics experimentally to explore whether the bats adapt their group decisions about communal roosts accordingly. In situations with low levels of conflict of interest, a minority of bats experiencing a roost as suitable was sufficient for a group consensus to use it communally. In contrast, if their interests diverged strongly, the bats no longer sought a compromise, but based their roosting decisions on individual preferences instead. Our results demonstrate that the rules applied to make group decisions can vary with the level of conflict among the individual interests of group members. Our findings are in agreement with predictions of the models and provide evidence for highly flexible group decisions within species.


Efficacy of salvage therapies for advanced acral melanoma after anti-PD-1 monotherapy failure: a multicenter retrospective study of 108 Japanese patients.
Anti-programmed cell death protein 1 (PD-1) monotherapy is one of the standard systemic therapies for advanced melanoma; however, the efficacy of salvage systemic therapies after PD-1 monotherapy failure (PD-1 MF), particularly in acral melanoma (AM), the main clinical melanoma type in Japanese patients, is unclear. This study aimed to investigate the efficacy of salvage systemic therapies in Japanese patients with AM after PD-1 MF. The study included 108 patients with advanced AM (palm and sole, 72; nail apparatus, 36) who underwent salvage systemic therapy at 24 Japanese institutions. We mainly assessed the objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). Thirty-six (33%) patients received ipilimumab, 23 (21%) received nivolumab and ipilimumab (nivo/ipi), 10 (9%) received cytotoxic chemotherapy, 4 (4%) received BRAF and MEK inhibitors (BRAFi/MEKi), and the remaining 35 (32%) continued with PD-1 monotherapy after disease progression. The ORRs in the ipilimumab, nivo/ipi, cytotoxic chemotherapy, and BRAFi/MEKi groups were 8, 17, 0, and 100%, respectively. The nivo/ipi group showed the longest OS (median, 18.9 months); however, differences in ORR, PFS, and OS between the groups were insignificant. The OS in the nivo/ipi group was higher in the palm and sole groups than in the nail apparatus group (median: not reached vs. 8.7 months, p < 0.001). Cox multivariate analysis demonstrated that nail apparatus melanoma independently predicted unfavorable PFS and OS (p = 0.006 and 0.001). The total OS (from PD-1 monotherapy initiation to death/last follow-up) was insignificant between the groups. Nivo/ipi was not more effective than cytotoxic chemotherapy and ipilimumab after PD-1 MF in patients with advanced AM. The prognosis after PD-1 MF would be poorer for nail apparatus melanoma than for palm and sole melanoma.


Plasma levels of phospholipase A2-IIA in patients with different types of malignancies: prognosis and association with inflammatory and coagulation biomarkers.
It is well-known that the plasma level of group IIA phospholipase A2 (sPLA2-IIA) is increased in patients with malignant diseases, but whether the up-regulated enzyme expression is directly related to tumorigenesis or a consequence of tumor-associated inflammation remains unresolved. In this study we analyzed circulating levels of sPLA2-IIA, C-reactive protein (CRP), fibrinogen, factor VIII (FVIII), von Willebrand factor (vWF), and antithrombin as biomarkers of inflammation and coagulation in patients with various types of malignancies. Underlying tumor entities were lung, esophageal, gastric, pancreatic, colorectal, head and neck, and hepatocellular carcinomas as well as multiple myeloma and non-Hodgkin's lymphoma. Plasma levels of sPLA2-IIA are shown to be markedly increased in all types of analysed malignancies in comparison to the normal range (22.8 ± 4.5 μg/L versus <1.9 μg/L). Levels of sPLA2-IIA correlate positively with CRP (p < 0.001), fibrinogen (p < 0.01), FVIII (p < 0.05), and vWF (p < 0.05) and negatively with antithrombin levels (p < 0.05). Kaplan-Meier analyses revealed a statistically prolonged survival time of patients with lower sPLA2-IIA concentrations (<4 μg/L) in comparison to those with elevated concentrations (>4 μg/L) of this enzyme. In conclusion, the study shows that the measurement of plasma sPLA2-IIA levels has prognostic values in patients with different types of malignancies. The association of sPLA2-IIA levels with CRP, fibrinogen, FVIII, and vWF levels supports the importance of inflammatory processes for the up-regulation of sPLA2-IIA during cancer progression.


Distressed community index as a predictor of presentation and postoperative outcomes in ventral hernia repair.
We evaluated the impact of socioeconomic status on presentation, management, and outcomes of ventral hernias. The Abdominal Core Health Quality Collaborative was queried for adult patients undergoing ventral hernia repair. Socioeconomic quintiles were assigned using the Distressed Community Index (DCI): prosperous (0-20), comfortable (21-40), mid-tier (41-60), at-risk (61-80), and distressed (81-100). Outcomes included presenting symptoms, urgency, operative details, 30-day outcomes, and one-year hernia recurrence rates. Multivariable regression evaluated 30-day wound complications. 39,494 subjects were identified; 32,471 had zip codes (82.2%).Urgent presentation (3.6% vs. 2.3%) and contaminated cases (0.83% vs. 2.06%) were more common in the distressed group compared to the prosperous group (p < 0.001). Higher DCI correlated with readmission (distressed: 4.7% vs prosperous: 2.9%,p < 0.001) and reoperation (distressed 1.8% vs prosperous: 0.92%,p < 0.001). Wound complications were independently associated with increasing DCI (p < 0.05). Clinical recurrence rates were similar at one-year (distressed: 10.4% vs prosperous: 8.6%, p = 0.54). Inequity exists in presentation and perioperative outcomes for ventral hernia repair and efforts should be focused on increasing access to elective surgery and improving postoperative wound care.


The impact of social network dynamics on engagement in drug use reduction programs among men and women who use drugs.
Cross-sectional studies have shown strong relationships between social network characteristics and substance use disorder (SUD) treatment engagement. The current study examined associations between longitudinal changes in egocentric social networks of male and female people who use drugs (PWUD) and engagement in drug use reduction programs, broadly defined as either formal SUD treatment or self-help groups. Using data from an HIV prevention and care study in Baltimore, MD, this study categorized PWUD into those who engaged and did not engage in any drug use reduction programs over two follow-ups during a one-year observation window. The study used multivariate logistic generalized estimating equations (GEE) to examine associations between network composition and stability measures and drug use reduction program engagement, stratified by gender. Of the 176 subjects participating in drug use reduction programs at baseline, 56.3% remained engaged at one year. Among both male and female respondents, higher turnover into non-kin networks was associated with increased odds of engagement in drug use reduction programs (AOR 1.4; 95% CI: 1.1-1.9, AOR 1.3; 95% CI: 1.0-1.8, respectively). For males, retention of intimate partner networks was associated with increased odds of program engagement (AOR 2.9; 95% CI: 1.1-7.6); for females, higher turnover into kin networks was associated with decreased odds of engagement (AOR 0.8; 95% CI: 0.5-1.0). Evaluation of associations between social network characteristics and drug use reduction program engagement appears to benefit from longitudinal analyses that are stratified by gender. Efforts to improve retention in formal SUD treatment or self-help groups might consider intervening through social networks, perhaps by increasing overall levels of social support.


High-pitch dual-source CT coronary angiography with low volumes of contrast medium.
To assess the effect of lower volumes of contrast medium (CM) on image quality in high-pitch dual-source computed tomography coronary angiography (CTCA). One-hundred consecutive patients (body weight 65-85 kg, stable heart rate ≤65 bpm, cardiac index ≥2.5 L/min/m(2)) referred for CTCA were prospectively enrolled. Patients were randomly assigned to one of five groups of different CM volumes (G30, 30 mL; G40, 40 mL; G50, 50 mL; G60, 60 mL; G70, 70 mL; flow rate 5 mL/s each, iodine content 370 mg/mL). Attenuation within the proximal and distal coronary artery segments was analysed. Mean attenuation for men and women ranged from 345.0 and 399.1 HU in G30 to 478.2 and 571.8 HU in G70. Mean attenuation values were higher in groups with higher CM volumes (P < 0.0001) and higher in women than in men (P < 0.0001). The proportions of segments with attenuation of at least 300 HU in G30, G40, G50, G60 and G70 were 89 %, 95 %, 98 %, 98 % and 99 %. CM volume of 30 mL in women and 40 mL in men proved to be sufficient to guarantee attenuation of at least 300 HU. In selected patients high-pitch dual-source CTCA can be performed with CM volumes of 40 mL in men or 30 mL in women. • High-pitch dual-source coronary angiography is feasible with low contrast media volumes. • Traditional injection rules still apply: higher volumes result in higher enhancement. • The patient's gender is a co-factor determining the level of contrast enhancement. • Volumes can be reduced down to 30-40 mL in selected patients.


Myocardial involvement in eosinophilic granulomatosis with polyangiitis evaluated with cardiopulmonary magnetic resonance.
Patients with eosinophilic granulomatosis with polyangiitis (EGPA) most commonly die from cardiac causes, however, cardiac involvement remains poorly characterised and the relationship between cardiac and pulmonary disease is not known. This study aimed to characterise myocardial and pulmonary manifestations of EGPA, and their relationship. Prospective comprehensive cardiopulmonary investigation, including a novel combined cardiopulmonary magnetic resonance imaging (MRI) technology, was performed in 13 patients with stable EGPA. Comparison was made with 11 prospectively recruited matched healthy volunteers. Stable EGPA was associated with focal replacement and diffuse interstitial myocardial fibrosis (myocardial extracellular volume 26.9% vs. 24.7%; p = 0.034), which drove a borderline increase in left ventricular mass (56 ± 9 g/m2 vs. 49 ± 8 g/m2; p = 0.065). Corrected QT interval was significantly prolonged and was associated with the severity of myocardial fibrosis (r = 0.582, p = 0.037). Stable EGPA was not associated with increased myocardial capillary permeability or myocardial oedema. Pulmonary tissue perfusion and capillary permeability were normal and there was no evidence of pulmonary tissue oedema or fibrosis. Forced expiratory volume in one second showed a strong inverse relationship with myocardial fibrosis (r = -0.783, p = 0.038). In this exploratory study, stable EGPA was associated with focal replacement and diffuse interstitial myocardial fibrosis, but no evidence of myocardial or pulmonary inflammation or pulmonary fibrosis. Myocardial fibrosis was strongly associated with airway obstruction and abnormal cardiac repolarisation. Further investigation is required to determine the mechanisms underlying the association between heart and lung disease in EGPA and whether an immediate immunosuppressive strategy could prevent myocardial fibrosis formation.


Propofol (2,6-diisopropylphenol) is an applicable immersion anesthetic in the axolotl with potential uses in hemodynamic and neurophysiological experiments.
The Mexican axolotl (Ambystoma mexicanum) is an important model species in regenerative biology. Traditionally, axolotls are anesthetized using benzocaine or MS-222, both of which act to inhibit voltage gated sodium channels thereby preventing action potential propagation. In some neurophysiological experiments this is not desirable; therefore we tested propofol as an alternative anesthetic in the axolotl. We evaluated benzocaine, MS-222, and propofol's cardiovascular effects, effects on action potential propagation in the spinal cord, and gross limb regenerative effects. We found that propofol is applicable as a general anesthetic in the axolotl allowing for neurophysiological experiments and yielding a stable anesthesia with significantly less cardiovascular effect than both benzocaine and MS-222. Additionally, propofol did not affect gross limb regeneration. In conclusion we suggest the consideration of propofol as an alternative immersion anesthetic to benzocaine and MS-222.


CCR 20th Anniversary Commentary: Simpson's Paradox and Neoadjuvant Trials.
The research article by Carey and colleagues, published in the April 15, 2007, issue of Clinical Cancer Research, described the relationship between response to neoadjuvant chemotherapy and outcome by tumor subtype. Today neoadjuvant clinical trials are often designed to provide correlative data to help identify predictive biomarkers or to focus on poor-risk patients identified by residual disease after neoadjuvant treatment.


The effect of p53 gene expression on the inhibition of cell proliferation by paclitaxel.
We evaluated the relationship between p53 status and paclitaxel (PTX)-induced inhibition of the growth of human stomach cancer cells. We made use of two human stomach cancer cell lines, MKN45 and MKN28. Growth inhibition in response to PTX was evaluated by MTT method. We used flow cytometry to monitor the cell cycle and western blot analysis to evaluate the expression of signaling molecules. PTX inhibited the proliferation of both stomach cancer cell lines in a dose-dependent manner. However, PTX cytotoxicity was stronger in MKN28 cells. Flow cytometric analysis showed that 1 muM PTX enhanced the percentage of MKN 45 cells in the sub-G1 phase of the cell cycle, whereas it increased the percentage of MKN 28 cells arrested at G2/M phase. 1 muM PTX was found to increase cyclin B1 production in MKN28 cells, but not in MKN 45 cells. In contrast, PTX-treatment led to an increase in the cleaved form of caspase-3 in MKN45, but not MKN28 cells. An inhibitor of p53, pifithrin-alpha, antagonized the expression of the cleaved form of caspase-3 in MKN45 cells. Both p53 status and cyclin-B1 expression might be useful for predicting the therapeutic response of stomach cancer to PTX.


Hypercalcemic crisis associated with the hypereosinophilic syndrome.
A patient with the idiopathic hyperosinophilic syndrome had severe, life-threatening hypercalcemia, a previously unreported complication of this unusual disease. Postmortem examination revelaed multiorgan eosinophilic infiltration and diffuse metastatic calcifications, but it did not disclose a definitive cause for the persistent hypercalcemia. It is concluded that the marked proliferation of eosinophils was the probable etiologic factor. Proposed mechanisms for this complication include (1) the destruction of bone by an expanding eosinophilic cell mass with subsequent calcium mobilization and (2) the production of a hypercalcemic humoral substance, possibly by the patient's eosinophils or as a consequence of their presence.


Nuurcala obesa sp. n. (Blattida, Caloblattinidae) from the Lower Cretaceous Yixian Formation in Liaoning Province, China.
Nuurcala obesa sp. n., in the cockroach family Caloblattinidae, is described from the Lower Cretaceous Yixian Formation (Liaoning Province, China) based on a combination of differential characters of fore- and hind wing venation, colouration and body structures. Systematically, Nuurcala (Vršanský, 2003), known from the Cretaceous sediments of Bon Tsagaan and Khurilt, Mongolia, is closely related to other genera of Caloblattinidae known from the Jurassic and Cretaceous localities in other parts of Asia.


Central but not basolateral amygdala mediates memory for positive affective experiences.
Rats were trained in an 8-arm radial maze on a task in which memory for magnitude of reinforcement was tested. Rats received a single trial per day consisting of a study phase and a test phase. In the study phase, the animals received 1 or 7 pieces of food on different arms of the maze. After the study phase, the rats were delayed for 5 s, 5 min or 15 min. After the delay the animals were allowed to choose between the two arms presented in the study phase. The correct response, leading to an additional reinforcement, was to select the arm in which the animal had received the 7 pieces of food. After learning this task to a criterion of 80% or better performance on blocks of 10 trials for each delay, the animals received electrolytic lesions of the basolateral or central amygdala. After recovery from surgery animals were tested at each delay. The results indicate that there were no deficits at any delay with basolateral amygdala lesions. In contrast, lesions of the central amygdala produced a marked deficit at the 5- and 15-min delays, but no deficit at the 5-s delay. Based on the assumption that in this task memory for magnitude of reinforcement is a function of the formation of reinforcement-spatial location associations resulting in the activation of affective experiences, it is concluded that the central but not basolateral amygdala is involved in the coding of positive affect information.


Protein-like proton exchange in a synthetic host cavity.
The mechanism of proton exchange in a metal-ligand enzyme active site mimic (compound 1) is described through amide hydrogen-deuterium exchange kinetics. The type and ratio of cationic guest to host in solution affect the rate of isotope exchange, suggesting that the rate of exchange is driven by a host whose cavity is occupied by water. Rate constants for acid-, base-, and water-mediated proton exchange vary by orders of magnitude depending on the guest, and differ by up to 200 million-fold relative to an alanine polypeptide. These results suggest that the unusual microenvironment of the cavity of 1 can dramatically alter the reactivity of associated water by magnitudes comparable to that of enzymes.


Triglycerides: Emerging Targets in Diabetes Care? Review of Moderate Hypertriglyceridemia in Diabetes.
Moderate hypertriglyceridemia is exceedingly common in diabetes, and there is growing evidence that it contributes to residual cardiovascular risk in statin-optimized patients. Major fibrate trials yielded inconclusive results regarding the cardiovascular benefit of lowering triglycerides, although there was a signal for improvement among patients with high triglycerides and low high-density lipoprotein (HDL)-the "diabetic dyslipidemia" phenotype. Until recently, no trials have examined a priori the impact of triglyceride lowering in patients with diabetic dyslipidemia, who are likely among the highest cardiovascular-risk patients. In the recent REDUCE IT trial, omega-3 fatty acid icosapent ethyl demonstrated efficacy in lowering cardiovascular events in patients with high triglycerides, low HDL, and statin-optimized low-density lipoprotein (LDL). The ongoing PROMINENT trial is examining the impact of pemafibrate in a similar patient population. Emerging evidence suggests that lowering triglycerides may reduce residual cardiovascular risk, especially in high-risk patients with diabetic dyslipidemia.


Three-dimensional internal mammary lymphoscintigraphy: implications for radiation therapy treatment planning for breast carcinoma.
Conservative surgery combined with radiation therapy for the treatment of early breast carcinoma has been shown to achieve both a high rate of local tumor control and good cosmetic results with a minimum of complications. Whether the internal mammary lymph nodes (IMNs) should be included in the treatment volume is a topic of considerable controversy. Radionuclide internal mammary node lymphoscintigraphy (IMN-LS) can locate these nodes in three dimensions. We have analyzed the results of IMN-LS in 167 patients imaged at the Dana-Farber Cancer Institute and treated at the Joint Center for Radiation Therapy between 1977 and 1980. The location of the IMNs was found variable from patient to patient. At least one IMN was not included within tangential fields arbitrarily arranged to have a medial entrance point 3.0 cm across the midline in 17% of evaluable patients. However, 48% and 66% of patients had IMNs that could be adequately treated with fields positioned only 1.0 cm or 2.0 cm across midline, respectively. We conclude that when treatment of the IMNs is warranted, IMN-LS not only assures their complete coverage in the majority of patients but also may help reduce the amount of heart and lung irradiated.


Retinoic Acid Induces Ubiquitination-Resistant RIP140/LSD1 Complex to Fine-Tune Pax6 Gene in Neuronal Differentiation.
Receptor-interacting protein 140 (RIP140) is a wide-spectrum coregulator for hormonal regulation of gene expression, but its activity in development/stem cell differentiation is unknown. Here, we identify RIP140 as an immediate retinoic acid (RA)-induced dual-function chaperone for LSD1 (lysine-specific demethylase 1). RIP140 protects LSD1's catalytic domain and antagonizes its Jade-2-mediated ubiquitination and degradation. In RA-induced neuronal differentiation, the increased RIP140/LSD1 complex is recruited by RA-elevated Pit-1 to specifically reduce H3K4me2 modification on the Pax6 promoter, thereby repressing RA-induction of Pax6. This study reveals a new RA-induced gene repressive mechanism that modulates the abundance, enzyme quality, and recruitment of histone modifier LSD1 to neuronal regulator Pax6, which provides a homeostatic control for RA induction of neuronal differentiation.


Inhibition of Epithelial-to-Mesenchymal Transition (EMT) in Cancer by Nitric Oxide: Pivotal Roles of Nitrosylation of NF-κB, YY1 and Snail.
Treatment of cancer cell lines with high levels of nitric oxide (NO) via NO donors, such as DETANONOate, inhibits cell growth and survival pathways and sensitizes resistant tumor cells to apoptosis by chemoimmunotherapeutic drugs. In addition, we recently have reported that NO also inhibits the epithelial-to-mesenchymal transition (EMT) phenotype in metastatic cancer cell lines via dysregulation of the nuclear factor (NF)-κB/Snail/Yin Yang 1 (YY1)/Raf kinase inhibitor protein circuitry. The mechanism underlying NO-mediated dysregulation of this circuit was investigated, namely, NO-mediated inhibition of the activity of the transcription factors NF-κB, Snail, and YY1. We hypothesized that one mechanism of NO-mediated inhibition may invoke the NO-induced S-nitrosylation of these transcription factors. We demonstrate in metastatic and EMT+ human prostate carcinoma cell lines that treatment with NO results in the S-nitrosylation of NF-κB (p50), Snail, and YY1 and inhibits their activities, resulting in the reversal of the EMT phenotype into a mesenchymal-to-epithelial transition phenotype. These findings suggest that NO donors may be potential therapeutic agents in both the reversal of resistance and the inhibition of EMT and metastasis.


Catalytic asymmetric dearomatization of phenols via divergent intermolecular (3 + 2) and alkylation reactions.
The catalytic asymmetric dearomatization (CADA) reaction has proved to be a powerful protocol for rapid assembly of valuable three-dimensional cyclic compounds from readily available planar aromatics. In contrast to the well-studied indoles and naphthols, phenols have been considered challenging substrates for intermolecular CADA reactions due to the combination of strong aromaticity and potential regioselectivity issue over the multiple nucleophilic sites (O, C2 as well as C4). Reported herein are the chiral phosphoric acid-catalyzed divergent intermolecular CADA reactions of common phenols with azoalkenes, which deliver the tetrahydroindolone and cyclohexadienone products bearing an all-carbon quaternary stereogenic center in good yields with excellent ee values. Notably, simply adjusting the reaction temperature leads to the chemo-divergent intermolecular (3 + 2) and alkylation dearomatization reactions. Moreover, the stereo-divergent synthesis of four possible stereoisomers in a kind has been achieved via changing the sequence of catalyst enantiomers.


Removal of phosphate using iron oxide nanoparticles synthesized by eucalyptus leaf extract in the presence of CTAB surfactant.
This study investigated the use of cetyltrimethylammonium bromide (CTAB) as a stabilizer in green synthesis to improve the reactivity of iron oxide nanoparticles (IONP). Results show that efficiency in removing phosphate increased from 71.0% to 97.3%. To understand how to improve the reactivity of IONP by CTAB: firstly, characterizations of IONP before and after phosphate removal by SEM, EDS, FTIR, XPS show the adsorption of P onto the IONP; secondly, batch experiments indicate that the adsorption capacity of phosphate increased when temperature or initial phosphate concentration increased and decreased with an increase in both adsorbent dose and pH. Adsorption followed the pseudo-second-order kinetics model and the equilibrium data fitted well to the Langmuir isotherm. Thermodynamic data confirmed the spontaneous and endothermic nature of the adsorption process. Finally, it was proposed that the adsorption of phosphate using CTAB-modified IONP was mainly associated with inner-sphere complexing mechanism and electrostatic attraction.


Effects of temperature and of heat shock on the expression and action of the colicin A lysis protein.
At low temperature, the synthesis of the colicin A lysis protein in Escherichia coli was slowed down, and consequently its functioning was retarded. The rates were restored when the bacteria were shifted for 10 min to 42 degrees C, except in an rpoH mutant, suggesting that one or more proteins regulated by sigma 32 is necessary for expression of colicin A lysis protein.


Involvement of tissue transglutaminase in the stabilisation of biomaterial/tissue interfaces important in medical devices.
Tissue transglutaminase (tTG) has recently been established as a novel cell surface adhesion protein that binds with high affinity to fibronectin in the pericellular matrix. In this study, we have made use of this property to enhance the biocompatibility of poly(epsilon-caprolactone) (PCL), a biomaterial currently used in bone repair. Poly(epsilon-caprolactone) discs were first coated with fibronectin and then tTG. The surface localisation of the two proteins was confirmed using ELISA and the tTG shown to be active on the surface by incorporation of biotin cadaverine into the fibronectin coating. When human osteoblasts (HOBs) were seeded onto the coated polymer surfaces in serum free medium, the surface coated with fibronectin and then tTG showed an increase in the spreading of the cells as compared to the surface coated with fibronectin alone, when analysed using environmental scanning electron microscopy. The presence of tTG had no effect on HOB cell differentiation when analysed by determining alkaline phosphatase activity. The use of tTG as a novel adhesion protein in this way may therefore have considerable potential in forming a stable tissue/biomaterial interface for application in medical devices.


Treatment of ulcerated haemangiomas with a non-coherent pulsed light source: brief initial clinical report.
Ulceration is the most common complication of infantile haemangiomas and constitutes an authentic therapeutic challenge because of associated pain, infection, haemorrhage and subsequent scarring. To report our experience with an intense pulsed light (IPL) system in the treatment of ulcerated haemangiomas. Case 1: A 4-month-old girl, with haemangioma affecting the entire cutaneous surface of the left limb, developed four ulcerations on the inner aspect of this extremity. Two sessions with an IPL system using a triple pulse mode, a 570-nm lower cut-off filter and a fluence of 38 J/cm2 were performed. Case 2: A 5-month-old girl with ulcerated labial haemangioma that previously failed to respond to intralesional corticoids was treated with an IPL system device. Three sessions using a triple pulse mode with a 570-nm lower cut-off filter and a fluence of 48 J/cm2 were realized. Good results were rapidly obtained after two and four sessions of IPL treatment, respectively. Pain was soon relieved and complete epithelization was obtained by between 1 and 2 months in both patients. Although our experience is rare, we believe that IPL devices may be an effective alternative treatment of ulcerated haemangiomas.


Aseismic slip and recent ruptures of persistent asperities along the Alaska-Aleutian subduction zone.
The frictional properties and slip behaviors of subduction thrusts play a key role in seismic and tsunami hazard assessment, especially in weakly coupled "seismic gaps". Here, we rely on GPS observations in the Shumagin Gap of the Aleutian subduction zone to derive the slip distribution of the 2020 Mw 7.8 Simeonof Island, Alaska earthquake and of the subsequent afterslip during the first 87-day period. Our modeling results show that the mainshock ruptured at depths of ∼30-40 km beneath Simeonof Island. Kinematic and stress-driven models indicate that the afterslip occurred both updip and downdip of the mainshock rupture. Physically plausible locking models derived from interseismic GPS velocities suggest that the 2020 Simeonof and 2021 Mw 8.2 Chignik earthquakes ruptured persistent asperities on the subduction thrust. We infer that there are several additional persistent asperities at depths of 20-50 km west ∼157°W. However, it is still uncertain whether there are additional locked asperities at shallow depths because of the current lack of geodetic observations close to the trench.


Structural insights into the membrane microdomain organization by SPFH family proteins.
The lateral segregation of membrane constituents into functional microdomains, conceptually known as lipid raft, is a universal organization principle for cellular membranes in both prokaryotes and eukaryotes. The widespread Stomatin, Prohibitin, Flotillin, and HflK/C (SPFH) family proteins are enriched in functional membrane microdomains at various subcellular locations, and therefore were hypothesized to play a scaffolding role in microdomain formation. In addition, many SPFH proteins are also implicated in highly specific processes occurring on the membrane. However, none of these functions is understood at the molecular level. Here we report the structure of a supramolecular complex that is isolated from bacterial membrane microdomains and contains two SPFH proteins (HflK and HflC) and a membrane-anchored AAA+ protease FtsH. HflK and HflC form a circular 24-mer assembly, featuring a laterally segregated membrane microdomain (20 nm in diameter) bordered by transmembrane domains of HflK/C and a completely sealed periplasmic vault. Four FtsH hexamers are embedded inside this microdomain through interactions with the inner surface of the vault. These observations provide a mechanistic explanation for the role of HflK/C and their mitochondrial homologs prohibitins in regulating membrane-bound AAA+ proteases, and suggest a general model for the organization and functionalization of membrane microdomains by SPFH proteins.


Triptorelin for the treatment of adenomyosis: A multicenter observational study of 465 women in Russia.
To evaluate the effectiveness of triptorelin for the treatment of adenomyosis, the benign invasion of endometrial tissue into the myometrium, as a fertility-preserving alternative to the gold standard hysterectomy. In this multicenter, open-label, observational study in Russia, performed from November 3, 2011, to August 24, 2015, we assessed the efficacy and safety of triptorelin 3.75 mg administered intramuscularly every 28 days in Russian women who were gonadotropin-releasing hormone agonist treatment-naïve, aged 25-40 years, and had a diagnosis of endometriosis or adenomyosis with heavy menstrual bleeding. We performed a medical record review, interviews to assess symptom severity, and pelvic assessments including transvaginal ultrasound. Data were obtained at first injection of triptorelin (visit 1), on the day of last injection (visit 2), 6 months after last injection (visit 3), and 9 months after last injection (visit 4). Significance was assessed by Wilcoxon signed rank test. A total of 465 women were included. There was a significant improvement from baseline in severity of heavy menstrual bleeding in 390/463 (84.2%) of women 6 months after last injection (P<0.0001). Severity of dysmenorrhea, abnormal uterine bleeding, and pelvic pain was decreased at visit 3 compared with baseline (P<0.0001). Endometriosis symptoms stopped in 253/262 (96.6%) of women at visit 2 and in 243/263 (92.4%) of women at visit 3. Pregnancy was reported in 116/465 (24.9%) women within 9 months following the end of treatment. Triptorelin has a favorable safety profile, is highly efficacious in treating clinical symptoms of adenomyosis, and improves reproductive function. ClinicalTrials.gov registration number: A-38-52014-191, registered October 2011.


Sixteen-Week Interventional Study to Evaluate the Clinical Effects and Safety of Rivastigmine Capsules in Chinese Patients with Alzheimer's Disease.
Rivastigmine is a cholinesterase inhibitor, approved for the treatment of mild-to-moderate dementia of Alzheimer's type. To explore the efficacy and safety of the maximal tolerated dose of rivastigmine capsules in Chinese patients with mild-to-moderate Alzheimer's disease (AD). The study was a multicenter, open-label, single-arm, phase IV clinical study in mild-to-moderate drug-naïve AD patients treated with rivastigmine capsules. The primary endpoint was the changes in the total scores of Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-Cog) from baseline to week 16. Secondary endpoints included changes in the scores of the following assessment scales and safety: Alzheimer's Disease Cooperative Study; Activities of Daily Living; Mini-Mental Status Examination (MMSE); Neuropsychiatry Index (NPI), and Caregiver Burden Inventory. 222 patients were enrolled. Of these, 136 (75.1%) patients received and maintained the effective dose (≥6 mg/d) of rivastigmine for at least 4 weeks. The ADAS-Cog scale score improved in rivastigmine-treated patients at week 16 compared with baseline (p < 0.001) by 2.0 (95% CI: -3.0 to -1.1) points, which met the pre-defined superiority criteria. NPI-10 and NPI-12 scores improved by 3.6 and 4.0 points at week 16 (p = 0.001, p < 0.001), respectively. A total of 107 patients (59.1%) experienced adverse effects (AEs) during the study; common AEs included nausea (20.5%), vomiting (16.6%), anorexia (7.8%), dizziness (7.7%), and diarrhea (7.2%). This was the first phase IV study on rivastigmine in mainland China. The study preliminarily demonstrated that rivastigmine capsules showed good tolerability and efficacy in mild-to-moderate AD patients with the maximal tolerated dose.


A comparison between lymphangiography and pelvic node dissection in the staging of prostatic cancer.
On 40 consecutive patients with prostatic cancer who had pedal lymphangiography during the initial evaluation and, subsequently, underwent pelvic node dissection or biopsy, a surprisingly high number had falsely positive (59 per cent) or negative (36 per cent) x-ray findings. Initially the tumors were considered clinically to be stage B in 24 cases, stage C in 13 and stage D in 3. After lymph node dissection only 17 tumors were still considered to be stage B and 7 were stage C, while 16 tumors were actually stage D. This surgical staging is important for the further management of the patient as well as the prognosis, Pedal lymphangiogrpahy alone is unreliable for accurate assessment of the regional lymph node status in clinically localized prostatic cancer.


Cerebral perfusion in patients with chronic neck and upper back pain: preliminary observations.
The purpose of this study was to determine the correlation between cerebral perfusion levels, Neck Disability Index (NDI) scores, and spinal joint fixations in patients with neck pain. Forty-five adult patients (29 were female) with chronic neck/upper thoracic pain during exacerbation were studied. The subjects were grouped according to NDI scores: mild, moderate, and severe. The number of painful/blocked segments in the cervical and upper thoracic spine and costovertebral joints, pain intensity using the visual analog scale, and regional cerebral blood flow of the brain using single-photon emission computed tomography (SPECT) were obtained. The SPECT was analyzed semiquantitatively. Analysis of variance tests were conducted on total SPECT scores in each of the NDI groups (P < .05). Univariate correlations were obtained between blockage, pain, and SPECT scores, as well as age and duration. A multivariate analysis was then conducted. Group 1 (mild) consisted of 14 patients. Cerebral perfusion measured by SPECT was normal in all 8 brain regions. Group 2 (moderate) consisted of 16 patients. In this group, a decrease in cerebral perfusion was observed (range, 20%-35%), predominantly in the parietal and frontal zones. Group 3 (severe) consisted of 15 patients. In this group, the decrease in cerebral perfusion observed was from 30% to 45%, again predominantly in the parietal and frontal zones. A significant difference was found between NDI groups ("moderate" and "severe" showed significantly greater hypoperfusion than "mild"). Total blockage score correlated with SPECT scores at r = 0.47, P = .001. In a multivariate analysis, NDI scores contributed 39% of the variance of SPECT scores. In this group of patients with neck and/or upper back pain, NDI scores strongly predicted cerebral hypoperfusion. Spinal joint dysfunction may be involved via hyperactivity in the regional sympathetic nervous system.


Sex-specific hemispheric differences in cortical activation to a bimodal odor.
Most odorants we experience in every day life are bimodal in that they activate both the main olfactory and the intranasal trigeminal system. Few studies have investigated whether true bimodal odorants are processed differently than unimodal odorants. The aim of the study was to address sex-dependent hemispheric differences in olfactory event-related potentials. Event-related potentials (ERP) of the bimodal stimulant peppermint oil were recorded in 34 healthy subjects (17 women). No sex-related differences in olfactory sensitivity, trigeminal sensitivity or hedonic ratings of the stimuli were found. Although perceived similarly by men and women, results indicated a sex-differentiated hemispheric response to bimodal odors. Women generally expressed larger amplitudes and longer latencies over their left hemisphere, whereas men demonstrated a similar pattern over their right hemisphere. This effect was most evident for the early sensory derived ERP components indicating a sex-dependent difference in the sensory processing of bimodal odors.


Photodegradation kinetic study and stability-indicating assay of danazol using high-performance liquid chromatography.
A selective high-performance liquid chromatographic procedure for the stability-indicating determination of danazol in the presence of its photolytic degradation products is demonstrated. The photolysis was carried out in glass vials and quartz cell under UV light at 254 nm. Satisfactory results were obtained for the assay and recovery testing with RSD values less than 2%. Kinetic parameters evaluated comprise the order of reaction and the rate constants of the degradation of the danazol irradiated in glass vials or quartz cell.


Crossroads of Wnt and Hippo in epithelial tissues.
Epithelial tissues undergo constant growth and differentiation during embryonic development and to replace damaged tissue in adult organs. These processes are governed by different signaling pathways that ultimately control the expression of genes associated with cell proliferation, patterning, and death. One essential pathway is Wnt, which controls tubulogenesis in several epithelial organs. Recently, Wnt has been closely linked to other signaling pathways, such as Hippo, that orchestrate proliferation and apoptosis to control organ size. There is evidence that epithelial cell junctions may sequester the transcription factors that act downstream of these signaling pathways, which would represent an important aspect of their functional regulation and their influence on cell behavior. Here, we review the transcriptional control exerted by the Wnt and Hippo signaling pathways during epithelial growth, patterning, and differentiation and recent advances in understanding of the regulation and crosstalk of these pathways in epithelial tissues.


Effects of early isolation on layer II neurons in the entorhinal cortex of the guinea pig.
Previous studies showed that early environmental conditions severely affect the morphology of the granule cells in the hippocampal dentate gyrus and pyramidal neurons in fields CA3 and CA1. The aim of the present study was to determine whether early isolation affects neuron morphology in layer II of the entorhinal cortex, from which the perforant path to the dentate gyrus and CA3 takes its origin. Male and female guinea pigs were assigned at 6-7 days of age to either a control (social) or an isolated environment where they remained for 80-90 days. The brains were Golgi-Cox stained and neurons were sampled from layer II of the entorhinal cortex. Morphometric analysis was carried out on star cells, the most abundant neuron population. Isolated males had star cells with less dendritic branches, a shorter dendritic length and a smaller dendritic spine density than control males. In contrast, isolated females had more dendritic branches than control females, though this difference was of small magnitude. While isolated males had star cells with a smaller soma than control males, isolated females had a soma larger than control females. In both environments sex differences were found in the star cell morphology. In the control environment males had more dendritic branches, a greater dendritic length, a larger soma but a smaller spine density than females. In the isolated environment males had less branches, a shorter dendritic length, a smaller spine density and a smaller soma than females. The results indicate that early isolation affects the structure of the star cells in the entorhinal cortex and that males and females react to isolation in an opposite manner. A similar sexually dimorphic response to early isolation was previously observed in the dentate gyrus and fields CA3 and CA1. The presence of widespread effects of isolation in the entorhinal cortex and numerous hippocampal structures suggests that the outcome of early isolation might be a change in learning and memory functions requiring the hippocampal region.


How many calories are necessary during critical illness?
Several nutritional alternatives exist to provide critically ill patients sufficient calories to meet metabolic demands. Intuitively, investigators, nutritionists, and clinicians have pursued the goal of providing high-calorie nutrition support, believing that this would improve outcomes. There is little evidence, however, that meeting caloric goals is of significant benefit. In fact, accumulating data suggest that feeding patients below previously described caloric goals is associated with better outcomes, including decreases in hospital stay, ventilator dependence, use of antibiotics, and even mortality. This suggests that permissive underfeeding could replace the paradigm of meeting measured caloric goals. Prospective evidence to support adoption of permissive underfeeding is lacking, however. Appropriate clinical studies are necessary to prove its safety and efficacy.


The Composition and Functional Capacities of Saliva Microbiota Differ Between Children With Low and High Sweet Treat Consumption.
Excess sugar consumption-common in youth-is associated with poor health. Evidence on the relationship between sugar consumption and the oral microbiome, however, remains scarce and inconclusive. We explored whether the diversity, composition, and functional capacities of saliva microbiota differ based on the consumption of select sugary foods and drinks ("sweet treats"). Using 16S rRNA gene sequencing, we characterized saliva microbiota from 11 to 13-year-old children who participated in the Finnish Health in Teens (Fin-HIT) cohort study. The sample comprised children in the lowest (n = 227) and highest (n = 226) tertiles of sweet treat consumption. We compared differences in the alpha diversity (Shannon, inverse Simpson, and Chao1 indices), beta diversity (principal coordinates analysis based on Bray-Curtis dissimilarity), and abundance (differentially abundant operational taxonomic units (OTUs) at the genus level) between these low and high consumption groups. We performed PICRUSt2 to predict the metabolic pathways of microbial communities. No differences emerged in the alpha diversity between low and high sweet treat consumption, whereas the beta diversity differed between groups (p = 0.001). The abundance of several genera such as Streptococcus, Prevotella, Veillonella, and Selenomonas was higher in the high consumption group compared with the low consumption group following false discovery rate correction (p < 0.05). Children with high sweet treat consumption exhibited higher proportions of nitrate reduction IV and gondoate biosynthesis pathways compared with the low consumption group (p < 0.05). To conclude, sweet treat consumption shapes saliva microbiota. Children who consume a high level of sweet treats exhibited different compositions and metabolic pathways compared with children who consume low levels of sweet treats. Our findings reveal novel insights into the relationship between sugary diets and oral microbiota.


Early versus delayed reduction and pinning of type III displaced supracondylar fractures of the humerus in children: a comparative study.
To determine whether children with Type III displaced supracondylar fractures of the humerus that were pinned in a delayed fashion, defined as more than eight hours after fracture, had a greater need for open reduction than patients with similar fractures pinned more urgently, within eight hours after the trauma. Also, to determine whether those patients treated later fared any worse than patients treated earlier. Retrospective review of consecutive patients. Level I pediatric trauma center at a tertiary children's hospital. Fifty-eight consecutive patients, twenty-three with early pinning and thirty-five with delayed pinning. A subgroup of sixteen patients was followed for detailed clinical outcome. Closed or open reduction and percutaneous pinning Need for open reduction in either group. A separate subgroup was examined for carrying angle and evidence of low-grade compartment syndrome (such as grip strength and range of motion). There was no difference in the need for open reduction in the group that was delayed and pinned more than eight hours following fracture. Follow-up examination showed no clinical difference between the two groups in any parameter measured. These results indicate that many supracondylar fractures of the humerus can be treated safely in a delayed manner with an excellent clinical result and without unduly prolonging the hospital stay (such as with traction). This allows the patient to be NPO and the surgeon to operate in daylight hours, saving time, hospital resources, and fatigue.


Using magnetic coupling to improve multiple resonance NMR probe circuits.
Multiple resonant NMR circuits are an especially important aspect of modern NMR detectors. Today NMR researchers can carry out direct observe, indirect observe and double or triple resonance experiments on many different nuclides without having to change the NMR probe. The price for this convenience is loss of efficiency. In this paper it is explained how by using magnetic coupling and symmetric multiple resonance circuits the efficiency of these experiments can be improved over capacitively coupled circuits to 50 Ω ports.


[Significance of computed tomography evaluation before revision stapes surgery].
Stapedectomy and, more recently, stapedotomy have been widely accepted as the primary surgical techniques to improve conductive hearing in patients suffering from otosclerosis. Unsuccessful outcomes are infrequent, but revision surgery may become necessary. We have analyzed the value of computed tomography (CT) scanning following unsuccessful stapes surgery. In a total of 37 CT scans, the depth of insertion, angle between prosthesis and footplate, location of prosthesis within the oval niche, visibility of the prosthesis, dehiscence of the superior semicircular canal, and extent of otospongiotic foci were evaluated and compared with the audiometric results. There was no significant correlation between CT parameters and audiologic results, except for patients with cochlear otosclerosis or lateral dislocation of the piston. One previously unknown dehiscence of the superior semicircular canal was diagnosed. Otospongiotic foci were seen in 13 ears (35%). Displacements of the stapes piston and rare causes for an insufficient result, such as a dehiscence of the superior semicircular canal, can be diagnosed accurately by CT. However, correlation between the audiologic results and the findings on CT scans was possible in only a few cases. Nevertheless, CT scans provide additional information for surgical planning in revision stapes surgery and may become increasingly important to reduce unanticipated intraoperative risks; they may even guide the surgeon not to perform unnecessary revision surgeries.


Addition of olivetol to crackers decreases malondialdehyde content and produces malondialdehyde-olivetol adducts.
This study was undertaken to investigate the malondialdehyde-trapping ability by m-diphenols and the consequent decrease of malondialdehyde in foods. Olivetol was added to crackers, which were prepared with wheat flour and either oxidized or fresh sunflower, linseed, and camelina oils. When crackers were prepared with oxidized oils, olivetol-containing crackers contained less malondialdehyde (∼30%) than control crackers. This decrease of malondialdehyde content was parallel to the formation of malondialdehyde-olivetol adducts (250-1300 ng/g). When fresh oils were employed, storage produced more malondialdehyde (300-700%) in control than in olivetol-containing crackers. This decrease of malondialdehyde content was also parallel to the formation of malondialdehyde-olivetol adducts (10-90 ng/g). In both cases, the formation of adducts required the contribution of either formaldehyde or acetaldehyde. Obtained results suggest that olivetol not only removed malondialdehyde, but also short chain aldehydes, therefore contributing to the decrease of the content of these toxic aldehydes in phenolic-enriched crackers.


Continuous physical examination during subcortical resection in awake craniotomy patients: Its usefulness and surgical outcome.
To evaluate the value of physical examination as a monitoring tool during subcortical resection in awake craniotomy patients and surgical outcomes. Authors reviewed medical records of patients underwent awake craniotomy with continuous physical examination for pathology adjacent to the eloquent area. Between January 2006 and August 2015, there were 37 patients underwent awake craniotomy with continuous physical examination. Pathology was located in the left cerebral hemisphere in 28 patients (75.7%). Thirty patients (81.1%) had neuroepithelial tumors. Degree of resections were defined as total, subtotal, and partial in 16 (43.2%), 11 (29.7%) and 10 (27.0%) patients, respectively. Median follow up duration was 14 months. The reasons for termination of subcortical resection were divided into 3 groups as follows: 1) by anatomical landmark with the aid of neuronavigation in 20 patients (54%), 2) by reaching subcortical stimulation threshold in 8 patients (21.6%), and 3) by abnormal physical examination in 9 patients (24.3%). Among these 3 groups, there were statistically significant differences in the intraoperative (p=0.002) and early postoperative neurological deficit (p=0.005) with the lowest deficit in neuronavigation group. However, there were no differences in neurological outcome at later follow up (3-months p=0.103; 6-months p=0.285). There were no differences in the degree of resection among the groups. Continuous physical examination has shown to be of value as an additional layer of monitoring of subcortical white matter during resection and combining several methods may help increase the efficacy of mapping and monitoring of subcortical functions.


Characterization of nitrous oxide emission from a rice-duck farming system in South China.
Agricultural activities are important contributors to the emissions of greenhouse gases. This study ascertained the dynamic emission of nitrous oxide (N(2)O) from a paddy field under a rice-duck farming system in South China. Two different cultivation and fertilizer treatments, namely, organic fertilizer + ducks (OF+D) and chemical fertilizer + ducks (CF+D) treatments, were employed in this study. Experimental data showed that diurnal variations of N(2)O emission were highly correlated with the activities of ducklings. The rates of N(2)O emission were normally increased in the early morning and late afternoon due to the frequent movement of ducklings at these time periods. Our study further revealed that the rates of N(2)O emission from the paddy field varied with the types of fertilizers used as well as with the stages of the rice growth. In general, the rates of N(2)O emission were higher for the CF+D treatment than for the OF+D treatment, whereas more N(2)O was emitted from the paddy field at the tillering stage than at the heading stage. The global warming potential with the use of the organic fertilizer was about 22% lower than with the use of the chemical fertilizer.


Chloride cells and chloride exchange in the skin of a sea-water teleost, the shanny (Blennius pholis L.).
The fine structure of the skin and its importance in chloride outfluxes were investigated in a sea-water teleost, the shanny (Blennius pholis L.). The epidermis is composed of three cells types: epithelial cells, mucous cells and chloride cells. These chloride cells typically contain a great number of mitochondria and an extensive agranular reticulum extending through the whole cell body. They open at the surface of the epidermis into an apical pit. An undifferentiated small cell is often observed near these chloride cells and probably corresponds to the "adjacent chloride cell". The values of chloride outfluxes through the skin and the gills are respectively 5333+/-884 muEq.h-1.kh-1 and 4479+/-2521 muEq.h-1.kg-1; n = 6; t degrees = 13+/-0.5 degrees C. Thus the ratio between skin chloride outflux and total chloride outflux is 64.7 +/- 9.3%.


[Radionuclide ventriculography. I. Fundamentals and methods (author's transl)].
Using local time activity curves parameters are calculated which depend on the local wall motion of the heart cavities. These functional parameters allow the determination of the contours of the heart cavities and the assessment of segmental wall motion disorders. The left ventricular ejection fraction has been calculated by enddiastolic and endsystolic counts using a method which takes into account background inhomogeneity.


Anthropogenic Noise and Physiological Stress in Wildlife.
The ecological impacts of increasing levels of anthropogenic noise in marine and freshwater systems are of growing public interest. Recent emphasis on the physiological approaches to identifying the impacts of noise has led to increased recognition that anthropogenic noise is an environmental stressor. We briefly review the research on noise-induced physiological stress. Additionally, we summarize findings from a controlled playback experiment that explored the relationship between traffic noise and physiological stress in anurans (frogs and toads), an aquatic group that relies on acoustic communication for survival and reproduction.


Thyroid follicular oncogenesis in iodine-deficient and iodine-sufficient areas: search for alterations of the ras, met and bFGF oncogenes and of the Rb anti-oncogene.
To gain insights into the role of iodine deficiency in favoring thyroid tumorigenesis (particularly of the follicular histotype), 22 Sicilian patients with thyroid tumors were selected for having lived permanently in either one of two areas of different iodine availability. Eleven patients (age 46.1 +/- 14.6 years, mean +/- SD; 10 females and 1 male) were from the iodine-deficient (ID) areas of the provinces of Messina and Catania (mean urinary excretion of iodine = 48.1 micrograms/24 hours). Thyroid tumors were follicular or Hürthle cell adenomas (no. = 3), follicular carcinomas (FC, no. = 4), papillary carcinomas (PC, no. = 2) and anaplastic carcinomas (no. = 2). Eleven patients (age 47.1 +/- 15.2 years; 10 females and 1 male) were from the metropolitan area of Messina, an area of relative iodine-sufficiency (IS) (urinary excretion of iodine = 95.2 micrograms/24 hours). These 11 patients had serum levels of TSH that were significantly lower than the corresponding values of the 11 patients from the ID area (0.76 +/- 0.33 vs 1.80 +/- 1.22 mU/l, p = 0.01) The tumors of the 11 patients from the IS area were: follicular or Hürthle cell adenomas (no. = 6), Hürthle cell carcinoma (no. = 1), FC (no. = 2), PC (no. = 2). Molecular biology studies revealed that both the normal as well as the tumor tissue of all 22 patients did not harbor any of the three classical activating mutations (codons 12, 13 and 61) in any of the three ras oncogenes. Similar negative results were obtained as far as loss of heterozygosity of the retinoblastoma (Rb) anti-oncogene is concerned. Immunohistochemistry studies were performed to investigate expression of c-met and basic fibroblast growth factor (bFGF) proto-oncogenes. Only one Hürthle cell carcinoma and the two PC from the IS group, and one FC and the two PC from the ID group stained for the c-met oncogene. Expression of c-met was greater (3+) in the four PC (concerning 70-80% of the tumor cells) than in the other two cancers (1+; < 5% of the tumor cells). In the IS group, positivity for bFGF was detected in 3/6 adenomas, 1/2 FC, the Hürthle cell carcinoma and the two PC. In the ID group, positivity for bFGF was observed in 2/3 adenomas, 2/4 FC, the two PC and the two anaplastic carcinomas. The 8 positive cases from the ID group had a greater level of bFGF expression than the 7 positive cases from the IS group (intensity of staining = 2.0+ vs 1.57+). Interestingly, the greatest expression of bFGF was seen in the cases with peri-tumoral lymphocytic infiltration from either group. In the ID group correlations between (i.) pre-intervention serum TSH and intensity of tumoral staining for bFGF, (ii.) serum TSH and per cent of tumoral cells reactive with anti-bFGF and (iii.) between intensity of staining for bFGF and per cent of tumoral cells bFGF +ve were higher than in the IS group. We conclude that activating mutations of ras, loss of DNA from the Rb locus and over-expression of both c-met and bFGF are of no pathogenetic relevance in driving thyroid tumorigenesis of iodine-deficient areas.


Natural and synthetic β-carboline as a privileged antifungal scaffolds.
The discovery of antifungal agents with novel structure, broad-spectrum, low toxicity, and high efficiency has been the focus of medicinal chemists. Over the past decades, β-carboline scaffold has attracted extensive attention in the scientific community due to its potent and diverse biological activities with nine successfully marketed β-carboline-based drugs. In this review, we summarized the current states and advances in the antifungal activity of natural and synthetic β-carbolines. Additionally, the structure-activity relationships and their antifungal mechanisms targeting biofilm, cell wall, cell membrane, and fungal intracellular targets were also systematically discussed. In summary, β-carbolines have the great potential to develop new efficient scaffolds to combat fungal infections.


Phosphodiesterase inhibitory properties of losartan. Design and synthesis of new lead compounds.
A 4-centre PDE4 pharmacophore search has been carried out in several 3D-databases containing compounds belonging to different therapeutic areas. Losartan, an angiotensin-II antagonist, has been identified as a new lead compound for developing PDE4 inhibitors. New families of compounds derived from losartan has been synthesized and their PDE inhibition has been measured.


Microemulsion-based lycopene extraction: Effect of surfactants, co-surfactants and pretreatments.
Lycopene is a potent antioxidant that has received extensive attention recently. Due to the challenges encountered with current methods of lycopene extraction using hazardous solvents, industry calls for a greener, safer and more efficient process. The main purpose of present study was application of microemulsion technique to extract lycopene from tomato pomace. In this respect, the effect of eight different surfactants, four different co-surfactants, and ultrasound and enzyme pretreatments on lycopene extraction efficiency was examined. Experimental results revealed that application of combined ultrasound and enzyme pretreatments, saponin as a natural surfactant, and glycerol as a co-surfactant, in the bicontinuous region of microemulsion was the optimal experimental conditions resulting in a microemulsion containing 409.68±0.68 μg/glycopene. The high lycopene concentration achieved, indicates that microemulsion technique, using a low-cost natural surfactant could be promising for a simple and safe separation of lycopene from tomato pomace and possibly from tomato industrial wastes.


Conductive disturbances in the transcatheter aortic valve implantation setting: An appraisal of current knowledge and unmet needs.
New-onset conduction disturbances, including left bundle branch block and permanent pacemaker implantation, remain a major issue after transcatheter aortic valve implantation. Preprocedural risk assessment in current practice is most often limited to evaluation of the baseline electrocardiogram, whereas it may benefit from a multimodal approach, including ambulatory electrocardiogram monitoring and multidetector computed tomography. Physicians may encounter equivocal situations during the hospital phase, and the management of follow-up is not fully defined, despite the publication of several expert consensuses and the inclusion of recommendations regarding the role of electrophysiology studies and postprocedural monitoring in recent guidelines. This review provides an overview of current knowledge and future perspectives regarding the management of new-onset conduction disturbances in the setting of transcatheter aortic valve implantation, from the preprocedural phase to long-term follow-up.


[Cost-effectiveness of a hallux valgus day-surgery program].
The development of one-day surgery units has shown to be a better use of health resources without reducing quality. The objective of this study was to evaluate the effectiveness and quality criteria of ambulatory surgery program in the Hallux valgus process. A retrospective study was conducted on a sample of 753 patients who underwent a Hallux valgus process at our institution between 2002 and 2012 (292 in ambulatory surgery cohort and 461 in hospitalization group). The cost-process was evaluated using the Weighted Care Unitas a measuring unit. Secondary data were collected as regards discharge criteria and patient satisfaction. A significant difference was found between Weighted Care Unit spending on in-patient surgery and out-patient surgery. Both samples were comparable and no differences were found between diagnosis and intervention. The admission rate after ambulatory surgery was 2.39%, and the substitution index increased to 56.04%. The ambulatory surgery program was given a satisfaction rating of 84.6 out of 100. The results of our study indicate that it is possible to maximize the substitution index of the Hallux valgus process leading to a better use of resources and a high degree of patient satisfaction.


Long-term survival after surgical revascularization for moderate ischemic mitral regurgitation.
We sought to characterize patient survival and degree of late mitral regurgitation (MR) in patients undergoing surgical revascularization with moderate ischemic MR. We retrospectively reviewed 251 patients undergoing coronary artery bypass graft (CABG) surgery between 1991 and 2001 with 3+ ischemic MR, including 31 patients who had concomitant mitral annuloplasty. Univariate and multivariable testing was employed. Actuarial 1-, 5-, and 10-year survival was 84.0%, 67.5%, and 37.1% in the overall group of 251 patients. Independent predictors of long-term mortality were age 70 years or more (hazard ratio 2.50 [95% confidence interval 1.82 to 3.44]), prior myocardial infarction (3.99 [2.15 to 7.39]), unstable angina (2.27 [1.69 to 3.04]), chronic renal failure (4.87 [3.13 to 7.58]), atrial fibrillation (2.21 [1.65 to 2.96]), left internal mammary artery to left anterior descending artery graft (0.28 [0.18 to 0.43]), preoperative beta-blocker (0.43 [0.28 to 0.67]), ejection fraction (0.71/10% [0.64 to 0.80]), left atrium size (0.88/mm [0.84 to 0.92]), diffuse wall motion abnormalities (2.83 [1.77 to 4.55]), and mitral leaflet restriction (3.85 [2.46 to 5.99]). The model controlled for the performance of annuloplasty, which did not emerge as an independent predictor. Patients undergoing annuloplasty did have less mean late MR than those having CABG alone (p = 0.005). Overall, 57.8% of patients (63 of 109) with follow-up echocardiograms had improvement in grade of MR compared with baseline. In 54 of 95 patients (56.8%), intraoperative transesophageal echocardiography downgraded the degree of MR compared with the preoperative study. Patients with moderate ischemic MR undergoing CABG had relatively poor long-term survival, with significant differences when stratified according to preoperative characteristics. Performance of mitral annuloplasty reduced the degree of regurgitation but was not a predictor of long-term survival. Intraoperative transesophageal echocardiography frequently downgraded the degree of MR.


Inactivation of protease nexin-1 by xanthine oxidase-derived free radicals.
Neuronal viability is affected by reactive oxygen species. Lipid peroxidation is often defined as a major reason for cellular breakdown. Additionally, certain indispensable proteins are possible targets for excessively formed reactive oxygen species. Evidence is given here that protease nexin-1 (PN-1), an endogenous thrombin inhibitor and neurite outgrowth promoter, is inactivated by xanthine oxidase-derived free radicals. Varying protection by superoxide dismutase and catalase was observed, depending on the reaction conditions. The water-soluble alpha-tocopherol analogues MDL 74,406 (R(+)-3,4-dihydro-6-hydroxy-N,N,N-2,5,7,8-heptamethyl-2H-1-benzopy ran-2- ethanaminium 4-methylbenzenesulfonate), MDL 74,180DA (2,3-dihydro-2,2,4,6,7-pentamethyl-3-(4-methyl-piperazino)-1-benzo furan-5-ol dihydro-chloride) and trolox also protected PN-1. Neurodegeneration may be triggered by oxidative inactivation of protease inhibitors such as PN-1. Protection of PN-1 in Alzheimer's or Parkinson's diseases, could be a possible target for a therapeutic function of antioxidants in these diseases.


Amino-carboxyl cellulose for adsorption of Cd2+ and Pb2.
An amino-carboxyl cellulose was synthesized using the grafting of glycine on the aldehyde cellulose through a Schiff base reaction for the adsorption of heavy metals with Cd2+ and Pb2+ as the representative. Higher affinity of the amino-carboxyl cellulose was found at pH 4.5-5.0 for Cd2+ and 4.0-5.5 for Pb2+. The equilibrium was achieved within 30 min. The adsorption capacities of amino-carboxyl cellulose (Cd2+: 85.7 mg g-1, Pb2+: 115.1 mg g-1, Cu2+: 68.2 mg g-1, Co2+: 60.1 mg g-1, Ni2+ 48.5 mg g-1 and Zn2+: 52.8 mg g-1) at 30 °C were observed. A mild increase in the adsorption capacities of Cd2+ and Pb2+ from 15 to 45 °C was observed. Adsorption data correlated well with the Langmuir and pseudo-second order equations, illustrating chemisorption of Cd2+ and Pb2+ by the amino-carboxyl cellulose. The adsorption of the amino-carboxyl cellulose for Cd2+ and Pb2+ was a spontaneous and endothermic. The amino-carboxyl cellulose owned a high reusability after 4 cycles.


Priorities in testis cancer care during Covid-19 Pandemic.
There is little information on how to prioritize testis cancer (TC) patients' care during COVID-19 pandemic in order to relieve its pressure on the health care systems. To describe the recommendations for diagnosis, treatment and follow-up of patients with TC amidst COVID- 19 pandemic. Pubmed search and review of the main urological association guidelines on TC. The biology of TC requires immediate care of patients during diagnosis, initial surgical therapy and management of recurrent disease. Active surveillance is the first choice of management and should be offered to all compliant clinical stage I TC patients provided they understand the need to self-isolate. Active surveillance may also help decrease the demand for intensive care unit beds, ventilators, personal protective equipment, and other critical hospital and human resources by minimizing surgeries without compromising patient outcomes. Complications of therapy and symptomatic patients represent medical emergencies and should be treated immediately. Telemedicine may be useful during follow-up periods. Most stages of testis cancer require urgent care; however, all recommendations must be adapted to local health care priorities considering that most of these patients are at low risk of severe COVID-19 infection.


A SWOT Analysis of the Updated National HIV/AIDS Strategy for the U.S., 2015-2020.
In July 2015, President Barack Obama released an updated National HIV/AIDS Strategy (NHAS) for the United States to guide HIV efforts through the year 2020. A federal action plan to accompany the updated NHAS will be released in December 2015. In this editorial, we offer a strengths, weaknesses, opportunities and threats analysis with the aim of increasing discussion of ways to truly fulfill the promise of the updated NHAS and to address barriers that may thwart it from achieving its full potential.


Developmental Programming: Prenatal Testosterone Excess on Liver and Muscle Coding and Noncoding RNA in Female Sheep.
Prenatal testosterone (T)-treated female sheep manifest peripheral insulin resistance, ectopic lipid accumulation, and insulin signaling disruption in liver and muscle. This study investigated transcriptional changes and transcriptome signature of prenatal T excess-induced hepatic and muscle-specific metabolic disruptions. Genome-wide coding and noncoding (nc) RNA expression in liver and muscle from 21-month-old prenatal T-treated (T propionate 100 mg intramuscular twice weekly from days 30-90 of gestation; term: 147 days) and control females were compared. Prenatal T (1) induced differential expression of messenger RNAs (mRNAs) in liver (15 down, 17 up) and muscle (66 down, 176 up) (false discovery rate < 0.05, absolute log2 fold change > 0.5); (2) downregulated mitochondrial pathway genes in liver and muscle; (3) downregulated hepatic lipid catabolism and peroxisome proliferator-activated receptor (PPAR) signaling gene pathways; (4) modulated noncoding RNA (ncRNA) metabolic processes gene pathway in muscle; and (5) downregulated 5 uncharacterized long noncoding RNA (lncRNA) in the muscle but no ncRNA changes in the liver. Correlation analysis showed downregulation of lncRNAs LOC114112974 and LOC105607806 was associated with decreased TPK1, and LOC114113790 with increased ZNF470 expression. Orthogonal projections to latent structures discriminant analysis identified mRNAs HADHA and SLC25A45, and microRNAs MIR154A, MIR25, and MIR487B in the liver and ARIH1 and ITCH and miRNAs MIR369, MIR10A, and MIR10B in muscle as potential biomarkers of prenatal T excess. These findings suggest downregulation of mitochondria, lipid catabolism, and PPAR signaling genes in the liver and dysregulation of mitochondrial and ncRNA gene pathways in muscle are contributors of lipotoxic and insulin-resistant hepatic and muscle phenotype. Gestational T excess programming of metabolic dysfunctions involve tissue-specific ncRNA-modulated transcriptional changes.


Multiple ileal polyps associated with gastrointestinal perforation in a 2-day-old neonate.
We experienced a very rare case of a gastrointestinal perforation due to multiple ileal polyps. The patient was a 2-day-old boy who weighed 1,430 g at birth. At neonatal day 2 subdiaphragmatic free air was noted and an emergency operation was performed. During surgery a distended ileum approximately 5 cm in size was found approximately 40 cm distal from the ileocecum, and a perforation was discovered in the distended portion of the intestine. Approximately 8 cm of the ileum was resected, including the distended portion of the intestine, and an ileostomy was performed. Examination of the resected specimen revealed three pedunculated polyps with a perforation proximal to the polyps.


Sox10 and Itgb1 interaction in enteric neural crest cell migration.
SOX10 involvement in syndromic form of Hirschsprung disease (intestinal aganglionosis, HSCR) in humans as well as developmental defects in animal models highlight the importance of this transcription factor in control of the pool of enteric progenitors and their differentiation. Here, we characterized the role of SOX10 in cell migration and its interactions with β1-integrins. To this end, we crossed the Sox10(lacZ/+) mice with the conditional Ht-PA::Cre; beta1(neo/+) and beta1(fl/fl) mice and compared the phenotype of embryos of different genotypes during enteric nervous system (ENS) development. The Sox10(lacZ/+); Ht-PA::Cre; beta1(neo/fl) double mutant embryos presented with increased intestinal aganglionosis length and more severe neuronal network disorganization compared to single mutants. These defects, detected by E11.5, are not compensated after birth, showing that a coordinated and balanced interaction between these two genes is required for normal ENS development. Use of video-microscopy revealed that defects observed result from reduced migration speed and altered directionality of enteric neural crest cells. Expression of β1-integrins upon SOX10 overexpression or in Sox10(lacZ/+) mice was also analyzed. The modulation of SOX10 expression altered β1-integrins, suggesting that SOX10 levels are critical for proper expression and function of this adhesion molecule. Together with previous studies, our results strongly indicate that SOX10 mediates ENCC adhesion and migration, and contribute to the understanding of the molecular and cellular basis of ENS defects observed both in mutant mouse models and in patients carrying SOX10 mutations.