Diagnostic Accuracy of the Electrocardiography Criteria for Left Ventricular Hypertrophy (Cornell Voltage Criteria, Sokolow-Lyon Index, Romhilt-Estes, and Peguero-Lo Presti Criteria) Compared to Transthoracic Echocardiography.
We aimed to evaluate the diagnostic utility of the widely used left ventricular hypertrophy (LVH) electrocardiography (ECG) criteria (Cornell Voltage Criteria [CVC], Sokolow-Lyon Index [SLI], Romhilt-Estes [REC], and Peguero-Lo Presti [PLP] Criteria) compared with the left ventricular mass measured by echocardiography. In this prospective diagnostic accuracy study, we screened all consecutive adults (18 to 65 years) who presented to our academic emergency department (ED) with increased blood pressure (≥130/85 mmHg) between January 2016 and January 2017, and we enrolled a convenience sample of 165 patients in our study. The attending emergency physician managed all patients as per their primary complaint. The consulting cardiologist performed a transthoracic echocardiogram (TTE) of the patient and calculated the left ventricular mass (LVM) according to the American Society of Echocardiography (ASE) formula. After completing the patient recruitment phase, researchers evaluated all ECGs and calculated scores for SLI, CVC, REC, and PLP. We used contingency tables to calculate the diagnostic utility metrics of all ECG criteria. The prevalence of LVH by TTE was 31.5%. CVC, SLI, REC, and PLP criteria correctly identified (true positive rate) abnormal LVM in only 3.9%, 1.9%, 9.6%, and 19.2% of the patients, respectively. CVC, SLI, REC score and PLP criteria performed poorly with extremely low sensitivities (3.9%, 1.9%, 10%, 19.2%) and poor accuracies (67.3%, 64.9%, 57.7%, 69.7%). ECG voltage criteria's clinical utility in estimating LVM and LVH is low, and it should not be used for this purpose.


The mechanism of action of phosphodiesterase type 5 inhibitors in the treatment of lower urinary tract symptoms related to benign prostatic hyperplasia.
Clinical trials of phosphodiesterase type 5 inhibitors (PDE5-Is) have consistently demonstrated a significant reduction in lower urinary tract symptoms (LUTS) and small urinary flow rate changes in men with benign prostatic hyperplasia (BPH). This review presents the proposed mechanisms of action of PDE5-Is in the treatment of BPH-LUTS focusing on the localization of PDE5 isoenzymes in the pelvic structures; smooth muscle relaxation in the bladder, prostate, and supporting vasculature; increased blood perfusion of the bladder and prostate; and modulation of sensory impulses from these organs. Literature describing in vitro, preclinical, or clinical studies of pathologic processes contributing to LUTS or effects of PDE5 inhibition on the lower urinary tract (LUT) was selected for review. We objectively assessed and summarized the published data focusing on articles published within the past 10 yr. Articles before the time cut-off were included if historically relevant. The PDE5 isoenzymes are highly expressed in the LUT including the bladder, prostate, and their supporting vasculature. In vitro assays have demonstrated PDE5-Is by regulating cyclic guanosine monophosphate (cGMP) degradation and enhancing the nitric oxide/cGMP signaling pathway to relax human smooth muscle strips from the prostate, bladder, and LUT arteries. In animals characterized by ischemia/hypoxia of the genitourinary tract, treatment with PDE5-Is increases bladder and prostate tissue oxygenation. PDE5-Is have been shown to reduce nonvoiding contractions and bladder afferent nerve firing in decerebrate spinal cord-injured rats, and to reduce mechanosensitive afferent activities of both Aδ- and C-fibers in an irritated or overextended bladder model.


Alterations in MicroRNA gene expression profile in liver transplant patients with hepatocellular carcinoma.
Hepatocellular carcinoma (HCC) can lead to liver failure which renders to liver transplant. miRNAs might be detected as biomarkers in subclinical stage of several hepatobiliary disorders like HCC. Therefore, in the present study, alterations in miRNAs as biomarkers were detected in LT patients with HCC. Fourteen tissue samples composed of 5 rejected and 9 non-rejected ones were used for studying the miRNAs expression pattern using LNA-array probe assay and the result was evaluated by in house SYBR Green Real-time PCR protocols on 30 other tissue samples composed of 10 rejected and 20 non-rejected ones for the selected miRNAs. All samples were collected from liver transplanted patients with HCC. The study results revealed that in rejected patients compared to non-rejected ones, hsa-miR-3158-5p, -4449, -4511, and -4633-5p were up-regulated and hsa-miR-122-3p, -194-5p, 548as-3p, and -4284 were down-regulated. ROC curve analysis also confirmed that miR194-5p and -548as-3p in up-regulated and also, miR-3158-5p, -4449 in down-regulated microRNAs are significantly important molecules in rejection. Finally, the tissue levels of specific miRNAs (especially hsa-miR-3158-5p, -4449, -194-5p and -548as-3p) significantly correlated with the development of HCC, which can be present as biomarkers after further completing studies.


Dietary influences on cell proliferation in bone marrow.
Oral dietary protein-calorie malnutrition was used in rats to study the influence of malnutrition on the distribution of the dividing cells in the bone marrow (stem cells) over the compartments of the cell cycle. A 5-day period of malnutrition induced an increase in the percentage of cells in the G0/G1 phase of the cell cycle while simultaneously inducing a statistically significant decrease in the percentage of cells in S phase. Similar results were obtained after a 14-day period of malnutrition. Nutritional replenishment after 5 and 14 days of dietary deprivation induced a rapid recovery of the percentage of S phase cells and a decrease in the percentage of cells in the G0/G1 phase of the cell cycle. Malnutrition and nutritional replenishment did not influence hemoglobin concentration and platelet numbers in the peripheral blood, but leucocyte numbers increased significantly after short-term replenishment. These results demonstrate a decrease in the percentage of proliferating bone marrow cells after short periods of deficiency and general malnutrition. The results also demonstrate that bone marrow cells recover quickly after nutritional replenishment. In malnourished cancer patients, suspected of bone marrow insufficiency and receiving therapy that potentially impairs bone marrow proliferation, a short period of nutritional replenishment preceding treatment could possibly be marrow-protective.


Institutional quality, financial development and the influence of environmental factors on carbon emissions: evidence from a global perspective.
This study explores the moderating role of institutional quality on carbon emissions using data from a global panel regarding renewable energy consumption, foreign direct investment, economic growth and financial development between 2002 and 2019. Using the two-step system generalized method of moments, the results illustrate that in the panel data, renewable energy usage and foreign direct investment inflow enhance environmental quality, while financial development and economic growth lower it. The results show that many countries' quality institutions cannot yet adequately mitigate the harmful impact of each environmental factor and protect the environment; however, the institutional quality interaction term confirms the significant moderating effect of all explanatory variables on environmental quality in the panel data. The findings also confirm the existence of the environmental Kuznets curve and demonstrate the pollution halo hypothesis. The findings in this paper may be useful for policymakers when enacting stricter environmental regulations.


Analysis of resorbable mesh implants in short-term human muscular fascia cultures: a pilot study.
Alteration in fascial tissue collagen composition represents a key factor in hernia etiology and recurrence. Both resorbable and non-resorbable meshes for hernia repair are currently used in the surgical setting. However, no study has investigated so far the role of different implant materials on collagen deposition and tissue remodeling in human fascia. The aim of the present study was to develop a novel ex vivo model of human soft tissue repair mesh implant, and to test its suitability to investigate the effects of different materials on tissue remodeling and collagen composition. Resorbable poly-4-hydroxybutyrate and non-resorbable polypropylene mesh implants were embedded in human abdominal fascia samples, mimicking common surgical procedures. Calcein-AM/Propidium Iodide vital staining was used to assess tissue vitality. Tissue morphology was evaluated using Mallory trichrome and hematoxylin and eosin staining. Collagen type I and III expression was determined through immunostaining semi-quantification by color deconvolution. All analyses were performed after 54 days of culture. The established ex vivo model showed good viability at 54 days of culture, confirming both culture method feasibility and implants biocompatibility. Both mesh implants induced a disorganization of collagen fibers pattern. A statistically significantly higher collagen I/III ratio was detected in fascial tissue samples cultured with resorbable implants compared to either non-resorbable implants or meshes-free controls. We developed a novel ex vivo model and provided evidence that resorbable polyhydroxybutyrate meshes display better biomechanical properties suitable for proper restoration in surgical hernia repair.


Dexamethasone stimulates insulin receptor synthesis in cultured rat hepatocytes.
The ability of the glucocorticoid dexamethasone to modulate the insulin receptor was examined directly in primary cultures of hepatocytes prepared from adult male rats. Hepatocytes were cultured in a defined medium in the presence and absence of dexamethasone, 0.1 microM. The exposure of hepatocytes to dexamethasone resulted in a time-dependent (steady state by 32 h) increase in insulin binding in both intact hepatocytes and Triton X-100-soluble extracts (total insulin receptor content). The enhanced insulin binding found in soluble extracts of dexamethasone-treated hepatocytes was the result of an increase in insulin receptor number without a change in receptor affinity. In order to assess the mechanism by which dexamethasone "up-regulates" the insulin receptor, the heavy isotope density-shift technique was used to analyze insulin receptor turnover in control and dexamethasone-treated hepatocytes. Hepatocytes were initially cultured for 32 h in standard culture media containing only "light" (14C, 12C, 1H) amino acids. In hepatocytes exposed to dexamethasone, a 417% increase in insulin binding in Triton X-100-soluble extracts was observed. After 32 h, when steady state binding is achieved in dexamethasone-treated cultures, parallel cultures of hepatocytes incubated in the absence and presence of dexamethasone were washed and subsequently cultured in media containing "heavy" amino acids (15N, 13C, 2H). The time-dependent disappearance of light insulin receptor (receptor degradation) and appearance of heavy insulin receptor (receptor synthesis) were monitored using CsCl gradients to resolve the two density species of receptor. At steady state, the rate of receptor synthesis (k8) was 2.94 and 0.62 fmol of insulin bound h-1 in dexamethasone-treated and control hepatocytes, respectively. In contrast to this large increase in the rate of receptor synthesis observed in dexamethasone-treated cells, the first order rate constant for decay (k d) was the same in dexamethasone-treated (0.074 h-1) and in control (0.077 h-1) hepatocytes. We therefore conclude that glucocorticoid-induced up-regulation of the insulin receptor in the liver is due to stimulation of insulin receptor synthesis.


Moving messages in the developing brain-emerging roles for mRNA transport and local translation in neural stem cells.
The mammalian cerebral cortex is a complex brain structure integral to our higher cognition. During embryonic cortical development, radial glial progenitors (RGCs) produce neurons and serve as physical structures for migrating neurons. Recent discoveries highlight new roles for RNA localization and local translation in RGCs, both at the cell body and at distal structures called basal endfeet. By implementing technologies from the field of RNA research to brain development, investigators can manipulate RNA-binding proteins as well as visualize single-molecule RNAs, live movement of mRNAs and their binding proteins, and translation. Going forward, these studies establish a framework for investigating how post-transcriptional RNA regulation helps shape RGC function and triggers neurodevelopmental diseases.


6-Methylsalicylic acid synthetase from Penicillium patulum. Some catalytic properties of the enzyme and its relation to fatty acid synthetase.
1. The specificity of 6-methylsalicylic acid synthetase with respect to the priming substrate was studied. If acetyl-CoA was replaced by propionyl-CoA 6-ethylsalicylic acid was synthesized. The rate of this synthesis was about 13% that of 6-methylsalicylic acid synthesis in presence of acetyl-CoA. 2. 6-Methylsalicylic acid synthetase contains an acetyl transferase activity as demonstrated by the transfer of acetyl residues from acetyl-CoA to pantetheine. This transferase also catalyses propionyl transfer but only with an about 13 times slower rate. 3. Analogous to fatty acid synthetase, treatment with iodoacetamide converts 6-methylsalicylic acid synthetase into a malonyl-CoA decarboxylase. Under certain conditons the iodoacetamide-treated enzyme could catalyse 6-methylsalicylic acid formation from malonyl CoA and NADPH without the external addition of acetyl CoA.


Children placed in out-of-home care: risk factors for involvement with the juvenile justice system.
In previous research, child maltreatment has been associated with several negative outcomes, including delinquency. This study uses administrative data to examine risk factors, including the severity and chronicity of maltreatment, for juvenile justice involvement among children, ages 7 to 17, who were placed in out-of-home care in Florida (N = 13,212). The results of multivariate Cox regression analysis indicated that among specific types of maltreatment, sexual abuse was associated with the risk of faster placement only in a detention center. Additionally, findings from this study suggest that maltreatment chronicity but not maltreatment severity increases the chances of earlier involvement with the juvenile justice system among children who were placed in an out-of-home care. Implications of these findings are discussed.


Corpus analysis of problem-based learning transcripts: an exploratory study.
Problem-based learning (PBL) is one of the most researched areas of medical education; numerous studies and meta-analyses have examined its overall effectiveness compared with that of traditional methods. Fewer studies have looked at the processes occurring within the PBL group, considering that a key difference between PBL and traditional teaching is the amount of talking in which students engage: a typical PBL week might involve 3-5 hours of talk. Little research has attempted to capture the vocabulary used or to analyse the cognitive processes that occur during PBL discussions and that might contribute to the advantages of this method of learning. We professionally transcribed a recording of a facilitator and seven students engaging in a PBL case consisting of three sessions. The text was analysed by using Wmatrix2 (UCREL, Lancaster University, UK), a powerful linguistic program used for corpus analysis. This allowed the inter-sessional comparative quantification of the use of technical vocabulary, as well as of reasoning, questioning and explaining episodes. We have compared the frequency of technical words and of reasoning, explaining and questioning episodes between sessions and related these differences to the focus of each session. We have been able to build concordances of important words and phrases within sentences which can be used to identify and monitor examples of questioning, explaining and reasoning. In this exploratory study we have shown that corpus analysis can be a useful tool with which to analyse PBL transcriptions. This technique can be used to monitor the development of a technical vocabulary and skills in scientific and clinical reasoning as students progress through a PBL curriculum. We propose this methodology will become a powerful tool to help explore the much wider cognitive and linguistic developments of students and facilitators as they engage in PBL discourse.


Neuroglobin plays as tumor suppressor by disrupting the stability of GPR35 in colorectal cancer.
The incidence of colorectal cancer (CRC) has increased in recent years. Identification of accurate tumor markers has become the focus of CRC research. Early and frequent DNA methylation tends to occur in cancer. Thus, identifying accurate methylation biomarkers would improve the efficacy of CRC treatment. Neuroglobin (NGB) is involved in neurological and oncological diseases. However, there are currently no reports on epigenetic regulation involvement of NGB in CRC. NGB was downregulated or silenced in majority CRC tissues and cell lines. The hypermethylation of NGB was detected in tumor tissue, but no or a very low methylation frequency in normal tissues. Overexpression of NGB induced G2/M phase arrest and apoptosis, suppressed proliferation, migration, invasion in vitro, and inhibited CRC tumor growth and angiogenesis in vivo. Isobaric tag for relative and absolute quantitation (Itraq)-based proteomics identified approximately 40% proteins related to cell-cell adhesion, invasion, and tumor vessel formation in the tumor microenvironment, among which GPR35 was proved critical for NGB-regulated tumor angiogenesis suppression in CRC. NGB, an epigenetically silenced factor, inhibits metastasis through the GPR35 in CRC. It is expected to grow into a potential cancer risk assessment factor and a valuable biomarker for early diagnosis and prognosis assessment of CRC.


The effect of chlorhexidine mouth rinses on oral Candida in a group of leukemic patients.
Eighteen leukemic patients were examined for the presence of Candida albicans in the oral cavity. Fifteen patients were found to be Candida "carriers." Nine of the patients were put on a chlorhexidine mouth rinse regimen. Although chlorhexidine was clearly fungicidal in vitro, no decrease in Candida titer was obtained with the mouth rinse. The ineffectiveness of the drug in vivo might be due to the specific location of Candida organisms in the oral mucosa.


Minimally Invasive Anterolateral Ligament Reconstruction of the Knee.
Anterior cruciate ligament (ACL) tears are among the most common knee injuries, and multiple reconstructive techniques have been described. However, studies frequently report an inability to duplicate native, dynamic knee function, particularly rotationally. This residual joint laxity that occasionally follows an ACL reconstruction can cause further problems post surgical intervention, including meniscal tears and especially late osteoarthritic change. Additionally, ACL graft retears are a concern, particularly in young patients. Although these undesired sequelae of ACL reconstruction could be a by-product of insufficient ACL reconstruction methods related to either graft placement or problems with graft healing and biology, it is also possible that failure to additionally address lateral extra-articular structures after ACL injury could play a role in the residual knee laxity of the affected knee. The purpose of this article is to show a minimally invasive technique for extra-articular anterolateral ligament reconstruction.


Oxygen binding in blood of Xenopus laevis (Amphibia) and evidence against Root effect.
Blood oxygen binding was examined in the amphibian, Xenopus laevis, with the particular aim of determining whether the O2 capacity is diminished when blood pH is lowered, which is known as the Root effect in blood of some fishes. Hemoglobin-bound O2 concentration, [O2Hb], was determined by the Lex-O2-Con technique, and both total hemoglobin, [Hb]tot, and Met-hemoglobin, [MetHb], contents were measured spectrophotometrically. From these measurements were calculated the oxygen capacity, O2cap, and the content of active hemoglobin, [Hb]act, i.e. the difference between [Hb]tot and [MetHb]. The main finding was the independence of the ratio of O2cap/[Hb]act on pH, when differences between samples in [Hb]tot and the presence of MetHb, which was particularly pronounced at low pH, where properly accounted for. It is concluded that the Root effect does not exist in blood of the amphibian Xenopus laevis.


Heterogeneity of Fibroblasts and Myofibroblasts in Pulmonary Fibrosis.
Idiopathic Pulmonary Fibrosis (IPF) is the most common form of interstitial lung diseases of unknown eathiopathogenesis, mean survival of 3-5 years and limited therapeutics. Characterized by a loss of alveolar type II epithelial cells and aberrant activation of stromal cells, considerable effort was undertaken to characterize the origin and activation mechanisms of fibroblasts and myofibroblasts in IPF lungs. In this review, the origin and contribution of fibroblast and myofibroblasts in lung fibrosis will be summarized. Lineage tracing experiments suggested that interstitial lung fibroblasts and lipofibroblasts, pericytes and mesothelial cells differentiate into myofibroblasts. However, epithelial and bone marrow derived cells may give rise to collagen expressing fibroblasts but do not differentiate into myofibroblasts. There is great heterogeneity in fibroblasts and myofibroblasts in fibrotic lungs. Further, there is evidence for the expansion of pericyte derived myofibroblasts and loss of lipofibroblasts and lipofibroblast derived myofibroblasts in IPF.


Blockade of JAK2 signaling produces immunomodulatory effect to preserve pancreatic homeostasis in severe acute pancreatitis.
JAK/STAT plays an important role in cytokine signal transduction and it is potentially involved in the proinflammatory response during the early phase of severe acute pancreatitis (SAP). However, whether JAK2 activity is upregulated and whether JAK2 inhibition plays a role in the maintenance of pancreatic homeostasis during SAP is incompletely understood. Here we show that JAK2/STAT3 activity is highly elevated in SAP and blockade of JAK2 by AG-490 protects against SAP-induced pancreatic inflammation and injury. Gene expression and ELISA studies showed that JAK2 inhibition altered the cytokine profiles in both the circulation and pancreases. Further analysis revealed that JAK2 inhibition restored the level of cytokines critical for macrophage polarization towards M2 macrophage. Our findings suggest that pharmacological targeting at JAK2/STAT signalling may be an effective choice of therapeutic interventions against SAP.


[Pertrochanteric femoral fracture in elderly patients--injury pattern and management with gamma nailing].
A group of 128 elderly patients (> 75 years) suffering from peritrochanteric fractures of the femur were treated by the gamma nailing procedure. Results were 81% very good to good and 7% fair. The lethality rate was 8% for the first 4 months. No cases of deep infection, no fractures of the femur following nailing, and no problems with the lag screw were noticed.


A novel design for solar collector used for water heating application having nanofluid as working medium: CFD modeling and simulation.
A solar collector is a simple and cheap device that converts solar radiation into valuable heat energy. The thermal performance of the solar collectors can be enhanced significantly with the suspension of nanoparticles in the base fluid. A novel design for a solar-assisted water heater (SWH) is proposed in the current study, and the effect of nanofluid has been investigated on the thermal efficiency of the SWH. The use of nanofluid is one of the prominent methods in comparison to other techniques for improving the performance of solar collectors. Therefore, the base working fluid, i.e., water is mixed with the alumina nanoparticles of average particle size of 30 nm, and they are assumed to be spherical. The flow and thermal characteristics of nanofluid through the solar water heater are simulated numerically with the help of the Eulerian-Eulerian two-phase model using the finite volume method (FVM). The commercial package ANSYS Fluent, is used for modeling the problem under transient conditions with a pressure-based solver. In comparison to a conventional flat plate collector, the proposed solar water heater consists of a corrugated absorber-plate and the effect of the radius of curvature has been investigated on the heat transfer and collector efficiency. With the proposed design, the heat transfer area available with the riser tubes increases remarkably and it leads to a 43% and 14% increase in heat transfer augmentation and collector efficiency, in comparison to the conventional solar water heater.


In vitro secretion profile of pro-inflammatory cytokines IL-1β, TNF-α, IL-6, and of human beta-defensins (HBD)-1, HBD-2, and HBD-3 from human chorioamniotic membranes after selective stimulation with Gardnerella vaginalis.
Preterm labor associated with infection is a major clinical condition; in this work, we analyze the response of human chorioamniotic membranes stimulated with Gardnerella vaginalis. Using a two-compartment experimental model, 1 × 10(6) CFU/mL of G. vaginalis were added to either the amnion or choriodecidua face or to both. Concentrations of IL-1β, TNF-α, and IL-6, as well as human beta defensins (HBD) 1-3 were quantified by ELISA. In comparison with control conditions and regardless of the stimulation modality, IL-1β and IL-6 increased 4-fold and 28-fold, respectively, in the choriodecidual compartment. HBD-1 increased 2-fold mainly in the amniotic compartment when the stimulus was applied directly to this region. HBD-2 and HBD-3 increased an average of 2- and 8-fold, respectively, in the choriodecidual region. Stimulation with G. vaginalis induced a tissue-specific secretion profile of 1L-1β, IL-6, and HBD 1-3 in the chorioamniotic membranes.


Synthesis, characterization and DNA-binding properties of rac-[Ru(5,6-dmp)2(dppz)]2+--enantiopreferential DNA binding and co-ligand promoted exciton coupling.
The new mixed ligand complex [Ru(5,6-dmp)2(dppz)]Cl2 [5,6-dmp = 5,6-dimethyl-1,10-phenanthroline, dppz = dipyrido[3,2-a:2',3'-c]phenazine] has been isolated and its DNA-binding properties studied by employing UV-visible (UV-Vis), steady-state and time-resolved emission and circular dichroism spectral methods, viscometry, thermal denaturation and cyclic/differential pulse voltammetric techniques. The complex acts as a 'molecular light-switch' on binding to DNA, but the enhancement in emission intensity is only 75% of that of the parent complex [Ru(phen)2(dppz)]2+ (phen = 1,10-phenanthroline). The emission decay curves and quenching studies suggest two different DNA-binding modes both involving intercalation of the dppz ligand of [Ru(5,6-dmp)2(dppz)]Cl2. The characteristic red-shift of the induced CD signal, which is not observed for the phen analogue, arises from exciton coupling. The hydrophobicity and polarizability of 5,6-dmp co-ligand strongly favour the formation of a stable structural and electronic scaffold on the DNA surface for the unbound molecules to couple with the DNA-bound complexes facilitating spontaneous assembly of novel extended molecular aggregates using DNA as a helical nanotemplate. This observation is consistent with the shift in Ru(II)/Ru(III) redox potential to more positive values with a dramatic drop in peak current on binding of the 5,6-dmp complex to calf thymus (CT) DNA. Equilibrium dialysis experiments monitored by CD spectroscopy unambiguously reveal the preferential binding of the delta-enantiomer to the right-handed calf thymus (CT) DNA. The 5,6-dmp complex exhibits preferential binding to [d(AT)6]2 over [d(GC)6]2 and the complex aggregates formed consist of six [Ru(5,6-dmp)2(dppz)]2+ cations per base pair of [d(AT)6]2; however, only one [Ru(phen)2(dppz)]2+ cation per base pair is involved in DNA binding.


DCG-IV inhibits synaptic transmission by activation of NMDA receptors in area CA1 of rat hippocampus.
We investigated the synaptic depressant action of the metabotropic glutamate receptor group II agonist, (2S,1'R,2'R,3'R)-2-(2',3'-dicarboxycyclopropyl)-glycine (DCG-IV), in area CA1 of rat hippocampus. A brief bath application of DCG-IV (10 microM) caused a rapidly reversible depression to 0.57 +/- 0.22 (i.e., 43%) of baseline excitatory postsynaptic potential (epsp) slope. This depression could not be attenuated by the metabotropic glutamate receptor antagonists alpha-methyl-L-CCGI/(2S,3S,4S)-2-methyl-2-(carboxycyclopropyl++ +)glycine (MCCG), (RS)-alpha-methyl-4-tetrazolyphenylglycine (MTPG) or (S)-2-amino-2-methyl-4-phosphonobutanoic acid alpha-methyl-AP4) (MAP4). However, the DCG-IV-induced depression could be reversed by the NMDA receptor antagonist, D(-)-2-amino-5-phosphonopentanoic acid (AP5; 50 microM), and partially reversed by the adenosine A1 receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX; 5 microM). These results strongly suggest that DCG-IV is an agonist at NMDA receptors and provide further evidence against a role for metabotropic glutamate receptor group II in synaptic transmission in area CA1 of rat hippocampus.


Focal Adhesion Kinase (FAK) Overexpression and Phosphorylation in Oral Squamous Cell Carcinoma and their Clinicopathological Significance.
Focal adhesion kinase (FAK) is involved in progression of various cancers, and FAK overexpression has been associated with cancer invasion and metastasis. However, the involvement of FAK expression in the clinicopathological malignancy of oral squamous cell carcinoma (OSCC) remains unknown. In addition, there is no consensus regarding the role of p16 expression in OSCC. In this study, the immunohistochemically measured expression of FAK, phosphorylated FAK (FAKpY397) and p16 expressions and their associations with clinicopathological features and 5-year survival rates were examined in surgical samples from 70 patients with primary OSCC. FAK and FAKpY397 were expressed at high levels in 42 cases (60.0%) and 34 cases (48.6%), respectively, and 9 cases (12.9%) were positive for p16. FAK expression was significantly correlated with local recurrence, subsequent metastasis, and the mode of invasion. FAKpY397 expression was significantly correlated with both N classification and the mode of invasion. p16 expression was significantly correlated with clinical stage only. Patients having high expression of FAK, FAKpY397, or both showed significantly worse prognosis, but p16 expression showed no significant relation to prognosis. The results suggested that overexpression and phosphorylation of FAK in OSCC may affect cancer progression, such as local invasion and lymph node metastasis, and thereby contribute to life prognosis.


Study on the possibility of developing food-grade hydrophobic bio-aerogels by using an oleogel template approach.
The feasibility of producing food-grade hydrophobic bio-aerogels by supercritical-carbon dioxide (SC-CO2) extraction of oil from oleogels was investigated for the first time. Medium chain triglycerides (MCT) oil was gelled using ethylcellulose (EC) at increasing concentration (10, 15, 20% w/w) and grade (EC20, 45, 100), eventually in combination with fillers. Different SC-CO2 oil extraction procedures were tested. The acquired results show that both oleogel formulation and extraction conditions can steer the EC scaffold structure. The increase in EC concentration and grade resulted in oleogels more structurally stable to SC-CO2 extraction. The application of a pulsed extraction procedure allowed obtaining a low-density (0.39 g/cm3) EC scaffold presenting 60% oil. Addition of freeze dried lettuce powder improved macrostructure homogeneity. The obtained results lay the foundations for developing food-grade hydrophobic bio-aerogels, which are expected to present unique oil absorption and bioactive delivery features.


An emotional-response model of bipolar disorders integrating recent findings on amygdala circuits.
Because of our classification system limitations for defining psychiatric disorders and understanding their physiopathology, a new research area based on dimensions has emerged. It consists of exploring domains derived from fundamental behavioral components linked to neurobiological systems. Emotional processing is among the most affected dimensions in bipolar disorders (BD), but is excluded from the definition criteria. The purpose of this review is to synthesize the emotional responses disruption during the different phases of BD, using intensity and valence as the two key characteristics of emotions. We integrate those emotional disruptions into an original, emotion-based model contrasting with the current diagnostic frame built on mood. Emotional processing is underpinned by cortico-limbic circuits involving the amygdala. Recent publications showed the crucial role of the amygdala in emotional processes triggered by stimuli of negative, but also positive valence. We show how these neuroscience data can provide physiological basis for emotional disturbances observed in BD. We conclude with translational perspectives to improve the current knowledge about neural substrates underlying altered emotional responses characterizing BD.


Early responses to 3 mm resilient stabilization appliance therapy for sub-acute and chronic temporomandibular disorder pain predict 12-months follow-up outcomes.
Objective: To estimate whether outcomes at 12-month follow-up may be predicted by an intermediate and early response to a 3 mm resilient splint therapy for unilateral arthralgia and myofascial pain assessed at 3- and 6-month follow-ups.Methods: Data obtained from one retrospective cohort study consisting of 78 patients suffering from chronic and sub-acute unilateral arthralgia and myofascial pain who were managed with 3 mm resilient splint therapy were subjected to analysis.Results: Baseline visual analog scale (VAS) intensity, gender as well as changes in the intensity of VAS pain at 3- and 6-month follow-ups predicted unilateral arthralgia and myofascial pain group membership (p < .001). The function classified 83.3% of the cross-validated and 87.2% of original grouped cases correctly.Discussion: The proposed model may be used to timely identify patients who are at risk of developing prolonged non-responsive unilateral arthralgia and myofascial pain chronicity.


Screening and characterization of membrane damaging effects in tissue culture.
A leakage test system for specific detection, measurement and characterization of membrane damage in human lung fibroblasts is discussed. Examples of applications with various types of substances are presented, i.e. tobacco smoke compounds; animal, plant and microbial cytolysins; membrane damaging antibiotics.


The macro domain protein family: structure, functions, and their potential therapeutic implications.
Macro domains are ancient, highly evolutionarily conserved domains that are widely distributed throughout all kingdoms of life. The 'macro fold' is roughly 25kDa in size and is composed of a mixed α-β fold with similarity to the P loop-containing nucleotide triphosphate hydrolases. They function as binding modules for metabolites of NAD(+), including poly(ADP-ribose) (PAR), which is synthesized by PAR polymerases (PARPs). Although there is a high degree of sequence similarity within this family, particularly for residues that might be involved in catalysis or substrates binding, it is likely that the sequence variation that does exist among macro domains is responsible for the specificity of function of individual proteins. Recent findings have indicated that macro domain proteins are functionally promiscuous and are implicated in the regulation of diverse biological functions, such as DNA repair, chromatin remodeling and transcriptional regulation. Significant advances in the field of macro domain have occurred in the past few years, including biological insights and the discovery of novel signaling pathways. To provide a framework for understanding these recent findings, this review will provide a comprehensive overview of the known and proposed biochemical, cellular and physiological roles of the macro domain family. Recent data that indicate a critical role of macro domain regulation for the proper progression of cellular differentiation programs will be discussed. In addition, the effect of dysregulated expression of macro domain proteins will be considered in the processes of tumorigenesis and bacterial pathogenesis. Finally, a series of observations will be highlighted that should be addressed in future efforts to develop macro domains as effective therapeutic targets.


Characterization and regulation of heart adenosine 3':5'-monophosphate-dependent protein kinase isozymes.
There is broad species variation in the type of cAMP-dependent protein kinase isozyme present in supernatant fractions of heart homogenates as determined by DEAE-cellulose chromatography, Isozyme I, which elutes at less than 0.1 M NaCl, is predominant in mouse and rat hearts; while isozyme II, which elutes at greater than 0.1 M NaCl, is the predominant type in beef and guinea pig. Human and rabbit hearts contain about equal amounts of the two types. The type I heart kinases are more easily dissociated into free regulatory and catalytic subunits by incubation with histone than are the type II kinases, and the separated regulatory and catalytic subunits of isozyme II of rat heart reassociate more rapidly than the subunits of isozyme I under the conditions used. The data from several experiments using rat heart indicate that the basal activity ratio of the protein kinase in crude extracts (approximately 0.15) is due mainly to basal endogenous cAMP and that cAMP elevation accounts entirely for the epinephrine effect on the enzyme. Addition of epinephrine and 1-methyl-3-isobutylxanthine to the perfusate causes a rapid (1 min) increase in cAMP, active supernatant protein kinase, and active phosphorylase in perfused hearts of both rat (mainly isozyme I) and guinea pig (mainly isozyme II). The elevation percentage in cAMP is about the same in the two species, but the increase in active protein kinase is greater in rat heart. If hearts from either animal are perfused continually (10 min) with epinephrine (0.8 muM) and 1-methyl-3-isobutylxanthine (10 muM), the cAMP level, active protein kinase, and active phosphorylase remain elevated. Likewise, all parameters return rapidly to the basal levels when epinephrine and 1-methyl-3-isobutylxanthin are removed. Most of the epinephrine effect on the rat heart supernatant kinase is retained at 0 degrees if cAMP is removed by Sephadex G-25 chromatography, although this procedure completely reverses the epinephrine effect in the guinea pig heart. The epinephrine effect on the rabbit heart kinase (approximately equal amounts of isozymes I and II) is partially reversed by Sephadex G-25. These species differences can be accounted for by differences in association-dissociation behavior of the isozymes in vitro. The data suggest that epinephrine causes activation of both isozymes. The activity present in the particulate fraction comprises nearly half of the total cAMP-dependent protein kinase activity in homogenates of rabbit heart. Triton X-100 extracts of low speed particulate fractions from hearts of each species tested, including rat heart, contain predominantly or entirely the type II isozyme, suggesting differences in intracellular distribution of the isozymes. The binding of the protein kinase to the particulate fraction is apparently due to the properties of the regulatory subunit component. Differences in topographical distribution of the isozymes could provide for differences in either physiological regulation or substrate specificity.


Older patients with nonspecific complaints at the Emergency Department are at risk of adverse health outcomes.
Older adults at the Emergency Department (ED) often present with nonspecific complaints (NSC) such as 'weakness' or 'feeling unwell'. Health care workers may underestimate illness in patients with NSC, leading to adverse health outcomes. This study compares characteristics and outcomes of NSC-patients versus specific complaints (SC) patients. Cohort study in patients ≥ 70 years in two Dutch EDs. NSC was classified according to the BANC-study-framework based on the medical history in the ED letter, before additional diagnostics took place. A second classification was performed at the end of the ED visit/hospital admission. Primary outcomes were functional decline, institutionalization, and mortality at 30 days. 26% (n = 228) of a total of 888 included patients presented with NSC. Compared with SC-patients, NSC-patients were older, more frail, and more frequently female. NSC-patients had a higher risk of functional decline and institutionalization at 30 days (adjusted ORs 1.84, 95% CI 1.27 - 2.72, and 2.46, 95% CI 1.51-4.00, respectively), but not mortality (adjusted OR 1.26, 95% CI 0.58 - 2.73). Reclassification to a specific complaint after the ED visit or hospital admission occurred in 54% of NSC-patients. NSC occur especially in older, frail female patients and are associated with an increased risk of functional decline and institutionalization, even after adjustment for worse baseline status. In half of the patients, a specific complaint revealed during ED or hospital stay. Physicians at the ED should consider NSC as a red flag needing appropriate observation and evaluation of underlying serious conditions and needs of this vulnerable patient group.


Should Commercial Diagnostic Testing Be Stimulated or Discouraged? Analyzing Willingness-to-Pay and Market Externalities of Three Commercial Diagnostic Tests in The Netherlands.
Consumers may purchase commercial diagnostic tests (CDT) without prior doctor consultation. This paper analyzes three CDT markets-commercial cholesterol tests (CCT), direct-to-consumer genetic health tests (DGT) and total body scans (TBS)-in the context of the universal, collectively financed health care system of the Netherlands. An online willingness-to-pay (WTP) questionnaire was sent to a representative sample of 1500 Dutch consumers. Using contingent valuation (CV) methodology, an array of bids for three self-tests were presented to the respondents. The results were extrapolated to the Dutch population and compared to current prices and follow-up medical utilization, allowing analysis from a societal perspective. Overall, 880 of 1500 respondents completed the questionnaire (response rate 59%). Of the respondents, 26-44% were willing to pay a positive amount for the CDT. Willingness-to-pay was correlated to age and household income, but not to health status or prior experience with these tests. At mean current prices of €29 for CCT, €229 for DGT and €1,650 for TBS, 3.3%, 2.5%, and 1.1%, were willing to purchase a CCT, DGT, and TBS, respectively. All three CDT resulted in net costs to the health system, estimated at €5, €16, and €44 per test, respectively. Reducing volumes by 90,000 CCTs (19%), 19,000 DGTs (5%) and 4,000 TBSs (2.5%) in 2019 would optimize welfare. Most respondents were unwilling to consume CDT at any price or only if the CDT were provided for free. However, for a small group of consumers, societal costs exceed private benefits. Therefore, CDT regulation could provide small welfare gains.


Fecal Calprotectin in Combination With Standard Blood Tests in the Diagnosis of Inflammatory Bowel Disease in Children.
Introduction: Fecal calprotectin (FC) is a useful non-invasive screening test but elevated levels are not specific to inflammatory bowel disease (IBD). The study aimed to evaluate the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of FC alone or FC in combination with other standard blood tests in the diagnosis of IBD. Methods: Children aged <17 years who had FC (normal range <50 μg/g) measured and underwent endoscopy over 33 months in Christchurch, New Zealand were identified retrospectively (consecutive sampling). Medical records were reviewed for patient final diagnoses. Results: One hundred and two children were included; mean age was 12.3 years and 53 were male. Fifty-eight (57%) of the 102 children were diagnosed with IBD: 49 with Crohn's disease, eight with ulcerative colitis and one with IBD-unclassified. FC of 50 μg/g threshold provided a sensitivity of 96.6% [95% confident interval (CI) 88.3-99.4%] and PPV of 72.7% (95% CI 61.9-81.4%) in diagnosing IBD. Two children with IBD however were found to have FC <50 μg/g. Sensitivity in diagnosing IBD was further improved to 98.3% (95% CI 90.7-99.1%) when including FC >50 μg/g or elevated platelet count. Furthermore, PPVs in diagnosing IBD improved when FC at various thresholds was combined with either low albumin or high platelet count. Conclusion: Although FC alone is a useful screening test for IBD, a normal FC alone does not exclude IBD. Extending FC to include albumin or platelet count may improve sensitivity, specificity, PPV and NPV in diagnosing IBD. However, prospective studies are required to validate this conclusion.


Alignment of the International Council of Nurses Advanced Practice Nursing Guideline Characteristics With Conceptual Frameworks: A Scoping Review.
Background: During the past 50 years, numerous conceptual frameworks have been used to describe and evaluate advanced practice nursing (APN) roles and outcomes. The International Council of Nurses (ICN) released an updated description of APN characteristics intersecting with currently utilized frameworks allows for assessing relevance to practice. Purpose: The review aimed to examine the alignment of established and commonly used conceptual frameworks related to advanced practice roles with the ICN APN guidelines characteristics. This will help identify a globally relevant framework for APN roles. Method: PubMed, Cumulative Index in Nursing and Allied Health Literature, and ProQuest Central databases were searched using terms that characterize APN and conceptual frameworks. To address currency and relevance of frameworks was applied to discovered frameworks identifying and reviewing in detail those which were cited more than 15 times during the last five years. Results: This search found over 1107 publications. Of these, nine conceptual frameworks met all inclusion criteria. The frameworks captured some of the characteristics described by the ICN. Eight addressed all categories but in a limited fashion. Implications for Practice: Reviewing recently and frequently cited frameworks can inform the applicability in the interested readers, own nursing practice. This review not only does this but also examines the global uptake and the relationship to international standards of APN to provide additional information on the frameworks' reach and worldwide transferability. However, further research examining the relevance of these frameworks in low- and lower-middle-income countries is needed to understand their importance.


Forearm vascular conductance during mental stress is related to the heart rate response.
The forearm vasodilator response to mental stress is multifactorial and widely variable among individuals. We evaluated the association between the heart rate and forearm vascular conductance (FVC) responses to a color word test in 101 healthy adults. We found a striking correlation between heart rate and FVC (r = 0.66, P < 0.001), which remained significant when controlling for subject characteristics, blood pressure, and catecholamines. This suggests that the mechanical stimulation is one of the key factors that contribute to the increase in FVC during mental stress.


Fluorescent labeling of DNA in solution with covalently bound acriflavin.
We have prepared a fluorescent derivative of DNA based on the acriflavin-Feulgen histological procedure for staining DNA. Our procedure involved binding acriflavin to DNA in solution by reacting the acriflavin with aldehydes formed on the deoxyribose of DNA by controlled removal of a few percent of the purine bases of the DNA. Partially depurinated DNA was reacted with the acriflavin reagent, and unbound acriflavin was removed by chromatography on Sephadex G-25 eluted with phosphate buffered guanidine -HCl. Such single-stranded depurinated DNA bound 0.36 acriflavin molecules per 100 purine bases per h of depurination. DNA containing one bound acriflavin per 200 bases reassociated at 85% of the value of control DNA. The acriflavin - DNA complex showed new absorption maxima at 466 and 370 nm. The fluorescent product had excitation maxima at 304 and 465 nm and an emission maximum at 502 nm. This labeling procedure should be useful in place of or in addition to radioactive labeling for DNA.


Early development of the kelp fly,Coelopa frigida (Diptera) ultrastructural changes within the polar granules during pole cell formation.
Changes in the fine structure of polar granules and distribution of these granules in the egg and pole cells during the earliest stages of embryonic development have been observed in the eggs ofCoelopa frigida. 1. Polar granules are composed of dense granules 25-35 Å in diameter. These dense granules associate in different patterns during the cleavage stages of theCoelopa egg. 2. From early cleavage until shortly before blastema formation (preblastoderm stage) the dense granules form globular subunits, 200-250 Å in diameter, within the polar granules. These subunits become more distinct in later cleavage stages. 3. With the formation of the blastema the globular subunits are transformed into electron dense rods of varying length and approximately the same diameter as the globular subunits. Groups of parallel rods are arranged in different directions within each polar granule. 4. When pole cells have been formed, all the polar granules within each cell associate to form a complex, shaped like a concave disc, on the distal side of the nucleus or on the side pointing toward neighboring pole cells. Those components contributed by individual polar granules can still be identified within the disc. 5. The possibility of a correlation between blastema formation (i.e., the arrival of nuclei in the pole plasm) and the structural change within polar granules as an indication of nucleocytoplasmic interaction is discussed.


The "fetoscope"--a new clinical tool for prenatal genetic diagnosis.
Our experience in 65 patients using a "fetoscope" and local anesthesia prior to saline abortion is described. Visualization of the intrauterine contents improved with experience, was optimum at 16 to 18 weeks' gestation, and was superior to the quality of photographic records. Four fetal skin biopsies and 6 amnion biopsies were done. Six blood samples were taken from the fetal surface of the placenta. The limitations of this instrument are described. No significant complications have occurred. Current and probable future indications for fetoscopy are reviewed. Until both the safety of the procedure is proved and problems of visualization due to limitation of visual field are solved, extreme caution is urged in the employment of this instrument in genetic high-risk pregnancy.


Dectin-1 deficiency alleviates diabetic cardiomyopathy by attenuating macrophage-mediated inflammatory response.
Cardiovascular diseases are the primary cause of mortality in patients with diabetes and obesity. Hyperglycemia and hyperlipidemia in diabetes alters cardiac function, which is associated with broader cellular processes such as aberrant inflammatory signaling. Recent studies have shown that a pattern recognition receptor called Dectin-1, expressed on macrophages, mediates pro-inflammatory responses in innate immunity. In the present study, we examined the role of Dectin-1 in the pathogenesis of diabetic cardiomyopathy. We observed increased Dectin-1 expression in heart tissues of diabetic mice and localized the source to macrophages. We then investigated the cardiac function in Dectin-1-deficient mice with STZ-induced type 1 diabetes and high-fat-diet-induced type 2 diabetes. Our results show that Dectin-1 deficient mice are protected against diabetes-induced cardiac dysfunction, cardiomyocyte hypertrophy, tissue fibrosis, and inflammation. Mechanistically, our studies show that Dectin-1 is important for cell activation and induction of inflammatory cytokines in high-concentration glucose and palmitate acid (HG + PA)-challenged macrophages. Deficiency of Dectin-1 generate fewer paracrine inflammatory factors capable of causing cardiomyocyte hypertrophy and fibrotic responses in cardiac fibroblasts. In conclusion, this study provides evidence that Dectin-1 mediates diabetes-induced cardiomyopathy through regulating inflammation. Dectin-1 may be a potential target to combat diabetic cardiomyopathy.


Physiological response and secondary metabolites of three lavender genotypes under water deficit.
Lavandula genus is a considerable medicinal plant in pharmaceutical and cosmetics industries. Considering increasing threat of drought in the world, it is important to identify genotypes which can tolerate drought. It is also important to characterize quantity and quality of essential oils, and tolerance indicators of these genotypes against drought stress. Therefore, an experiment was conducted in Gorgan University of Agricultural Sciences and Natural Resources, Iran, during 2017 and 2018, to investigate these factors. It was a factorial experiment based on randomized complete block design with two treatments, three genotypes (Lavandula angustifolia cv. Hidcote, Lavandula angustifolia cv. Munstead, and Lavandula stricta), and four levels of drought stress (irrigation regimes) (I1: 100-90% (control), I2: 80-70%, I3: 60-50% and I4: 30-40% of field capacity) which was done with three repetitions. Drought increased amount of proline in leaves, antioxidant activity, activity of catalase, peroxidase, ascorbate peroxidase, and superoxide enzymes, malondialdehyde content, total flavonoids, total phenol, total sugar and essential oil percentage. The PCA analysis of different irrigation regimes showed that in the first component, the best traits are antioxidant enzymes CAT, SOD, APX, while in the second component, only the trait Catalase is the best trait. The results of PCA analysis in lavender genotypes showed that L. stricta exhibits the most affected physiological changes while trying to adjust to changes in the water status of the environment, under the imposed conditions and shows the highest resistance. But it reduced dry weight of aerial parts, relative water content of leaves, and efficacy of essential oil. Lavandula stricta genotype had the highest amount of essential oil, but the highest dry weight of the aerial parts and essential oil yield were related to L. angustifolia cv. Hidcote and L. angustifolia cv. Munstead genotypes. In all evaluated genotypes, with increasing drought stress, monoterpene compounds were decreased and sesquiterpene compounds were increased. Totally it was shown that drought effect on evaluated traits depends on genotype and nature of traits; this indicates that by choosing drought-tolerant genotypes in breeding programs, high quantity and quality of essential oil, as well as tolerance to drought stress can be achieved.


Predictors of swallowing outcome in patients treated with surgery and radiotherapy for advanced oral and oropharyngeal cancer.
Retaining effective swallowing is a key element when optimising outcomes in the management of head and neck cancer. We report the functional swallowing outcomes for a cohort of 31 individuals with advanced oral and oropharyngeal cancer who underwent free or pedicled flap reconstruction of surgical defects. Swallowing was assessed pre and immediately post surgery and at four months post treatment. Swallowing assessments were related to site, size and volume of defect and composition of flap reconstruction. The effect of radiotherapy on swallowing was assessed among 17 of the 31 individuals who were submitted to radiotherapy after surgery. The proportion of patients on a total oral diet four months post treatment varied significantly by site of defect (Fishers exact test p=0.006), from 100% (7/7) of patients with a lateral defect to only 22% (2/9) of patients with a central defect. The proportion of patients on a total oral diet at the final assessment did not vary by flap reconstruction or radiotherapy.


Reactivation of transgene expression by alleviating CpG methylation of the Rous sarcoma virus promoter in transgenic quail cells.
In this study, we investigated the relative expression of the Rous sarcoma virus (RSV) promoter-driven expression of enhanced green fluorescent protein (EGFP) in fibroblasts of transgenic quails. We analyzed the direct influence of CpG methylation of the RSV promoter on the transcriptional activity of delivered transgenes. Embryonic fibroblasts collected from homozygous transgenic quail (TQ2) were treated with 50 μM of DNA methyltransferase inhibitor followed by 5-aza-2'-deoxycytidine (5-azadC) for 48 h, and changes in expression were then analyzed by flow cytometry. The results show a significant increase of EGFP expression in TQ2 embryonic fibroblasts (QEFs) (2.64% to 79.84%). Subsequent methylation-specific amplification revealed that 5-azadC significantly reduced the CpG methylation status in the RSV promoters of the QEFs (86.42 to 48.41%); even after 5-azadC was withdrawn, CpG methylation remained decreased in expanded culture (16.28%). Further analysis showed that potential transcription factor binding sites existed in the CpG methylation site of the RSV promoter. These results may provide the basis for understanding the epigenetic mechanism responsible for transgenic animal production and genetic preservation.


Risks and benefits of timely screw removal after thoracolumbar spine fractures treated with non-fusion technique.
Percutaneous-short segment screw fixation (SSSF) without bone fusion has proven to be a safe and effective modality for thoracolumbar spine fractures (TLSFs). When fracture consolidation is confirmed, pedicle screws are no longer essential, but clear indications for screw removal following fracture consolidation have not been established. In total, we enrolled 31 patients with TLSFs who underwent screw removal following treatment using percutaneous-SSSF without fusion. Plain radiographs, taken at different intervals, measured local kyphosis using Cobb' angle (CA), vertebra body height (VBH), and the segmental motion angle (SMA). A visual analogue scale (VAS) and the Oswestry disability index (ODI) were applied pre-screw removal and at the last follow-up. The overall mean CA deteriorated by 1.58° (p < 0.05) and the overall mean VBH decreased by 0.52 mm (p = 0.001). SMA preservation was achieved in 18 patients (58.1%) and kyphotic recurrence occurred in 4 patients (12.9%). SMA preservation was statistically significant in patients who underwent screw removal within 12 months following the primary operation (p = 0.002). Kyphotic recurrence occurred in patients with a CA ≥ 20° at injury (p < 0.001) with a median interval of 16.5 months after screw removal. No patients reported worsening pain or an increased ODI score after screw removal. Screw removal within 12 months can be recommended for restoration of SMA with improvement in clinical outcomes. Although, TLSFs with CA ≥ 20° at the time of injury can help to predict kyphotic recurrence after screw removal, the clinical outcomes are less relevant.


High intensity interval training exercise as a novel protocol for cardiac rehabilitation program in ischemic Egyptian patients with mild left ventricular dysfunction.
Exercise-based Cardiac rehabilitation (CR) plays a major role in reducing mortality and morbidity in patients with coronary artery disease (CAD). The standard protocol is usually of moderate intensity exercise. High-intensity interval training (HIIT) consists of alternating periods of intensive aerobic exercise with periods of passive or active moderate/mild intensity recovery. This study aimed to assess HIIT program for ischemic patients attending CR after percutaneous coronary intervention (PCI) who have mild left ventricular dysfunction and to compare its effect on the functional capacity and quality of life with standard exercise CR program. Our study included 40 patients with documented CAD, who participated in the outpatient CR program in Ain Shams University hospital (Al-Demerdash Hospital) divided into two equal groups, each included 20 patients. Group A included the patients who underwent standard cardiac rehabilitation program, while group B joined the high intensity interval training exercise protocol. Groups A and B showed significant improvement in all items of comparison; especially functional capacity, lipid profile and quality of life. Group B showed better improvements in the emotional well-being items of QOL parameters. We emphasize the positive effects of exercise-based CR program on patients with CAD and mild left ventricular dysfunction after PCI. The novel high intensity cardiac training proved to be safe and at least as beneficial as the standard moderate intensity cardiac training protocols, with better quality of life improvement.


The ProSeal laryngeal mask airway: a review of the literature.
To analyze and summarize the published literature relating to the ProSeal LMA (PLMA): a modification of the "classic LMA" (cLMA) with an esophageal drain tube (DT), designed to improve controlled ventilation, airway protection and diagnosis of misplacement. Articles identified through Medline and EMBASE searches using keywords "Proseal", "ProSeal" and "PLMA". Hand searches of these articles and major anesthetic journals from January 1998 to March 2005. Searches identified 59 randomized controlled trials or clinical studies and 79 other publications. Compared to the cLMA, PLMA insertion takes a few seconds longer. First attempt insertion success for the PLMA is lower, but overall success is equivalent. Airway seal is improved by 50%. The DT enables early diagnosis of mask misplacement, allows gastric drainage, reduces gastric inflation and may vent regurgitated stomach contents. Evidence suggests, but does not prove, that the correctly placed PLMA reduces aspiration risk compared with the cLMA. PLMA use is associated with less coughing and less hemodynamic disturbance than use of a tracheal tube (TT). Comparative trials of the PLMA with other supraglottic airways favour the PLMA. Clinicians have extended the use of the PLMA inside and outside the operating theatre including use for difficult airway management and airway rescue. The PLMA has similar insertion characteristics and complications to other laryngeal masks. The DT enables rapid diagnosis of misplacement. The PLMA offers significant benefits over both the cLMA and TT in some clinical circumstances. These and clinical experience with the PLMA are discussed.


Bariatric surgery and skeletal health: A narrative review and position statement for management by the European Calcified Tissue Society (ECTS).
Numerous studies have demonstrated detrimental skeletal consequences following bariatric surgery. A working group of the European Calcified Tissue Society (ECTS) performed an updated review of existing literature on changes of bone turnover markers (BTMs), bone mineral density (BMD), and fracture risk following bariatric surgery and provided advice on management based on expert opinion. Based on observational studies, bariatric surgery is associated with a 21-44% higher risk of all fractures. Fracture risk is time-dependent and increases approximately 3 years after bariatric surgery. The bariatric procedures that have a malabsorptive component (including Roux-en-Y Gastric bypass (RYGB) and biliopancreatic diversion (BPD)) have clearly been associated with the highest risk of fracture. The extent of high-turnover bone loss suggests a severe skeletal insult. This is associated with diminished bone strength and compromised microarchitecture. RYGB was the most performed bariatric procedure worldwide until very recently, when sleeve gastrectomy (SG) became more prominent. There is growing evidence that RYGB is associated with greater reduction in BMD, greater increase in BTMs, and higher risk of fractures compared with SG but RCTs on optimal management are still lacking. In all patients, it is mandatory to treat vitamin D deficiency, to achieve adequate daily calcium and protein intake and to promote physical activity before and following bariatric surgery. In post-menopausal women and men older than 50 years, osteoporosis treatment would be reasonable in the presence of any of the following criteria: i) history of recent fragility fracture after 40 years of age, ii) BMD T-score ≤ -2 at hip or spine, iii) FRAX score with femoral neck BMD exceeding 20% for the 10-year major osteoporotic fracture probability or exceeding 3% for hip fracture. Zoledronate as first choice should be preferred due to intolerance of oral formulations and malabsorption. Zoledronate should be used with caution due to hypocemia risk. It is recommended to ensure adequate 25-OH vitamin D level and calcium supplementation before administering zoledronate. The bariatric procedures that have a malabsorptive component have been associated with the highest turnover bone loss and risk of fracture. There is a knowledge gap on osteoporosis treatment in patients undergoing bariatric surgery. More research is necessary to direct and support guidelines.


Guest editorial: special section on biomedical applications of vibrational spectroscopic imaging.
This Special Section Guest Editorial provides an overview of the topical area and an introduction to the articles featured in the special section.


Ultra-Small High-Entropy Alloy Nanoparticles: Efficient Nanozyme for Enhancing Tumor Photothermal Therapy.
High-entropy alloys nanoparticles (HEANPs) are receiving extensive attention due to their broad compositional tunability and unlimited potential in bioapplication. However, developing new methods to prepare ultra-small high-entropy alloy nanoparticles (US-HEANPs) faces severe challenges owing to their intrinsic thermodynamic instability. Furthermore, there are few reports on studying the effect of HEANPs in tumor therapy. Herein, the fabricated PtPdRuRhIr US-HEANPs act as bifunctional nanoplatforms for the highly efficient treatment of tumors. The US-HEANPs are engineered by the universal metal-ligand cross-linking strategy. This simple and scalable strategy is based on the aldol condensation of organometallics to form the target US-HEANPs. The synthesized US-HEANPs exhibit excellent peroxidase-like (POD-like) activity and can catalyze the endogenous hydrogen peroxide to produce highly toxic hydroxyl radicals. Furthermore, the US-HEANPs possess a high photothermal conversion effect for converting 808 nm near-infrared light into heat energy. In vivo and in vitro experiments demonstrated that under the synergistic effect of POD-like activity and photothermal action, the US-HEANPs can effectively ablate cancer cells and treat tumors. It is believed that this work not only provides a new perspective for the fabrication of HEANPs, but also opens the high-entropy nanozymes research direction and their biomedical application.


[Silica-associated systemic sclerosis occurring after an occupational exposure to arc welding].
Crystalline silica-associated systemic sclerosis can occur in people operating arc welding. Diffuse scleroderma was diagnosed in a 57-year old plumber-welder suffering from inflammatory polyarthralgias, Raynaud's phenomenon, sclerodactyly, diffuse cutaneous scleroderma, telangiectasias, esophageal damage, pulmonary arterial hypertension and pulmonary fibrosis associated with the presence of anti-nucleosome antibodies. During his professional activity the patient was frequently exposed to high atmospheric concentrations of crystalline silica generated by arc-welding. The diagnosis of Erasmus syndrome associated with systemic sclerosis and pulmonary silicosis was retained. A report of work-related illness (table 17 in Tunisia) was made.


Antigens in immune complexes from patients with breast cancer. Identification of autoantigens in immune complexes isolated from breast cancer effusions.
Sera and effusion fluids of patients with breast cancer (BC) contain immune complexes (IC). Antigens present in these complexes were isolated as follows: a pool of effusions from patients with BC was fractionated with ammonium sulfate. The proteins precipitating at 40% saturation were further fractionated by filtration through a Sephadex G-200 column. The material recovered in the first peak (molecules larger than monomeric IgG) was brought to pH 3.0 to dissociate the IC, and the mixture was filtered through a column of Sephacryl S-300 at pH 3.0. Proteins smaller than monomeric IgG were collected, radioiodinated, and used as antigens (125Ag) to search for corresponding antibodies in sera of patients with BC (BCS) and of healthy individuals (NHS). 125Ag was reacted with the sera and the immune complexes obtained were precipitated with an antiserum to human Ig and analyzed by SDS-polyacrylamide gel electrophoresis followed by autoradiography. Both NHS and BCS contained antibodies against two antigens; one of these appeared as a strong band of 17KD, the other as a doublet of approximately 25KD. It is concluded that some of the proteins in the IC from patients with BC are auto-antigens. No BC-specific antigens were identified.


Non-crystallographic nets with freely acting, non-abelian local automorphism groups.
Non-crystallographic (NC) nets are defined as periodic nets whose automorphism groups are not isomorphic to any isometry group in Euclidean space. This work focuses on a simple class of NC nets, restricted to nets with non-abelian, freely acting local automorphism groups. A general method is presented to derive such NC nets from crystallographic nets and some non-trivial examples are explored. It is shown that the labelled quotient graph of these nets does not necessarily possess non-trivial automorphisms which exchange cycles having the same net voltage. However, barycentric representations of these nets systematically display vertex collisions.


Inactivation of the hMSH3 mismatch repair gene in bladder cancer.
Deficiency in the DNA mismatch repair (MMR) is frequently involved in various cancers. The hMSH3 gene is one of the human MMR genes whose role in bladder cancer is not known. We hypothesized that down-regulation of the hMSH3 gene might be involved in bladder cancer. In this study we analyzed this gene with regard to frame-shift mutation, single nucleotide polymorphism (SNP), a 9bp repeat in exon 1, loss of heterozygosity (LOH), immunohistochemistry, and methylation status in 102 bladder cancer samples. Immunohistochemistry revealed that hMSH3 expression in bladder cancer was significant decreased compared to normal epithelium (p<0.0001). An inverse correlation with pathological grade was found. The frame-shift mutation in the (A) 8 tract was lacking in bladder cancer. There was no significantly difference between bladder cancer samples and healthy controls' with regard to SNP and the 9bp repeat. In bladder cancer, presence of the codon 222 polymorphism, LOH, and the 9bp repeats in exon 1 had a correlation with either pathological stage or pathological grade. Presence of the codon 1036 polymorphism had significant correlation with pathological stage and a trend to correlation with pathological grade. After 5-aza-dC treatment, MSH3 expression was significantly enhanced in TCC and UMUC bladder cancer cells when compared to untreated cells. This is the first report suggesting that genetic and epigenetic alterations in the human MSH3 gene might play a significant role in the progression of bladder tumors.


Occurrence and spatial distribution of legacy and novel brominated flame retardants in seawater and sediment of the South China sea.
The occurrence and spatial distribution of polybrominated diphenyl ethers (PBDEs) and novel brominated flame retardants (NBFRs) in seawater and surficial sediment samples (N = 19 and 45, respectively) from the South China Sea (SCS) in 2018 were investigated, and the correlation between BFRs and site parameters (total organic carbon, depth, etc.) were assessed by principal component analysis. The concentration ranges of ΣPBDEs in seawater and sediments were 0.90-4.40 ng/L and 0.52-22.67 ng/g dry weight (dw), respectively, while those of ΣNBFRs were 0.49-37.42 ng/L and 0.78-82.29 ng/g dw, respectively. BDE-209 and decabromodiphenyl ethane were the predominant BFRs, accounting for 38.65% and 36.94% in seawater and 26.71% and 68.42% in sediments, respectively. Notably, tris(2,3-dibromopropyl)isocyanurate and 2,4,6-tris(2,4,6-tribromophenoxy)-1,3,5-triazine, seldomly detected in aquatic matrices worldwide, were detected for the first time in the study area, and their relatively high levels and detection frequencies indicate the ubiquitous application of these NBFRs in the Pearl River Delta. Zhuhai and Jiangmen are the main sources of NBFRs in the SCS. Preliminary risk assessment on NBFRs using hazard quotient indicates low to medium risks to marine organisms at some sites. The occurrence of NBFRs in the SCS highlights the prioritization of more toxicological information on these compounds.


Alarm Calling in Plateau Pika (Ochotona curzoniae): Evidence from Field Observations and Simulated Predator and Playback Experiments.
Acoustic communication plays a vital role in passing or sharing information between individuals. Identifying the biological meaning of vocal signals is crucial in understanding the survival strategies of animals. However, there are many challenges in identifying the true meaning of such signals. The plateau pika (Ochotona curzoniae) is a call-producing mammal endemic to the Qinghai-Tibet plateau (QTP) and considered a keystone species owing to its multiple benefits in alpine rangeland ecosystems. Previous studies have shown that plateau pikas emit alarm calls as part of their daily activities. However, only field observations have been used to identify these alarm calls of the plateau pika, with no attempts at using playback experiments. Here, we report the alarm calling of plateau pikas through field observations as well as simulated predator and playback experiments in the Eastern QTP from 2021 to 2022. We found that both female and male adults emitted alarm calls, the signals of which comprised only one syllable, with a duration of 0.1-0.3 s. There were no differences in the characteristics between the observed alarm calls and those made in response to the simulated predator. The duration of the alarm call response varied with altitude, with plateau pikas living at higher altitudes responding at shorter durations than those at lower altitudes.


The potential value of cuprotosis in myocardial immune infiltration that occurs in pediatric congenital heart disease in response to surgery with cardiopulmonary bypass.
Cardiopulmonary bypass may cause malfunction in the myocardium. Cuproptosis is a novel cell death aggregating mitochondrial proteins. However, the research on cardiopulmonary bypass-caused heart tissue injury in immune infiltration and cuproptosis is limited. Immune infiltration, enrichment analysis, protein-protein interaction network, and medication prediction are applied to reanalysis differentially expressed genes and cuproptosis-related genes in gene expression omnibus data set GSE132176. Seven cuproptosis related genes (PDHA1, LIPT1, LIAS, DLST, DLD, DLAT, and DBT) and dendritic cells and Th1 cells are involved in heart tissue injury in response to surgery with cardiopulmonary bypass. Immune infiltration and cuproptosis are potential mechanisms by which cardiopulmonary bypass surgery may cause damage to heart tissue, which may be a new therapeutic target.


Human immunodeficiency virus infection in women.
This article describes current epidemiologic trends in HIV infection in women worldwide and in the United States, the natural history of HIV infection in women as currently understood, clinical management of HIV-infected women in those areas in which it differs from men, and multiple issues relating to pregnancy and childbearing in HIV-infected women.


Antigen processing and presentation: TAPping into ABC transporters.
Adaptive, cell-mediated immunity involves the presentation of antigenic peptides on class I MHC molecules at the cell surface. This requires an ABC transporter associated with antigen processing (TAP) to transport antigenic peptides generated in the cytosol into the endoplasmic reticulum (ER) for loading onto class I MHC. Recent crystal structures of bacterial ABC transporters suggest how the transmembrane domains of TAP form a peptide-binding cavity that acquires peptides from the cytosol, and following ATP-induced conformational changes, the peptide-binding cavity closes to the cytosol and instead opens to the ER lumen for peptide release. Extensive biochemical studies show how transport is driven by ATP binding and hydrolysis on an asymmetric pair of cytosolic nucleotide-binding domains, which are physically coupled to the peptide-binding site to propagate conformational changes through the protein.


Molecular Characterization, Drug Resistance and Virulence Analysis of Constitutive and Inducible Clindamycin Resistance Staphylococcus aureus Strains Recovered from Clinical Samples, Tehran - Iran.
Macrolide-lincosamide streptogramin B family is one of the important alternative antibiotics for treating staphylococcal infections. The aim of this study was to determine the characteristics and prevalence of antibiotic resistance genes in different coagulase types of clinical Staphylococcus aureus strains. In the present study, 86 isolates with different phenotypes of MLSB resistance were investigated. In vitro susceptibility was assessed by the disk diffusion and broth microdilution methods. PCR assays were used to detect resistance-related genes. Coagulase and SCCmec types were identified by multiplex PCR assay. The prevalences of constitutive MLSB, inducible MLSB, and MS phenotypes were found to be 23%, 14.2%, and 4.9%, respectively. The rates of resistance to mupirocin, fusidic acid, and tigecycline were found to be 9.3%, 4.6%, and 2.3%, respectively. The top three predominant resistance genes were mecA, tet(M), erm(C) representing 75.6, 50, and 40.7% of isolates. mupA (7%), fusB (3.5%), and fusC (1.2%) genes were also detected among tested isolates. Coagulase types were mainly type II (34.9%), followed by III (32.6%), V (20.9%), and I (11.6%). These findings indicated high resistance rate and low genetic variability with the prominence of coa type II, highlighting the particular importance of diagnosis of these strains to avoid treatment failure.


Thrombin promotes the expression of thrombospondin-1 and -2 in a rat model of intracerebral hemorrhage.
Spontaneous intracerebral hemorrhage (ICH) is one of the most severe types of stroke. Thrombin has been reported to participate in brain repair following ICH and play an important role in angiogenesis. Our previous studies have shown that ICH induces angiogenesis in damaged rat brain, accompanied by upregulation of expression of thrombospondin (TSP)-1 and TSP-2. The aim of the present study was to investigate whether the expression of TSP-1 and TSP-2 was regulated by thrombin in rat brain following ICH. A rat model of ICH was induced by injection of autologous blood into the right globus pallidus (GP). Hirudin, a thrombin specific inhibitor, or thrombin was injected into the GP. Immunohistochemistry, quantitative real-time reverse-transcription polymerase chain reaction (RT-PCR) and western blot assays were applied. Results showed that ICH induced an increase in the expression of TSP-1 mRNA and TSP-2 mRNA after ICH, whereas hirudin significantly inhibited the expression of TSPs mRNA after ICH (P<0.05). In contrast, sole thrombin treatment in normal rats induced strong expression of TSP-1 or TSP-2 in the blood vessels around the damaged brain region when compared with those without thrombin treatment. Western blot analysis data confirmed that the protein levels of TSPs were significantly increased when compared with those in the sham control group (P<0.01). These findings support that thrombin positively regulates the expression of TSP-1 and TSP-2 after ICH, which may be involved in modulating angiogenesis in injured brains following ICH.


Malignant melanoma prognostic factors 3: surgical margins.
Narrow margins of excision for melanomas less than 0.85 mm thick neither shorten the length of survival nor increase the local recurrence rate. Similarly, narrow margins of excision for melanomas greater than 0.85 mm thick do not adversely affect the survival rate. However, for thicker melanomas, the local recurrence rate increases when the surgical margin is reduced to less than 3 cm.


Characterization of iron walnut in different regions of China based on phytochemical composition.
Little is known about the phytochemical composition of iron walnuts. Differences in the geographical origin of iron walnuts associated with economic benefits should also be examined. In this study, the phytochemical composition (fatty acids, Vitamin E, total polyphenols and flavonoids, amino acids, and minerals) of iron walnuts in China was investigated. The results showed that there were significant differences (p < 0.05) in the phytochemical composition of iron walnut oils and flours from different regions. Positive (r > 0.5, p < 0.05) and negative (r < - 0.5, p < 0.05) correlations were found between amino acids/minerals and amino acids/oleic acid, with the highest correlation coefficient (r = 0.742, p < 0.05) between Cu and tyrosine. In addition, based on the 12 phytochemical fingerprints selected by random forest, a geographical-origin identification model for iron walnuts was established, with a corresponding correct classification rate of 96.6%. The top three phytochemical fingerprints for the geographical-origin identification of iron walnut were microelements, macroelements, and antioxidant composition, with contribution rates of 61.7%, 18.1%, and 9.9%, respectively.


Altered cellular functions in a PC-12 cell clone chronically infected with retrovirus.
We characterized retrovirus-induced changes in PC-12 cell function and neuronal differentiation. PC-12 cells were infected with a neurotropic retrovirus (temperature-sensitive Moloney murine leukemia virus, mutant BA-1). We isolated a cell clone from this infected culture that displayed altered response to nerve growth factor; increased choline acetyltransferase activity; and decreased basal and nerve growth factor-stimulated acetylcholinesterase activity. In addition, Kirsten murine sarcoma virus infection of and subsequent expression of the v-ras oncogene in PC-12 cells induced neurite extension, enhanced choline acetyltransferase activity, and limited the growth potential of the infected cells.


Minimally invasive techniques and indocyanine angiography in anterior abdominal wall reconstruction after multiple laparotomies.
Anterior abdominal wall reconstruction surgery in patients who have undergone multiple laparotomies is associated with a high risk of complications. For this reason, minimally invasive surgery techniques are used to avoid abdominal compartment syndrome, to enhance wound healing and to reduce postoperative pain and blood loss. This paper presents a case of a patient who was admitted to the Department of General Surgery in Puck Hospital as a result of extensive anterior abdominal wall deformation with an end descending colostomy. A single-stage procedure was performed: specifically, digestive tract reconstruction followed by anterior abdominal wall reconstruction using intraoperative angiography of indocyanine green in infrared light.


The cost of premature death from cancer attributable to alcohol: Productivity losses in Europe in 2018.
More than 1.9 million people die from cancer each year in Europe. Alcohol use is a major modifiable risk factor for cancer and poses an economic burden on society. We estimated the cost of productivity lost due to premature death (under 65 years of age) from alcohol-attributable cancer in the European Union (EU) plus Iceland, Norway, Switzerland, and the United Kingdom (UK) in 2018. We estimated cancer deaths attributable to alcohol using a Levin-based population attributable fractions method and cancer deaths in 2018 from the Global Cancer Observatory. Lost productivity was estimated for all alcohol-attributable cancer deaths by sex, cancer site, and country. Productivity losses were valued using the human capital approach. An estimated 23,300 cancer deaths among people aged less than 65 in the EU plus Iceland, Norway, Switzerland and the UK in 2018 were attributable to alcohol (18,200 males, 5100 females). This equated to €4.58 billion in total productivity losses in the region and 0.027 % of the European Gross Domestic Product (GDP). The average cost per alcohol-attributable cancer death was €196,000. Productivity lost to alcohol-attributable cancer per capita was highest in Western Europe. Hungary, Romania, Slovakia, Latvia, Lithuania, and Portugal had the highest rate of premature mortality from alcohol-attributable cancer and the highest productivity lost as a share of national GDP. Our study provides estimates of lost productivity from alcohol-attributable cancer death in Europe. Cost-effective strategies to prevent alcohol-attributable cancer deaths could result in economic benefits for society and must be prioritised.


Generation of human embryonic stem cell lines (WAe001-A-67,WAe001-A-68) with TEAD1 and TEAD4 expression by the PiggyBac transposon system.
Transcription factors TEAD1 and TEAD4 play an important role in development, differentiation, cell growth and proliferation. To further understand the exact role of TEAD1 and TEAD4 in these processes. We generated TEAD1 and TEAD4 doxycycline-inducible expression human embryonic stem cell lines (WAe001-A-67 and WAe001-A-68) by PiggyBac transposon system. These cell lines retained normal morphology and karyotype, normal expression of pluripotent markers, and differentiation potential. These cell lines can be used to verify whether the TEAD1 and TEAD4 play a role in stem cell and cell lineage differentiation.


Persistence of IgA in neonatal saliva following breast feeding.
Breast milk antibodies have been shown to persist in the mouths of neonates for some hours following feeding. The decrease in concentration following a feed probably reflects the flushing action of salivary flow combined with swallowing.


Creation of arbitrary time-sequenced line spectra with an electro-optic phase modulator.
We use a waveguide-based electro-optic phase modulator, driven by a nanosecond-timescale arbitrary waveform generator, to produce an optical spectrum with an arbitrary pattern of peaks. A programmed sequence of linear voltage ramps, with various slopes, is applied to the modulator. The resulting phase ramps give rise to peaks whose frequency offsets relative to the carrier are equal to the slopes of the corresponding linear phase ramps. This simple extension of the serrodyne technique provides multi-line spectra with peak spacings in the 100 MHz range.


Initiation of protein synthesis. Binding of messenger RNA.
Complexes between 30 S ribosomal subunits and fMet-tRNA are formed during incubation of 30 S subunits with fMet-tRNA and all other components for initiation of protein synthesis, except R17 bacteriophage RNA. That these complexes serve as intermediates in the binding of messenger RNA is demonstrated directly by the finding that upon addition of R17 RNA, fMet-tRNA in preformed fMet-RNA-30 S complexes preferentially enters fMet-tRNA-30 S-R17 RNA complexes. On the other hand, incubation of 30 S ribosomal subunits with R17 RNA and all other components for initiation except fMet-tRNA does not yield 30 S-R17 RNA complexes that can act subsequently as functional intermediates in the binding of fMet-tRNA: formation of fMet-tRNA-30 S-R17 RNA complexes does not occur when fMet-tRNA is added and further binding of R17 RNA to 30 S subunits is prevented by specific inhibitors. These experiments lead to an unambiguous order of events in the sequence of initiation, in which binding of fMet-tRNA to the small ribosomal subunit must occur before messenger RNA can be bound and phased correctly. Complexes between fMet-tRNA and 60 S subunits are in rapid equilibrium with the free components, and have a half-life of less than 2 min at 37 degrees. This explains why such complexes are not detected in sucrose gradients, unless they are first fixed with glutaraldehyde. Attachment of R17 RNA, however, results in formation of an fMet-tRNA-30 S-R17 RNA complex that is stabilized greatly; fMet-tRNA in this complex exchanges only very slowly with free fMet-tRNA. Initiation factor IF-3 has two functions in initiation. The first is to direct the binding of messenger RNA to the 30 S-fMet-tRNA complex. This function is not needed when initiation complex formation occurs on ApUpG triplets, in which case the second function of IF-3 is detected, that of providing free 30 S subunits for initiation. The ability of IF-3 to bind directly to R17 RNA may be related to its requirement in messenger RNA recognition. However, since IF-3 exhibits a greater affinity for the 30 S subunit than for R17 RNA, it appears that the recognition function of IF-3 is expressed while IF-3 is associated with the 30 S subunit.


Ceftibuten and bactericidal kinetics. Comparative in vitro activity against Enterobacteriaceae producing extended spectrum beta-lactamases.
Ceftibuten, compared to cefixime, cefetamet, cefpodoxime, loracarbef, cefprozil, cefuroxime, cefaclor, and cefadroxil, was the most active oral cephalosporin derivative against Enterobacteriaceae producing plasmid-encoded broad spectrum beta-lactamases. In a pharmacodynamic model, ceftibuten was bactericidal for Haemophilus influenzae and Streptococcus pneumoniae at concentrations simulating human serum levels following 200 mg, p.o., b.i.d.


Glutathione S transferase-theta (GSTT1) genetic polymorphism among Chinese, Malays and Indians in Singapore.
Glutathione S-transferase-theta (GSTT1) is subject to a genetic polymorphism where approximately 50% of a Caucasian population are homozygous for the null allele. Because of the possible association of the polymorphism with increased cancer risk in individuals, we genotyped by polymerase chain reaction 187 normal Chinese, 167 normal Malays and 152 normal Indians from Singapore and Malaysia. The proportion of Chinese, Malays and Indians with the null genotype were 58%, 38% and 16% respectively and mirrored previously reported frequencies of the GSTM1 null genotype in these populations. The frequency of the combined GSTM1 and GSTT1 null genotypes among Chinese, Malays and Indians were 37%, 22% and 5% respectively. The similarity with predicted frequencies indicated no interaction between the two genetic polymorphisms.


Cardiac sympathetic dysinnervation in Type 2 diabetes mellitus with and without ECG-based cardiac autonomic neuropathy.
To evaluate the presence and extent of global and regional distributions of cardiac sympathetic dysinnervation in Type 2 diabetes mellitus I-123-metaiodobenzylguanidine (I-123-MIBG) scintigraphy was applied to 15 Type 2 (noninsulin-dependent) diabetic patients with ECG-based cardiac autonomic neuropathy (> or = two of five age-related cardiac reflex tests abnormal) and 15 clinically comparable Type 2 diabetic patients without ECG-based cardiac autonomic neuropathy. Myocardial perfusion abnormalities were excluded by 99 m-Tc-methoxyisobutylisonitrile (99 m-MIBI) scintigraphy. Both in Type 2 diabetic patients with and without, ECG-based autonomic neuropathy, only one patient (7%) was found to have a normal homogeneous uptake of I-123-MIBG compared to 14 patients (93%) with a reduced I-123-MIBG uptake. The uptake of I-123-MIBG in the posterior myocardium of diabetic patients was smaller than in the anterior, lateral, and septal myocardium (P< .001, P< .001, P< .001, respectively). Diabetic patients with ECG-based cardiac autonomic neuropathy demonstrated a more pronounced reduction of the posterior I-123-MIBG myocardial uptake than diabetic patients without (P< .01). The mean global and the anterior, lateral, septal, and apical myocardial I-123-MIBG uptake was comparable between the two groups. The uptake of the posterior myocardial region correlated with all indices of heart rate variation at rest and during deep breathing. A correlation between global or regional myocardial I-123-MIBG uptake and QT interval was not observed. The study demonstrates that cardiac sympathetic dysinnervation is common in Type 2 diabetes mellitus both with and without ECG-based cardiac autonomic neuropathy. In Type 2 diabetes mellitus, the posterior myocardium is predominantly affected and the extent of dysinnervation is more pronounced in the presence of ECG-based cardiac autonomic neuropathy.


Traction apophysitis of the knee: A case report.
We report a case of a 12-year-old boy who presented with infrapatellar pain, with subsequent diagnosis of traction apophysitis of the knee (Sinding-Larsen-Johansson disease). Conventional radiographs are frequently reported with no significant findings in the acute setting, leading to ultrasound as the modality of choice for diagnostic efficacy of apophyseal traction injuries in young athletes. Sinding-Larsen-Johansson disease has a 2%-5% incidence in children aged 10-15 years, with the most common cause related to sporting activities related to jumping.


Workforce shortage for general surgeons: results from the Society for Surgery of the Alimentary Track (SSAT) surgeon shortage survey.
Population shifts among surgeons and the general populous will contribute to a predicted general surgeon shortage by 2020. The Public Policy and Advocacy Committee of the Society for Surgery of the Alimentary Tract designed and conducted a survey to assess perceptions and possible solutions from important stakeholders: practicing surgeons of the society, general surgery residents, and medical students. Responses from 1,208 participants: 658 practicing surgeons, 183 general surgery residents, and 367 medical students, were analyzed. There was a strong perception of a current and future surgeon shortage. The majority of surgeons (59.3 %) and residents (64.5 %) perceived a current general surgeon shortage, while 28.6 % of medical students responded the same. When asked of a perceived general surgery shortage in 20 years, 82.4, 81.4, and 51 % said "yes", respectively. There were generational differences in responses to contributors and solutions for the impending shortage. Surgeons placed a high value on improving reimbursement, tort reform, and surgeon burnout, while residents held a strong interest in a national loan forgiveness program and improving lifestyle barriers. Our survey offers insight into possible solutions to ward off a surgeon shortage that should be addressed with programmatic changes in residency training and by reform of the national health care system.


Patterns of National Cancer Institute-Sponsored Clinical Trial Enrollment in Black Adolescents and Young Adults.
Both adolescent and young adult (AYA) and Black or African American (hereafter referred to as Black) cancer patients are historically under-enrolled in cancer treatment trials (CTT). The purpose of this study was to quantify enrollment of Black AYAs in National Cancer Institute (NCI)-sponsored CTTs overall and by age, sex, and cancer diagnosis during 2000-2015. Utilizing data from NCI's Cancer Therapy Evaluation Program and the Surveillance, Epidemiology and End Results (SEER) Program, we assessed CTT enrollment in Black patients with cancer and measured changes in enrollment over time between the study periods 2000-2007 and 2008-2015. Enrollment patterns were compared across age groups (≤14 years [y], 15-19y, 20-29y, 30-39y and 40+ years), sex, and cancer diagnosis. From 2000 through 2015, <3% of Black AYAs (20-39y) enrolled on CTTs. While AYAs had significantly higher cancer incidence than children, 20.5% fewer Black AYAs enrolled on CTTs. Enrollment was lowest among Black males 20-29y, with a mean of 18 enrolling in CTTs annually. The proportion of AYA enrollees who were Black did not change significantly over time periods (2000-2007 vs 2008-2015). Few Black AYAs enroll in CTTs each year. Given known benefits of clinical trial participation and the well-documented racial and age-related differences in cancer outcomes, addressing barriers to enrollment in these patients may, in turn, reduce disparities. Targeted interventions aimed at increasing the CTT enrollment of Black cancer patients, particularly young Black men, are urgently needed. This study documents that compared with Black children, Black adolescent, and young adult (AYA) patients were less likely to enroll in NCI-sponsored CTTs from 2000 to 2015. Black AYA male enrollment decreased with increasing age, highlighting disparities among this specific population in CTT enrollment.


Development and nationwide implementation of a postdischarge responsive parenting intervention program for very preterm born children: The TOP program.
A previous randomized controlled trial has suggested the effectiveness of a Dutch postdischarge responsive parenting program for very preterm (VPT) infants, indicating that nationwide implementation was justified. This paper describes the development and nationwide implementation of the intervention, known as the TOP program, which consisted of three phases. In the preparation phase (2006-2010), a theory of change and the structure of the TOP program were developed, and funding for phase two, based on a positive Business Case, was obtained. In the pilot implementation phase (2010-2014), intervention strategies were developed for a real-world setting, capacity and adoption were increased, systematic evaluations were incorporated, and sustained funding was obtained. In the full-implementation phase (2014-2019), all Dutch Healthcare Insurers reimbursed the TOP program, enabling VPT infants to participate in the program without charge. By 2018, the number of interventionists that provided the TOP program had increased from 37 to 91, and all level III hospitals and 65% of regional hospitals in the Netherlands referred VPT infants. Currently, the program reaches 70% of the Dutch target population and parental satisfaction with the TOP program is high. After a 12-year implementation period, the TOP program forms part of routine care in the Netherlands.