BAIBA Does Not Regulate UCP-3 Expression in Human Skeletal Muscle as a Response to Aerobic Exercise.
β-Aminoisobutyric acid (BAIBA) has shown to modulate uncoupling protein (UCP)-1 expression, which is mainly expressed in white adipose tissue; however, no studies to date have analyzed its potential effect on the main uncoupling protein of skeletal muscle, UCP-3. The main goal of this study was to assess the potential effect of acute aerobic exercise on serum BAIBA and skeletal muscle UCP-3. The secondary goal was to assess the potential involvement of the transcription factors proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) and peroxisome proliferator-activated receptor alpha (PPARα), as well as free fatty acids (FFAs) in UCP-3 expression. A tertiary goal of the study was to evaluate the potential effect of consuming a preexercise meal on the outcome of the first 2 objectives. In a randomized crossover design, untrained participants performed 2 acute cycling sessions (350 kcal at 70% of their VO2peak) after 2 experimental conditions: (1) consumption of a multi-macronutrient shake and (2) a fasting period of 8 hours. Blood samples were taken at baseline, preexercise, postexercise, 1 hour, and 4 hours postexercise, and muscle biopsies were taken at the last 4 time points. UCP-3 protein concentration and expression, as well as the mRNA expression of PGC-1α and PPARα, were measured in muscle, and BAIBA, glucose, and FFA were measured in serum. Aerobic exercise failed to induce a significant effect on serum BAIBA, PGC-1α, and PPARα regardless on the feeding condition. Despite the lack of effect of exercise on the previous variables, UCP-3 expression and protein concentration significantly increased in the shake condition. The expression of human skeletal muscle UCP-3 as a result of exercise might be controlled by factors other than BAIBA.


An improved method for the purification of DNA-dependent RNA polymerase from Escherichia coli.
DNA-dependent RNA polymerase from Escherichia coli was purified further by elution through heparin-Sepharose CL-6B column after the enzyme was obtained, partially purified, using Burgess and Jendrisak's method [(1975)Biochemistry 14, 4634] The total yield of the pure protein was 10 mg from 50 g of E.coli cells. The method was found to be very reproducible and convenient. The enzyme preparation had 60% active molecules and the elongation rate of RNA synthesis by this enzyme was measured to be 11 bases/s over delta D111 T7 DNA.


A Pretargeted Imaging Strategy for Immune Checkpoint Ligand PD-L1 Expression in Tumor Based on Bioorthogonal Diels-Alder Click Chemistry.
The use of antibodies as tracers requires labeling with isotopes with long half-lives due to their slow pharmacokinetics, which creates prohibitively high radiation dose to non-target organs. Pretargeted methodology could avoid the high radiation exposure due to the slow pharmacokinetics of antibodies. In this investigation, we reported the development of a novel pretargeted single photon emission computed tomography (SPECT) imaging strategy (atezolizumab-TCO/[99mTc]HYNIC-PEG11-Tz) for evaluating immune checkpoint ligand PD-L1 expression in tumor based on bioorthogonal Diels-Alder click chemistry. The radioligand [99mTc]HYNIC-PEG11-Tz was achieved by the synthesis of a 6-hydrazinonicotinc acid (HYNIC) modified 1,2,4,5-tetrazine (Tz) and subsequently radiolabeled with technetium-99m (Tc-99m). The stability of [99mTc]HYNIC-PEG11-Tz was evaluated in vitro, and its blood pharmacokinetic test was performed in vivo. Atezolizumab was modified with trans-cyclooctene (TCO). The [99mTc]HYNIC-PEG11-Tz and atezolizumab-TCO interaction was tested in vitro. Pretargeted H1975 cell immunoreactivity binding and saturation binding assays were evaluated. Pretargeted biodistribution and SPECT imaging experiments were performed in H1975 and A549 tumor-bearing modal mice to evaluate the PD-L1 expression level. [99mTc]HYNIC-PEG11-Tz was successfully radiosynthesized with a specific activity of 9.25 MBq/μg and a radiochemical purity above 95 % as confirmed by reversed-phase HPLC (RP-HPLC). [99mTc]HYNIC-PEG11-Tz showed favorable stability in NS, PBS, and FBS and rapid blood clearance in mice. The atezolizumab was modified with TCO-NHS ester to produce a conjugate with an average 6.4 TCO moieties as confirmed by liquid chromatograph-mass spectrometer (LC-MS). Size exclusion HPLC revealed almost complete reaction between atezolizumab-TCO and [99mTc]HYNIC-PEG11-Tz in vitro, with the 1:1 Tz-to-mAb reaction providing a conversion yield of 88.65 ± 1.22 %. Pretargeted cell immunoreactivity binding and saturation binding assays showed high affinity to H1975 cells. After allowing 48 h for accumulation of atezolizumab-TCO in H1975 tumor, pretargeted in vivo biodistribution revealed high uptake of the radiotracer in the tumor with a tumor-to-muscle ratio of 27.51 and tumor-to-blood ratio of 1.91. Pretargeted SPECT imaging delineated the H1975 tumor clearly. Pretargeted biodistribution and SPECT imaging in control groups demonstrated a significantly reduced tracer accumulation in the A549 tumor. We have developed a HYNIC-modified Tz derivative, and the HYNIC-PEG11-Tz was labeled with Tc-99m with a high specific activity and radiochemical purity. [99mTc]HYNIC-PEG11-Tz reacted rapidly and almost completely towards atezolizumab-TCO in vitro with the 1:1 Tz-to-mAb reaction. SPECT imaging using the pretargeted strategy (atezolizumab-TCO/[99mTc]HYNIC-PEG11-Tz) demonstrated high-contrast images for high PD-L1 expression H1975 tumor and a low background accumulation of the probe. The pretargeted imaging strategy is a powerful tool for evaluating PD-L1 expression in xenograft mice tumor models and a potential candidate for translational clinical application.


Correction: Evidence for Reduced Drug Susceptibility without Emergence of Major Protease Mutations following Protease Inhibitor Monotherapy Failure in the SARA Trial.
[This corrects the article DOI: 10.1371/journal.pone.0137834.].


Looking for the niche: substance delivery into the lateral ventricle of the brain: the osmotic minipump system.
The infusion of different substances into the left ventricle of the brain allows substances to reach the subventricular zone, one of the neural stem cell niches in the adult brain. Implantation of an osmotic minipump delivers proteins, virus and drugs directly into the lateral ventricle to act locally. Here we describe this method consisting on a cannula implanted into the lateral ventricle and linked to an osmotic minipump via catheter. The cannula is fixed over the brain and the minipump is placed subcutaneously. This system can be maintained from days up to several weeks and ensures constant and regular delivery of the desired biological product.


Ginsenoside Rb1 ameliorates cisplatin-induced learning and memory impairments.
Ginsenoside Rb1 (Rb1), a dominant component from the extract of Panax ginseng root, exhibits neuroprotective functions in many neurological diseases. This study was intended to investigate whether Rb1 can attenuate cisplatin-induced memory impairments and explore the potential mechanisms. Cisplatin was injected intraperitoneally with a dose of 5 mg/kg/wk, and Rb1 was administered in drinking water at the dose of 2 mg/kg/d to rats for 5 consecutive wk. The novel objects recognition task and Morris water maze were used to detect the memory of rats. Nissl staining was used to examine the neuron numbers in the hippocampus. The activities of superoxide dismutase, glutathione peroxidase, cholineacetyltransferase, acetylcholinesterase, and the levels of malondialdehyde, reactive oxygen species, acetylcholine, tumor necrosis factor-α, interleukin-1β, and interleukin-10 were measured by ELISA to assay the oxidative stress, cholinergic function, and neuroinflammation in the hippocampus. Rb1 administration effectively ameliorates the memory impairments caused by cisplatin in both novel objects recognition task and Morris water maze task. Rb1 also attenuates the neuronal loss induced by cisplatin in the different regions (CA1, CA3, and dentate gyrus) of the hippocampus. Meanwhile, Rb1 is able to rescue the cholinergic neuron function, inhibit the oxidative stress and neuroinflammation in cisplatin-induced rat brain. Rb1 rescues the cisplatin-induced memory impairment via restoring the neuronal loss by reducing oxidative stress and neuroinflammation and recovering the cholinergic neuron functions.


Amyloid beta-proteins 1-40 and 1-42(43) in the soluble fraction of extra- and intracranial blood vessels.
To investigate the process of amyloid beta-protein (A beta) accumulation in cerebral amyloid angiopathy (CAA), the levels of A beta were determined in the soluble fraction of extra- and intracranial blood vessels and leptomeninges obtained at autopsy. Two enzyme immunoassays were employed that are known to sensitively and specifically quantify two A beta species, A beta 1-40 and 1-42(43). A beta was detectable in the intracranial blood vessels and leptomeninges with the latter containing the highest levels, while it was undetectable in the extracranial blood vessels. Thus the levels of soluble A beta correlated well with the predilection sites for CAA. Among individuals aged 20 to 90, the A beta levels in the leptomeninges increased sharply in those aged 50 to 70 and thereafter tended to decline. However, only slight degrees of CAA were detected by immunocytochemistry, even when those leptomeninges contained high levels of A beta comparable with those in Alzheimer's disease. The level of A beta 1-42 was almost always severalfold that of A beta 1-40 in the soluble fraction of leptomeninges. This is in good agreement with the immunocytochemical result showing the presence of A beta 40-negative, A beta 42(43)-positive meningeal vessels. These results indicate that A beta 1-42 is the initially deposited species in CAA and that the disruption of A beta homeostasis precedes A beta deposition in the meningeal vessels.


Bilateral extensive xanthelasma palpebrarum.
A case of xanthelasma palpebrarum with extensive and disfiguring involvement of all four eyelids in a patient without abnormal serum lipid levels is reported.


Determinants of Primary School Non-Enrollment and Absenteeism: Results from a Retrospective, Convergent Mixed Methods, Cohort Study in Rural Western Kenya.
Education is a key element in the socioeconomic development required to improve quality of life in Kenya. Despite the introduction of free primary education, primary school enrollment and attendance levels remain low. Drawing on qualitative and quantitative data, this study explores the determinants of non-enrollment and absenteeism in rural western Kenya and potential mitigation strategies to address these issues. The study was conducted in Bwaliro village in rural western Kenya. A random sample of 64 students was obtained by blocking the village primary school's student population according to grade level, gender, and orphan status. Qualitative and quantitative data were collected through interviews with parents, guardians, and key informants, and focus group discussions with students. Quantitative data were compared using chi-square tests, Student's T-test, and Poisson regressions. Qualitative data were analyzed using thematic content analysis. Malaria, menstruation, and lack of money were among the most notable determinants of primary school dropout and absenteeism, and these factors disproportionately impacted orphans and female students. Potential mitigation strategies suggested by the community included provision of malaria treatment or prevention, reduction in education costs, expansion of the established school-feeding program, and provision of sanitary pads. Despite free primary education, numerous factors continue to prevent children in rural western Kenya from attending primary school. The findings suggest that interventions should primarily target orphaned and female students. Prior to implementation, suggested mitigation strategies should be assessed for cost-effectiveness.


Loophole-free Bell inequality violation with superconducting circuits.
Superposition, entanglement and non-locality constitute fundamental features of quantum physics. The fact that quantum physics does not follow the principle of local causality1-3 can be experimentally demonstrated in Bell tests4 performed on pairs of spatially separated, entangled quantum systems. Although Bell tests, which are widely regarded as a litmus test of quantum physics, have been explored using a broad range of quantum systems over the past 50 years, only relatively recently have experiments free of so-called loopholes5 succeeded. Such experiments have been performed with spins in nitrogen-vacancy centres6, optical photons7-9 and neutral atoms10. Here we demonstrate a loophole-free violation of Bell's inequality with superconducting circuits, which are a prime contender for realizing quantum computing technology11. To evaluate a Clauser-Horne-Shimony-Holt-type Bell inequality4, we deterministically entangle a pair of qubits12 and perform fast and high-fidelity measurements13 along randomly chosen bases on the qubits connected through a cryogenic link14 spanning a distance of 30 metres. Evaluating more than 1 million experimental trials, we find an average S value of 2.0747 ± 0.0033, violating Bell's inequality with a P value smaller than 10-108. Our work demonstrates that non-locality is a viable new resource in quantum information technology realized with superconducting circuits with potential applications in quantum communication, quantum computing and fundamental physics15.


Planar Tc99m--sestamibi scintimammography should be considered cautiously in the axillary evaluation of breast cancer protocols: results of an international multicenter trial.
Lymph node status is the most important prognostic indicator in breast cancer in recently diagnosed primary lesion. As a part of an interregional protocol using scintimammography with Tc99m compounds, the value of planar Tc99m sestamibi scanning for axillary lymph node evaluation is presented. Since there is a wide range of reported values, a standardized protocol of planar imaging was performed. One hundred and forty-nine female patients were included prospectively from different regions. Their mean age was 55.1 +/- 11.9 years. Histological report was obtained from 2.987 excised lymph nodes from 150 axillas. An early planar chest image was obtained at 10 min in all patients and a delayed one in 95 patients, all images performed with 740-925 MBq dose of Tc99m sestamibi. Blind lecture of all axillary regions was interpreted by 2 independent observers considering any well defined focal area of increased uptake as an involved axilla. Diagnostic values, 95% confidence intervals [CI] and also likelihood ratios (LR) were calculated. Node histology demonstrated tumor involvement in 546 out of 2987 lymph nodes. Sestamibi was positive in 30 axillas (25 true-positive) and negative in 120 (only 55 true-negative). The sensitivity corresponded to 27.8% [CI = 18.9-38.2] and specificity to 91.7% [81.6-97.2]. The positive and negative LR were 3.33 and 0.79, respectively. There was no difference between early and delayed images. Sensitivity was higher in patients with palpable lesions. This work confirmed that non tomographic Tc99m sestamibi scintimammography had a very low detection rate for axillary lymph node involvement and it should not be applied for clinical assessment of breast cancer.


Diagnostic and prognostic value of SHOX2 and SEPT9 DNA methylation and cytology in benign, paramalignant, and malignant ascites.
Cytology remains the gold standard for the detection of malignant cells in ascites. However, its sensitivity is limited. The aim of this study was to evaluate DNA methylation biomarkers for the differential diagnosis of benign (ascites in patients without malignancy), malignant (ascites in cancer patients directly caused by malignancy), and paramalignant (ascites in cancer patients caused by comorbidities but not by malignancy) ascites. A cohort of 283 patients (134 cancer patients, 149 patients with benign diseases) presenting with ascites was prospectively enrolled. Ascites was evaluated by means of cytopathological investigation and DNA methylation of SHOX2 and SEPT9 in the cell-free and cellular fraction. DNA methylation in bisulfite-converted DNA was determined using quantitative methylation specific real-time PCR. Cytopathological and DNA methylation results were evaluated with regard to diagnosis and overall survival (OS). Patients with positive DNA methylation had a poor overall survival compared to methylation-negative patients (hazard ratio: HR = 1.97, p = 0.001). In multivariate survival analysis, DNA methylation was an independent prognostic parameter (p = 0.003) together with age (HR = 1.03, p < 0.001) and the presence of malignant disease (HR = 1.87, p < 0.001). The combination of methylation with cytopathological analyses led to a 42 % increase in the detection rate of malignant ascites, resulting in 37 % positively diagnosed cancer patients and a specificity of 97 %. Among cancer patients, patients with DNA methylation-positive ascites showed an adverse clinical course (HR = 1.63, p = 0.039). DNA methylation testing adds diagnostic and prognostic information and might constitute an effective ancillary method for the differential diagnosis of malignant, paramalignant, and benign ascites.


Cost-effectiveness of national mandatory screening of all admissions to English National Health Service hospitals for meticillin-resistant Staphylococcus aureus: a mathematical modelling study.
In December, 2010, National Health Service (NHS) England introduced national mandatory screening of all admissions for meticillin-resistant Staphylococcus aureus (MRSA). We aimed to assess the effectiveness and cost-effectiveness of this policy, from a regional or national health-care decision makers' perspective, compared with alternative screening strategies. We used an individual-based dynamic transmission model parameterised with national MRSA audit data to assess the effectiveness and cost-effectiveness of admission screening of patients in English NHS hospitals compared with five alternative strategies (including no screening, checklist-activated screening, and high-risk specialty-based screening), accompanied by patient isolation and decolonisation, over a 5 year time horizon. We evaluated strategies for different NHS hospital types (acute, teaching, and specialist), MRSA prevalence, and transmission potentials using probabilistic sensitivity analyses. Compared with no screening, mean cost per quality-adjusted life-year (QALY) of screening all admissions was £89,000-148,000 (range £68,000-222,000), and this strategy was consistently more costly and less effective than alternatives for all hospital types. At a £30,000/QALY willingness-to-pay threshold and current prevalence, only the no-screening strategy was cost effective. The next best strategies were, in acute and teaching hospitals, targeting of high-risk specialty admissions (30-40% chance of cost-effectiveness; mean incremental cost-effectiveness ratios [ICERs] £45,200 [range £35,300-61,400] and £48,000/QALY [£34,600-74,800], respectively) and, in specialist hospitals, screening these patients plus risk-factor-based screening of low-risk specialties (a roughly 20% chance of cost-effectiveness; mean ICER £62,600/QALY [£48,000-89,400]). As prevalence and transmission increased, targeting of high-risk specialties became the optimum strategy at the NHS willingness-to-pay threshold (£30,000/QALY). Switching from screening all admissions to only high-risk specialty admissions resulted in a mean reduction in total costs per year (not considering uncertainty) of £2·7 million per acute hospital, £2·9 million per teaching, and £474,000 per specialist hospital for a minimum rise in infections (about one infection per year per hospital). Our results show that screening all admissions for MRSA is unlikely to be cost effective in England at the current NHS willingness-to-pay threshold, and our findings informed modified guidance to NHS England in 2014. Screening admissions to high-risk specialties is likely to represent better resource use in terms of cost per QALY gained. UK Department of Health.


Monoclonal antibodies against leucoagglutinin-reactive human T-lymphocyte surface components. I. Characterization of cellular binding sites.
The binding specificities of three biologically active anti-lymphocyte monoclonal antibodies (MoAb) (K46M, K3G, and 3-19-2) produced against human T-cell surface components reactive with the mitogenic lectin leucoagglutinin from Phaseolus vulgaris (La) were analysed. K46M is a strong T-cell mitogen, while K3G and 3-19-2 inhibited cell-mediated cytotoxicity. Resting peripheral blood lymphocytes (PBL) contained 4-16% K46M+ cells, 8-35% K3G+ cells, and less than 0.3-4% 3-19-2+ cells. After stimulation with T-cell mitogens the proportion of K46M+ and 3-19-2+ cells increased markedly (mean 59 and 30% positive cells, respectively), while the increase in K3G+ cells was less prominent (38%). K46M-reactive structures were expressed on mature T cells and probably also on B cells. K3G reacted with B and T cells while 3-19-2 showed a broader specificity reacting also with erythrocytes. All three MoAb reacted with lipid extracts of resting and activated PBL as well as with purified neutral glycolipids of lymphoid origin. In addition 3-19-2 reacted with lipid extracts of erythrocytes. K46M immuno-precipitated four surface peptides from lectin-stimulated PBL. Their apparent molecular weights were 53,000, 42,000, and 16,000 (doublet). The 53,000 and 42,000 MW peptides were identified as the alpha and beta chains of the T-cell antigen receptor. The identity of the 16,000 MW peptides is presently unknown. K3G and 3-19-2 did not specifically precipitate any lymphocyte surface peptide.


Corrigendum: Dry eye disease severity and impact on quality of life in type II diabetes mellitus.
[This corrects the article DOI: 10.3389/fmed.2023.1103400.].


Static and dynamic electro-optic properties of a SmC* phase in surface stabilized geometry and dispersed in the polymer matrix.
Comparative electro-optical measurements have been made on a ferroelectric liquid crystal (FLC) in surface stabilized geometry and confined to an ellipsoidal cavity within a polymer matrix. The static and dynamic electro-optical characteristics were measured for both systems and show qualitatively similar behaviours. A fast switching and important bistability were observed and characterized as a function of the applied electric field strength. The switching time between the two stable states of the surface stabilized cell was found to be longer than that found for the composite films. We argue that the faster switching dynamic of the FLC in cavities is due to the enhance of the rotational mobility of the molecules, probably (and partly) because of the "soft" anchoring character of the molecules at the cavity walls. Using a collective switching model in the high field regime, which assume a linear coupling between the spontaneous polarization and the local cavity electric field, we give an estimate of the rotational viscosity of the FLC molecules in the droplets.


Bronchoscopic cryosurgery for metastatic tumor causing central airway obstruction: A case report.
Bronchoscopic cryotherapy has been considered as one of the optional interventions for unresectable malignant central airway obstruction (CAO). And it provides high safety and effectiveness in airway patency re-establishment. This report describes the interventional bronchoscopic cryotherapy for a patient with CAO caused by squamous cell carcinoma of the esophagus. We display a series of dramatic change of chest radiographs before and after the intervention. A 70-year-old man with squamous cell carcinoma of the middle third of the esophagus (initial staging, pT2N0M0; stage IIB; in January 2017) underwent Video-assisted esophagectomy and reconstruction with a gastric conduit via a substernal route. Following Chest computed tomography and positron emission tomography revealed disease progression with paratracheal metastases. Progressive dyspnea and chest pain lasted for a month, and he was admitted to the ER. Blood gas analysis revealed type I respiratory failure (pH, 7.445; PaO2, 69.4 mmHg; PaCO2, 40.6 mmHg). Other laboratory data were grossly normal. Chest radiography revealed a total left lung collapse. Chest CT identified a tumor blocking the left mainstem bronchus with the consolidation of the left lung. Dexamethasone and epinephrine inhalation were administered for initial symptom relief. Bronchoscopy performed 4 days after admission revealed a huge tumor completely occluding the left mainstem bronchus orifice. The occlusion was completely resolved following cryotherapy. Then, the first course of palliative chemotherapy with cisplatin plus fluorouracil, followed by the second course a month later, was administered. The latest chest radiograph showed a patent airway. The patient's condition remained stable for at least the following 2 months. Malignant CAO is a rare but potentially life-threatening condition. Several acceptable bronchoscopy techniques exist for treatment. Cryotherapy has high safety and effectiveness in airway patency re-establishment.


Plasma exchange as a treatment for endogenous glycosaminoglycan anticoagulant induced haemorrhage in a patient with myeloma kidney.
A 57-year-old man with end-stage renal failure secondary to myeloma kidney developed haemorrhagic complications due to endogenous glycosaminoglycan anticoagulant production. Glycosaminoglycan levels and anticoagulant effect were reduced by plasma exchange and this contributed to control of the haemorrhagic manifestations.


Tools for Thought: The Case of Mathematics.
The objective of this article is to take into account the functioning of representational cognitive tools, and in particular of notations and visualizations in mathematics. In order to explain their functioning, formulas in algebra and logic and diagrams in topology will be presented as case studies and the notion of manipulative imagination as proposed in previous work will be discussed. To better characterize the analysis, the notions of material anchor and representational affordance will be introduced.


Practical use of telemedicine in the chronically ventilated infant.
Telemedicine, or the use of electronic communication technology to improve patient health, is becoming more widely adopted as a means of bringing together patients, providers and family members to facilitate evaluation, monitoring, diagnosis and treatment. A particularly vulnerable group consists of children with dependence on technology, such as chronic mechanical ventilation. This chapter will provide an overview of how telehealth technology is currently being used, for supporting this patient population through 1) inpatient support 2) integration with the medical home 3) bridging care transitions 4) remote patient management and 5) multispecialty consultations. We will also discuss the impact on quality and cost, the current research environment and practical points for implementation into clinical practice.


Teleonomical optimization of a fractal model of the pulmonary arterial bed.
Modeling the pulmonary arterial tree (PAT) is considered here as an optimal synthesis problem. Firstly, a class of candidate models is specified: the three-dimensional symmetric dichotomous fractal trees of elastic tubes described by Womersley's equations. Secondly, the parameters are shown to be constrained by interactions of PAT with the rest of the body; these constraints are used to limit the volume of the parametric space to which attention will be directed in the synthesis step. Thirdly, a teleonomical hypothesis is proposed: a naturally selected PAT must have a minimal input impedance under conditions keeping total arterial volume and distensibility as small as possible. This hypothesis is translated in mathematical terms and the resulting cost-function minimized in the limited parametric volume. The optimal model has parameter values and an impedance spectrum corresponding satisfactorily with real data. Moreover this model gives a clear picture of the internal hemodynamic behavior of PAT as an impedance matching device.


Irisin as a mediator between obesity and vascular inflammation in Chinese children and adolescents.
This study aims to characterize the role of Irisin in obesity and early onset metabolic and vascular sequelae in Chinese children. Furthermore, we aim to examine whether Irisin mediate endothelial cells dysfunction and vascular inflammation which eventually leads to obesity. We quantified plasma Irisin levels using enzyme-linked immunosorbent assay (ELISA) among 85 lean and 120 obese children, and assessed the association of Irisin levels with anthropometric, metabolic, cardiovascular and inflammatory parameters of obese children comparing with lean children. We further characterized the markers for endothelial cells and inflammation between obese and lean children to assess potential correlations. In addition, a potential direct effect of Irisin on the expression of endothelial adhesion molecules was assessed in human coronary artery endothelial cells. Irisin levels from obese children was significantly lower than lean children, and this reduced Irisin levels is correlated with certain physical parameters of studied children. Moreover, we identified significant inverse associations between inflammation markers of endothelial activation with Irisin levels in obese children. Multiple regression analyses confirm Irisin serves as a strong predictor of SDS-SBP, Ang-2, ICAM-1, E-selectin and hsCRP levels, independent of SDS-BMI. Lifestyle intervention results in a significant improvement of these cardiovascular and inflammatory parameters, and these were accompanied by a significant improvement of Irisin levels and weight loss. Finally, in the mediation effect model, our data showed that Irisin changes act as partial mediators of the relationship between SDS-BMI changes and changes in inflammatory and endothelial parameters for ICAM-1, E-selectin and hsCRP after controlling for covariates. Likewise, on the cellular level, Irisin inhibition hsCPR, ICAM-1 and E-selectin expression in endothelial cells, whereas Ang-2, VCAM-1 and eNOS expression were unaffected. Our study showed that Irisin levels change may indicate the early stages of cardiovascular disease in obese children.


Paternalistic leadership as an antecedent: Examining the comprehensive model of nurse's life satisfaction.
Paternalistic leadership style has progressively intrigued organisational behaviour study in the last two decades. An abundance of research is integrating the existing literature on leadership and positive organizational culture to better understand the processes through which leadership leads to life satisfaction. One such mechanism through which specific leaders influence life satisfaction is work-family conflict (WFC) and family-work conflict (FWC). Paternalistic leadership is a significant antecedent to develop subordinates' life satisfaction because it integrates discipline with fatherly support. However, no research exists to date on the effect of paternalistic leaders on subordinate' WFC and FWC, which in turn affects their life satisfaction. The current study examines the impact of paternalistic leadership on employee life satisfaction using a sample of 198 nurses from public sector hospitals of Sindh province in Pakistan. The data was collected through survey questionnaires, and Smart-PLS-SEM was used to test the proposed hypotheses. The primary goal of this study was to investigate the relationship between paternalistic leadership and life satisfaction. At the same time, there were significant mediation effects on life satisfaction. The findings indicate that paternalistic leadership positively impacted life happiness through decreasing followers' WFC. However, it has a detrimental influence on FWC, which mediates the effect on subordinates' life satisfaction.


The role of the ankle plantar flexor muscles in trip recovery during walking: a computational modeling study.
Reactive lower limb muscle function during walking plays a role in balance, stability, and ultimately fall prevention. The objective of this study was to evaluate muscle and joint function used to regain balance after trip-based perturbations during walking. How are lower limb muscles used to recover from external tripping during walking? The dominant legs of 20 healthy adult participants with similar athletic backgrounds were tripped using a split-belt instrumented treadmill. High- and medium-intensity trips were simulated by deceleration of the dominant leg at initial contact from the speed of 1.1 m/s to 0 m/s and back to 1.1 m/s in 0.4 s and 0.8 s, respectively. Lower limb kinematics, kinetics, and muscle forces following perturbations were computed to pre-perturbation values using statistical parametric mapping (SPM) paired t-test. A greater ankle dorsiflexion angle (mean difference: 5.3°), ankle plantar flexion moment (mean difference: 0.6Nm/kg), and gastrocnemius and soleus muscle forces (mean difference: 4.27N/kg and 13.56N/kg for GAS and SOL, respectively) were observed post-perturbation step despite the magnitude of the perturbation. This study concludes that adequate timely response of ankle function during a compensatory step is required for a successful recovery after tripping during walking in young healthy adults. Weakness in plantar flexors suggests insufficient ankle moments, which ultimately can result in falls. The findings of this paper can be used as a reference for the joint moments and range of motion needed to recover trips in the design of assistive devices. In addition to that, clinicians can use the estimated values of muscle forces and the pattern of muscle activities to design targeted training in fall prevention among the elderly.


The influence of thermal trauma on pro- and anticoagulant activity of erythrocyte-derived microvesicles.
The goal of this research was to study the influence of erythrocyte-derived microvesicles on hemostasis parameters during burn. It was found that the number of microvesicles derived from washed erythrocytes of burn patients after 1 day of storage at 37°C was 4.2 times bigger than the number of microvesicles derived from erythrocytes of healthy donors. Hemocoagulation properties of erythrocyte-derived microvesicles of burn patients also change: according to the results of thromboelastography their procoagulant activity increases significantly, at the same time their antithrombin and fibrinilytic activity decrease. Thus, we can conclude that hepercoagulation during burn is to a certain extent caused by the disruption of the balance between procoagulant activity of erythrocyte-derived microvesicles and their antithrombin and fibrinolytic activity. Hypercoagulation effect of erythrocyte-derived microvesicles increases during burn not just because of their changed properties but also due to their increased number after thermal trauma.


Preparation and characterization of phosphatidyl-agar oligosaccharide liposomes for astaxanthin encapsulation.
Surface modification of liposomes is an effective way to maintain the physicochemical activity of encapsulated substances. A novel astaxanthin (Ast)-based vesicle carrier system, namely, phosphatidyl-agar oligosaccharide (Ptd-AOS) liposomes (Lip), was prepared to improve the structural stability and in vitro digestibility of astaxanthin. During the transphosphatidylation reaction of synthesizing Ptd-AOS from phosphatidylcholine (PC) and AOS with different degrees of polymerization, phosphatidyl galactose (Ptd-Gal) and phosphatidyl neoagarobiose (Ptd-NA2) showed higher yields (85 and 96%, respectively). In terms of morphology, modified liposomes exhibited smaller particle sizes and more uniform dispersion compared with PC-Ast-Lip. In addition, the astaxanthin in the modified liposomes showed enhanced stability during liposome characterization and in vitro digestion. The transformations of astaxanthin in the modified liposomes were distributed in the range of 57-74% compared with free astaxanthin (25%). These findings suggest that the modification of liposomes by Ptd-AOS has potential applications in the delivery of functional ingredients.


Characterizing single crystal surfaces using high resolution electron diffraction.
Characterization and controlled manipulation of surfaces is a crucial factor in modern processing of the technologically relevant Si(100) surface. Using spot profile analyzing low energy electron diffraction, the morphological changes from a single stepped vicinal Si(100) surface to a single-domain (2x1) reconstructed surface have been investigated in situ during Si deposition. The temperature range for formation of this kinetically-stabilized single-domain surface was found to be 400-500 degrees C. This single-domain surface could be preserved for further characterization and experiments after quenching to room temperature.


Standardized Anatomic and Regenerative Facial Fat Grafting: Objective Photometric Evaluation 1 to 19 Months After Injectable Tissue Replacement and Regeneration.
A standardized technique for facial fat grafting, injectable tissue replacement and regeneration (ITR2), incorporating new regenerative approaches, was developed to address anatomic volume losses in superficial and deep fat compartments as well as skin aging. The aim of this study was to track the short- and long-term effects of facial fat grafting by ITR2 in the midfacial zone over 19 months. Twenty-nine females were analyzed for midfacial volume changes after autologous fat transfer with ITR2 with varying fat parcel sizes. Volumes were evaluated with an imaging system to calculate differences between a predefined, 3-dimensional midfacial zone measured preoperatively and after fat grafting. Patient data were analyzed collectively and by age (<55 and >55 years). Collective analysis revealed a trend of initial volume loss during Months 1 to 7 followed by an increase during Months 8 to 19, averaging 56.6% postoperative gain, and ending at an average of 52.3% gain in volume by 14 to 19 months. A similar trend was observed for patients <55 years of age, with a 54.1% average postoperative gain and a greater final average of 75.2%. Conversely, patients >55 years of age revealed a linear decay from 60.6% to 29.5%. Multiple regression analysis revealed no statistically significant influence of weight change throughout the study. A dynamic change in facial volume was observed, with an initial decrease in facial volume followed by a rebound effect, by 19 months after treatment, of improved facial volume regardless of the amount of fat injected. Volume improvement was greater in patients <55 years old, whereas in patients >55 years old, volume gradually decreased. This study represents the first time that progressive improvement in facial volume has been shown 19 months after treatment.


Diagnoses and Management of Drug Hypersensitivity and Anaphylaxis in Cancer and Chronic Inflammatory Diseases: Reactions to Taxanes and Monoclonal Antibodies.
Due to the increase in utilization of chemotherapies and antibodies, drug hypersensitivity reactions have increased dramatically worldwide, preventing the use of first-line therapies and impacting patients' survival and quality of life. Some of the more frequently used medications in cancer include taxanes for ovarian, lung, breast, and prostate cancers. Monoclonal antibodies are used in the treatment of neoplastic, autoimmune, and inflammatory diseases, and their clinical applications are becoming broader. Monoclonal antibody targets include CD20, HER-2, EGFR, IL-6 receptor, TNF-α, CD30, VEGF-A, IgE, and more, and examples of immune-mediated and inflammatory diseases that respond to monoclonal antibodies include rheumatoid arthritis, Crohn's disease, ulcerative colitis, juvenile idiopathic arthritis, psoriasis and psoriatic arthritis, Wegener's granulomatosis, microscopic polyangiitis, ankylosing spondylitis, plaque psoriasis, and asthma. Neoplastic diseases include non-Hodgkin's lymphoma, chronic lymphocytic leukemia, and colorectal, breast, gastric, and lung cancer. The clinical presentation of drug hypersensitivity reactions ranges from mild cutaneous reactions to life-threatening symptoms including anaphylaxis. Rapid drug desensitization (RDD) has become a groundbreaking approach to the management of immediate drug hypersensitivity reactions IgE and non-IgE mediated. It is the only effective procedure that enables sensitized patients to receive the full treatment dose safely, thus representing an important advance in the patients' treatment and prognosis. The aim of this review is to provide an update on hypersensitivity reactions to commonly used monoclonal and taxanes, their clinical presentations, diagnosis, and the use of RDD for their management.


Adolescents and Norplant: preliminary findings of side effects.
The purpose of this study was to investigate side effects such as menstrual irregularities, weight gain, and blood pressure changes among adolescent females who had been implanted with Norplant eight or more months. A retrospective chart review was completed on adolescents who received care through an outpatient adolescent gynecology service. Subjects (n = 110) with an average age of 17.2 years were implanted with Norplant between March 1991 and February 1992. The mean length of time since implantation was 12.7 months and 64% were African-American. Data collected included: dates of all medical visits; presence of acne, mood changes, and menstrual patterns following implantation. Measurements of blood pressure and weight were taken at implantation and at all subsequent visits. Weights for Caucasian females at the last visit were significantly higher than at baseline (P < .02). With regard to the African-American females' weight, significant differences were found between baseline weight and each follow-up visit. Although we could not determine the bleeding patterns in 22% of our study sample, almost 40% of the adolescent females followed reported their bleeding to be light as well as regular and cyclic. Weight gain was the most frequently observed side-effect of Norplant in adolescents in this study.


Silicosis among pottery workers--New Jersey.
In March 1985, two cases of silicosis in former employees of a sanitary-ware pottery (i.e., a manufacturer of china plumbing fixtures) were identified from death certificates by the New Jersey State Department of Health (NJSDH). A site visit to the pottery in January 1987 revealed potential overexposure of employees to crystalline silica throughout the plant. This report summarizes the investigation of employee exposure to silica.


The effects of the antiprotozoal drugs metronidazole and furazolidone on trophozoites of Giardia lamblia (P1 strain).
The effects of metronidazole and furazolidone on Giardia lamblia trophozoites were analyzed by video-light and transmission electron microscopy. In addition, growth curves were drawn based on four concentrations of the drugs. The IC50 was 4.6 microM for metronidazole and 2.9 microM for furazolidone. By light microscopy we observed that metronidazole-treated cells maintained the characteristic body shape, but many showed bubbles in the dorsal and ventral surfaces. The effects of furazolidone include changes in the morphology (the cells were roundish) and also cytoplasmic extrusions. When observed by transmission microscopy, cells treated with metronidazole appeared rounder than usual and membranous structures were observed in the cytoplasm. Cells treated with furazolidone showed the cytoplasm depleted of its contents and great changes in volume. Our results show that furazolidone was more effective than metronidazole and its effects were observed in cells treated with 1 microg/ml (the lowest concentration) as early as 6 h after the start of exposure.


Forensic medicine in the Indo-Pacific region: history and current practice of forensic medicine.
A brief history of forensic medicine in the Indo-Pacific region followed by the extent of medical education imparted to undergraduates and current practice in various countries of the region are examined.


Substance P and 5-HT in granules isolated from an intestinal argentaffin carcinoid.
Intestinal argentaffin carcinoids, thought to originate from enterochromaffin cells, occasionally contain large amounts of substance P-like immunoreactivity in addition to 5-HT. The cytoplasmic granules of one such tumour were isolated. The granules, which in the electron microscope were shown to be argentaffin, contained both substance P-like immunoreactivity and 5-HT. The results support the view that substance P is localized in a population of enterochromaffin cells where it is stored in the cytoplasmic granules together with 5-HT.


Clinical implications of very low on-treatment platelet reactivity in patients treated with thienopyridine: the POBA study (predictor of bleedings with antiplatelet drugs).
This study was designed to define the hyperresponse to thienopyridine (very low on-treatment platelet reactivity [VLTPR]) as the most predictive threshold value of platelet reactivity index vasodilator-stimulated phosphoprotein (PRI VASP) for the prediction of non-access site-related bleeding events. We also aimed to identify predictors of bleeding and VLTPR in patients treated with thienopyridines. New P2Y12 blockers and platelet monitoring has been proposed to optimize platelet inhibition after acute coronary syndromes and improve ischemic outcomes. However, bleeding complications remain the Achilles' heel of antiplatelet therapy, and platelet monitoring could be useful to evaluate this risk. A total of 1,542 consecutive patients undergoing coronary stenting for ACS were included in the present study (287 taking clopidogrel 75 mg, 868 taking clopidogrel 150 mg, and 387 taking prasugrel 10 mg). During 6-month follow-up, 9% of patients (n = 139) experienced nonaccess site-related Bleeding Academic Research Consortium bleeding complications. These patients were more often women and nondiabetic and had lower PRI VASP values than others (p < 0.001). Receiver-operating characteristic curve analysis (0.71, p < 0.01) identified a threshold value for VLTPR of PRI VASP ≤10% to predict bleeding events with a sensitivity of 17% and a specificity of 97%. Although prasugrel was the main predictor of VLTPR in the whole population (odds ratio: 10.2, 95% confidence interval: 3.0 to -34.2; p < 0.001), VLTPR was the strongest and independent predictor of bleeding (odds ratio: 4.7, 95% confidence interval: 2.7 to 8.3; p < 0.001). The present study identified VLTPR (PRI VASP ≤10%) as the strongest predictor of bleeding complications in patients treated with thienopyridines. This marker could be useful for tailored therapy and bleeding prevention.


About the composition of self-relevance: Conjunctions not features are bound to the self.
Sui and colleagues (Journal of Experimental Psychology: Human Perception and Performance, 38, 1105-1117, 2012) introduced a matching paradigm to investigate prioritized processing of instructed self-relevance. They arbitrarily assigned simple geometric shapes to the participant and two other persons. Subsequently, the task was to judge whether label-shape pairings matched or not. The authors found a remarkable self-prioritization effect, that is, for matching self-related trials verification was very fast and accurate in comparison to the non-matching conditions. We analyzed whether single features or feature conjunctions are tagged to the self. In particular, we assigned colored shapes to the labels and included partial-matching trials (i.e., trials in which only one feature matched the label, whereas the other feature did not match the label). If single features are tagged to the self, partial matches would result in interference, whereas they should elicit the same data pattern as non-matching trials if only feature conjunctions are tagged to the self. Our data suggest the latter; only feature conjunctions are tagged to the self and are processed in a prioritized manner. This result emphasizes the functionality of self-relevance as a selection mechanism.


Assessment of the in vivo adaptive response to mechanical loading.
The primary responsibility of the skeleton is to bear the loads involved in physical activity without sustaining damage. This capability involves a mechanism in which bone cells "assess" the suitability of the bones' existing architecture in relation to their prevailing loading environment and adapt or maintain it accordingly. It is widely assumed that the loading-related variable to which the bone cells respond is the strain engendered within the bone tissue. Strain-related adaptation is essential for normal bone development, regulation of strength in relation to exercise, healing of fractures and the success of orthopedic interference. The most widespread failure of this adaptive response is osteoporosis. Although strain-related bone adaptation can be investigated in these situations in humans in vivo, both the inputs and outputs are difficult to assess and control, and the tissues are unavailable for study. As a consequence much of our understanding of the mechanisms involved in strain-related adaptation have come from studies in animals where the strains within the bone are measured, the loads imposed on the bones can be controlled, and the adaptive changes to cells and architecture determined. Although many animals have been used in the past (1-3), now the most commonly used animal is the mouse. Normal and transgenic mice are available and inbred strains of mice are well characterized physiologically (4). Most importantly, the techniques for measuring strains in mouse bones, loading these bones in a controlled manner, and assessing changes in architecture are all available. This chapter outlines the techniques involved in these three phases of investigation in mouse bone.


Myoinositol decreases N-nitroso-N-methylurethane induced lung surfactant deficiency.
Administration of 7.5 mg/kg body wt. of N-nitroso-N-methylurethane subcutaneously to rabbits decreased disaturated phosphatidylcholine, phosphatidylglycerol, and increased the minimum surface tension of alveolar lavage return. As compared to rabbits treated with N-nitroso-N-methylurethane alone, myoinositol supplementation (3-7 g/kg per day) of N-nitroso-N-methylurethane treated animals largely prevented both the decrease in disaturated phosphatidylcholine, and the increase in minimum surface tension. Myoinositol may be an important nutrient following damage of alveolar epithelium.


[Generalized peritonitis. Morbidity and mortality with respect to the development of oncotic pressure in the early postoperative period].
A group of forty patients with generalized peritonitis was studied comparing their clinical evolution and mortality with the plasma coloidosmotic pressure values (COP). Twentynine patients survived without complications (Group I) this patients had the higher mean COP values, 17.56 mm Hg at the beggining and 19.06 mm Hg at the end of the study. Three patients showed complications directly related with peritonitis but finally survived (Group II). Their mean COP values were 16.08 mm Hg at the beggining and 13.44 mm Hg at the end. Eight patients died (Group III) lower mean COP values were obtained in this group; 13.5 at the begging and 11.94 at the end. Despite the same kind of medical and surgical treatment, response was very different in each group. Lower values of COP were found as clinical avolution worsened. A very low inicial value or failure to raise it despite the treatment may be considered as a bad prognosis sing.


Supraventricular tachycardia in children.
Several different mechanisms are responsible for paroxysmal supraventricular tachycardia in children. Different forms of tachycardia occur at different age. Atrio-ventricular reentry tachycardia results from the presence of congenital atrio-ventricular bypass tracts and is frequently encountered at all ages. Infants may present with ectopic atrial tachycardia or atrial flutter. Atrio-ventricular node reentry tachycardia becomes more frequent in adolescence. Atrial scarring resulting from open heart surgery predisposes to complex intra-atrial reentry. Certain forms of congenital and acquired heart disease are associated with specific types of arrhythmia. Many children with paroxysmal supraventricular tachycardia do not require any therapy. The decision to proceed with treatment should be based on the frequency and severity of symptoms and on the effect of arrhythmia on the quality of life. Infants require medical treatment because of the difficulty to recognize symptoms of tachycardia and a risk of heart failure. Patients with Wolff-Parkinson-White syndrome as well as those with significant heart disease are at risk of sudden death. Syncope in children with paroxysmal tachycardia may indicate a severe fall in cardiac output from extremely rapid heart rate. Patients with potentially life-threatening arrhythmia should not participate in competitive physical activities. Treatment options have undergone significant evolution over the past decade. Indications for the use of specific antiarrhythmic medications have been refined. Contemporary catheter ablation procedures employ different forms of energy allowing for safe and effective procedures. Catheter ablation is the treatment of choice for symptomatic paroxysmal tachycardia in school children and in some infants who failed medical treatment. Surgery is the preferred treatment in few selected cases. The goal of this review is to present the state of the art approach to the diagnosis and management of paroxysmal supraventricular tachycardia in infants, children and adolescents.


Iodine nutrition in ewes. 2. Effects of low to high iodine intake by ewes on the I content of biological fluids and plasma immunoglobulins G in newborn lambs.
1. In two experiments samples of blood and organs were taken from newborn and young lambs born to five groups of ewes that received different dietary iodine (I) levels. Dietary I contents (mg/kg dry matter [DM]) in pregnancy and lactation, respectively, were: Experiment 1--0.36 and 0.26 for group C, 2.01 and 1.94 for group D; Experiment 2--0.13 and 0.12 for group A, 0.22 and 0.20 for group B, 10.77 and 8.88 for group E. 2. I intake of ewes had no effect on birthweight, body weight gain, or mortality between birth and wk 2 of life. No difference between the groups was recorded in the weights of brain, heart, lungs, and liver of lambs killed at birth. However, the weight of both the thyroid lobes in lambs from group E was lower than that of the other groups. The I content of the thyroid lobes of lambs from group A was 30-40% lower than that of the other groups. 3. The plasma inorganic iodine (PII) of lambs from birth to d42 of life was affected by ewe I intake, except for groups A and B, during the first 16 h of life. The PII of lambs increased with the I intake via milk in each group. The ratio of PII of lambs at birth/PII of ewes at d7 prepartum was 3.77, 2.96, 1.68, 1.39 and 8.62, respectively, for groups A, B, C, D and E. 4. The high I intake by group E ewes induced a higher plasma T4 concentration in lambs at birth. The decrease in plasma immunoglobulins G (IgG) recorded for the lambs in this group might be explained by this increase in plasma concentration.


Critical analysis of the intraoperative parathyroid hormone decrease during parathyroidectomy for secondary and tertiary hyperparathyroidism.
This study aims to determine whether intraoperative parathyroid hormone monitoring helps to predict early surgical outcomes in patients with renal hyperparathyroidism and evaluate the impact on decision making during surgery. A prospective study was conducted. Serial samples of the intraoperative parathyroid hormone were collected; 2 of these were taken before the excision, and 2 were taken after the planned parathyroid resection (10 minutes and 15 minutes). We tested the criterion of an intraoperative parathyroid hormone percentage decay ≥80% of the highest value of the basal samples as a predictor of success. Of the 228 patients, parathyroidectomy achieved success in 92.1%. In patients with secondary hyperparathyroidism, the failure group showed a tendency to stabilize or even increase the intraoperative parathyroid hormone values from the 10-minute measure (577 pg/mL) to the 15-minute measure (535 pg/mL) (P = .903). Conversely, intraoperative parathyroid hormone continued to drop in those with a successful outcome: 245 pg/mL (10 minutes) and 206 pg/mL (15 minutes) (P < .001). The failure group had a significantly lower percentage decay (P < .001) from baseline when compared with the success group. The intraoperative parathyroid hormone influenced the surgical management in up to 7% of the cases. The intraoperative parathyroid hormone dosage method showed an accuracy of 86%, a sensitivity of 88%, and specificity of 67%. In patients with renal hyperparathyroidism undergoing parathyroidectomy, the use of intraoperative parathyroid hormone may help to predict an early therapeutic outcome with high sensitivity and accuracy by indicating the operation's success when there is an 80% reduction of baseline intraoperative parathyroid hormone 15 minutes after removal of the enlarged glands, an associated continuous decrease in serum intraoperative parathyroid hormone levels between 10 and 15 minutes, and achievement of plasma target values <500 pg/mL.


Stress routes clients to the proteasome via a BAG2 ubiquitin-independent degradation condensate.
The formation of membraneless organelles can be a proteotoxic stress control mechanism that locally condenses a set of components capable of mediating protein degradation decisions. The breadth of mechanisms by which cells respond to stressors and form specific functional types of membraneless organelles, is incompletely understood. We found that Bcl2-associated athanogene 2 (BAG2) marks a distinct phase-separated membraneless organelle, triggered by several forms of stress, particularly hyper-osmotic stress. Distinct from well-known condensates such as stress granules and processing bodies, BAG2-containing granules lack RNA, lack ubiquitin and promote client degradation in a ubiquitin-independent manner via the 20S proteasome. These organelles protect the viability of cells from stress and can traffic to the client protein, in the case of Tau protein, on the microtubule. Components of these ubiquitin-independent degradation organelles include the chaperone HSP-70 and the 20S proteasome activated by members of the PA28 (PMSE) family. BAG2 condensates did not co-localize with LAMP-1 or p62/SQSTM1. When the proteasome is inhibited, BAG2 condensates and the autophagy markers traffic to an aggresome-like structure.


Effect of phenylalanine- or tryptophan-loaded liposomes on the rheological properties of AA and SS erythrocytes.
Phenylalanine or tryptophan was incorporated into AA and SS red blood cells by a liposomal transport system which was previously shown by Kumpati to inhibit and reverse sickling of intact SS red blood cells in vitro. In the present study, the effect of phenylalanine or tryptophan incorporation on the rheological properties was evaluated. The incorporation of phenylalanine or tryptophan into red blood cells decreased the viscosity of deoxy SS red blood cells which reached a level close to that for normal red blood cells due to the antisickling effect. These results demonstrate that this liposomal transport system which transferred phenylalanine or tryptophan into intact red cells and did not have any adverse effect on red cell metabolism or function did correct the viscosity of deoxy SS red cells by its antisickling effect. This method may have significant therapeutic implications in the treatment of sickle cell disease.


Aortic Arch Mapping by Computed Tomography for Actual Anatomic Studies in Times of Emerging Endovascular Therapies.
The latest advances in treatment of aortic arch pathologies increasingly included endovascular technologies. For those purposes, more detailed knowledge about the specific anatomic features are of particular interest, especially with regard on the need for better suitable stent grafts or even development of "off-the-shelf" stents. The study enrolled patients undergoing computed tomography of the chest for other reasons than screening for aortic disease. Patients with aortic pathologies were excluded. Finally, 118 patients were included. Anatomic features of the aortic arch, the supra-aortic branches, distances and takeoff angles as well as specific diameters were assessed and analyzed with respect to the patients height, weight, age, and sex. A significant variability of all measurements was observed. Nonetheless, 4 recurrent types of aortic arch geometry were identified: (1) Classic arch (39%), (2) Gothic arch (39%), (3) Rectangle arch (11.9%), and (4) Plain arch (8.5%). Furthermore, the aortic diameter continuously decreased from the beginning of the ascending aorta during the after 200 mm by 24.8% (31.8 ± 3.6 mm to 23.9 ± 3.1 mm in mean). Distances from the aortic annulus to the supra-aortic branches takeoff points showed significant gender- and age-related differences with larger distances in the older and male (P < 0.001). Observed takeoff angles were 44.9 ± 15.9° for the brachiocephalic trunk, 25.7 ± 15.5° for the left common carotid artery, and 28.8 ± 14.5° for the left subclavian artery. Observed anatomic features were highly variable. It seemed that a "standard aortic arch" does not exist. Until today, the aortic arch as a dynamic and 3-dimensional entity is not fully understood. The development of "off-the-shelf" stents in the near future will be limited by this complexity and variability.


A global dynamic runoff application and dataset based on the assimilation of GPM, SMAP, and GCN250 curve number datasets.
Runoff modelling is a crucial element in hydrologic sciences. However, a global runoff database is not currently available at a resolution higher than 0.1°. We use the recently developed Global Curve Number dataset (GCN250) to develop a dynamic runoff application (2015 - present) and that can be accessed via a Google Earth Engine application. We also provide a global mean monthly runoff dataset for April 2015-2021 in GeoTIFF format at a 250-meter resolution. We utilize soil moisture and GPM rainfall to dynamically retrieve the appropriate curve number and generate the corresponding runoff anywhere on Earth. Mean annual global runoff ratio results for 2021 were comparable to the runoff ratio from the Global Land Data Assimilation System (0.079 vs. 0.077, respectively). Mean annual global runoff from GCN and GLDAS were within 11% each other for 2020-2021 (0.18 vs. 0.16 mm/day, respectively). The GCN250 runoff application and the dataset are useful for many water applications such hydrologic design, land management, water resources management, and flood risk assessment.


The binding in vitro of the intermediate filament protein vimentin to synthetic oligonucleotides containing telomere sequences.
The ability of the intermediate filament subunit protein vimentin to bind synthetic oligonucleotide telomere models containing repeat sequences from Oxytricha (T4G4), Saccharomyces (TGTGTG3), or Tetrahymena (T2G4) was investigated in vitro with a filter binding assay and a gel overlay assay. At low ionic strength, vimentin bound these oligonucleotides with high affinity. At higher ionic strength, the vimentin-oligonucleotide complex was less stable, such that approximately 30% of the initial binding remained at 150 mM KCl. One mole of vimentin tetramer bound approximately 1 mol of telomere oligonucleotide. Vimentin bound well oligonucleotides containing either a random duplex or random 3'-overhang, but showed a reduced affinity for a blunt-ended oligonucleotide. A control random sequence oligonucleotide was not bound by vimentin. The oligonucleotide-binding site of vimentin was shown to be localized in the non-alpha-helical N-terminal domain by assays employing purified proteolytic fragments of vimentin. Preliminary results in the gel overlay assay show that other members of the intermediate filament family, nuclear lamins A-C, all bind the synthetic oligonucleotide containing the telomere repeat sequence of Oxytricha.


Trichosanthes dioica fruit ameliorates experimentally induced arsenic toxicity in male albino rats through the alleviation of oxidative stress.
The present work was focused to evaluate the ameliorative property of aqueous extract of Trichosanthes dioica fruit (AQ T. dioica fruit) against arsenic-induced toxicity in male Wistar albino rats. AQ T. dioica fruit was administered orally to rats at 50 and 100 mg/kg body weight for 20 consecutive days prior to oral administration of sodium arsenite (10 mg/kg) for 10 days. Then the rats were sacrificed for the evaluation of body weights, organ weights, hematological profile, serum biochemical profile, and hepatic and renal antioxidative parameters viz. lipid peroxidation, reduced and oxidized glutathione, glutathione-S-transferase, glutathione peroxidase, glutathione reductase, superoxide dismutase, catalase, and DNA fragmentation. Pretreatment with AQ T. dioica fruit at both doses markedly and significantly normalized body weights, organ weights, hematological profiles, and serum biochemical profile in arsenic-treated animals. Further, AQ T. dioica fruit pretreatment significantly modulated all the aforesaid hepatic and renal biochemical perturbations and reduced DNA fragmentation in arsenic-intoxicated rats. Therefore, from the present findings, it can be concluded that T. dioica fruit possessed remarkable value in amelioration of arsenic-induced hepatic and renal toxicity, mediated by alleviation of arsenic-induced oxidative stress by multiple mechanisms in male albino rats.


Nipple reconstruction using modified C-V flap with purse-string sutures for maintenance of long-term nipple projection.
The most common concern in nipple reconstruction is the loss of long-term nipple projection. This study aimed to demonstrate a novel method of nipple reconstruction using a modified C-V flap combined with purse-string sutures in the nipple base to maintain nipple projection. From January 2018 to July 2021, patients who underwent nipple reconstruction using the novel modified C-V flap method and conventional C-V flap were retrospectively reviewed. The ratio of projection at the 3, 6, and 12-month postoperative follow-up to the initial nipple projection was calculated and compared. A total of 116 patients were included in this study, which was comprised of 41 patients in the conventional C-V flap group (conventional) and 75 patients in the modified C-V flap with purse-string sutures group (modified). The modified group showed a significantly higher ratio of nipple projection maintenance at postoperative 3 months (79.82%, conventional; 87.25%, modified; p < 0.001), 6 months (68.29%, conventional; 73.18%, modified; p < 0.001), and 12 months (53.98%, conventional; 60.19%, modified; p < 0.001), and a significantly lower revision rate (13/75 patients, 17.33%) than the conventional group (16/41 patients, 39.02%) (p = 0.009) during a mean of 17.67-month follow-up. Nipple reconstruction using a modified C-V flap with purse-string sutures in the nipple base is a safe and effective method for the maintenance of long-term nipple projection owing to the reduction and stabilization of the nipple base.


Arg-liposome-amplified colorimetric immunoassay for selective and sensitive detection of cystatin C to predict acute kidney injury.
Cystatin C (Cys C) has been considered as a novel biomarker of kidney disease, which is thought to be a better indicator of glomerular filtration rate than creatinine (Scr) in the prediction of acute kidney injury (AKI). Hence, there is strong need to develop a precise, rapid and simple detection method for Cys C. Here we reported a Arg-liposome-amplified colorimetric immunoassay for the detection of Cys C to predict AKI. Cys C antibodies are conjugated on the surface of magnetic beads (MBs) and arginine (Arg)-loaded liposomes to form Ab1-MBs and Ab2-Arg-liposomes, respectively. When Ab1-MBs captured Cys C, Ab2-Arg-liposomes are added and incubated to form the immuno-sandwich complex. After magnetic separation, the surfactant Triton ×100 is added to damage the liposomes, leading to the release of Arg which can induce the gold nanoparticles aggregation. Therefore, the discoloration can be used for visual and quantitative detection of Cys C. Notably, the method has a linear relation in the range of 10-100 μg/L for Cys C with a limit of detection 4.32 μg/L, which is lower than some of the previous reports. In addition, the AKI mice serum samples were tested by the developed method, which were in good agreement with ELISA results. More intriguingly, the results of cisplatin induced acute kidney injury in mice showed that the method could be used to evaluate the protective effect of astragalus membranaceus (AM) on AKI by detecting Cys C in serum, providing a new strategy for screening renal protective drugs. Accordingly, a rapid and highly sensitive Cys C detection system was established with great potential for clinical diagnostics.


Paraplegia in the rat induced by aortic cross-clamping: model characterization and glucose exacerbation of neurologic deficit.
Spinal cord damage caused by ischemia is a serious, underappreciated, and relatively refractory problem in clinical practice. Research is hampered by a lack of experimental models that appropriately mimic clinical situations. A new model of paraplegia in the rat is presented and evaluated by standard neurologic deficit scoring (1, 4, 18, and 24 hours after occlusion) and by computerized activity monitoring (1 and 18 hours after occlusion). Rats underwent temporary occlusion of the thoracic aorta for 10, 15, or 20 minutes. Experimental groups received glucose (2 gm/kg) and demonstrated a significant elevation in blood glucose (p = 0.001) and were significantly more neurologically impaired at all four time periods (p less than or equal to 0.005) than the ischemic control group, which received equivalent volumes of normal saline solution. Significant differences in neurologic deficit were noted with direct clinical examination and computerized activity monitoring. With the use of the latter system, statistical differences were detected in total distance traveled and number of vertical movements. We conclude the following: (1) Paraplegia is reliably and reproducibly achieved in this rat model; (2) because of the rat's more extensive behavioral repertoire when compared with other models of spinal ischemia (e.g., rabbit), more end points can be monitored and more subtle behavioral deficits discerned; (3) computerized activity monitoring can distinguish varying degrees of neurologic deficit and correlates with clinical neurologic deficit scoring; and (4) glucose exacerbates paraplegia in this model.


Three-Step Model for Polarized Sorting of KIF17 into Dendrites.
Kinesin and dynein motors drive bidirectional cargo transport along microtubules and have a critical role in polarized cargo trafficking in neurons [1, 2]. The kinesin-2 family protein KIF17 is a dendrite-specific motor protein and has been shown to interact with several dendritic cargoes [3-7]. However, the mechanism underlying the dendritic targeting of KIF17 remains poorly understood [8-11]. Using live-cell imaging combined with inducible trafficking assays to directly probe KIF17 motor activity in living neurons, we found that the polarized sorting of KIF17 to dendrites is regulated in multiple steps. First, cargo binding of KIF17 relieves autoinhibition and initiates microtubule-based cargo transport. Second, KIF17 does not autonomously target dendrites, but enters the axon where the actin cytoskeleton at the axon initial segment (AIS) prevents KIF17 vesicles from moving further into the axon. Third, dynein-based motor activity is able to redirect KIF17-coupled cargoes into dendrites. We propose a three-step model for polarized targeting of KIF17, in which the collective function of multiple motor teams is required for proper dendritic sorting.


Mechanisms of disease: WNK-ing at the mechanism of salt-sensitive hypertension.
Potassium deficiency is associated with an increased prevalence of hypertension. Increasing potassium intake lowers blood pressure via an unknown mechanism. WNK (with no lysine) kinases are a novel family of large serine/threonine protein kinases. A large deletion from the first intron of the WNK1 gene results in increased levels of expression of WNK1 and causes Gordon's syndrome, of which hypertension and hyperkalemia are features. WNK1 activates the Na(+)/Cl(-) cotransporter NCC and the epithelial Na(+) channel ENaC, and inhibits the renal K(+) channel ROMK. Enhanced Na(+) reabsorption and inhibition of K(+) secretion resulting from increased WNK1 expression probably contribute to hypertension and hyperkalemia in Gordon's syndrome. Here, we review the role of dietary K(+) deficiency in the pathogenesis of salt-sensitive hypertension and summarize recent findings indicating that WNK1 might mediate renal Na(+) retention and hypertension in K(+) deficiency.


K(+)- and temperature-evoked taurine efflux from hypothalamic astrocytes.
Hypothalamic astrocytes in culture released taurine, a suspected inhibitory amino acid neurotransmitter/neuromodulator/osmoregulator, in response to isoosmotically increasing extracellular K+ in a dose-dependent fashion. In the absence of added Ca2+, basal release levels rose to approach those obtained after exposure to 60 mM K+ in the presence of 2.5 mM Ca2+, and were only partially lowered by the addition of 10 mM Mg2+. Stimulation with K+ (60 mM) did not further increase taurine efflux above the high basal levels seen in the absence of Ca2+. Under standard conditions complete replacement of Na+ with choline Cl had little effect on basal taurine release, but reduced K(+)-evoked (60 mM) efflux by 60%. The temperature dependence of the basal levels of taurine released from hypothalamic astrocytes was similar to that seen for cultured cerebellar astrocytes and neurons over the range 5-50 degrees C. Taurine release increased from 5 to 15 degrees C, remained constant between 15 and 33 degrees C, decreased between 33 and 37 degrees C and increased thereafter. The infection point of increased basal taurine release seen around 37 degrees C (most prominent in astrocytes), may be of physiological significance. Results presented also show that the ion (Na+, Ca2+ and K+) sensitivities of taurine efflux for cultured hypothalamic astrocytes are similar to those previously reported for cultured astrocytes from the cerebellum.


Health beliefs on type 2 diabetes: a methodological research for development and psychometric evaluation of "DIABA" (Diabetes-related Instrument to Assess Beliefs of Adolescents) health beliefs on type 2 diabetes.
Several reports have shown an increase in the number of type-2 diabetics among adolescents creating an extra burden for this age group. However, there is no instrument assessing adolescents' attitude toward this disease. This study aims at designing a psychometric tool for assessing adolescents' health beliefs regarding type-2 diabetes. In this methodological research, 770 boy and girl adolescents (between 13 and 15) from Tehran participated through multistage sampling. The Inclusion criteria were: junior high school students, students' willingness for participation and not suffering from type-1 or type-2 diabetes. The questionnaire was designed by extensive literature review and the related existing questionnaires, as well as considering the research team's comments. The validity of the questionnaire was determined through face and content validity. The construct validity was determined through exploratory and confirmatory factor analysis. Reliability was measured via internal consistency coefficient (ICC) and internal consistency reliability was measured by Cronbach Alpha. SPSS 16 and EQS6.1 were used for data analysis. The pool of questions had 57 items, and by removing similar (23 questions) or inappropriate sentences (8 questions), a draft questionnaire with 26 questions was designed. No items were removed in the face validity phase. Based on the results of CVR and CVI, six items and 4 items in the exploratory factor analysis were removed. Finally, a questionnaire with 16 items in 4 dimensions of perceived self-efficacy, behavioral beliefs, perceived susceptibility and perceived severity was obtained. The results of confirmatory factor analysis confirmed the model. The internal consistency coefficient was confirmed measuring Cronbach Alpha at 0.78 and ICC = 0.73. The questionnaire designed can be employed as a reliable and valid instrument to assess the psychological perceptions and health beliefs of adolescents with respect to type-2 diabetes.


Early evaluation of atrial high rate episodes using remote monitoring in pacemaker patients: Results from the RAPID study.
Remote monitoring (RM) of implantable cardiac devices has enabled continuous surveillance of atrial high rate episodes (AHREs) with well-recognized clinical benefits. We aimed to add evidence on the role of the RM as compared to conventional follow-up by investigating the interval from AHRE onset to physician's evaluation and reaction time in actionable episodes. A total of 97 dual-chamber pacemaker recipients were followed with RM (RM-ON group; N = 64) or conventional in-office visits (RM-OFF group; N = 33) for 18 months. In-office visits were scheduled at 1, 6, 12, and 18 months in the RM-OFF group and at 1 and 18 months in the RM-ON group. The overall AHRE rate was 1.98 per patient-year (95% confidence interval [CI], 1.76-2.20) with no difference between the two groups (RM-ON vs. RM-OFF weighted-HR, 0.88; CI, 0.36-2.13; p = .78). In the RM-ON group, 100% AHREs evaluated within 11 days from onset, and within 202 days in the RM-OFF group, with a median evaluation delay 79 days shorter in the RM-ON group versus the RM-OFF group (p < .0001). Therapy adjustment in actionable AHREs occurred 77 days earlier in the RM-ON group versus the control group (p < .001). In the RM-ON group, there were 50% less in-office visits as compared to the RM-OFF group (p < .001). In our pacemaker population with no history of atrial fibrillation, RM allowed significant reduction of AHRE evaluation delay and prompted treatment of actionable episodes as compared to biannual in-office visit schedule.


Pulmonary artery diameters measured by multidetector-row computed tomography in healthy adults.
The range of the diameters of pulmonary arteries (PA) is not fully shown in the current literature. Contrast-enhanced computed tomography (CT) of the thorax might be used for measuring diameters of the PA. To determine the diameters of PAs in subjects with normal PA pressure by using thoracic CT. 126 subjects aged between 19 and 46 years, having normal thoracic CTs (5-mm slice thickness) and normal PA pressures ((25 mmHg, determined by echocardiography), were included in the study. The diameters of the main, right, and left PAs were measured by using multidetector CT. The main PA diameters of all the subjects showed a normal distribution, and the mean was 24.0 ± 2.8 mm. The main PA diameters in male and female subjects also showed a normal distribution. The difference between the sexes for the main PA diameters was not significant (P=0.08). There were correlations between main PA diameter and body-mass index (BMI) (R=0.41, P=0.001) and weight (R=0.34, P=0.001). However, there was no significant correlation between main PA diameter and height (R=0.05, P=0.6). This study suggests that diameters of the main PA and its main branches show a normal distribution in subjects having normal PA pressures. Based on our findings, the upper limits of the main, right, and left PA diameters are 29.5 mm,19.8 mm, and 22.1 mm, respectively, in healthy adults.


Fenestrated blood vessels in human skeletal muscle.
In a fine structural study of 32 skeletal muscle biopsies, rare examples of fenestrated blood vessels (FV) were found in three cases. In view of similar observations reported in a case of Duchenne muscular dystrophy, it is suggested that FV albeit rare may occur in skeletal muscle at least under pathologic conditions. These aberrant FV may be derived from adjacent dermis and/or epineurium which are known to contain occasional FV. Alternatively, the occurrence of fenestrae may reflect a nonspecific alteration in pre-existing continuous endothelium. The significance, if any, of their presence in skeletal muscle is unknown.


Fetal genes in mother's blood: a novel mechanism for telegony?
Telegony is a discredited genetic phenomenon that a previous male may influence the characteristics of offspring subsequently borne by the same female to another male. Although its reality was acknowledged by such authorities as Charles Darwin and Herbert Spencer, it has been met with skepticism because of a lack of understanding of the theoretical basis for telegony. With the discovery of fetal genes in mother's blood, the penetration of somatic cells by sperm, and the ability of RNA to program genome rearrangement, mechanisms might exist for telegony.


Chlordecone potentiation of CCl4 hepatotoxicity in ovariectomized rats.
Previous reports from this laboratory have established the propensity of chlordecone to potentiate the hepatotoxicity and lethality in male and female rats. The present study was designed to investigate the hepatotoxicity of CCl4 in chlordecone (CD) pretreated, ovariectomized rats. Ten days after bilateral ovariectomy, the rats were maintained on a dietary protocol of either 0 or 10 ppm chlordecone and on the day 15, they received a single i.p. injection of either corn oil (1 ml/kg) or 25 microliter CCl4/kg in corn oil. Hepatic function, serum enzyme levels and histopathological changes were assessed 24 h after CCl4 challenge as functional biochemical, and morphological parameters of hepatotoxicity. Hepatobiliary function was markedly impaired and serum enzyme levels were elevated in ovariectomized rats receiving the same treatment but not significantly different from normal females receiving the chlordecone and CCl4 combination. Histological findings indicated a greater degree of centrilobular hepatic necrosis accompanied by extensive fatty infiltration. This study suggests that chlordecone sensitizes the liver in ovariectomized rats as well to amplify the toxic effects of CCl4.


Clinical management of complex motor stereotypies.
This paper will review complex motor stereotypies and provide a summary of the current proposed treatment pathway.


Left ventricular false tendons: anatomic, echocardiographic, and pathophysiologic insights.
Left ventricular (LV) false tendons are chordlike structures that traverse the LV cavity. They attach to the septum, to the papillary muscles, or to the free wall of the ventricle but not to the mitral valve. They are found in approximately half of human hearts examined at autopsy. Although it has been more than 100 years since their initial description, the functional significance of these structures remains largely unexplored. It has been suggested that they retard LV remodeling by tethering the walls to which they are attached, but there are few data to substantiate this. Some studies have suggested that false tendons reduce the severity of functional mitral regurgitation by stabilizing the position of the papillary muscles as the left ventricle enlarges. LV false tendons may also have deleterious effects and have been implicated in promoting membrane formation in discrete subaortic stenosis. This article reviews current understanding of the anatomy, echocardiographic characteristics, and pathophysiology of these structures.


Maternal perception of fetal movements in late pregnancy is affected by type and duration of fetal movement.
A reduction in fetal movements has been proposed to identify pregnancies at risk of stillbirth. The utility of this approach is limited by variability in maternal perception of fetal movements. We aimed to determine the proportion of fetal movements observed by ultrasound that were maternally perceived and identify factors that affected maternal perception. During 30-min recordings, women (n = 21) depressed a trigger upon perception of a fetal movement, while an ultrasound operator recorded observed movements according to the fetal parts involved. Women perceived between 2.4% and 81.0% (median 44.8%) of movements observed on scan. Synchronous movement of the fetal trunk and limbs was more likely to be recognized than either part in isolation (60.5% versus 37.5% and 30%, respectively). The ultrasound operator judged the fetus to be moving for a significantly greater proportion of the time than mothers (median 1.5% of total recording time versus 0.7%). There was no significant relationship between the ability to perceive fetal activity and placental site, parity, amniotic fluid index or maternal body mass index. Variations in maternal perception of fetal movements may affect detection of a clinically significant reduction in fetal movements for some women.


Predictors of Transplant-Free Survival After the Norwood Procedure.
Birth weight, preterm delivery, and size for gestational age are surrogate markers for development that are commonly used in congenital heart surgery. Understanding the associations of these variables with patient outcomes is of great importance. This study included all patients with hypoplastic left heart syndrome who underwent a Norwood procedure at a single institution from 1995 to 2018. Low birth weight was defined as weight less than 2.5 kg, and preterm delivery occurred at less than 37 weeks' gestation. Overall and conditional analyses were performed to evaluate for association with outcomes after the Norwood procedure. Secondary analyses evaluated the association of development measures with postoperative length of stay and ventilator duration. In total, 303 neonates (60% male) underwent the Norwood procedure and were followed for a median of 3.9 years (interquartile range, 0.5 to 10.4 years). Median birth weight was 3.1 kg (interquartile range, 2.8 to 3.4 kg). Patients with low birth weight had decreased transplant-free survival compared with patients with a normal birth weight (hazard ratio, 1.7; 95% confidence interval, 1.03 to 2.82; P = .039). When conditioning on survival to second-stage palliation, patients born small for gestational age had decreased transplant-free survival compared with patients born at appropriate size for gestational age (hazard ratio, 2.8; 95% confidence interval, 1.31 to 6.09; P = .008). Patients delivered preterm had a longer hospital length of stay (median, 55 days vs 31 days; P = .02) and more ventilator days compared with patients delivered at term (median, 7 days vs 4 days; P = .004). Various developmental markers have differing prognostic importance for patients undergoing the Norwood procedure. Understanding these differences can help guide preoperative decision making and patient selection.


Decolorization of textile azo dye and Congo red by an isolated strain of the dissimilatory manganese-reducing bacterium Shewanella xiamenensis BC01.
Shewanella xiamenensis BC01 (SXM) was isolated from sediment collected off Xiamen, China and was identified based on the phylogenetic tree of 16S rRNA sequences and the gyrB gene. This strain showed high activity in the decolorization of textile azo dyes, especially methyl orange, reactive red 198, and recalcitrant dye Congo red, decolorizing at rates of 96.2, 93.0, and 87.5%, respectively. SXM had the best performance for the specific decolorization rate (SDR) of azo dyes compared to Proteus hauseri ZMd44 and Aeromonas hydrophila NIU01 strains and had an SDR similar to Shewanella oneidensis MR-1 in Congo red decolorization. Luria-Bertani medium was the optimal culture medium for SXM, as it reached a density of 4.69 g-DCW L(-1) at 16 h. A mediator (manganese) significantly enhanced the biodegradation and flocculation of Congo red. Further analysis with UV-VIS, Fourier Transform Infrared spectroscopy, and Gas chromatography-mass spectrometry demonstrated that Congo red was cleaved at the azo bond, producing 4,4'-diamino-1,1'-biphenyl and 1,2'-diamino naphthalene 4-sulfonic acid. Finally, SEM results revealed that nanowires exist between the bacteria, indicating that SXM degradation of the azo dyes was coupled with electron transfer through the nanowires. The purpose of this work is to explore the utilization of a novel, dissimilatory manganese-reducing bacterium in the treatment of wastewater containing azo dyes.


Mandibular ceramic veneers: an examination of diverse cases integrating form, function, and aesthetics.
Mandibular anterior ceramic veneers, though used less frequently than maxillary anterior ceramic veneers, are highly useful for certain case conditions. The learning objective of this article is to explore the indications, tooth preparation design, provisionalization considerations, and placement procedures for these conservative aesthetic restorations. In addition, their functional utility, tissue biocompatibility, and variances from maxillary anterior ceramic veneers are discussed by means of several different case reports.


Epidermal growth factor regulates Ca2+ uptake in primary cultured renal proximal tubule cells: involvement of cAMP, PKC and cPLA2.
Epidermal growth factor (EGF) is known to play an important role in modulating renal transport functions. Thus, we investigated the effect of EGF on Ca(2+) uptake and its related signals in the primary cultured rabbit renal proximal tubule cells. EGF (50 ng/ml, 1 h) stimulated Ca(2+) uptake. Its effect was blocked by AG 1478 (an EGF receptor antagonist), genistein or herbimycin A (tyrosine kinase inhibitors). EGF increased intracellular cAMP level and SQ 22536 (an adenylate cyclase inhibitor), Rp-cAMP (a cAMP analogue), or PKI (a protein kinase A inhibitor) blocked the EGF-induced stimulation of Ca(2+) uptake. EGF-induced stimulation of Ca(2+) uptake was also blocked by neomycin or U-73122 (phospholipase C inhibitors), staurosporine, H-7, or bisindolylmaleimide I (protein kinase C inhibitors), nifedipine or methoxyverapamil (L-type Ca(2+) channel blockers). It increased IPs formation by 167 +/- 5% compare to control within 90 s. On the other hand, EGF increased [(3)H]-arachidonic acid release, which was significantly blocked by PKC inhibitors. In addition, PGE(2), one of cyclooxygenase metabolites, and 5,6-EET, one of cytochrome P-450 metabolites, increased Ca(2+) uptake. These results suggest that cAMP, PLC/PKC, and PLA(2) are involved in EGF-induced stimulation of Ca(2+) uptake.


Synthesis and characterization of sintered beta-tricalcium phosphate: A comparative study on the effect of preparation route.
Beta-tricalcium phosphate (β-TCP) was prepared by three different routes namely, wet chemical coprecipitation, sol-gel and solution combustion synthesis. The synthesized powders were calcined at different temperatures and characterized for phase evolution study, thermal analysis, Fourier transform infrared (FTIR) spectroscopy, microstructural study for comparative analysis. The optimal thermal treatment required to prepare pure β-TCP powders was determined and after calcination of the synthesize powders prepared by different routes, pure β-TCP was obtained. The sintering temperature required to prepare fully dense β-TCP completely free from α-form was identified. The powders were then used to make dense and compact bodies sintered at 1200 and 1250°C. The sintering behaviour of the dense bodies was analysed using dilatometry, densification and microstructural study. It was found that the pellet prepared from powder synthesized via co-precipitation route attained maximum density compared to the pellets prepared from powders synthesized via sol-gel and solution combustion route.


Hysteroscopy and three-dimensional ultrasonography in uterine diverticulum diagnosis: a case report.
The authors describe a case report of a uterine diverticulum in a postmenopausal woman with abnormal uterine bleeding, confirmed by 3-dimensional ultrasonography and hysteroscopy. They comment on the clinical significance of this rare lesion.


Biophysical and morphological changes in the stratum corneum lipids induced by UVB irradiation.
UV irradiation induces a variety of responses in the epidermis, including sunburn cell formation, epidermal hyperplasia, and epidermal permeability barrier disruption. The aim of present study was to assess the effects of UVB irradiation in the intercellular lipids in murine stratum corneum. Adult hairless mice were exposed to a single UVB dose (0.15 J/cm(2)), the Fourier transform infrared (FT-IR) spectroscopic study was performed to investigate the effect on the biophysical changes in the stratum corneum lipids, barrier function was monitored by transepidermal water loss (TEWL) measurement, and the morphological alterations of stratum corneum was examined by electron microscopy using ruthenium tetroxide postfixation. The FT-IR spectroscopic study revealed that there was the shift to higher wavenumbers of the symmetric and asymmetric stretching peaks near 2850 and 2920 cm(-1) respectively at days 3-4 after a single UVB irradiation, reflecting to the increase in motional freedom of lipids hydrocarbon chains, call as disordering of lipids. Moreover, A single UVB irradiation also caused a significant increase in TEWL, the increase in TEWL began after 2 days and peaked at day 4. Electron microscopic observations revealed that marked morphological abnormalities in the intercellular domains, including abnormal profile of lamellar granules and its contents at the interface between stratum corneum and stratum granulosum and the persistence of the nuclei in the stratum corneum. Moreover, the separated fragmentary lipid lamellae, excessive numbers of lamellae in stacks, both the elongated and enlarged lacuna as well as the extracellular whorls were present within the widen space of the stratum corneum. The both of biophysical and morphological changes of the stratum corneum lipids may reflect to the mechanisms of perturbation of the epidermal permeability barrier induced by UVB irradiation.


The CIRSE Retrievable IVC Filter Registry: Retrieval Success Rates in Practice.
CIRSE established a registry of retrievable filter use with the primary aim of determining the success of IVC Filter retrieval and associated complications. Secondary endpoints included filter indications, imaging strategies before retrieval, filter dwell times, and anticoagulation status. A web-based electronic registry was hosted between 01/12/2010 and 30/06/2012. Data entry occurred at the date of IVC filter retrieval and included items such as filter type, indication for filter insertion, access route, dwell time, retrieval success, complications, reasons for failed retrieval, and anticoagulation status. 671 filter retrievals were entered (male:female 333:295, mean age 55, median 57). Retrieval data were not entered in 43/671 leaving 628 patients for analysis. The 4 commonest retrievable filters used were the Celect in 182 patients, the OPTEASE in 161, ALN in 120, and Gunther Tulip in 98. Filters were inserted for absolute indications 40%, relative indications in 31%, and prophylactic in 24%, with 5% missing. Mean filter dwell time was 90 days. Filters were successfully retrieved in 576/628 patients (92%). The mean dwell time for successful retrievals was 85 days versus 145 days for unsuccessful retrievals (p = 0.001). Major complications occurred in 2 patients (0.03%). In summary, the CIRSE retrievable filter registry demonstrates a retrieval rate of 92% across a range of filter types, with a low major complication rate, reflecting current practice. There is an increase in trend of retrievable filter use for relative and prophylactic indications.


CircRNA-vgll3 promotes osteogenic differentiation of adipose-derived mesenchymal stem cells via modulating miRNA-dependent integrin α5 expression.
Adipose-derived mesenchymal stem cells (ADSCs) are promising candidate for regenerative medicine to repair non-healing bone defects due to their high and easy availability. However, the limited osteogenic differentiation potential greatly hinders the clinical application of ADSCs in bone repair. Accumulating evidences demonstrate that circular RNAs (circRNAs) are involved in stem/progenitor cell fate determination, but their specific role in stem/progenitor cell osteogenesis, remains mostly undescribed. Here, we show that circRNA-vgll3 originating from the vgll3 locus markedly enhances osteogenic differentiation of ADSCs; nevertheless, silencing of circRNA-vgll3 dramatically attenuates ADSC osteogenesis. Furthermore, we validate that circRNA-vgll3 functions in ADSC osteogenesis through a circRNA-vgll3/miR-326-5p/integrin α5 (Itga5) pathway. Itga5 promotes ADSC osteogenic differentiation and miR-326-5p suppresses Itga5 translation. CircRNA-vgll3 directly sequesters miR-326-5p in the cytoplasm and inhibits its activity to promote osteogenic differentiation. Moreover, the therapeutic potential of circRNA-vgll3-modified ADSCs with calcium phosphate cement (CPC) scaffolds was systematically evaluated in a critical-sized defect model in rats. Our results demonstrate that circRNA-vgll3 markedly enhances new bone formation with upregulated bone mineral density, bone volume/tissue volume, trabeculae number, and increased new bone generation. This study reveals the important role of circRNA-vgll3 during new bone biogenesis. Thus, circRNA-vgll3 engineered ADSCs may be effective potential therapeutic targets for bone regenerative medicine.