Effect of Preoperative Intravitreal Bevacizumab on the Surgical Outcome of Neovascular Glaucoma at Different Stages.
To evaluate the effect of preoperative intravitreal bevacizumab (IVB) injection on the surgical outcome of Ahmed glaucoma valve (AGV) implantation according to the angle status in neovascular glaucoma (NVG) eyes. This retrospective study included 70 NVG patients who underwent AGV implantation and were followed up for at least 12 months. An IVB injection before AGV implantation was administered to 45 eyes (IVB group), while it was not administered to 25 eyes (control group). Subgroup analyses were done at different stages in terms of the extent of peripheral anterior synechiae (PAS). Mean follow-up period after AGV implantation was 27 ± 15 months. The IVB group showed higher prevalence of the eyes with less than 50% of PAS than that of the control group (78% versus 44%). The overall success rate 1 year postoperatively was 80% and 64% for the IVB and control groups, respectively (P = 0.142). When PAS extent was less than 50%, preoperative IVB had a marginally positive effect on surgical outcome (HR = 0.39, P = 0.064, per 1-time IVB injection). Preoperative IVB may enhance the success rate of AGV implantation in NVG eyes, before PAS has extensively formed. Further prospective randomized studies controlling the extent of PAS are warranted.


Processing of TCP pilin by TcpJ typifies a common step intrinsic to a newly recognized pathway of extracellular protein secretion by gram-negative bacteria.
Biogenesis of the Vibrio cholerae toxin-coregulated pilus (TCP) requires the activities of at least seven accessory proteins. We demonstrate that a portion of this pathway involves a novel processing step in which a hydrophilic leader peptide is proteolytically removed from TcpA by the gene product characterized in this report, TcpJ, to yield the mature, export-competent form of the pilin. Cleavage of the pilin leader peptide is independent of known signal peptidases as demonstrated by pilin-processing profiles in Escherichia coli strains conditionally defective for production of leader peptidase or grown in the presence of the antibiotic globomycin. Additionally, pilin cleavage did not rely on the SecA protein, as evidenced by TcpA processing in azide-treated cells. These results suggest that TcpJ is representative of a new class of proteins involved in SecA-independent proteolytic cleavage of a set of atypical leader peptides during extracellular export.


Strength and durability performance of alkali-activated rice husk ash geopolymer mortar.
This paper describes the experimental investigation carried out to develop the geopolymer concrete based on alkali-activated rice husk ash (RHA) by sodium hydroxide with sodium silicate. Effect on method of curing and concentration of NaOH on compressive strength as well as the optimum mix proportion of geopolymer mortar was investigated. It is possible to achieve compressive strengths of 31 N/mm(2) and 45 N/mm(2), respectively for the 10 M alkali-activated geopolymer mortar after 7 and 28 days of casting when cured for 24 hours at 60°C. Results indicated that the increase in curing period and concentration of alkali activator increased the compressive strength. Durability studies were carried out in acid and sulfate media such as H2SO4, HCl, Na2SO4, and MgSO4 environments and found that geopolymer concrete showed very less weight loss when compared to steam-cured mortar specimens. In addition, fluorescent optical microscopy and X-ray diffraction (XRD) studies have shown the formation of new peaks and enhanced the polymerization reaction which is responsible for strength development and hence RHA has great potential as a substitute for ordinary Portland cement concrete.


Calcium mobilization in isolated epithelial cells of the endolymphatic sac.
Endolymphatic sac epithelial cells were isolated from the endolymphatic sac of the guinea pig by enzymatic and mechanical dissociation. The intracellular free calcium ion concentrations ([Ca2+]i) of the isolated cells were determined using the Ca(2+)-sensitive dye fura-2. The isolated cells were classified into two types, i.e. light and dark cells. In the resting state, [Ca2+]i in the cells was variable in both types of cells. In the presence of 200 microM ATP, there was a rapid rise in [Ca2+]i. These findings suggest that endolymphatic sac epithelial cells may have receptor-mediated Ca channels which may play an important role for a nerve-mediated local feedback system of the endolymphatic sac to regulate homeostasis of endolymph volume, pressure and electrolyte balance.


Sharp sensitivity bounds for mediation under unmeasured mediator-outcome confounding.
It is often of interest to decompose the total effect of an exposure into a component that acts on the outcome through some mediator and a component that acts independently through other pathways. Said another way, we are interested in the direct and indirect effects of the exposure on the outcome. Even if the exposure is randomly assigned, it is often infeasible to randomize the mediator, leaving the mediator-outcome confounding not fully controlled. We develop a sensitivity analysis technique that can bound the direct and indirect effects without parametric assumptions about the unmeasured mediator-outcome confounding.


Studies by small-angle X-ray scattering of the quaternary structure of the beta-haemocyanin of Helix pomatia.
Helix pomatia beta-haemocyanin was studied in solution by small-angle X-ray scattering. The following molecular parameters were determined: molecular weight = 9.02 X 10(6), volume = 14000 nm3, radius of gyration = 18.4 nm, radius of the spherical subunits = 2.5 +/- 0.2 nm. With these data, and with information of dissociation products described in a former paper, a model of the molecule was built whose theoretical scattering curve showed good agreement with the experimental one. The model consists of 160 spherical subunits of a radius of 2.5 nm; 12 rings each built up of 10 spheres form the outer wall of a hollow cylinder; 20 subunits are situated at the inner side of each end.


Interorgan ammonia metabolism in liver failure.
In the post-absorptive state, ammonia is produced in equal amounts in the small and large bowel. Small intestinal synthesis of ammonia is related to amino acid breakdown, whereas large bowel ammonia production is caused by bacterial breakdown of amino acids and urea. The contribution of the gut to the hyperammonemic state observed during liver failure is mainly due to portacaval shunting and not the result of changes in the metabolism of ammonia in the gut. Patients with liver disease have reduced urea synthesis capacity and reduced peri-venous glutamine synthesis capacity, resulting in reduced capacity to detoxify ammonia in the liver. The kidneys produce ammonia but adapt to liver failure in experimental portacaval shunting by reducing ammonia release into the systemic circulation. The kidneys have the ability to switch from net ammonia production to net ammonia excretion, which is beneficial for the hyperammonemic patient. Data in experimental animals suggest that the kidneys could have a major role in post-feeding and post-haemorrhagic hyperammonemia.During hyperammonemia, muscle takes up ammonia and plays a major role in (temporarily) detoxifying ammonia to glutamine. Net uptake of ammonia by the brain occurs in patients and experimental animals with acute and chronic liver failure. Concomitant release of glutamine has been demonstrated in experimental animals, together with large increases of the cerebral cortex ammonia and glutamine concentrations. In this review we will discuss interorgan trafficking of ammonia during acute and chronic liver failure. Interorgan glutamine metabolism is also briefly discussed, since glutamine synthesis from glutamate and ammonia is an important alternative pathway of ammonia detoxification. The main ammonia producing organs are the intestines and the kidneys, whereas the major ammonia consuming organs are the liver and the muscle.


False-negative contrast-enhanced spectral mammography: use of more than one imaging modality and application of the triple test avoids misdiagnosis.
A 50-year-old woman presented with chest tenderness. On examination, both breasts were lumpy. Bilateral mammography showed heterogeneously dense parenchyma, with possible stromal distortion laterally on the right at the 0900 position. On ultrasound (US), a corresponding 13×9×10 mm irregular hypoechoic mass with internal vascularity was noted and both breasts had a complex heterogeneous fibroglandular background pattern. US-guided core biopsy with marker clip insertion was performed with the diagnosis of a grade 2 invasive ductal carcinoma (IDC). In view of the parenchymal pattern on mammography and US, contrast-enhanced spectral mammography (CESM) was performed for local staging. Mild background enhancement was noted, but there was no enhancement at the lesion site. The patient elected to have bilateral mastectomies and sentinel node biopsies. Final histopathology showed a node negative 11 mm grade 2 oestrogen and progesterone receptor positive, IDC.


Analgesic and Anti-Inflammatory Activities of Methanol Extract of Ficus pumila L. in Mice.
This study investigated possible analgesic and anti-inflammatory mechanisms of the methanol extract of Ficus pumila (FP(MeOH)). Analgesic effects were evaluated in two models including acetic acid-induced writhing response and formalin-induced paw licking. The results showed FP(MeOH) decreased writhing response in the acetic acid assay and licking time in the formalin test. The anti-inflammatory effect was evaluated by λ-carrageenan-induced mouse paw edema and histopathological analyses. FP(MeOH) significantly decreased the volume of paw edema induced by λ-carrageenan. Histopathologically, FP(MeOH) abated the level of tissue destruction and swelling of the edema paws. This study indicated anti-inflammatory mechanism of FP(MeOH) may be due to declined levels of NO and MDA in the edema paw through increasing the activities of SOD, GPx, and GRd in the liver. Additionally, FP(MeOH) also decreased the level of inflammatory mediators such as IL-1β, TNF-α, and COX-2. HPLC fingerprint was established and the contents of three active ingredients, rutin, luteolin, and apigenin, were quantitatively determined. This study provided evidence for the classical treatment of Ficus pumila in inflammatory diseases.


Relationship between microvascular resistance and perfusion in patients with reperfused acute myocardial infarction.
Despite its prognostic importance, accurate assessment of microvascular perfusion in patients with ST elevation acute myocardial infarction (STEMI) is difficult. As a new tool, the index of microvascular resistance (IMR) measurement provides us a new opportunity for interrogating microvascular condition after STEMI. In this study, we measured IMR in infarct-related artery (IRA) and explored its relation with other indices which have been suggested to evaluate microvascular perfusion in patients with reperfused STEMI. Forty-two patients with STEMI treated successfully with primary percutaneous coronary intervention (pPCI) were prospectively included. After 48 hours following pPCI, patients were recatheterized and IMR, coronary flow reserve (CFR), systolic and mean coronary wedge pressures (CWPs and CWPm) pressure-derived collateral flow index (CFIp) were measured in IRA by using intracoronary pressure-temperature sensor tipped guide wire. Myocardial blush grade was assessed from the second angiogram. Coronary flow velocity pattern (diastolic deceleration time: DDT) was examined with transthoracic echocardiography 48 hours after pPCI. Percentage of ST-segment recovery was calculated from surface ECG (STR%). IMR well correlated with CWPs (r = 0.70, P < 0.001), CWPm (r = 0.59, P < 0.001), CFIp (r = 0.65, P < 0.001), CFR (r =-0.50, P = 0.001), and DDT (r =-0.59, P = 0.001). Correlations of IMR to non/semiinvasive indices like myocardial blush grades (MBG) (r =-0.42, P = 0.007) and STR (r =-0.37, P = 0.024) are somewhat weaker. Given its simplicity of measurement, independence from the presence of an epicardial stenosis, and good correlation with all measures of microvascular obstruction used in this study, IMR may prove to be a valuable modality for evaluating the microcirculation.


Contractility of the ovarian vascular bed during the oestrous cycle and early pregnancy in gilts.
The vasoconstrictor activity of the ovarian vascular bed in vitro was investigated during the oestrous cycle and early pregnancy. Gilts were killed during the follicular phase (Days 20 to +1; N = 5) or luteal phase (Days 11 to 13; N = 4) of the oestrous cycle, or on Day 13 of pregnancy (N = 5). Immediately before death, a sample of vena cava blood was obtained for determination of progesterone and oestrogen (oestrone and oestradiol-17 beta) concentrations. One ovary was removed, cannulated, perfused in vitro, and subjected to 10-min infusions of saline (vehicle control) and noradrenaline. Vasoconstriction was provoked by electrical stimulation at the end of each infusion. Ovaries from luteal-phase gilts exhibited greater (P less than 0.01) vasoconstriction than did ovaries from follicular-phase and pregnant gilts at the end of saline and noradrenaline infusions. The oestrogen to progesterone ratio was less (P less than 0.01) for luteal-phase and pregnant than for follicular-phase gilts. Vasoconstriction was negatively correlated (r = -0.99, P less than 0.01) with the oestrogen to progesterone ratio in systemic blood of gilts during the oestrous cycle but not during early pregnancy (r = +0.39, P greater than 0.10), possibly due to an effect of the conceptuses.


Hormesis, epitaxy, the structure of liquid water, and the science of homeopathy.
According to the western medical establishment, homeopathy is both "unscientific" and "implausible". A short overview of its history and the methods it uses, however, easily reveals that homeopathy is a true science, fully grounded on the scientific method and on principles, such as, among others, the Arndt-Schultz law, hormesis, and epitaxy, whose plausibility has been clearly and definitely demonstrated in a number of scientific publications and reports. Through a review of the scientific literature, an explanation of the basic principles of homeopathy is proposed based on arguments and evidence of mainstream science to demonstrate that, in spite of the claims of conventional medicine, homeopathy is both scientific and plausible and that there is no reasonable justification for its rejection by the western medical establishment. Hopefully, this hurdle will be overcome by opening academic institutions to homeopathy to enlarge the horizons of medical practice, recover the value of the human relationship with the patient, and through all this, offer the sick a real alternative and the concrete perspective of an improved quality of life.


Effectiveness of Liraglutide and Lixisenatide in the Treatment of Type 2 Diabetes: Real-World Evidence from The Health Improvement Network (THIN) Database in the United Kingdom.
The glucagon-like peptide-1 receptor agonists liraglutide and lixisenatide are effective at reducing glycated hemoglobin (HbA1c) levels in patients with type 2 diabetes mellitus (T2DM). Although liraglutide has demonstrated superior efficacy in head-to-head clinical trials, real-world evidence of comparative effectiveness is lacking. This observational study aimed to assess the effectiveness of liraglutide versus lixisenatide in UK clinical practice. Electronic medical records from The Health Improvement Network (THIN) UK primary care database were analyzed. Patients aged ≥18 years, diagnosed with T2DM, and prescribed liraglutide or lixisenatide between 01 May 2013 and 31 December 2015 were included in the study. Adjusted linear regression models compared the difference in mean change in HbA1c, body mass index (BMI), and systolic blood pressure (SBP) after 12-month follow-up. The proportion of patients achieving glycemic control (HbA1c <6.5%, <7.0%, <7.5%); HbA1c reduction >1%; and weight reduction ≥3% within 12 months were determined. Cox proportional hazards modeling was used to evaluate the effect of treatment on time to achieving HbA1c and weight reduction targets. Healthcare resource use (HCRU) (GP, secondary care, hospitalizations) was compared using analysis of covariance. The primary outcome was assessed in 579 liraglutide and 213 lixisenatide new users. Fully adjusted linear regression indicated that liraglutide reduced HbA1c significantly more than lixisenatide (mean treatment difference -0.30; 95% CI -0.56, -0.04; p = 0.025). Compared to lixisenatide, liraglutide recipients were 2.5 times more likely to achieve HbA1c <6.5% (p = 0.0002). Liraglutide users were also more likely to achieve HbA1c <7.0% (HR 2.10; p < 0.0001), <7.5% (HR 1.65; p < 0.0001), and >1% HbA1c reduction (HR 1.29; p = 0.0002). BMI and SBP reductions were greater for the liraglutide group but results were not significant. HCRU was comparable between treatment groups. These results from the THIN database indicate that liraglutide treatment provided better outcomes related to glycemic control. Novo Nordisk.


Completeness of Descriptions of Repetitive Transcranial Magnetic Stimulation Intervention: A Systematic Review of Randomized Controlled Trials of rTMS in Depression.
Repetitive transcranial magnetic stimulation (rTMS) is an innovative therapeutic option in major depressive disorder (MDD). A complete description of the procedure in reports of randomized controlled trials (RCTs) is a prerequisite for implementation of rTMS in clinical practice. The aim of this study was to evaluate the completeness of descriptions of the intervention in RCTs assessing rTMS in MDD. We performed a systematic review of RCTs evaluating rTMS in MDD and published until August 2016. We searched PubMed, the Cochrane library, and PsycINFO to identify eligible trials. The completeness of the intervention description was evaluated by the use of an adapted-to-rTMS version of the Template for Intervention Description and Replication (TIDieR) checklist. We defined core items that are the most essential to be reported. Missing information was then sought from additional sources and by e-mailing authors. We identified 98 trials reporting 134 interventions. None of the interventions were completely described in the full text of the articles, even after searching additional sources. After contacting the authors, 14 (10.4%) of 134 interventions were completely described. The core items were completely described in 74 (55.2%) of 134 interventions after contacting the authors. We found that rTMS interventions delivered in RCTs are incompletely reported, which prevents their adequate implementation in clinical practice and accurate interpretation of their efficacy. We encourage authors, editors, and reviewers to use the existing reporting guidelines and specifically the TIDieR checklist when describing the intervention. We provide an adapted-to-rTMS TIDieR checklist that could help in the reporting of future trials.


Microarray analysis of early and late passage chicken embryo fibroblast cells.
Primary cultured cells derived from normal tissue have a limited lifespan due to replicative senescence and show distinct phenotypes such as irreversible cell cycle arrest and enlarged morphology. Studying senescence-associated genetic alterations in chicken cells will provide valuable knowledge of cellular growth characteristics, when compared with normal and rapidly growing cell lines. Microarray analysis of early- and late-passage (passage 4 and 18, respectively) primary chicken embryo fibroblast (CEF) cells was performed with a 4X44K chicken oligo microarray. A total of 1,888 differentially expressed genes were identified with a 2-fold level cutoff that included 272 upregulated and 1,616 downregulated genes in late-passage senescent CEF cells. Bioinformatic analyses were performed using Ingenuity Pathway Analysis (IPA, http://www.ingenuity.com). Of the 1,888 differentially expressed genes in senescent CEF cells, 458 were identified as functionally known genes and only 61 genes showed upregulation. Because senescent cells generally showed the deactivated states of most cellular mechanisms for proliferation and energy metabolism, intensified analysis on upregulated genes revealed that the molecular mechanisms in senescent CEF cells are characterized by the suppression of cell cycle and proliferation, progression of cell death including apoptosis, and increased expression of various secreting factors. These regulatory pathways may be opposite to those found in the immortal CEF cell line, such as the DF-1 immortal line. Further comparison of differentially expressed genes between senescent and immortal DF-1 CEF cells showed that 35 genes overlapped and were oppositely regulated. The global gene expression profiles may provide insight into the cellular mechanisms that regulate cellular senescence and immortalization of CEF cells.


Facile Dehydrogenation of Ethane on the IrO2(110) Surface.
Realizing the efficient and selective conversion of ethane to ethylene is important for improving the utilization of hydrocarbon resources, yet remains a major challenge in catalysis. Herein, ethane dehydrogenation on the IrO2(110) surface is investigated using temperature-programmed reaction spectroscopy (TPRS) and density functional theory (DFT) calculations. The results show that ethane forms strongly bound σ-complexes on IrO2(110) and that a large fraction of the complexes undergo C-H bond cleavage during TPRS at temperatures below 200 K. Continued heating causes as much as 40% of the dissociated ethane to dehydrogenate and desorb as ethylene near 350 K, with the remainder oxidizing to COx species. Both TPRS and DFT show that ethylene desorption is the rate-controlling step in the conversion of ethane to ethylene on IrO2(110) during TPRS. Partial hydrogenation of the IrO2(110) surface is found to enhance ethylene production from ethane while suppressing oxidation to COx species. DFT predicts that hydrogenation of reactive oxygen atoms of the IrO2(110) surface effectively deactivates these sites as H atom acceptors, and causes ethylene desorption to become favored over further dehydrogenation and oxidation of ethane-derived species. The study reveals that IrO2(110) exhibits an exceptional ability to promote ethane dehydrogenation to ethylene near room temperature, and provides molecular-level insights for understanding how surface properties influence selectivity toward ethylene production.


Identification and Characterization of Trajectories of Cardiac Allograft Vasculopathy After Heart Transplantation: A Population-Based Study.
Cardiac allograft vasculopathy (CAV) is a major contributor of heart transplant recipient mortality. Little is known about the prototypes of CAV trajectories at the population level. We aimed to identify the different evolutionary profiles of CAV and to determine the respective contribution of immune and nonimmune factors in CAV development. Heart transplant recipients were from 4 academic centers (Pitié-Salpêtrière and Georges Pompidou Hospital, Paris, Katholieke Universiteit Leuven, and Cedars-Sinai, Los Angeles; 2004-2016). Patients underwent prospective, protocol-based monitoring consisting of repeated coronary angiographies together with systematic assessments of clinical, histological, and immunologic parameters. The main outcome was a prediction for CAV trajectory. We identified CAV trajectories by using unsupervised latent class mixed models. We then identified the independent predictive variables of the CAV trajectories and their association with mortality. A total of 1301 patients were included (815 and 486 in the European and US cohorts, respectively). The median follow-up after transplantation was 6.6 (interquartile range, 4-9.1) years with 4710 coronary angiographies analyzed. We identified 4 distinct profiles of CAV trajectories over 10 years. The 4 trajectories were characterized by (1) patients without CAV at 1 year and nonprogression over time (56.3%), (2) patients without CAV at 1 year and late-onset slow CAV progression (7.6%), (3) patients with mild CAV at 1 year and mild progression over time (23.1%), and (4) patients with mild CAV at 1 year and accelerated progression (13.0%). This model showed good discrimination (0.92). Among candidate predictors assessed, 6 early independent predictors of these trajectories were identified: donor age (P<0.001), donor male sex (P<0.001), donor tobacco consumption (P=0.001), recipient dyslipidemia (P=0.009), class II anti-human leukocyte antigen donor-specific antibodies (P=0.004), and acute cellular rejection ≥2R (P=0.028). The 4 CAV trajectories manifested consistently in the US independent cohort with similar discrimination (0.97) and in different clinical scenarios, and showed gradients for overall-cause mortality (P<0.001). In a large multicenter and highly phenotyped prospective cohort of heart transplant recipients, we identified 4 CAV trajectories and their respective independent predictive variables. Our results provide the basis for a trajectory-based assessment of patients undergoing heart transplantation for early risk stratification, patient monitoring, and clinical trials. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04117152.


MicroRNAs in sensorineural diseases of the ear.
Non-coding microRNAs (miRNAs) have a fundamental role in gene regulation and expression in almost every multicellular organism. Only discovered in the last decade, miRNAs are already known to play a leading role in many aspects of disease. In the vertebrate inner ear, miRNAs are essential for controlling development and survival of hair cells. Moreover, dysregulation of miRNAs has been implicated in sensorineural hearing impairment, as well as in other ear diseases such as cholesteatomas, vestibular schwannomas, and otitis media. Due to the inaccessibility of the ear in humans, animal models have provided the optimal tools to study miRNA expression and function, in particular mice and zebrafish. A major focus of current research has been to discover the targets of the miRNAs expressed in the inner ear, in order to determine the regulatory pathways of the auditory and vestibular systems. The potential for miRNAs manipulation in development of therapeutic tools for hearing impairment is as yet unexplored, paving the way for future work in the field.


The role of 5-lipoxygenase in Aggregatibacter actinomycetemcomitans-induced alveolar bone loss.
Leukotrienes (LTs) are pro-inflammatory lipid mediators formed by the enzyme 5-lipoxygenase (5-LO). The involvement of 5-LO metabolites in periodontal disease (PD) is not well defined. This study aimed to assess the role of 5-LO in experimental PD induced by Aggregatibacter actinomycetemcomitans (Aa). In vivo experiments were carried out using SV129 wild-type (WT) and 5-LO-deficient (5lo-/- ) mice inoculated with Aa. Osteoclasts were stimulated in vitro with AaLPS in the presence or not of selective inhibitors of the 5-LO pathway, or LTB4 or platelet-activating factor (PAF), as PAF has already been shown to increase osteoclast activity. In 5lo-/- mice, there were no loss of alveolar bone and less TRAP-positive osteoclasts in periodontal tissues, after Aa inoculation, despite local production of TNF-α and IL-6. The differentiation and activity of osteoclasts stimulated with AaLPS were diminished in the presence of BLT1 antagonist or 5-LO inhibitor, but not in the presence of cysteinyl leukotriene receptor antagonist. The osteoclast differentiation induced by PAF was impaired by the BLT1 antagonism. In conclusion, LTB4 but not CysLTs is important for Aa-induced alveolar bone loss. Overall, LTB4 affects osteoclast differentiation and activity and is a key intermediate of PAF-induced osteoclastogenesis.


Connectin content and its post-mortem changes in fish muscle.
Connectin was isolated from fish dorsal myofibrils by an SDS-gel filtration method and estimated to account for approximately 13% of the total myofibrillar proteins. There was no significant difference in the amount of connectin among seven fish species but rabbit skeletal myofibrils contained a slightly higher content (16%) of connectin. The high molecular weight connectins from carp and rabbit both showed a doublet band, consisting of bands 1 and 2, on SDS-polyacrylamide gel electrophoresis using a large-pore gel. However, rabbit band 1 (a component of the connectin doublet) was found to migrate more slowly than carp band 1. During post-mortem ageing of the muscles, it was observed that the band 1 component rapidly disappeared with a concomitant increase in band 2 component and then the band 2 component was transformed slowly into faster migrating components. These results suggest that post-mortem ageing has qualitatively similar effects on the submolecular compositions of carp and rabbit connectins. However, the apparent rate of disappearance of the band 1 component was considerably higher in carp muscle than that in rabbit muscle.


A Prospective Evaluation of Intraoperative Indocyanine Green Fluorescence Angiography for Soft Tissue Sarcomas.
Postoperative wound complications after resection of soft-tissue sarcomas are challenging. Indocyanine green (ICG) angiography has previously been used to predict wound complications, but not for soft-tissue sarcomas. We aimed to evaluate whether this technology could help lower wound complications after soft-tissue sarcoma resections. We conducted a prospective study from 10/2017 to 9/2019 using ICG angiography during sarcoma resection surgery. Rates of wound complications were compared with a historical control consisting of surgeries before utilization of ICG angiography. A total of 88 patients were included in the study. We found significantly lower rates of infection (11.8% versus 38%; P = 0.03) and wound dehiscence (11.8% versus 42.3%; P = 0.02) in the ICG angiography cohort compared with the historical controls. ICG angiography use during soft-tissue sarcoma resections is promising technology and warrants further investigation to help reduce postoperative complications.


Treatment of Hip Microinstability with Arthroscopic Capsular Plication: A Retrospective Case Series.
Hip microinstability is defined as hip pain with a snapping and/or blocking sensation accompanied by fine anatomical anomalies. Arthroscopic capsular plication has been proposed as a treatment modality for patients without major anatomic anomalies and after failure of properly administered conservative treatment. The purpose of this study was to determine the efficacy of this procedure and to evaluate potential predictors of poor outcome. A review of 26 capsular plications in 25 patients was conducted. The mean postoperative follow-up period for the remaining patients was 29 months. Analysis of data included demographic, radiological, and interventional data. Calculation of pre- and postoperative WOMAC (Western Ontario and McMaster Universities Osteoarthritis) index was performed. Pre- and postoperative sports activities and satisfaction were also documented. A P<0.05 was considered significant. No major complications were identified in this series. The mean pre- and postoperative WOMAC scores were 62.6 and 24.2, respectively. The WOMAC index showed statistically significant postoperative improvement (P=0.0009). The mean satisfaction rate was 7.7/10. Four patients with persistent pain underwent a periacetabular osteotomy. A lateral center edge angle ≤21° was detected in all hips at presentation. We were not able to demonstrate any difference in postoperative evolution with regard to the presence of hip dysplasia (P>0.05), probably because the sample size was too small. Capsular plication can result in significant clinical and functional improvement in carefully selected cases of hip microinstability.


Effect of lutein and doxorubicin combinatorial therapy on S180 cell proliferation and tumor growth.
Multidrug resistance and toxicity significantly compromise the therapeutic efficacy for sarcomas. We aimed at evaluating the effect of lutein-doxorubicin (DOX) combinatorial therapy on inhibiting S180 (Sarcoma 180) cell proliferation and tumor growth. S180 cells in logarithmic growth phase were treated with lutein, DOX, or lutein-DOX combinatorial therapy for 48 h. The cell survival rate was determined by MTT assay. Apoptosis was detected by flow cytometry. The expression of PCNA, P53, and NF-κB was assessed by Western blot. Further, mice bearing S180 tumors received lutein, DOX, or lutein-DOX combinatorial therapy by oral gavage. Lutein-DOX combinatorial therapy significantly decreased the proliferation of S180 cells (p<0.01) in vitro. Also, the expression of proliferating cell nuclear antigen (PCNA) (p<0.05) and the apoptosis-relevant gene p53 were decreased, which resulted in increased cell apoptosis (p<0.05). The level of nuclear factor kappa B (NF-κB) was also decreased by the combinatorial therapy. Lutein-DOX combinatorial therapy reduced the cytotoxicity of DOX and reduced the inflammatory response. The inhibitory effect of lutein-DOX combinatorial therapy on cell proliferation was confirmed in vivo. The growth rate and size of the tumor at 30 d after treatment were significantly lower than those of the control group and DOX single therapy. Lutein and DOX synergistically inhibit sarcoma cell proliferation and tumor growth. This novel therapeutic regimen could potentially improve clinical outcome of sarcoma patients.


Long-term complications of laparoscopic ventral and incisional hernia repair.
To date, there have been no long-term follow-up studies of the results of laparoscopic ventral and incisional hernia repair. We evaluated the long-term complications of these repairs over a mean follow-up period of 64 months. Between March 1993 and April 2000, we retrospectively evaluated 9 patients who underwent ventral or incisional hernia repair with prosthetic material and one patient who received laparoscopic primary closure of a hernia defect. The prosthetic material polypropylene was used in one patient and an expanded-polytetrafluoroethylene patch was used in the other 8. In one patient, the hernia was closed directly. In 7 patients, the prosthesis was fixed by stapling or tacking with no transfacial suture fixation and a 2-cm prosthesis overlap. In 2 later patients, we modified our technique by fixing the prosthesis by stapling or tacking with transfacial suture fixation and using prosthesis overlap of more than 3 cm. There were 2 episodes of hernia recurrence (20%), one of which required reoperation. Both occurred in patients in whom we used the unmodified repair technique. One of the patients in whom we used the unmodified technique developed a seroma which resolved spontaneously without antibiotic therapy. One patient in whom we used the modified technique developed infection (10%) requiring removal of the prosthetic material. The 2 episodes of hernia recurrence occurred 40 months after laparoscopic treatment, and the case of infection occurred 11 months after treatment. There were no episodes of recurrence in patients who received the unmodified surgery and had hernia defects less than 42 cm2. To perform safe and effective laparoscopic repair of ventral or incisional hernias, it is necessary to use a prosthetic overlap of more than 3 cm from the edge of the hernia gate and to use transfacial suture fixation with nonabsorbable sutures. In addition, patients who undergo laparoscopic ventral or incisional hernia repair should be observed for more than 5 years.


Color Pattern on the Forewing of Micropterix (Lepidoptera: Micropterigidae): Insights into the Evolution of Wing Pattern and Wing Venation in Moths.
Wing patterns are key taxonomic characters that have long been used in descriptions of Lepidoptera; however, wing pattern homologies are not understood among different moth lineages. Here, we examine the relationship between wing venation and wing pattern in the genus Micropterix, among the most basal extant Lepidoptera, in order to evaluate the two existing predictive models that have the potential to establish wing pattern element homologies for the order. The location of wing pattern elements along the costal margin of the wing in Micropterix is consistent with the predictions of the model proposed for Tortricidae by Brown and Powell in 1991, later modified by Baixeras in 2002. The predictive power of this model for such distantly related taxa suggests that the model may hold across various superfamilies within Lepidoptera, and supports the long-held notion that fasciae, not spots, are the most likely primitive wing pattern elements for the order. In addition, the location of wing pattern elements suggests that the wing vein commonly termed Sc1 may in fact be a different vein, which Comstock identified in Trichoptera and referred to as "a."


Why formal learning theory matters for cognitive science.
This article reviews a number of different areas in the foundations of formal learning theory. After outlining the general framework for formal models of learning, the Bayesian approach to learning is summarized. This leads to a discussion of Solomonoff's Universal Prior Distribution for Bayesian learning. Gold's model of identification in the limit is also outlined. We next discuss a number of aspects of learning theory raised in contributed papers, related to both computational and representational complexity. The article concludes with a description of how semi-supervised learning can be applied to the study of cognitive learning models. Throughout this overview, the specific points raised by our contributing authors are connected to the models and methods under review.


Bronchoscopic laser surgery: which laser when and why.
The use of the carbon dioxide (CO2) and neodymium: yttrium aluminum garnet (Nd:YAG) lasers for the endoscopic management of patients with diseases of the tracheobronchial tree is discussed. Advantages and disadvantages of each wavelength are presented. It would appear that there should be unique indications for both of these laser systems; however, each can be used relatively safely and interchangeably if certain precautions are followed.


Breast cancer in Mexico: a pressing priority.
Breast cancer is a serious threat to the health of women globally, and an unrecognised priority in middle-income countries. This paper presents data from Mexico. It shows that breast cancer accounts for more deaths than cervical cancer since 2006. It is the second cause of death for women aged 30-54 and affects all socio-economic groups. Data on detection, although under-reported, show 6,000 new cases in 1990, and a projected increase to over 16,500 per year by 2020. Further, the majority of cases are self-detected and only 10% of all cases are detected in stage one. Mexico's social security systems cover approximately 40-45% of the population, and include breast cancer treatment. As of 2007, the rest of the population has the right to breast cancer treatment through the Popular Health Insurance. Despite these entitlements, services are lacking and interventions for early detection, particularly mammography, are very limited. As of 2006 only 22% of women aged 40-69 reported having a mammogram in the past year. Barriers exist on both the demand and supply sides. Lobbying, education, awareness-building and an articulated policy response will be important to ensure expanded coverage, access to and take-up of both treatment and early detection.


Cellular inhibition of protein tyrosine phosphatase 1B by uncharged thioxothiazolidinone derivatives.
As important regulators of cellular signal transduction, members of the protein tyrosine phosphatase (PTP) family are considered to be promising drug targets. However, to date, the most effective in vitro PTP inhibitors have tended to be highly charged, thus limiting cellular permeability. Here, we have identified an uncharged thioxothiazolidinone derivative (compound 1), as a competitive inhibitor of a subset of PTPs. Compound 1 effectively inhibited protein tyrosine phosphatase 1B (PTP1B) in two cell-based systems: it sensitized wild-type, but not PTP1B-null fibroblasts to insulin stimulation and prevented PTP1B-dependent dephosphorylation of the FLT3-ITD receptor tyrosine kinase. We have also tested a series of derivatives in vitro against PTP1B and proposed a model of the PTP1B-inhibitor interaction. These compounds should be useful in the elucidation of cellular PTP function and could represent a starting point for development of therapeutic PTP inhibitors.


Ethanol as a reinforcer for rats: factors of facilitation and constraint.
This review examines some particular approaches that have been used to investigate factors that facilitate or constrain the self-administration of ethanol by rats. A technique for increasing ethanol self-administration in rats, the prandial drinking method, was examined and the effect of body-weight reduction on drug intake was discussed. Emphasis was placed on how ethanol intake may be controlled by processes in addition to the direct pharmacological actions of the drug in the CNS. These processes may be physiological. Evidence was presented for a relationship between activity in the renin-angiotensin system and the self-administration of ethanol. These processes may also be environmental. Using the place-conditioning technique, demonstrations were presented of how the context or situation in which ethanol is experienced may determine whether preference or aversion for the drug develops. Such a diversity in the factors that can potentially control ethanol intake may complicate the identification of the causes of alcohol abuse, but this same diversity also holds out greater hope that manipulations may be found to reduce excessive drinking in humans.


Relevance of multidrug resistance proteins for intestinal drug absorption in vitro and in vivo.
Multidrug resistance proteins (p-glycoprotein and mrps) are becoming increasingly important to explain the pharmacokinetics and action of drugs. Located in epithelial and endothelial cells of the gastrointestinal tract, liver, kidney, blood brain barrier, choroid plexus and other organs, they are critical determinants for the movement of a large number of commonly prescribed drugs across cellular barriers. Here we provide a brief overview of the role of multidrug resistance proteins in drug absorption from the gastrointestinal tract. We address the different types of multidrug resistance proteins involved, describe experimental models to study the influence of these proteins on transcellular transport and discuss the impact of multidrug resistance proteins on overall drug bioavailability in vivo.


Health locus of control and self-management behaviours among individuals with ischaemic heart disease: protocol for a scoping review.
Ischaemic heart disease is a significant cause of morbidity and mortality worldwide. Self-management is a way to reduce the risk associated with ischaemic heart disease; however, some individuals may not have the ability or willingness to engage in self-management behaviours. One approach to identify an individual's readiness and capacity to engage in self-management behaviours is to assess their health locus of control. Based on the Individual and Family Self-Management Theory, this review's objectives are to describe: (1) how health locus of control affects the process of engaging in self-management behaviours, (2) impacts of health locus of control on outcomes associated with self-management behaviours and (3) potential contextual variations in the relationship between health locus of control and self-management behaviours. The scoping review will be guided by the Joanna Briggs Institute methodological framework. A comprehensive search will encompass seven electronic databases (Ovid Medline, CINAHL, EMBASE, APA PsycINFO, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, Scopus) and grey literature sources (ProQuest Dissertations, ClinicalTrials.gov). Collaborative efforts with library experts will inform our search strategies, building on insights from previous reviews centred on self-management and ischaemic heart disease. Two review authors will independently conduct the screening and data extraction processes; discrepancies will be resolved through consensus or discussion with a third review author. The review will include English studies from database inception, focusing on the health locus of control among adults with ischaemic heart disease. Findings will be presented graphically and tabularly, together with a narrative description. We will collect data from published and grey literature, meaning ethical approval is not necessary. Findings will be published in peer-reviewed journals and presented at academic conferences. Open Science Framework (https://doi.org/10.17605/OSF.IO/B4A6F).


Vitamin D supplementation for autoimmune hepatitis: A need for further investigation.
Autoimmune hepatitis is a chronic liver disease harboring an autoimmune basis and progressive character. Despite still obscurity in etiology and pathogenesis, some evidence supports the importance of sustaining the immune system. Vitamin D is a lipo-soluble vitamin, which has been identified as decreased in our body. It is often due to the daily habit change and decrease of individual sun exposure due to the increase of the ultraviolet-induced potential melanocytic transformation. Here, we emphasize the importance of vitamin D supplementation in patients affected with liver disease.


Visfatin expression in subcutaneous adipose tissue of pre-menopausal women: relation to hormones and weight reduction.
A novel adipokine, visfatin, was found to be related to adiposity in humans and regulated by a number of hormonal signals. The aim of this study was to investigate the relationships of visfatin expression in adipose tissue with potential regulatory factors such as insulin, testosterone and tumor necrosis factor-alpha (TNF-alpha) and to elucidate the effect of a diet induced weight reduction on adipose tissue mRNA expression and plasma levels of visfatin. Biopsies of subcutaneous abdominal adipose tissue (SCAAT) and plasma samples were obtained at the beginning of the study from 47 pre-menopausal women (age 38.7 +/- 1.7 years, body mass index (BMI) 27.9 +/- 1.4 kg m(-2)), consisting of 15 lean, 16 overweight and 16 obese subjects. The subgroup of 32 overweight/obese women (age 42.1 +/- 1.9 years, BMI 31.2 +/- 0.9 kg m(-2)) underwent a 12 week hypocaloric weight reducing diet and samples were obtained at the end of the diet. Biopsy samples were analysed for visfatin and TNF-alpha mRNA levels and plasma was analysed for relevant metabolites and hormones. In the group of 47 subjects visfatin mRNA expression in SCAAT was negatively correlated with plasma free testosterone (r = -0. 363, P < 0.05) and BMI (r = -0.558, P < 0.01) and positively associated with adipose tissue TNF-alpha mRNA expression (r = 0.688, P < 0.01). The diet resulted in the reduction of body weight and in the decrease of plasma insulin, free testosterone and TNF-alpha levels. In the group of overweight/obese subjects visfatin mRNA in SCAAT increased after the diet and the diet induced increase was positively correlated with the magnitude of body weight loss. Visfatin mRNA expression in SCAAT is associated with TNF-alpha expression, plasma free testosterone and BMI in pre-menopausal women. A weight reducing hypocaloric diet results in the increase of visfatin mRNA in SCAAT.


Development of an immune gene prognostic classifier for survival prediction and respond to immunocheckpoint inhibitor therapy/chemotherapy in endometrial cancer.
Immunotherapy has provided a promising therapeutic strategy for endometrial cancer (EC). The present study aims to develop a prognostic classifier based on immune-related genes (IRGs) to stratify EC patients. A total of 15 prognosis-related IRGs were further filtrated by multivariate Cox regression: LTA, TMSB15A, S100A14, PLA2G2A, PDGFRA, CLDN4, CTF1, PRLH, PTN, SST, HTR3E, NRP1, RORA, THRA and CBLC. A prognostic signature was constructed to split EC patients into the high-risk and low-risk group with statistically different survival outcomes, indicating good potential for the prognostic signature in survival surveillance. Furthermore, five compounds with potential anti-tumor effects were selected, including ciclopirox, ikarugamycin, vincamine, mevalolactone, and thiamazole. The abundance of follicular helper T cells, regulatory T cells and M0 macrophages were significantly enhanced in the high-risk group while resting memory CD4+ T cells, gamma delta T cells, M2 macrophages and resting mast cells were markedly elevated in the low-risk group. Memory activated CD4+ T cells, CD8+ T cells and activated mast cells were three most correlative with riskscore. An immunophenoscore (IPS) analysis revealed that patients of the low-risk group had a higher IPS and more inclined to respond to immune checkpoint inhibitors. Mutation analysis showed that patients of the low-risk group represented more tumor mutation burden but low riskscore, thus getting better prognosis. Patients of the low-risk group were more sensitive for gemcitabine, bleomycin, vinblastine, vinorelbine and methotrexate by prediction. We constructed a potential prognostic model and might offer new insight on the identification of new immune-related biomarkers and target therapy in EC.


The Synthesis of Polymeric Nanospheres and the Application as High-Temperature Nano-Plugging Agent in Water Based Drilling Fluid.
Nanoscale plugging agent is essential to wellbore stability of troublesome shale formation in the drilling of oil and gas wells. In this paper, polymeric nanospheres (PNS) with a double cross-linked structure were synthesized using monomers of styrene (ST), acrylamide (AM), 2-Acrylamide- 2-methylpropanesulfonic acid (AMPS), and dimethyl diallyl ammonium chloride (DMDAAC). PNS were characterized by FTIR, SEM and TGA. The plugging performance of PNS was analyzed using nitrogen adsorption experiments and SEM. And compatibility with water based drilling fluid (WBM) was studied. Experimental results showed that PNS had a mean particle size of 133 nm, and could retain about half of the original size after high temperature treatment under 150-200°C. TGA showed that the initial decomposition temperature of PNS is around 315°C. After plugging by PNS, both the specific surface area and pore volume of the shale cuttings decreased substantially compared with those of shale samples treated with water. Thus, PNS was thermal stable in WBM under high temperature and could effectively plug shale pores. Besides, PNS was beneficial to reduce both API and HTHP fluid loss of WBM.


Principles of hemodynamics for mechanical circulatory support: patho-physiological key aspects of assisted PCI.
It is essential to understand the pathophysiology of cardiogenic shock and the possible deterioration of contractile function during high-risk PCI in order to select those patients who could benefit from mechanical support thus choosing the most suitable device in every situation. Percutaneous ventricular assist devices (pVAD) provide hemodynamic support by improving cardiac output and mean arterial pressure, but their specific features result in different hemodynamic effects and degrees of myocardial ischemic protection and left ventricle unloading. These features, together with ease of use, specific contraindications and individual risk of complications, must be taken into account in the evaluation and selection of the device. The aim of this review is to illustrate the principles of left ventricular mechanic, including the pressure-volume loop analysis, in order to better understand and to quantify the different hemodynamic effects of pVAD supports and to explain the pathophysiological key aspects of assisted PCI.


Thermodynamic study of dihydrogen phosphate dimerisation and complexation with novel urea- and thiourea-based receptors.
Complexation of dihydrogen phosphate by novel thiourea and urea receptors in acetonitrile and dimethyl sulfoxide was studied in detail by an integrated approach by using several methods (isothermal titration calorimetry, ESI-MS, and (1)H NMR and UV spectroscopy). Thermodynamic investigations into H2PO4(-) dimerisation, which is a process that has been frequently recognised, but rarely quantitatively described, were carried out as well. The corresponding equilibrium was taken into account in the anion-binding studies, which enabled reliable determination of the complexation thermodynamic quantities. In both solvents the thiourea derivatives exhibited considerably higher binding affinities with respect to those containing the urea moiety. In acetonitrile, 1:1 and 2:1 (anion/receptor) complexes formed, whereas in dimethyl sulfoxide only the significantly less stable complexes of 1:1 stoichiometry were detected. The solvent effects on the thermodynamic parameters of dihydrogen phosphate dimerisation and complexation reactions are discussed.


Improved coronary vasodilatatory capacity by H.E.L.P. apheresis: comparing initial and chronic treatment.
Hypercholesterolemia impairs endothelial function and subsequently decreases coronary vasodilatatory capacity. We examined the quantitative effects of one single LDL apheresis on vasodilatatory capacity. Using N-13 ammonia as a tracer for dynamic quantitative positron emission tomography (PET), mean myocardial perfusion measurements were carried out before and 20 h later after LDL apheresis, both under resting conditions and after pharmacological vasodilatation with dipyridamole. LDL apheresis was carried out using the heparin induced extracorporeal LDL precipitation (H.E.L.P.) procedure. We examined 47 patients (12 women and 35 men), with angiographically-proven coronary artery disease. All of them suffered from hypercholesterolemia. Of the patients, 35 received a chronic weekly H.E.L.P. procedure (group A), while H.E.L.P. procedure treatment was started for the first time in 12 patients, who were subsequently enrolled in a chronic apheresis program (group B). H.E.L.P. apheresis was combined with cholesterol lowering drugs in all patients. Both groups underwent positron emission tomography twice (prior to LDL apheresis and 20 h later). In group A, LDL cholesterol levels decreased from 175 +/- 50 mg/dL to 60 +/- 21 mg/dL immediately after H.E.L.P. (77 +/- 25 mg/dL before the second PET). Corresponding values for fibrinogen levels were 287 +/- 75 mg/dL to 102 +/- 29 mg/dL (155 +/- 52 mg/dL), minimal coronary resistance dropped from 0.56 +/- 0.20 to 0.44 +/- 0.17 mm Hg x 100 g x min/mL (P < 0.0001). Plasma viscosity decreased by 7.8%. In group B, LDL cholesterol decreased from 187 +/- 45 mg/dL to 75 +/- 27 mg/dL (85 +/- 29 mg/dL) and fibrinogen from 348 +/- 65 mg/dL to 126 +/- 38 mg/dL (168 +/- 45 mg/dL). Minimal coronary resistance was reduced from 0.61 +/- 0.23 to 0.53 +/- 0.19 mm Hg x 100 g x min/mL (P < 0.01). Plasma viscosity was observed to decrease by 7.6%. The strong LDL drop in patients under chronic H.E.L.P. treatment has a significant impact on coronary vasodilatatory capacity within 20 h leading to an improved overall cardiac perfusion. Nearly the same effect can be seen in patients after their first H.E.L.P. treatment.


PODXL might be a new prognostic biomarker in various cancers: a meta-analysis and sequential verification with TCGA datasets.
BACKGROUND: Several studies have investigated the associations between the podocalyxin-like protein (PODXL) expression quantity or locations and cancers survival, but the results were far from conclusive. Therefore, we proceeded a meta-analysis on PODXL in various human cancers to find its prognostic value and followed confirmation using the TCGA datasets. We performed a systematic search, and 18 citations, including 5705 patients were pooled in meta-analysis. The results were verified with TCGA datasets. Total eligible studies comprised 5705 patients with 10 types of cancer. And the result indicated that PODXL high-expression or membrane-expression were significantly related to poor overall survival (OS). However, subgroup analysis showed a significant association between high expressed PODXL and poor OS in the colorectal cancer, pancreatic cancer, urothelial bladder cancer, renal cell carcinoma and glioblastoma multiforme. Then, we validated the inference using TCGA datasets, and the consistent results were demonstrated in patients with pancreatic cancer, glioblastoma multiforme, gastric cancer, esophageal cancer and lung adenocarcinoma. The result of meta-analysis showed that high expressed PODXL was significantly linked with poor OS in pancreatic cancer and glioblastoma multiforme, but not in gastric cancer, esophageal cancer or lung adenocarcinoma. And the membrane expression of PODXL might also associate with poor OS. PODXL may act as tumor promotor and may serve as a potential target for antitumor therapy.


Anesthetic management of tongue reduction in a case of Beckwith-Wiedemann syndrome.
Anesthesia for partial glossectomy in a premature child with Beckwith-Wiedemann syndrome presents as a unique challenge to the Anesthesiologist. Airway management in patients presenting with macroglossia is especially significant and requires meticulous preparation and pre-operative assessment. This report delineates the anesthetic concerns such as an anticipated difficult airway due to a large tongue, prematurity, hypoglycemia and an oral cavity surgery and their management.


Usability and acceptability of virtual reality for chronic pain management among diverse patients in a safety-net setting: a qualitative analysis.
The aim of this study was to understand the usability and acceptability of virtual reality (VR) among a racially and ethnically diverse group of patients who experience chronic pain. Using the Technology Acceptance Model theory, we conducted semistructured interviews and direct observation of VR use with English-speaking patients who experience chronic pain treated in a public healthcare system (n = 15), using a commercially available VR technology platform. Interviews included questions about current pain management strategies, technology use, experiences and opinions with VR, and motivators for future use. Before the study, none of the 15 participants had heard about or used VR for pain management. Common motivators for VR use included a previous history of substance use and having exhausted many other options to manage their pain and curiosity. Most participants had a positive experience with VR and 47% found that the VR modules distracted them from their pain. When attempting the navigation-based usability tasks, most participants (73%-92%) were able to complete them independently. VR is a usable tool for diverse patients with chronic pain. Our findings suggest that the usability of VR is not a barrier and perhaps a focus on improving the accessibility of VR in safety-net settings is needed to reduce disparities in health technology use. The usability and acceptability of VR are rarely studied in diverse patient populations. We found that participants had a positive experience using VR, showed interest in future use, and would recommend VR to family and friends.


The 6-year trajectory of non-traumatic knee symptoms (including patellofemoral pain) in adolescents and young adults in general practice: a study of clinical predictors.
(1) To assess the 1-year and 6-year courses of non-traumatic knee symptoms in adolescents and young adults presenting in general practice. (2) To identify prognostic factors for persistent knee symptoms at 1-year follow-up. Adolescents and young adults (12-35 years; n=172) with non-traumatic knee symptoms were included in the cohort study by their general practitioner (GP) and followed for 6 years. Multivariable logistic regression analysis was used to identify prognostic factors for persistent knee symptoms at 1-year follow-up and the area under the receiver operating curve (AUC) was calculated. Persistent knee symptoms in patients receiving a GP diagnosis of unspecified knee symptoms were reported by 41% of the patients at 1-year follow-up and by 19% of the available patients at 6-year follow-up. Patients receiving a GP diagnosis of patellofemoral pain syndrome had the worse prognosis, with 40% reporting persistent knee symptoms at 6-year follow-up. Prognostic factors associated with persistent knee symptoms at 1-year follow-up were BMI >25, low/middle education level, bilateral symptoms and self-reported absence of crepitus of the knee (AUC 0.80) for patients receiving a GP diagnosis of unspecified knee symptoms. For patients receiving a GP diagnosis of patellofemoral pain syndrome, prognostic factors were low/middle education level, poor health, having bilateral symptoms and self-report of a swollen knee (AUC 0.76). The prognosis of non-traumatic knee symptoms in adolescents and young adults in general practice is not as good as was previously assumed. Several prognostic factors collected at baseline were associated with persistent knee symptoms at follow-up. However, the results should be replicated in another larger study.


Self-absorption correction method based on intensity self-calibration of doublet lines.
The self-absorption effect in an optically thick plasma seriously affects the spectral line intensity and the measurement accuracy of laser-induced breakdown spectroscopy (LIBS). In this work, a self-absorption correction method based on intensity self-calibration of doublet lines belonging to the same multiplet is proposed. The K/Δλ0 parameter and self-absorption coefficient (SA) of the doublet lines of the analytical element can be calculated based on the measured actual lines intensity ratio and the K parameters ratio. Compared with the generally applied self-absorption correction methods, this method can effectively reduce the influence of laser energy and plasma plume fluctuations and the non-uniformity distribution of the element in the plasma, and is independent of the availability of Stark broadening coefficients. So it has obvious advantages of high computation efficiency, high analysis accuracy and good applicability. Univariate quantitative analysis results of aluminum (Al) show that the correlation coefficient of calibration curves and the measurement accuracy of elemental content have been significantly improved with the self-absorption correction.


Effects of immunization on cardiopulmonary alterations of gram-negative endotoxemia.
We studied the effects of an infusion of Serratia marcescens endotoxin on hemodynamic function, white blood cells, platelets, and the plasma levels of thromboxane B2 (TXB2) and 6-ketoprostaglandin F1 alpha (6-keto-PGF1 alpha) in awake monitored sheep. The animals were immunized using the core glycolipid (CGL) fraction of Escherichia coli J5 0111. An additional group of animals was studied after passive transfer of immune serum from the actively immunized CGL animals. Active immunization with CGL was effective in preventing the hematologic and hemodynamic changes as well as the elevations in TXB2 and 6-keto-PGF1 alpha seen during gram-negative endotoxemia. Passive immunization also reduced some of the deleterious effects of endotoxin infusion but was less effective than active immunization. This study demonstrates the potential of cross-specific immunization to protect against the cardiopulmonary alterations caused by gram-negative endotoxemia.


Identifying the number and location of body worn sensors to accurately classify walking, transferring and sedentary activities.
In order to perform fall risk assessments using wearable inertial sensors in older adults in their natural settings where falls are likely to occur, a first step is to automatically segment and classify sensor signals of human movements into the known `activities of interest'. Sensor data from such activities can later be used through quantitative and qualitative analysis for differentiating fallers from non-fallers. In this study, ten young adults participated in experimental trials involving several variations of walking, transferring and sedentary activities. Data from tri-axial accelerometers and gyroscopes were used to classify the aforementioned three categories using a multiclass support vector machine algorithm. Our results showed 100% accuracy in distinguishing walking, transferring and sedentary activities using data from a three-sensor combination of sternum and both ankles.


[Changes in monochromatic higher-order aberrations in different pupil sizes with accommodation in young emmetropes].
To study the effect of accommodation on monochromatic higher-order aberrations in different pupil sizes in the young emmetropes. Intervention trial design was used in the study. The monochromatic aberrations were measured in 12 eyes from 12 undulated young emmetropes in 4.0 mm, 3.0 mm, and 2.0 mm pupil sizes with a ray tracing wavefront aberrometer under accommodative stimuli from 0 to 4.00 D. RMS values of total high-order aberrations (HOAs), total coma, total higher-order astigmatism, total spherical, and total trefoil aberrations significantly decreased as pupil size decreased in the relax state. In 4.0 mm, 3.0 mm, and 2.0 mm pupil sizes, the average root mean square (RMS) value of total coma was the highest item of HOAs in the relaxed state. With accommodation up to 3.00 D, the RMS of HOAs remained constant but changed significantly at 4.00 D stimulation (P <0.05) in all these three pupil sizes. The 4th spherical aberration decreased and changed from positive to negative with increasing accommodation over 4.0 mm size, whereas it remained positive under all accommodative levels over the 3.0 mm and 2.0 mm zones, and no trend was found. The 3rd order trefoil 0 changed from negative to positive with increasing accommodation, with 4.0 mm, 3.0 mm, and 2.0 mm pupil sizes. In 4.0 mm, 3.0 mm, and 2.0 mm pupil sizes, under accommodative stimuli from 0.00 to 4.00 D, dramatical trends amongst the HOAs, spherical, coma, and trefoil aberrations were demonstrated. Most of the higher-order aberrations induced by accommodation deserves further investigation. Simple elimination of the higher-order aberrations will be replaced by the optimization of aberrations.


microRNA control of mouse and human pluripotent stem cell behavior.
In the past decade, significant progress has been made in understanding both microRNA function and cellular pluripotency. Here we review the intersection of these two exciting fields. While microRNAs are not required for the establishment and maintenance of pluripotency in early development and cell culture, respectively, they are critically important in the regulation of the cell cycle structure of pluripotent stem cells as well as the silencing of the pluripotency program upon differentiation. Pluripotent cells, both in vivo and in vitro, dominantly express a single family of microRNAs, which can promote the reprogramming of a somatic cell back to a pluripotent state. Here, we review the known mechanisms by which these and other microRNAs regulate the different aspects of the pluripotent stem cell program in both mouse and human.


AZD3409 inhibits the growth of breast cancer cells with intrinsic resistance to the EGFR tyrosine kinase inhibitor gefitinib.
AKT and MAPK signaling are involved in the resistance of breast cancer cells to the EGFR tyrosine kinase inhibitor gefitinib. RAS proteins are upstream mediators that transfer messages from surface receptors to intracellular signal transducers including MAPK and AKT pathways. AZD3409 is a novel prenyl inhibitor that has shown activity against both farnesyl transferase and geranylgeranyl transferase in isolated enzyme studies. We explored the activity of AZD3409 on breast cancer cell lines with high (SK-Br-3), intermediate (MDA-MB-361) or low (MDA-MB-468) sensitivity to gefitinib. We found that AZD3409 inhibits the growth of breast cancer cells in a dose-dependent manner, with the MDA-MB-468 and MDA-MB-361 cell lines showing higher sensitivity as compared with SK-Br-3 cells. Treatment with AZD3409 produced a significant reduction in the levels of activation of AKT in the three cell lines. AZD3409 also induced an increase in the expression of p27kip-1 and of hypophosphorylated forms of pRb2 in MDA-MB-468 cells that was associated with accumulation of cells in G0/G1 and the appearance of a sub-G1 peak suggestive of apoptosis. In contrast, AZD3409 produced a G2 arrest associated with reduced expression of pRb2 in MDA-MB-361 cells. A synergistic anti-tumor effect was observed when MDA-MB-468 or MDA-MB-361 cells were treated with both AZD3409 and gefitinib, whereas this combination was only additive in SK-Br-3 cells. However, treatment of breast cancer cells with AZD3409 and gefitinib did not produce a more significant blockade of AKT signaling as compared with gefitinib alone. These data suggest that AZD3409 might be active in gefitinib-resistant breast carcinoma.


The practical application of optimal appropriateness measurement on empirical data using Rasch models.
Optimal Appropriateness Measurement (OAM) is a general statistical method for the identification of examinees whose test scores might not be a valid indicator of their true latent ability or trait. The method is statistically very powerful and it pinpoints towards the direction of the suspected aberrance instead of simply identifying that a specific response pattern is, in some way, aberrant. The method has been traditionally used with multi-parameter IRMs for the identification of examinees with spuriously low and high scores. This article presents the practical application of the method, using Rasch models, in the context of a large-scale activity which aimed to provide secondary education schools with feedback about their students' performance on a high-stakes University entrance science test. Although researchers in the past claimed that OAM was not ready to be routinely used in practical settings, this article maintains that the practical use of OAM to answer specific educationally meaningful questions is feasible.


Seasonal abundance and parity of stock-associated Culicoides species (Diptera: Ceratopogonidae) in different climatic regions in southern Africa in relation to their viral vector potential.
Seasonal abundance and parity in Culicoides populations, in the vicinity of livestock, were determined at seven sites in five different climatic regions with 220 V down-draught blacklight-traps. In 418 collections made between October 1983 and December 1986, a total of 2,134,171 Culicoides, of which 342,571 were identified to species level and sexed, were collected; 267 of these collections (182,321 Culicoides) were graded for parity. In the frost-free summer rainfall area, Culicoides were collected in large numbers in light-traps throughout the year; this implies breeding and possible virus transmission throughout the winter in certain parts of South Africa. However, where frost occurred, Culicoides numbers usually peaked in late summer and dropped sharply after the first frost. In the latter areas, small Culicoides collections during winter may be due to low winter temperatures and rainfall; low temperatures negatively affect adult activity and reduce the rate of development of larvae and pupae; low rainfall would lead to a reduction of available larval habitats. Relatively large numbers of Culicoides were collected in winter in the temperature frost-free winter rainfall area. In each of the four summer rainfall areas, one Culicoides species remained dominant throughout the year: at two of these areas this species was C. imicola. Other abundant species in some of these summer rainfall areas were C. schultzei s.l. and C. zuluensis. In the winter rainfall area, C. zuluensis, C. magnus, C. gulbenkiani and C. imicola shared abundance. It was established that abdominal pigmentation is an indicator of parity in C. imicola in South Africa. With the increase in Culicoides numbers towards the end of summer, there was also a rise in the proportion of parous (pigmented) females in most Culicoides species, which signifies a higher vector potential for African horsesickness and bluetongue towards the end of summer. This coincides with the seasonal occurrence of viral diseases transmitted by Culicoides species. Nulliparous (unpigmented) females of all Culicoides species were present throughout the year at all sites where Culicoides were continuously collected, confirming uninterrupted breeding in these areas.


A dose-ranging study of selegiline in patients with Parkinson's disease: effect of platelet monoamine oxidase activity.
A dose-ranging study of selegiline was performed in patients with Parkinson's disease to determine the minimal dosage of the drug able to inhibit > or = 95% of platelet monoamine oxidase (MAO) activity. Different doses of selegiline (5 or 10 mg daily, 10 or 20 mg weekly) were studied in four groups of six patients with Parkinson's disease. Platelet MAO activity was measured before and after 1 month's treatment with selegiline. The doses of 5 or 10 mg daily and 20 mg (i.e., 10 mg x 2) weekly induced a complete inhibition of platelet MAO-B activity from day 7 to day 28 (96.0-99.5%). In contrast, platelet MAO-B inhibition was only 75.9% of the basal value after a dosage of 10 mg weekly. These results demonstrate that 20 mg weekly is the minimal dosage of selegiline able to induce a maximal and long-lasting inhibition of platelet MAO-B activity in patients with parkinsonism. Further clinical trials are needed to investigate the clinical efficacy of this dose.


Determination of catecholamines in urine using aminophenylboronic acid functionalized magnetic nanoparticles extraction followed by high-performance liquid chromatography and electrochemical detection.
A new method was developed for the simultaneous determination of three catecholamines in urine using aminophenylboronic acid functionalized magnetic nanoparticles extraction followed by high-performance liquid chromatography with electrochemical detection. Novel aminophenylboronic acid functionalized magnetic nanoparticles were prepared by multi-step covalent modification, and characterized by transmission electron microscopy, Fourier-transformed infrared spectroscopy, X-ray diffraction, and vibrating sample magnetometry. With the help of the high affinity between the boronate and cis-diol group, the particles were used for the highly selective separation and enrichment of three major catecholamines, norepinephrine, epinephrine, and dopamine. Effects of the pH of the feed solution, the extraction time, the composition of the buffer solution, the amount of the magnetic particles, the elution conditions, and the recycling of aminophenylboronic acid functionalized magnetic nanoparticles were explored. Under the optimized conditions, 13-17-fold enrichment factors were obtained. The linear ranges were 0.01-2.0 μg/mL for the studied analytes. The limits of detection and quantification were in the range of 2.0-7.9 and 6.7-26.3 ng/mL, respectively. The relative recoveries were in the range of 92-108%, with intraday and interday relative standard deviations lower than 6.8%. This method was successfully applied to analysis of catecholamines in real urine.


Correlated SVD and Its Application in Bearing Fault Diagnosis.
The singular value decomposition (SVD) based on the Hankel matrix is commonly used in signal processing and fault diagnosis. The noise reduction performance of SVD based on the Hankel matrix is affected by three factors: the reconstruction component(s), the structure of the Hankel matrix, and the point number of the analysis data. In this article, the three influencing factors are systematically studied, and a method based on correlated SVD (C-SVD) is proposed and successfully applied to bearing fault diagnosis. First, perform SVD analysis on the collected original signal. Then, the reconstructed component(s) determination method of SVD based on the combination of singular value ratio (SVR) and correlation coefficient is proposed. Then, based on the SVR, using the envelope kurtosis as the indicator, the optimal structure of the Hankel matrix (number of rows and columns) is studied. Then, the number of data points of the analysis signal is discussed, and the constraint range is given. Finally, the envelope power spectrum analysis is performed on the reconstructed signal to extract the fault features. The proposed C-SVD method is compared with the existing typical methods and applied to the simulated signal and the actual bearing fault signal, and its superiority is verified.


Six-year trends in dental pain and maternal education inequalities among Brazilian adolescents.
To analyse trends in dental pain prevalence among Brazilian adolescent students over 6 years, focusing on inequalities by maternal education. Data from the National Adolescent School-Based Health Survey (PeNSE) carried out in 2009 (n = 45 239), 2012 (n = 46 482) and 2015 (n = 35 592) were analysed, including ninth grade students from the 27 state capitals in Brazil who were of ages 11-17 years or older. Variables analysed were dental pain within the last 6 months (yes/no) and the following sociodemographic factors: age, sex, race, type of school and maternal schooling (years of study: ≤8; 9-11; ≥12). The prevalence of dental pain in the 3 years was compared using the Rao-Scott test. Relative and absolute measures of socioeconomic (maternal education) inequalities in dental pain were applied using the slope index of inequality (SII) and the relative concentration index (RCI). The prevalence of dental pain increased from 17.5% (95% CI = 16.9-18.2) in 2009 to 20.4% (95% CI = 19.7-21.1) in 2012, then to 21.8% (95% CI = 21.1-22.5) in 2015. All sociodemographic factors investigated were associated with dental pain in all survey years. There was an increasing proportion of the outcome in all categories of maternal education over the years studied. Absolute (SII) and relative (RCI) inequalities regarding of maternal education were found; these indicate higher levels of dental pain in the lower socioeconomic group in each study year. However, no significant changes in inequalities were found from 2009 to 2015. The prevalence of dental pain increased in the 2009-2012 and 2012-2015 periods, and social inequalities were found. Higher levels of dental pain persisted in the lower maternal education group. Inequalities remained stable over time. Broader actions to reduce the existing inequalities are needed and should be a priority for public policies.


[Cryopreservation of spermatozoa].
Sperm cryopreservation has revolutionized the field of assisted reproduction. However, it causes cryodamage to the structure and function of spermatozoa during the freezing-thawing process. Optimization of sperm cryopreservation is necessary for the preservation of male fertility. Cryodamage can be reduced effectively by such methods as improvement of semen quality before freezing, spermatozoal selection, addition of optimal cryoprotectants and application of appropriate thawing techniques. Recent studies focus on cryobiology, improvement of freezing-thawing methods, especially for poor quality semen, and evaluation criteria for post-thaw spermatozoa.


Safe and Effective Reduction Technique for Intertrochanteric Fracture with Ipsilateral Below-Knee Amputated Limb.
The positioning of the patient on the fracture table is critical for the successful reduction and operative fixation of intertrochanteric hip fractures. However, this manipulation is challenging with patients who have undergone amputations of their legs. A 97-year-old man presented to the emergency department with symptom of right hip pain following a mechanical fall. He had a below-knee amputation on his right leg following a traffic accident as a 19-year-old and had a below-knee patellar tendon bearing prosthesis fitted to his lower limb for mobility. Radiographs of his pelvis revealed a displaced intertrochanteric fracture of the right side femur. The patient was positioned on a fracture table, as in the standard procedure. The method of inverting the traction boot to accommodate the flexed knee and stump described by Al-Harthy could be used to provide traction and rotational control. Internal fixation was performed using a short femoral nail. Postoperatively, the patient could walk with full weight bearing using a prosthesis on his affected limb. The method of inverting the traction boot to accommodate the flexed knee and stump can be used safely and effectively to achieve and maintain fracture reduction during fixation of intertrochanteric fractures for patients with a below-knee amputated limb.


Genetic linkage studies of transferrin, pseudocholinesterase, and chromosome 1 loci.
Genetic linkage analysis of a pedigree with four different alleles for pseudocholinesterase (CHE1) gives a positive lod score of 0.37 at theta = 0.16 for linkage with transferrin (TF), a finding which supports previous reports of linkage between CHE1 and TF. Evaluation of linkage relations of CHE1 and TF using unreported families from our data bank fails to establish linkage with chromosome 1 loci (6-PGD, Rh, PGM1, AMY2 and FY). These results are consistent with recent studies which suggest that TF is on human chromosome 3.


Sensitive Quantification of Liensinine Alkaloid Using a HPLC-MS/MS Method and Its Application in Microvolume Rat Plasma.
Liensinine, an important alkaloid in lotus seed, exhibits multiple functions such as anti-AIDS, anticancer, antidepressant, and antihypertensive properties. In this study, a highly sensitive HPLC-MS/MS method was developed and validated for the quantification of liensinine in microvolume rat plasma as low as 45 μL. Chromatographic separation was carried out using a reverse-phase Gemini-C18 column (100 mm × 3 mm i.d. × 5 μm), and mass selective detection using multiple reaction monitoring was attained using an electrospray ionization source, which operated in the positive mode. Dauricine was used as the internal standard. The precursor-to-product ion transition m/z 611.15 > 206.10 was selected for the detection of liensinine; m/z 625.25 > 206.10 was used for the detection of dauricine. The developed method is linear over the concentration range of 0.05-1000 ng/mL with an excellent coefficient of determination (R 2 = 0.991). The recoveries ranged from 92.57% to 95.88% at three quality control levels. Intraday and interday precision and accuracy are less than 12.2% and 6.59%, respectively. The lower limit of quantification (LLOQ) is 0.05 ng/mL. The matrix effect was insignificant and acceptable. The validated method was successfully applied to the pharmacokinetic study of liensinine in rats. This method can be used for in vivo studies as well as quality control of traditional Chinese medicines and herbal tea containing liensinine alkaloid.


Locomotion in patients with spinal cord injuries.
Following central motor lesions, two forms of reorganization can be observed that lead to improved mobility: (1) the development of increased muscle tone and (2) the activation of spinal locomotor centers induced by specific treadmill training. Tension development is different from normal during spastic gait and appears to be independent of exaggerated monosynaptic stretch reflexes. Exaggerated stretch reflexes are associated with an absence or reduction of functionally essential polysynaptic reflexes. Based on observations of the locomotor capacity of the spinal cat, recent studies have indicated that spinal locomotor centers can be activated and trained in patients with complete or incomplete paraplegia when the body is partially unloaded. The level of electromyographic activity in the gastrocnemius muscle, however, is considerably lower in patients with central motor lesions than in persons without neurological impairments. During the course of a daily locomotor training program, the amplitude of gastrocnemius muscle electromyographic activity increases during the stance phase and inappropriate tibialis anterior muscle activity decreases. Such training programs can improve the ability of patients with incomplete paraplegia to walk on stationary surfaces. This article reviews the pathophysiology and functional importance of increased muscle tone and the effects of treadmill training on the locomotor pattern underlying new attempts to improve the mobility of patients with paraplegia.


Parasite virulence, host life history, and the costs and benefits of sex.
The widespread existence of sexual reproduction is widely considered to be one of the most pressing anomalies for evolutionary theory. One possible solution is that coevolution between hosts and parasites might favor sexual over asexual reproduction (the Red Queen hypothesis), provided infection is genotype specific and highly virulent. This requirement for high virulence has been seen as a limitation of the theory. In the present study, I solve for the cost of sex per reproductive time step of the host, as well as the minimum virulence required to select for sex. The results show that the cost of sex per time step increases with increases in the host's mortality rate, reaching twofold in annual host species. The results also show that high virulence is not required to select for sexual reproduction, especially in long-lived organisms. These findings might help to explain the paucity of parthenogenesis in organisms having long generation times.


Squamous cell carcinoma of the prostate.
Eleven case of squamous cell carcinoma of the prostate have been divided into four groups according to their histological features and natural history: a pure squamous cell carcinoma of the prostate (one case); b common prostatic adenocarcinoma with malignant squamous component after oestrogen treatment (two); c urothelial carcinoma of the prostate with malignant squamous cell metaplasia (four); and d urothelial carcinoma of the urinary bladder with squamous cell metaplasia growing into the prostate (four). The squamous portions may spread to invade the fibromuscular stroma and grow in prostatic ducts. Necrosis of comedo type and inflammatory infiltrates appeared in a number of cases. The survival times of nine patients ranged from 1 to 17 months. Squamous components were shown by immunohistochemistry to contain various keratin types, carcino-embryonic antigen and peanut agglutinin binding sites. Whenever a squamous cell carcinoma in the prostate is diagnosed histologically various possibilities as to its origin should be considered.


Administration of vaccine-boosted COVID-19 convalescent plasma to SARS-CoV-2 infected hamsters decreases virus replication in lungs and hastens resolution of the infection despite transiently enhancing disease and lung pathology.
The utility of COVID-19 convalescent plasma (CCP) for treatment of immunocompromised patients who are not able to mount a protective antibody response against SARS-CoV-2 and who have contraindications or adverse effects from currently available antivirals remains unclear. To better understand the mechanism of protection in CCP, we studied viral replication and disease progression in SARS-CoV-2 infected hamsters treated with CCP plasma obtained from recovered COVID patients that had also been vaccinated with an mRNA vaccine, hereafter referred to as Vaxplas. We found that Vaxplas dramatically reduced virus replication in the lungs and improved infection outcome in SARS-CoV-2 infected hamsters. However, we also found that Vaxplas transiently enhanced disease severity and lung pathology in treated animals likely due to the deposition of immune complexes, activation of complement and recruitment of increased numbers of macrophages with an M1 proinflammatory phenotype into the lung parenchyma.


Suspended carbon nanotube quantum wires with two gates.
Suspended single-walled carbon nanotube devices comprised of high-quality electrical contacts and two electrostatic gates per device have been prepared. Compared to nanotubes pinned on substrates, the suspended devices exhibit little hysteresis related to environmental factors and act as cleaner Fabry-Perot interferometers or single-electron transistors. The high-field saturation currents in the suspended nanotubes related to optical phonon or zone-boundary phonon scattering are significantly lower due to the lack of efficient heat sinking. The multiple-gate design may also facilitate future investigations into the electromechanical properties of nanotube quantum systems.


Phenolic constituents and antioxidant properties of Xanthosoma violaceum leaves.
An extract of Xanthosoma violaceum leaves was subjected to a polyphenol profile determination, including total polyphenols, and antioxidant activity evaluation. Analysis of the extract resulted in the isolation of a new flavone C-glycoside, apigenin 6-C-beta-D-glucopyranosyl-8-C-beta-D-apiofuranoside (1), as well as known flavone C-glycosides, including vitexin (2), isovitexin (3), isovitexin 4'-O-rhamnopyranoside (4), apigenin 6-C-[beta-D-glucopyranosyl-(1-->6)-beta-D-glucopyranoside] (5), and apigenin 6,8-diC-beta-D-glucopyranoside (6). The antioxidant activity of the extract was assessed by means of two different in vitro tests: bleaching of the stable 1,1-diphenyl-2-picrylhydrazyl radical (DPPH test) and peroxidation induced by the water-soluble radical initiator 2,2'-azobis(2-amidinopropane) hydrochloride, on mixed dipalmitoylphosphatidylcholine/linoleic acid unilamellar vesicles (LP-LUV test). In both tests used, the extract and a fraction II showed a significant antioxidant/free-radical scavenging effect (fraction II, EC(50) = 11.6 microg/mL) in comparison to alpha-tocopherol (EC(50) = 10.1 microg/mL).


Advances in treatment of achondroplasia and osteoarthritis.
Achondroplasia (ACH) is the prototype and most common of the human chondrodysplasias. It results from gain-of-function mutations that exaggerate the signal output of the fibroblast growth factor receptor 3 (FGFR3), a receptor tyrosine kinase that negatively regulates growth plate activity and linear bone growth. Several approaches to reduce FGFR3 signaling by blocking receptor activation or inhibiting downstream signals have been proposed. Five show promise in preclinical mouse studies. Two candidate therapies target the extracellular domain of FGFR3. The first is a decoy receptor that competes for activating ligands. The second is a synthetic blocking peptide that prevents ligands from binding and activating FGFR3. Two established drugs, statins and meclozine, improve growth of ACH mice. The strongest candidate therapy employs an analog of C-type natriuretic peptide (CNP), which antagonizes the mitogen-activated-protein (MAP) kinase pathway downstream of the FGFR3 receptor and may also act independently in the growth plate. Only the CNP analog has reached clinical trials. Preliminary results of Phase 2 studies show a substantial increase in growth rate of ACH children after six months of therapy with no serious adverse effects. A challenge for drug therapy in ACH is targeting agents to the avascular growth plate. The application of gene therapy in osteoarthritis offers insights because it faces similar technical obstacles. Major advances in gene therapy include the emergence of recombinant adeno-associated virus as the vector of choice, capsid engineering to target vectors to specific tissues, and development of methods to direct vectors to articular chondrocytes.


Flow-diverter in radiation-induced skull base carotid blowout syndrome: do not write it off!
Post-radiotherapy carotid blowout syndrome (CBS) of the skull base is a rare but often catastrophic complication of head and neck malignancies. The existing literature on the treatment of this condition with flow-diverting devices (FDD) is extremely limited and disappointing. We present a case of impending CBS in a patient previously irradiated for nasopharyngeal cancer that was successfully treated with use of multiple FDDs, adjunctive endonasal packing and delayed reinforcement with pedicled naso-septal flap, yielding an excellent outcome at 14-months follow-up. Notwithstanding the discouraging results in literature, our anecdotal experience suggests that endovascular reconstruction using FDD could be an option with long-term viability in post-radiotherapy CBS involving the skull base when reinforced with a vascularised naso-septal flap.


Career Success Criteria Clarity as a Predictor of Employment Outcomes.
Drawing on the goal-setting theory and social cognitive career theory (SCCT), this study empirically proposes an operational definition of career success criteria clarity (CSCC) and further explores its impact on career satisfaction, person-job fit, and subjective well-being through the mediating role of career decision-making self-efficacy (CDSE). A pilot study of 231 samples showed that the CSCC scale had good reliability and validity. To further test the effects of CSCC on crucial employment outcomes, as well as the mediating role of CDSE, 240 employees were included in an additional survey. Structural equation modeling path analysis supported all the expected hypotheses. Results indicated that: (1) CSCC was positively correlated to career satisfaction; (2) CSCC was positively correlated to person-job fit; (3) CSCC was positively correlated to subjective well-being; (4) CSCC was positively correlated to CDSE; (5) CDSE fully mediated the relationship between CSCC and career satisfaction; (6) CDSE fully mediated the relationship between CSCC and person-job fit; and (7) CDSE partly mediated the relationship between CSCC and subjective well-being. The results contributed to social cognitive career theory model and provided suggestions for both the career educators and consultants.


Mendelian randomization eradicates the causal relationship between educational attainment, household income, and oropharyngeal cancer.
It was reported that educational attainment and household income are associated with oropharyngeal cancer. However, whether such an association is causal is still unknown. The Mendelian randomization (MR) design was performed to disentangle their causal relationship. Initially, genetic variants proxied for educational attainment and household income were extracted from the largest genome-wide association studies (GWAS), and two oropharyngeal GWAS datasets were used in the discovery and validation stages separately. A reverse MR analysis was carried out to judge whether oropharyngeal cancer affects educational attainment and household income. The results from the two stages were combined using meta-analysis. The heterogeneity and horizontal pleiotropy were appraised using several methods. All selected genetic variants were valid. In the discovery stage, genetically elevated years of education might decrease the risk of oropharyngeal cancer (IVW OR = 0.148 [0.025, 0.872], p-value = 0.035), while such a result became insignificant in the validation stage (IVW p-value >0.05). Household income cannot change the risk of oropharyngeal cancer at both stages. The reverse MR suggested that oropharyngeal cancer should slightly alter household income (IVW OR = 1.001 [1.000, 1.003], p-value = 0.036) in the discovery set, but the result cannot be replicated in the validation stage. The meta-analysis did not find any significant results either. The results were also assessed by sensitivity analyses, and there was no heterogeneity or horizontal pleiotropy in the analyses. The statistical powers were all above 80% at the discovery stage. There should be no causal association between educational attainment, household income, and oropharyngeal cancer.


Inhibition of human tumor growth in nude mice by a conjugate of doxorubicin with monoclonal antibodies to epidermal growth factor receptor.
Monoclonal antibodies that recognize the extracellular domain of the epidermal growth factor receptor (mAb108) were conjugated with doxorubicin through a dextran bridge. Several antibody-drug conjugates, containing different amounts of doxorubicin, retained binding capacity to human epidermoid carcinoma (KB) cells overexpressing epidermal growth factor receptors. Slight decrease in drug cytotoxicity was seen in in vitro tests, as determined either by inhibition of thymidine incorporation into cells or by reduction in number and size of KB-cell colonies. Yet, when tested in vivo against KB tumor xenografted into nude mice, the anti-epidermal growth factor-receptor drug conjugates with high drug-substitution levels were significantly more effective than free doxorubicin, antibody alone, mixture of dextran-doxorubicin and antibody, or drug conjugated with irrelevant antibody. When the labile covalent bonds linking antibody to dextran bridge were stabilized by reduction, the therapeutic efficacy of the conjugate was markedly decreased. These results show that antibodies against the extracellular domain of the epidermal growth factor can deliver doxorubicin specifically and efficiently to tumor sites that express high receptor levels exerting a specific antitumor effect.


Genetic polymorphisms and cerebrovascular disease in children with sickle cell anemia from Rio de Janeiro, Brazil.
The aim of the present work was to examine possible genetic risk factors related to the occurrence of cerebrovascular disease (CVD) in Brazilian population, the frequency of β(S)-globin gene haplotypes and co-inheritance with α-thalassemia (-α(3.7kb)) and single nucleotide polymorphism of methylenetetrahydrofolate reductase (MTHFR-C677T), Factor V Leiden (FV-G1691A) and prothrombin (PT-G20210A) genes in children from Rio de Janeiro. Ninety four children with sickle cell anemia (SCA) were included, 24 patients with cerebrovascular involvement and 70 patients without CVD as control group. The mean age of children at the time of the cerebrovascular event was similar to the control group. The frequency of -α(3.7kb) thalassemia was similar in both groups (p=0.751). Children with Bantu/Atypical β(S)-globin gene haplotype presented 15 times more chance (OR=15.4 CI 95% 2.9-81.6) of CVD than the other β(S)-globin gene haplotypes. The C677T polymorphism of MTHFR gene was similar in both groups (p=0.085). No mutation in the FV Leiden or PT genes was found. A large study seems necessary to establish the role of these genetic polymorphisms in Brazilian miscegenated population.