Association of Ambulatory Ability on Complications and Medical Costs in Patients with Traumatic Spinal Cord Injury: A Decision-analytic Model.
Purpose The objective of this study was to determine the independent association of ambulatory ability with complications and medical costs in patients with spinal cord injury (SCI). Methods Patients with SCI between T1-T12 enrolled in the National Spinal Cord Injury Database (NSCID) provided a minimum one-year follow-up. Covariate-adjusted annual rates of important medical complications (pressure sore, urinary tract infection, hospitalization) and associated medical costs were determined over five years post-injury. Results A total of 1,753 patients provided data at one-year follow-up and 1,340 patients provided five-year data. At one-year post-injury, 82% of patients were non-ambulatory and 18% were ambulatory. After adjusting for important covariates, ambulatory status was associated with a lower annual probability of urinary tract infection (43% vs. 68%), pressure sore (12% vs. 35%), and hospitalization (23% vs. 34%). Covariate-adjusted base-case medical costs due to urinary tract infection, pressure sore, and hospitalization were 34% lower in ambulatory vs. non-ambulatory patients ($31,358 vs. $47,266) over five years. Probabilistic sensitivity analyses confirmed the base-case results. Conclusion In spinal cord-injured individuals, the ability to ambulate is independently associated with lower complication risks and associated medical costs over the five-year period following injury. Long-term clinical benefit and cost savings may be realized with assisted or unassisted ambulation in spinal cord-injured patients.


Bortezomib sensitizes non-Hodgkin's lymphoma cells to apoptosis induced by antibodies to tumor necrosis factor related apoptosis-inducing ligand (TRAIL) receptors TRAIL-R1 and TRAIL-R2.
Non-Hodgkin's lymphoma (NHL) is an increasingly common disease that, despite advances in antibody-targeted therapy, still requires novel therapeutic approaches. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) activates a major nonmitochondrial pathway for tumor cell killing through binding to a receptor family, some activating and some decoy. Agonistic antibodies to the receptors TRAIL-R1 and TRAIL-R2 can mimic many of the effects of TRAIL. We are investigating the effects of such agonistic antibodies, mapatumumab directed at TRAIL-R1 and lexatumumab directed at TRAIL-R2, on NHL cell lines. These antibodies induce apoptosis through caspase-8 but also activate BID to involve the mitochondrial pathway and activate caspase-9. In addition, we find signaling through both the nuclear factor-kappaB and c-Jun NH2-terminal kinase pathways. Because the proteasome inhibitor bortezomib also affects these pathways, we have investigated the combination of TRAIL-R antibodies and bortezomib and show enhanced apoptosis and signaling as well as enhanced killing of NHL cells in a severe combined immunodeficient mouse/human NHL cell line xenograft system. The combination of bortezomib and TRAIL signaling warrants further investigation as a therapeutic regimen. Understanding the multiple intracellular pathways of TRAIL activation may lead to rationally designed therapeutic trials.


Interventional Therapy for Pulmonary Embolism.
Patients with pulmonary embolism (PE) present with highly variable clinical symptoms and often have accompanying comorbidities. Timely diagnosis and treatment are critical to help prevent recurrence and increased morbidity/mortality. While open surgical thrombectomy was once reserved only for those with massive PE and hemodynamic compromise, it has been reevaluated with a focus on careful patient selection and early intervention. Lately, there has been increased interest in catheter-based interventions and in combining these with an open surgical component to decrease the magnitude of the intervention-for example, direct placement of large-bore thrombectomy devices directly into the right ventricle via sternotomy or subxiphoid approaches. In addition, improved diagnostic capabilities have allowed for expedited diagnosis and treatment of patients with life-threatening PE. At our institution, a hybrid room allows patients suspected of having a massive or submassive PE to undergo on-table contrast-enhanced cone-beam computed tomography scan, thus creating a high-resolution 3-dimensional image of the arterial system that can provide immediate guidance for therapeutic intervention. This review highlights the array of therapeutic options currently used in our armamentarium at the Houston Methodist DeBakey Heart & Vascular Center and describes our development of a pulmonary angioplasty procedure that we believe will greatly facilitate selective thrombus removal in the acute PE setting.


Effect of experimentally increased protein supply to postpartum dairy cows on plasma protein synthesis, rumen tissue proliferation, and immune homeostasis.
The effect of experimentally increasing the postpartum protein supply on plasma protein synthesis, rumen tissue proliferation, and immune homeostasis was studied using 8 periparturient Holstein cows in a complete randomized design. At calving, cows were assigned to abomasal infusion of water (CTRL) or casein (CAS) in addition to a lactation diet. Casein infusion was gradually decreased from 696 ± 1 g/d at +2 d relative to calving (DRTC) to 212 ± 10 g/d at +29 DRTC to avoid excessive supply. Synthesis rate of plasma proteins was measured at -14, +4, +15, and +29 DRTC by measuring [C]Phe isotopic enrichment in arterial plasma free Phe, total plasma proteins, and albumin after 3, 5, and 7 h of jugular ring[C]Phe infusion. Plasma volume was determined at +4 and +29 DRTC by dilution of a [I]BSA dose. Synthesis rate of tissue protein in biopsied rumen papillae was determined by measuring [C]Phe isotopic enrichment, and mRNA expression of selected genes was measured by real-time qPCR. Total and differential leukocyte counts were performed and immune responsiveness of monocytes was evaluated by tumor necrosis factor ɑ (TNFɑ) concentration on ex vivo whole blood stimulation with Escherichia coli lipopolysaccharide (LPS) and responsiveness of T-lymphocytes by interferon γ (IFNγ) concentration on stimulation with Staphylococcus aureus enterotoxin β (SEB). Further, ELISA plasma concentrations of IgM, IgA, and IgG were determined. The DRTC affected the majority of investigated parameters as expected. The CAS treatment increased milk protein yield (P = 0.04), and tended to lower TNFɑ (P = 0.06), and lowered IFNγ (P = 0.03) responsiveness per monocyte and lymphocyte, respectively, compared with CTRL. Further, fractional synthesis rate of albumin was greater at +4 DRTC for CAS compared with CTRL but did not differ by +29 DRTC (interaction: P = 0.01). In rumen papillae, synthesis rate of tissue protein was greater for CAS compared with CTRL (P < 0.01) and mRNA expression of genes for cell proliferation tended to be or were greater for CAS compared with CTRL (P ≤ 0.07). In conclusion, increased postpartum protein supply seem to enhance vital body functions as interpreted from increased liver synthesis of albumin, increased rumen papillae proliferation, and stabilized the ex vivo inflammatory responsiveness of leukocytes. Further studies are needed to enlighten the importance of increased postpartum protein supply in periparturient cows.


Maternal diabetes and changes in the hard tissues of primary teeth. III. A histologic and microradiographic study.
According to clinical studies, infants of diabetic mothers (IDM) seem to run a higher risk of mineralization disturbances in the enamel than normal healthy infants. In order to evaluate this observation at the histologic level, exfoliated primary incisors were collected from 74 IDM, representing two types of care during gestation and the perinatal period, and from 52 healthy children. The width of the neonatal line was evaluated in the enamel and the dentin by study of bucco-lingual undemineralized sections. Pre- and postnatal enamel was classified according to discolorations, deviations of prisms and hypoplasia. Microradiographic studies included measurements of the neonatal lines and classification of the degree of mineralization in the pre- and postnatal dental hard tissues. Irrespective of treatment, the IDM showed a significantly higher incidence of widened neonatal lines and also an increased frequency of postnatal disturbances compared to the controls. The observations are discussed against the background of the neonatal hypocalcemia reported in IDM.


Epigenetic reprogramming of IGF1 and leptin genes by serum deprivation in multipotential mesenchymal stromal cells.
Recent studies on the therapeutic effect of multipotential mesenchymal stem cells (MSCs) in various models of injury have shown that paracrine factors secreted by MSCs are responsible for tissue repair with very little engraftment. In this study we tested the hypothesis that MSCs under stress undergo epigenetic modifications that direct secretion of paracrine factors responsible for tissue repair. Microarray assays of MSCs that had been deprived of serum (SD-MSCs), to induce stress, demonstrated an increase in the expression of several angiogenic, prosurvival, and antiapoptotic factors, including insulin-like growth factor 1 (IGF1) and leptin. Real-time polymerase chain reaction assays demonstrated a >200-fold increase in the expression of IGF1 and leptin in SD-MSCs. Chromatin immunoprecipitation of SD-MSCs revealed histone tail modifications consistent with transcriptional activation of IGF1 and leptin promoters in a reversible manner. To identify the functional significance of the epigenetic changes in stressed MSCs, we tested the prosurvival properties of SD-MSCs and the ability of conditioned medium from SD-MSCs to enhance survival of apoptotic cancer cells. First, we showed that SD-MSCs are more resistant to oxidative damage than MSCs using alkaline comet assays. Next, we demonstrated that conditioned medium from SD-MSCs decreased staurosporin-induced cell death in the KHOS osteosarcoma cell line, and that this effect was partially reversed by immunodepletion of IGF1 or leptin from the conditioned medium. In conclusion, we demonstrate that serum deprivation induces epigenetic changes in MSCs to upregulate the expression of the proangiogenic and antiapoptotic factors IGF1 and leptin.


Case report: a large radicular cyst involving the entire maxillary sinus.
Cysts of the maxillary sinus of odontogenic origin have been well-documented in the literature. Most of these lesions involve the apex of the offending tooth and appear as a well-defined periapical radiolucency. Presented here is a case of an unusually large lesion, which involved the entire maxillary sinus and extended into the floor of the nose. The lesion also caused paresthesia on the affected side. The lesion was removed with conservative treatment without any postoperative complications.


Molecular-Scale Mechanistic Investigation of Oxygen Dissociation and Adsorption on Metal Surface-Supported Cobalt Phthalocyanine.
Ultrahigh vacuum scanning tunneling microscopy and density functional theory are used to investigate adsorption of oxygen on cobalt phthalocyanine (CoPc), a promising nonprecious metal oxygen reduction catalyst, supported on Ag(111), Cu(111), and Au(111) surfaces at the molecular scale. Four distinct molecular and atomic oxygen adsorption configurations are observed for CoPc supported on Ag(111) surfaces, which are assigned as O2/CoPc/Ag(111), O/CoPc/Ag(111), CoPc/(O)2/Ag(111), and (O)2/CoPc/Ag(111). In contrast, no oxygen adsorption is observed for CoPc supported on Cu(111) and Au(111) surfaces. The results show that for Ag(111), atomic O that is predominantly catalytically produced from the dissociation of molecular O2 at metal surface step edges is responsible for the observed adsorption configurations. However, Cu(111) binds atomic O too strongly, and Au(111) does not produce atomic O. These results show the active role of the supporting metal surface in facilitating oxygen adsorption on CoPc.


Ten years follow-up of histologically benign calcifications in the breast after vacuum-assisted stereotactic biopsy (VASB): Is additional mammographic follow-up warranted?
This study assessed the short-term and the long-term breast cancer rate in patients with benign histopathologic results after a vacuum-assisted stereotactic biopsy (VASB) for calcifications. In a retrospective cohort study, all consecutive patients who had a benign diagnosis after VASB to analyze breast calcifications. Data of breast cancer development at short-term (four years) and long-term follow-up was gathered. Breast cancer rates in our cohort were compared to the breast cancer incidence in the general population. Of 1376 patients who underwent VASB to analyze breast calcifications, 823 had a benign histopathologic diagnosis. During short-term follow-up, eight patients developed breast cancer. During the mean long-term follow-up period of 9.3 ± 3.1 years, 22 patients were diagnosed with ipsilateral breast cancer. The incidence rate of breast cancer after benign biopsy was comparable to the rate in the general population. In patients with VASB-confirmed benign calcifications of the breast, we found no excess incidence of ipsilateral breast cancer during ten years follow-up. Therefore, in patients with an increased risk of breast cancer (due to a history of breast cancer or familial risk) annual mammography should be sufficient. Patients with a population-based risk may be monitored via biennial mammography by the national screening program. More frequent screening would provide no benefit.


Preparation of HIV-1 Env protein and establishment of ultrasensitive detection method of HIV-1 gp41 antibody.
Preparation of HIV-1 Env protein and development of ultrasensitive detection method of HIV-1 gp41 antibody are challengeable tasks for early diagnosis of patients with HIV virus. The env gene fragments were obtained from the plasmid with HIV-1 env by PCR, and were cloned into T vector, and then were sequenced. The linear env gene fragments were prepared by Rapid Translation System (RTS) Linear Template Kit, the Env proteins were obtained by RTS Kit, and were purified by magnetic bead method. The Env protein's bioactivity was identified by Western Blotting. The prepared Env proteins were labeled with CdTe quantum dots (QDs), and the goat anti-HIV-1 gp41 IgG antibodies were detected by CdTe QDs-labeled Env proteins, the fluorescent signals were recorded by photoluminescent spectroscopy. Results show that the prepared Env proteins own bioactivity, the CdTe QDs-labeled Env proteins can combine with anti-HIV-1 gp41 IgG antibodies, and formed the Env-gp41-CdTe QDs complex, the fluorescent intensity of final products were negatively associated with the concentration of anti-HIV-1 gp41 IgG antibodies in sample, the limitation of detection is 100 pg/mL. In conclusion, HIV-1 Env proteins with bioactivity were successfully prepared by RTS, established CdTe QDs labeled Env proteins-based fluorescent immunoassay can successfully detect HIV-1 gp41 IgG antibodies, which has great potential in early diagnosis of HIV.


Isolation and characterization of novel microsatellite markers from the sika deer (Cervus nippon) genome.
Microsatellite markers are widely and evenly distributed, and are highly polymorphic. Rapid and convenient detection through automated analysis means that microsatellite markers are widely used in the construction of plant and animal genetic maps, in quantitative trait loci localization, marker-assisted selection, identification of genetic relationships, and genetic diversity and phylogenetic tree construction. However, few microsatellite markers remain to be isolated. We used streptavidin magnetic beads to affinity-capture and construct a (CA)n microsatellite DNA-enriched library from sika deer. We selected sequences containing more than six repeats to design primers. Clear bands were selected, which were amplified using non-specific primers following PCR amplification to screen polymorphisms in a group of 65 unrelated sika deer. The positive clone rate reached 82.9% by constructing the enriched library, and we then selected positive clones for sequencing. There were 395 sequences with CA repeats, and the CA repeat number was 4-105. We selected sequences containing more than six repeats to design primers, of which 297 pairs were designed. We next selected clear bands and used non-specific primers to amplify following PCR amplification. In total, 245 pairs of primers were screened. We then selected 50 pairs of primers to randomly screen for polymorphisms. We detected 47 polymorphic and 3 monomorphic loci in 65 unrelated sika deer. These newly isolated and characterized microsatellite loci can be used to construct genetic maps and for lineage testing in deer. In addition, they can be used for comparative genomics between Cervidae species.


Inhibition of destructive autoimmune arthritis in FcgammaRIIa transgenic mice by small chemical entities.
The interaction of immune complexes with the human Fc receptor, FcgammaRIIa, initiates the release of inflammatory mediators and is implicated in the pathogenesis of human autoimmune diseases, including rheumatoid arthritis and systemic lupus erythematosus, so this FcR is a potential target for therapy. We have used the three-dimensional structure of an FcgammaRIIa dimer to design small molecule inhibitors, modeled on a distinct groove and pocket created by receptor dimerization, adjacent to the ligand-binding sites. These small chemical entities (SCEs) blocked immune complex-induced platelet activation and aggregation and tumor necrosis factor secretion from macrophages in a human cell line and transgenic mouse macrophages. The SCE appeared specific for FcgammaRIIa, as they inhibited only immune complex-induced responses and had no effect on responses to stimuli unrelated to FcR, for example platelet stimulation with arachidonic acid. In vivo testing of the SCE in FcgammaRIIa transgenic mice showed that they inhibited the development and stopped the progression of collagen-induced arthritis (CIA). The SCEs were more potent than methotrexate and anti-CD3 in sustained suppression of CIA. Thus, in vitro and in vivo activity of these SCE FcgammaRIIa receptor antagonists demonstrated their potential as anti-inflammatory agents for autoimmune diseases involving immune complexes.


Muscle relaxant properties of chloramphenicol.
Experiments with the guinea pig ileum, guinea pig trachea, rat fundal strip, rat colon, rat vas deferens, and toad heart indicated that chloramphenicol inhibited smooth muscles, decreasing both the height and frequency of spontaneous contraction. Chloramphenicol-induced relaxation was not mediated through adrenergic, cholinergic, or histaminergic mechanisms. The degree of muscle relaxation was related to the concentration of chloramphenicol, and the relaxant effect could be reversed by removing chloramphenicol from site of action by washing. Its action appears to be direct on the muscle, possibly by interfering with the energy-generating mechanism.


Implementing system-wide risk stratification approaches: A review of critical success and failure factors.
Risk stratification has become a widely used tool for linking people identified at risk of health deterioration to the most appropriate evidence-based care. This article systematically reviews recent literature to determine key factors that have been identified as critical enablers and/or barriers to successful implementation of risk stratification tools at a system level. A systematic search found 23 articles and four promising protocols for inclusion in the review, covering the use to 20 different risk stratification tools. These articles reported on only a small fraction of the risk stratification tools used in health systems; suggesting that while the development and statistical validation of risk stratification algorithms is widely reported, there has been little published evaluation of how they are implemented in real-world settings. Controlled studies provided some evidence that the use of risk stratification tools in combination with a care management plan offer patient benefits and that the use of a risk stratification tool to determine components of a care management plan may contribute to reductions in hospital readmissions, patient satisfaction and improved patient outcomes. Studies with the strongest focus on implementation used qualitative and case study methods. Among these, the literature converged on four key areas of implementation that were found to be critical for overcoming barriers to success: the engagement of clinicians and safeguarding equity, both of which address barriers of acceptance; the health system context to address administrative, political and system design barriers; and data management and integration to address logistical barriers.


Genepolide, a sesterpene gamma-lactone with a novel carbon skeleton from mountain wormwood (Artemisia umbelliformis).
The sesterpene gamma-lactone genepolide (5) has been isolated from a Swiss horticultural variety of mountain wormwood (Artemisia umbelliformis) developed as a thujones-free alternative to native Western Alps wormwoods for the production of liqueurs. Genepolide is the formal Diels-Alder adduct of the exomethylene-gamma-lactone costunolide (2) and the diene myrcene (6), two poorly reactive partners in cycloaddition reactions, and its structure was elucidated through a combination of spectroscopic methods. An investigation on the thermal stability of mixtures of 2 and 6, as well as considerations on the sensitivity of 2 to Brønsted and Lewis acids, suggests that 5 is a genuine natural product and that the Swiss chemotype of A. umbelliformis contains Diels-Alderase enzymatic activity that is lacking in native mountain wormwoods from Western Alps. Remarkable differences in thermal and acid-catalyzed reactions of the cyclodecadiene moiety of 2 and 5 suggest that quaternarization at C-11 has far-reaching effects on the reactivity of their homoconjugated medium-sized diene system. The wide occurrence of this structural motif in sesquiterpenoids makes this issue worth a systematic investigation.


Transmyocardial Revascularisation by CO2 Laser.
Anatomical channels connecting the left ventricular chamber to the myocardial sinusoids supplying the left ventricle with oxygenated blood in the human heart were described by Dr Wearn in 1933. He microscopically confirmed these communicating vessels or tiny clusters of arteries by gelatin filling. The second type of these channels was located at the end of the vessels almost as though woven into the fabric of the muscular fibres. These irregular shaped blood vessels were called myocardial sinusoids. Three other early investigators described connecting channels. The first was Adrian Christian Thebesius, a Dutch physician in 1708 who described connections from the atrium the coronary veins which were called Thebesian veins. The second was the American physiologist F H Pratt who, in 1898, perfused blood though the ventricle alone in a cat, keeping it alive for more than an hour. Finally, the historical work of R T Grant who in 1926 reported that a congenitally deformed heart in a child had connecting cavities with the surrounding veins and arteries.


Morbid Obesity Alters Both Pharmacokinetics and Pharmacodynamics of Propofol: Dosing Recommendation for Anesthesia Induction.
The prevalence of obesity has markedly increased worldwide. Obese patients pose significant challenges to anesthesiologists with regard to accurate dosing of anesthetics due to potentially altered pharmacokinetics (PK). Here we determined the PK and pharmacodynamics (PD) of propofol for anesthesia induction in morbidly obese (MO) subjects (body mass index >35 kg/m(2)) at two dosing regimens: dosing based on total body weight and lean body weight (LBW), respectively. The propofol pharmacokinetic profile was well fitted with a two-compartment model. Both elimination clearance (223%-243% of controls, who had a body mass index <25 kg/m(2); P < 0.01) and peripheral compartment volume (156%-180% of controls; P < 0.01) were significantly increased in MO subjects, resulting in an equal or decreased propofol level in plasma (total body weight-based dosing). Furthermore, propofol PD (measured by the bispectral index) was adequately described by a PK/PD model that linked an effect compartment to the two-compartment PK model through a sigmoidal Emax model. All PD parameters except EC50 values (the half maximal effect concentration) were similar (P > 0.05) between MO subjects and controls. Morbid obesity led to a significant decrease (37.9%-38.6%; P < 0.01) in EC50 values, which suggests increased brain sensitivity to propofol in the MO population. Moreover, dose reduction (i.e., dosing based on LBW) generated identical anesthetic effects in MO subjects compared with controls. In conclusion, morbid obesity significantly altered both PK and PD of propofol. LBW was a better weight-based dosing scalar for anesthesia induction with propofol in MO subjects.


In vitro immunogenicity of various native and thermally processed bovine milk proteins and their mixtures.
In vitro immunogenicity of various native and thermally processed (72°C/15 s and 100°C/30 s) bovine milk protein fractions, their mixtures, whey, and skim milk, was studied by analyzing the immune response of T helper (Th) cells in human peripheral blood mononuclear cells. The secretion of Th type cytokines induced by the protein stimulants was quantified while determining the heat-induced protein denaturation. Purified whey proteins, caseins and whey fraction, and skim milk provoked substantial immune responses at various degrees, indicating their potent immunogenicity. The protein mixtures prepared using the fractionated whey proteins with or without caseins appeared less immunogenic in both native and heat-treated forms, implying their potential of producing less immunogenic dairy products. The 100°C/30 s treatment significantly altered the immunogenicity of most of the potent protein stimulants, which mostly coincided with their levels of protein denaturation. The 72°C/15 s treatment caused the least protein denaturation but altered the immunogenicity of several protein stimulants notably, including heat-stable caseins and α-lactalbumin.


Enhanced Catalytic Performance of Quasi-HKUST-1 for the Tandem Imine Formation.
Copper-based metal-organic framework (Cu3 (BTC)2 (H2 O)3 ]n ⋅nH2 OMeOH (HKUST-1) has been subjected to thermolysis under air atmosphere at different temperatures ranging from 100 to 300 °C. This treatment produces the partial removal of ligands, the generation of structural defects and additional porosity in a controlled way. The resulting defective materials denoted according to the literature as quasi-MOFs, were subsequently employed as heterogeneous catalysts in the one pot synthesis of N-benzylideneaniline from aniline and benzyl alcohol in open air as terminal oxidant at 70 °C under base- and dehydrating agent-free conditions. The Q-HKUST catalysts calcined at 240 °C (QH-240) was the most efficient in the series, promoting imine synthesis. Data from Knoevenagel condensation of malononitrile shows that in QH-240 the distances of Cu ions in HKUST-1 cavities are preserved, increasing the Knoevenagel activity, but a strong rearrangement takes place at 300 °C or above. The unsaturated copper active sites with simultaneous presence of micro- and mesopores in QH-240 are responsible for this excellent catalytic performance. The effective parameters on catalytic activity of QH-240 including deligandation temperature, the amount of catalyst, the ratio of reactants, and reaction temperature as well as the stability and recyclability of the catalyst were also investigated. The possible mechanism used by QH-240 follows alcohol aerobic oxidation and subsequent anaerobic condensation of aldehyde intermediate with aniline.


Stenosis quantification of coronary arteries in coronary vessel phantoms with second-generation dual-source CT: influence of measurement parameters and limitations.
The purpose of this study was to use second-generation dual-source CT to assess the influence of size, degree of stenosis, luminal contrast attenuation, and plaque geometry on stenosis quantification in a coronary artery phantom. Six vessel phantoms with three outer diameters (2, 3, and 4 mm), each containing three radiolucent plaques (72.2 HU) that simulated eccentric and concentric 43.8%, 75%, and 93.8% stenoses were made with a 3D printer system. These phantoms were filled with an iodine-saline solution mixture at luminal attenuations of 150, 200, 250, 300, and 350 HU and were attached to a cardiac motion simulator. Dual-source CT was performed with a standardized ECG-gated protocol (120 kV, 360 mAs per rotation) at a simulated heart rate of 70 beats/min. Two independent readers quantified the degree of stenosis using area-based measurements. All measurements were highly reproducible (intraclass correlation, ≥ 0.791; p < 0.001). The mean measured degree of stenosis for a phantom with a 3-mm outer diameter at 250-HU luminal attenuation was 49.0% ± 10.0% for 43.8% stenosis, 71.7% ± 9.6% for 75.0% stenosis, and 85.4% ± 5.9% for 93.8% stenosis. With decreasing phantom size, measurement error increased for all degrees of stenosis. The absolute error increased for measurements at a low luminal attenuation of 150 HU (p < 0.001) and for low-grade stenoses compared with medium-and high-grade stenoses (p < 0.001). The results are an overview of factors that influence stenosis quantification in simulated coronary arteries. Dual-source CT is highly reproducible and accurate for quantification of low-density stenosis in vessels with a diameter of 3 mm and attenuation of at least 200 HU for different degrees of stenosis and plaque geometry.


Kidney Disease in Childhood Cancer Survivors Treated With Radiation Therapy: A Comprehensive PENTEC Genitourinary Review.
Kidney injury is a known late and potentially devastating complication of abdominal radiation therapy (RT) in pediatric patients. A comprehensive Pediatric Normal Tissue Effects in the Clinic review by the Genitourinary (GU) Task Force aimed to describe RT dose-volume relationships for GU dysfunction, including kidney, bladder, and hypertension, for pediatric malignancies. The effect of chemotherapy was also considered. We conducted a comprehensive PubMed search of peer-reviewed manuscripts published from 1990 to 2017 for investigations on RT-associated GU toxicities in children treated for cancer. We retrieved 3271 articles with 100 fulfilling criteria for full review, 24 with RT dose data and 13 adequate for modeling. Endpoints were heterogenous and grouped according to National Kidney Foundation: grade ≥1, grade ≥2, and grade ≥3. We modeled whole kidney exposure from total body irradiation (TBI) for hematopoietic stem cell transplant and whole abdominal irradiation (WAI) for patients with Wilms tumor. Partial kidney tolerance was modeled from a single publication from 2021 after the comprehensive review revealed no usable partial kidney data. Inadequate data existed for analysis of bladder RT-associated toxicities. The 13 reports with long-term GU outcomes suitable for modeling included 4 on WAI for Wilms tumor, 8 on TBI, and 1 for partial renal RT exposure. These reports evaluated a total of 1191 pediatric patients, including: WAI 86, TBI 666, and 439 partial kidney. The age range at the time of RT was 1 month to 18 years with medians of 2 to 11 years in the various reports. In our whole kidney analysis we were unable to include chemotherapy because of the heterogeneity of regimens and paucity of data. Age-specific toxicity data were also unavailable. Wilms studies occurred from 1968 to 2011 with mean follow-ups 8 to 15 years. TBI studies occurred from 1969 to 2004 with mean follow-ups of 4 months to 16 years. We modeled risk of dysfunction by RT dose and grade of toxicity. Normal tissue complication rates ≥5%, expressed as equivalent doses, 2 Gy/fx for whole kidney exposures occurred at 8.5, 10.2, and 14.5 Gy for National Kidney Foundation grades ≥1, ≥2, and ≥3, respectively. Conventional Wilms WAI of 10.5 Gy in 6 fx had risks of ≥grade 2 toxicity 4% and ≥grade 3 toxicity 1%. For fractionated 12 Gy TBI, those risks were 8% and <3%, respectively. Data did not support whole kidney modeling with chemotherapy. Partial kidney modeling from 439 survivors who received RT (median age, 7.3 years) demonstrated 5 or 10 Gy to 100% kidney gave a <5% risk of grades 3 to 5 toxicity with 1500 mg/m2 carboplatin or no chemo. With 480 mg/m2 cisplatin, a 3% risk of ≥grade 3 toxicity occurred without RT and a 5% risk when 26% kidney received ≥10 Gy. With 63 g/m2 of ifosfamide, a 5% risk of ≥grade 3 toxicity occurred with no RT, and a 10% toxicity risk occurred when 42% kidney received ≥10 Gy. In patients with Wilms tumor, the risk of toxicity from 10.5 Gy of WAI is low. For 12 Gy fractionated TBI with various mixtures of chemotherapy, the risk of severe toxicity is low, but low-grade toxicity is not uncommon. Partial kidney data are limited and toxicity is associated heavily with the use of nephrotoxic chemotherapeutic agents. Our efforts demonstrate the need for improved data gathering, systematic follow-up, and reporting in future clinical studies. Current radiation dose used for Wilms tumor and TBI appear to be safe; however, efforts in effective kidney-sparing TBI and WAI regimens may reduce the risks of renal injury without compromising cure.


'Planning for a healthy baby and a healthy pregnancy': A critical analysis of Canadian clinical practice guidelines for the treatment of opioid dependence during pregnancy.
As opioid fatalities rise in North America, the need to improve the supports available to those who are dependent on opioids and pregnant has become more urgent. This paper discusses the social organisation of drug treatment supports for those who are pregnant, using Canadian clinical practice guidelines (CPGs) for methadone maintenance treatment (MMT) as a case study. Pregnant patients are a priority population for MMT, both in Canada and internationally; the regulatory bodies that oversee MMT in Canada are the provincial Colleges of Physician and Surgeons and Health Canada. The paper analyses MMT CPGs published by these agencies, comparing their general recommendations to those specific to pregnant patients. We demonstrate that the guidelines address few treatment considerations for pregnant patients, other than improved birth outcomes and child welfare, despite acknowledging their more complex needs. Drawing on social science studies of gender and drugs, we argue that MMT CPGs therefore perpetuate the intensified surveillance and foetal prioritisation that have long generated barriers to care for opiate-dependent pregnant patients. We also discuss how and why the CPGs ultimately only reinforced these current limitations in the drug treatment sector.


Implied Maximum Dose Analysis of Standard Values of 25 Pesticides Based on Major Human Exposure Pathways.
Worldwide jurisdictions are making efforts to regulate pesticide standard values in residential soil, drinking water, air, and agricultural commodity to lower the risk of pesticide impacts on human health. Because human may exposure to pesticides from many ways, such as ingestion, inhalation, and dermal contact, it is important to examine pesticide standards by considering all major exposure pathways. Analysis of implied maximum dose limits for commonly historical and current used pesticides was adopted in this study to examine whether worldwide pesticide standard values are enough to prevent human health impact or not. Studies show that only U.S. has regulated pesticides standard in the air. Only 4% of the total number of implied maximum dose limits is based on three major exposures. For Chlorpyrifos, at least 77.5% of the total implied maximum dose limits are above the acceptable daily intake. It also shows that most jurisdictions haven't provided pesticide standards in all major exposures yet, and some of the standards are not good enough to protect human health.


Library statistics of veterinary schools in the United States and Canada.
In cooperation with the American Veterinary Medical Association, questionnaires were sent to twentyone veterinary schools in the United States and Canada. Statistics on user population, the library collection, personnel, the institutional expenditures for educational and general purposes, as well as operating expenditures, were tabulated for fifteen of these schools.


Anti-histone H1 IgGs possess proliferative activity towards human T-leukaemia CEM cells.
The aim of this study was to characterize the proliferative activity of the anti-histone H1 IgGs towards human T-leukaemia CEM cells. Anti-histone H1 IgGs were purified from blood serum of systemic lupus erythematosus patients by precipitation of serum proteins with 50% ammonium sulfate followed by a sequential affinity chromatography on Protein G-Sepharose and histone H1-Sepharose columns. To avoid contamination with other proteins, anti-histone H1 IgGs were subjected to strongly acidic pH 2.0 during gel filtration through HPLC column. The effects of the anti-histone H1 IgGs on cell viability and cell cycle were tested by MTS-assay and flow cytometry, correspondingly. The cross-reactivity of the anti-histone H1 antibodies towards heterogenetic and cellular antigens was evaluated by Western-blot analysis. It was found that incubation of CEM cells with the HPLC-purified anti-histone H1 IgGs resulted in significant stimulation of cell growth by 46% after 48 h of incubation. These IgGs possess an antigenic poly-specificity to positively charged heterogenetic antigens and different cellular antigens. FITC-labeled and biotinylated anti-histone H1 IgGs are internalized by CEM cells and preferentially accumulated in the cytoplasm. The anti-histone H1 IgGs are shown to internalize human T-leukemia CEM and stimulate their proliferation. These IgGs are polyspecific toward cellular antigens.


Application of high pressure processing to kill Escherichia coli O157 in ready-to-eat meats.
Uncooked ready-to-eat (RTE) meats have previously been identified as vehicles for the transmission of the foodborne pathogen Escherichia coli O157. In this study, the potential for high pressure processing (HPP) to kill E. coli O157 in two RTE meats (Hungarian salami and All Beef salami) was investigated. The RTE meats were inoculated with a five-strain cocktail of E. coli O157, vacuum packed, and then pressure treated at 600 MPa with a hold time of 3 min. Samples were stored at 15 degrees C for 28 days. HPP initially reduced E. coli numbers on both RTE meats by greater than 4 log CFU/g. However, with enrichment and immunomagnetic separation we were able to recover E. coli O157 from the samples. During storage, the numbers of E. coli O157 increased on the All Beef samples but remained static on the Hungarian salami, which had a restrictive pH and water activity. Increasing the hold time to 6 or 9 min did not result in additional reduction of E. coli O157. The sensory appeal of the two products was not significantly changed by HPP as determined by a sensory panel (n = 50). Analysis of the reflected light parameters of luminance, green-red, and blue-yellow revealed no significant changes. The results of these experiments indicate that HPP has potential as a lethal treatment for E. coli O157 on RTE meats with minimal changes in consumer appeal.


Psychological assessment of gay and lesbian law enforcement applicants.
Psychological profiles and measures of law enforcement job performance were compared for gay, lesbian, and heterosexual samples. No differences were found in selection rates or ratings of job performance. Compared to heterosexual men, gay men scored higher on Minnesota Multiphasic Personality Inventory (MMPI) Scale 5 and lower on California Psychological Inventory (CPI) scales Wb and Sc. No significant MMPI or CPI differences were found for lesbian and heterosexual women.


Investigating Factors Associated with Depressive Symptoms of Chronic Kidney Diseases in China with Type 2 Diabetes.
Aim. To assess the depressive symptoms status of chronic kidney diseases in Nantong, China, with type 2 diabetes and to identify factors associated with depressive symptoms. Methods. In this cross-sectional analytic study, 210 type 2 diabetic patients were recruited from the Second Affiliated Hospital of Nantong University. Depressive symptoms were assessed with the depression subscale of the Hospital Anxiety and Depression Scale (HAD-D). The quality of life was measured with the RAND 36-Item Health Survey (SF-36). And the independent risk factors of depressive symptoms were assessed by using a stepwise forward model of logistic regression analysis. Results. The mean age of the study subjects was 57.66 years (SD: 11.68). Approximately 21.4% of subjects reported depressive symptoms (n = 45). Forward stepwise logistic regression analysis showed that female gender (P = 0.010), hypertension (P = 0.022), Stage IV (P = 0.003), and Stage V (P < 0.001) were significant risk factors for depressive symptoms. The quality of life of individuals with HAD-D score <11 was significantly better compared with individuals with HAD-D score ≥ 11. Conclusions. These results indicate that clinicians should be aware that female patients with chronic kidney diseases with T2DM in their late stage with hypertension are at a marked increased risk of depressive symptoms. Providing optimal care for the psychological health of this population is vital.


Hepatocarcinoma cell lines down-regulate matrix metalloproteinase-2 expression in human hepatic myofibroblasts.
Matrix metalloproteinases (MMPs) are a family of proteases that degrade extracellular matrix components and are involved in tumor progression and metastasis. We studied the pattern of expression of MMP-2 by human hepatoma cell lines and human hepatic myofibroblasts and its regulation in co-culture between these cell types. MMP-2 expression was studied by zymography and semi-quantitative RT-PCR. The expression of MT1-MMP (involved in MMP-2 activation) was studied by Western blot analysis and RT-PCR and the secretion of TIMP-2 by ELISA and RT-PCR. Myofibroblasts expressed high levels of MMP-2, MT1-MMP and TIMP-2. The hepatoma cell lines HepG2, HuH7 and Hep3B did not express MMP-2 and weakly expressed TIMP-2 and MT1-MMP. In co-culture, no modulation of MT1-MMP or TIMP-2 expression was observed. A strong decrease in myofibroblast MMP-2 expression was seen in the presence of hepatoma cell lines. This was partly reproduced by their conditioned media. We conclude that hepatoma cell lines down-regulate the expression of MMP-2 by myofibroblasts.


Blood clot initiation by mesocellular foams: dependence on nanopore size and enzyme immobilization.
Porous silica materials are attractive for hemorrhage control because of their blood clot promoting surface chemistry, the wide variety of surface topologies and porous structures that can be created, and the potential ability to achieve high loading of therapeutic proteins within the silica support. We show that silica cell-window size variation in the nanometers to tens of nanometers range greatly affects the rate at which blood clots are formed in human plasma, indicating that window sizes in this size range directly impact the accessibility and diffusion of clotting-promoting proteins to and from the interior surfaces and pore volume of mesocellular foams (MCFs). These studies point toward a critical window size at which the clotting speed is minimized and serve as a model for the design of more effective wound-dressing materials. We demonstrate that the clotting times of plasma exposed to MCF materials are dramatically reduced by immobilizing thrombin in the pores of the MCF, validating the utility of enzyme-immobilized mesoporous silicas in biomedical applications.


The anatomy and clinical significance of the collateral circulation between the internal and external carotid arteries through the ophthalmic artery.
Complete occlusion of the internal carotid artery is not necessarily associated with total disruption of cerebral blood flow distal to the site of the arterial obstruction. In fact, the flow of blood may be sufficient to maintain cerebral perfusion. This is accomplished by the shunting of blood from the external to the internal carotid artery by means of collateral circuits. While several major branch arteries of the external carotid artery may be recruited in this process, the ophthalmic artery is often the final common pathway before the anastomosis with the internal carotid artery. With the aim of elucidating these collateral circles, digital subtraction angiography was used to examine 100 patients with total occlusion of the internal carotid artery. These data were compared with those obtained using Doppler ultrasound, duplex scanning, and transcranial Doppler. Forty patients were excluded because there was no demonstrable collateral circulation, because the collateral circulation used the communicating arteries, or because the ophthalmic artery arose from the middle meningeal artery. Dynamic data were obtained by compressing the branches of the two external and common carotid arteries, and the blood vessels were identified by comparison with previous anatomic studies. We have constructed a precise map of the intra- and extracranial circles that connect the internal and external carotid arteries through the pathways that include the ophthalmic artery. This map demonstrates why apparently identical vascular occlusions may have divergent symptomatologies and clinical outcomes, which may range from the complete absence of symptoms to cerebral infarction.


Role of Using Nonsteroidal Anti-Inflammatory Drugs in Chemoprevention of Colon Cancer in Patients With Inflammatory Bowel Disease.
The process of inflammation occurs due to inflammatory mediators, including prostaglandins, cytokines, and tumor necrosis factor (TNF). All these mediators activate the process of tumorigenesis and dysplasia, leading to colitis-associated cancer. Several drugs used to decrease these mediators will help in the treatment of acute attacks and also help in prolonged remissions of the disease by using nonsteroidal anti-inflammatory drugs (NSAIDs), steroids, and biological factors. Reducing these inflammatory mediators also have a role in chemoprevention and prevent progression to colorectal carcinoma. The most researched drugs in this process of chemoprevention are NSAIDs as it has both cyclooxygenase-2 (COX-2) inhibitory and non-inhibitory effects. These drugs should be taken for a long time and in large doses to reach this effect, which puts the patient at risk for various side effects. Researchers will need to do more research in the future to find the lowest effective dose that can reach the chemopreventive effect. We used database Pubmed as the main source for data search and extracted articles exploring the relationship between NSAIDs and their role in chemoprevention of colorectal carcinoma in inflammatory bowel disease (IBD) patients. We chose 23 studies which included seven review articles. We found that inflammatory mediators have a key role in colitis-associated cancer.


Image guided radiation therapy boost in combination with high-dose-rate intracavitary brachytherapy for the treatment of cervical cancer.
The purpose of this study was to demonstrate the dosimetric and clinical feasibility of image guided radiation therapy (IGRT) combined with high-dose-rate (HDR) intracavitary brachytherapy (ICBT) to improve dose distribution in cervical cancer treatment. For 42 cervical cancer patients, magnetic resonance imaging (MRI) scans were acquired after completion of whole pelvic irradiation 45-46 Gy and 5 fractions of B + I (ICBT + IGRT) treatment were subsequently received. The high risk clinical target volume (HRCTV), intermediate risk clinical target volume (IRCTV), bladder, rectum, and sigmoid were contoured on the computed tomography (CT) scans. The total planning aim doses for HRCTV was D90% > 85 Gy, whilst constraints for rectum and sigmoid were D2cc < 75 Gy and D2cc < 90 Gy for bladder in terms of an equivalent dose in 2 Gy (EQD2) for external beam radiotherapy (EBRT) and brachytherapy boost. The IGRT plan was optimized on top of the ICBT dose distribution. A dosimetric comparison was made between B + I and optimized ICBT (O-ICBT) only. The mean D90% of HRCTV was comparable for B + I and O-ICBT (p = 0.82). For B + I plan, HRCTV D100%, IRCTV D100%, and IRCTV D90% were significantly increased by a mean of 10.52 Gy, 5.61 Gy, and 2.70 Gy, respectively (p < 0.01). The D2cc for bladder, rectum, and sigmoid were lower by a mean of 21.36, 6.78, and 10.65 Gy, respectively (p < 0.01). The mean rectum V60 Gy value over 42 patients was almost the same for both techniques but for bladder and sigmoid B + I had higher V60 Gy mean values as compared with the O-ICBT. B + I can improve dose distribution in cervical cancer treatment; it could be useful for tumors extended beyond the reach of intracavitary/interstitial brachytherapy (IC/ISBT) or for centers that are inexperienced or ill-equipped with IC/ISBT techniques. Additional confirmatory prospective studies with larger numbers of patients and longer follow-up are required to validate the durability.


Carbon dioxide effects on luminol and 1,10-phenanthroline chemiluminescence.
Luminol and 1,10-phenanthroline are widely used chemiluminescent (CL) reagents for the analysis of a wide range of metals and inorganic and organic complexes. While the fundamental mechanism for luminol and 1,10-phenantholine chemiluminescence is understood, the analytical application of these reagents is largely empirical and often poorly described mechanistically. For example, CL signals observed from metal-luminol systems are strongly dependent on the pH of the sample, even though the final pH of the reaction mixture is controlled to a narrow range by a buffer. Other investigators report significant changes in CL signal due to freshness and the acidity of reagents. Our work shows that many of these effects are due to dissolved CO2 present or formed in the analytical system. The hypothesis that carbon dioxide plays a pivotal role in enhancing luminol CL is supported by direct manipulation of CO2(aq) concentrations by the addition of CO2(g) or carbonic anhydrase. In contrast, Cu(II) analysis using the CL reagent 1,10-phenanthroline is completely quenched in the presence of CO2(aq). A plausible mechanism for these observations involves the reaction between superoxide, produced in these analytical systems, and CO2(aq) to form the peroxycarbonate radical, *C04-. The formation of *CO4- has very important analytical implications since this species appears to enhance or quench the CL signal from luminol and 1,10-phenanthroline, respectively.


Yeast expressed ArtinM shares structure, carbohydrate recognition, and biological effects with native ArtinM.
Recent advances in glycobiology have revealed the essential role of lectins in deciphering the glycocodes at the cell surface to generate important biological signaling responses. ArtinM, a d-mannose-binding lectin isolated from the seeds of jackfruit (Artocarpus heterophyllus), is composed of 16 kDa subunits that are associated to form a homotetramer. Native ArtinM (n-ArtinM) exerts immunomodulatory and regenerative effects, but the potential pharmaceutical applicability of the lectin is highly limited by the fact that its production is expensive, laborious, and impossible to be scaled up. This led us to characterize a recombinant form of the lectin obtained by expression in Saccharomyces cerevisiae (y-ArtinM). In the present study, we demonstrated that y-ArtinM is similar to n-ArtinM in subunit arrangement, oligomerization and carbohydrate binding specificity. We showed that y-ArtinM can exert n-ArtinM biological activities such as erythrocyte agglutination, stimulation of neutrophil migration and degranulation, mast cell degranulation, and induction of interleukin-12 and interleukin-10 production by macrophages. In summary, the expression of ArtinM in yeast resulted in successful production of an active, recombinant form of ArtinM that is potentially useful for pharmaceutical application.


Efficient Conjugated Polymer-Methyl Viologen Electron Transfer System for Controlled Photo-Driven Hydrogen Evolution.
Photodriven hydrogen production has been a good strategy in solar energy utilization. In this work, we use a water-soluble negatively charged polythiophene derivative as photosensitizer to produce hydrogen from aqueous solution containing methyl viologen (MV2+), ethylenediaminetetraacetic acid disodium salt (EDTA), and a colloidal platinum catalyst upon exposure to xenon lamp (>420 nm) or natural sunlight. The supramolecular assembly and dis-assembly processes of MV2+ and cucurbit[8]uril (CB[8]) was further used to reversibly "turn-on" and "turn-off" hydrogen generation of the polymer system. This research offers a proof-of-concept to control hydrogen generation in demand, which is an advantage for hydrogen utilization and storage.


Screening, early detection, and diagnosis of pulmonary arterial hypertension: ACCP evidence-based clinical practice guidelines.
Pulmonary arterial hypertension (PAH) occurs as an idiopathic process or as a component of a variety of disease processes, including chronic thromboembolic disease, connective tissue diseases, congenital heart disease, and exposure to exogenous factors including appetite suppressants or infectious agents such as HIV. This article reviews evidence for screening in susceptible patient groups and the approach to diagnosing PAH when it is suspected, and provides specific recommendations for applying this evidence to clinical practice.


Interactive Effects of Agitation and Cognitive Impairment on Odor Identification in Patients With Late-Life Depression.
Late-life depression (LLD) is a risk factor for cognitive decline in older adults, and odor identification (OI) deficits are an early indicator of cognitive decline with LLD. However, neuropsychiatric symptoms (NPSs) are common in LLD and are associated with OI deficits. In subjects with LLD, when OI deficits forecast cognitive decline, whether and how NPS affects the relationship between OI and cognition still must be further explored. To comprehensively explore the potential effects of various NPSs on the relationship between OI and cognition in participants with LLD. There were 167 patients with LLD and 105 normal elderly (NE) participants. The odor identification test (Sniffin' Sticks), cognitive function assessments (global cognition, memory, executive function, attention, language, visual space), and an NPS assessment (the neuropsychiatric inventory questionnaire) were performed on the subjects. In patients with LLD, the relationship among OI, cognition and NPSs was examined using correlation analysis and moderation analysis. In patients with LLD, OI was positively correlated with cognition (global cognition, memory, executive function, attention, language) and negatively associated with NPSs (agitation and aberrant motor behavior). In NE group, OI was correlated with executive function. Moderation analysis showed that there was an interactive effect of agitation and cognitive impairment (language deficit or attention deficit) on OI in patients with LLD. The coexistence of agitation and language or attention deficit was associated with worse OI in subjects with LLD. Agitation should be considered since OI predicts cognitive decline in patients with LLD.


Lipids of Rhizopus arrhizus Fischer.
The lipids of Rhizopus arrhizus Fischer mycelia and sporangiospores were extracted, isolated, and separated by thin-layer, liquid, and gas chromatography. Structural confirmations of the compounds were made by a gas chromatographmass spectrometer combination. The n-heptane fraction contained squalene (1%) as a major hydrocarbon constituent. Other major lipid classes detected were free fatty acids, naturally occurring methyl esters of fatty acids, triglycerides, sterols, and polar lipids. The polar lipids (44.4%) were found in the highest concentrations, and the triglycerides (22.1%), sterols (16.7%), and free fatty acids (11.7%) were present in lesser concentrations. This is the first report of naturally occuring methyl esters of long-chain fatty acids being present in fungal mycelium. There appears to be a preference for incorporation of unsaturated acids into the complex lipids, with the exception of the triglycerides. The major saturated fatty acids in the mycelium were palmitic (C(16)) and arachidic (C(20)), whereas the major unsaturated acids were oleic (C(18:1)) and linoleic (C(18:2)), respectively.


GDF15 is a heart-derived hormone that regulates body growth.
The endocrine system is crucial for maintaining whole-body homeostasis. Little is known regarding endocrine hormones secreted by the heart other than atrial/brain natriuretic peptides discovered over 30 years ago. Here, we identify growth differentiation factor 15 (GDF15) as a heart-derived hormone that regulates body growth. We show that pediatric heart disease induces GDF15 synthesis and secretion by cardiomyocytes. Circulating GDF15 in turn acts on the liver to inhibit growth hormone (GH) signaling and body growth. We demonstrate that blocking cardiomyocyte production of GDF15 normalizes circulating GDF15 level and restores liver GH signaling, establishing GDF15 as a bona fide heart-derived hormone that regulates pediatric body growth. Importantly, plasma GDF15 is further increased in children with concomitant heart disease and failure to thrive (FTT). Together these studies reveal a new endocrine mechanism by which the heart coordinates cardiac function and body growth. Our results also provide a potential mechanism for the well-established clinical observation that children with heart diseases often develop FTT.


A surgical case of frontal lobe epilepsy due to focal cortical dysplasia accompanied by olfactory nerve enlargement: case report.
A 45-year-old man came to our clinic due to refractory general tonic seizure and an attack of unintended yelling. Magnetic resonance imaging (MRI) demonstrated mild cortical hyperintensity on fluid attenuated inversion recovery (FLAIR) image in the left basal frontal area. Enlargement of the left olfactory nerve was also detected below the affected gyrus. Subtotal resection of the MRI-visible epileptogenic lesion was performed without any neurological deficit. The final pathological diagnosis was focal cortical dysplasia (FCD) type IIa. Seizures and yelling attacks subsided after surgery. Extracerebral abnormalities, including cranial nerve enlargement, are common in patients with hemimegalencephaly. However, such abnormalities are rare with FCD.


Onset of chronic myeloid leukemia with complex karyotype in a pregnant patient: case report and revision of literature.
Approximately 10%-12% of patients in chronic-phase chronic myeloid leukemia (CP-CML) have additional chromosomal aberrations at diagnosis; moreover, CML occurs in up to 10% of pregnancy-associated leukemias, with an annual incidence of 1 per 100,000 pregnancies. In this report we describe the case of a 36-year-old female with CP-CML diagnosed in the 18th week of pregnancy and with a new complex variant translocation t(4;9;22;21)(q24;q34;q11;q22) and an additional chromosomal aberration t(1;20)(p36;p11). In consideration of her pregnancy, the patient strictly monitored her blood cell count without any specific treatment. At 32 weeks of pregnancy, the patient delivered via cesarean section a healthy baby girl. After 10 days from childbirth, dasatinib was started at a standard dosage of 100 mg/day and 3 months later complete cytogenetic response and major molecular response were obtained, with the achievement of an optimal response according to European Leukemia Net recommendations and showing efficacy of this tyrosine kinase inhibitor (TKI) in the presence of a complex karyotype.


Protective effect of quercetin against arsenite-induced COX-2 expression by targeting PI3K in rat liver epithelial cells.
Abnormal expression of cyclooxygenase-2 (COX-2) and prostaglandin (PG)E(2) is an important mediator in inflammation and tumor promotion. Arsenite is a well-known metalloid carcinogen that is strongly associated with increased risk of liver cancer, but the underlying mechanism remains to be clarified. The present study demonstrates that COX-2 expression and PGE(2) secretion are up-regulated by arsenite in rat liver epithelial (RLE) cells. The possible inhibitory effect of quercetin, a naturally occurring dietary flavonol, on arsenite-induced COX-2 expression and PGE(2) production was investigated. Pretreatment with quercetin resulted in the reduction of arsenite-induced expression of COX-2 and production of PGE(2). The arsenite-induced phosphorylation of Akt, p70S6K, and extracellular signal-regulated protein kinases (ERKs), but not p38, was inhibited by quercetin treatment. An ex vivo kinase assay revealed that quercetin suppressed arsenite-induced phosphoinositide 3-kinase (PI3K) activity upstream of Akt in RLE cell lysates. Ex vivo pull-down assays demonstrated that quercetin directly bound with PI3K to inhibit PI3K activity. Moreover, LY294002 (a PI3K inhibitor) significantly attenuated COX-2 expression and PGE(2) production in arsenite-treated RLE cells. These results suggest that quercetin suppresses arsenite-induced COX-2 expression mainly by blocking the activation of the PI3K signaling pathway, which may contribute to its chemopreventive potential.


Mitral regurgitation in ventricular premature contractions. The role of the papillary muscle.
In view of the possibility that the mechanism of mitral regurgitation following premature ventricular contractions may contribute to the understanding of mitral regurgitation in clinically important causes of nonrheumatic mitral insufficiency, we studied 320 premature ventricular contractions in eight dogs. Since the papillary muscle is an important component of the mitral valvular complex, the extent and course of lengthening and shortening of the papillary muscle was investigated with ultrasonic crystals implanted within the anterolateral papillary muscle. Lengthening and shortening of a segment of the free wall of the left ventricle was measured simultaneously with identical crystals in three dogs. During sinus rhythm, lengthening of the papillary muscle always began well before the onset of isovolumic contraction of the left ventricle and continued throughout isovolumic contraction, indicating that lengthening occurred during closure of the mitral valve. When lengthening was prevented by premature ventricular contractions, left atrial v waves occurred. These observations indicate that lengthening of the papillary muscle during the latter part of diastole is required for proper closure of the mitral valve and that inadequate lengthening can result in mitral regurgitation.


Plasma C-reactive protein in early pregnancy and preterm delivery.
Systemic maternal infections have been associated with preterm delivery. The authors examined the association of C-reactive protein (CRP), a marker of inflammation, with preterm delivery. This nested case-control study was conducted within Project Viva in Massachusetts between 1999 and 2002. Subjects were 117 women who delivered preterm (< 37 weeks' gestation) and 117 controls (term deliveries) matched on age, race/ethnicity, and smoking status. High-sensitivity CRP assays were performed on early-pregnancy (5.3-19.3 weeks' gestation) plasma samples. Odds ratios and 95% confidence intervals were estimated by using conditional logistic regression adjusted for matching factors, gestational age at blood collection, and prepregnancy body mass index. Median concentration of CRP was 3.2 mg/liter in cases versus 2.4 mg/liter in controls. No significant association was found between quartiles of CRP and preterm delivery. However, CRP levels exceeding the threshold defined in the literature were associated with increased risk of preterm delivery (odds ratio = 2.55, 95% confidence interval: 1.05, 6.02 for CRP > or = 8 mg/liter). The association was stronger among cases who experienced spontaneous delivery (odds ratio = 4.64, 95% confidence interval: 0.94, 22.96) versus indicated delivery (odds ratio = 1.42, 95% confidence interval: 0.44, 4.61). These findings suggest that very high CRP levels in early pregnancy are associated with preterm delivery.


External validation of a high-sensitive troponin I algorithm for rapid evaluation of acute myocardial infarction in a Danish cohort.
An accelerated diagnostic algorithm for ruling-in or ruling-out myocardial infarction (MI) after 1 hour (1 h) has recently been derived and internally validated for the Siemens ADVIA Centaur TNIH assay. We aimed to validate the diagnostic performance of the TNIH 0 h/1 h algorithm ad modum Boeddinghaus in a Danish cohort. Patients with chest pain suggestive of MI were prospectively enrolled. High-sensitive troponin I (TNIH) was measured at admission (0 h) and after 30 minutes (30 m), 1 h, and 3 hours (3 h). We externally validated the TNIH 0 h/1 h algorithm ad modum Boeddinghaus in Danish patients. Moreover, we applied the algorithm using the second TNIH measurement at 30 m instead of 1 h. We enrolled 1003 patients: median (Q1-Q3) age 64 (52-74) years, 42% female, and 23% with previous MI. Myocardial infarction was the final diagnosis in 9% of patients. Median (Q1-Q3) times from admission to 30 m and 1 h blood draw were 35 min (30-37 min) and 67 min (62-75 min), respectively. Using the 0 h and 1 h results, 468 (47%) patients were assigned to rule-out, 104 (10%) to rule-in, and 431 (43%) to the observational zone. This resulted in a negative predictive value of 100% (95% confidence interval: 99.2-100%), sensitivity of 100% (95.9-100%), positive predictive value of 79.8 (70.8-87.0%), and specificity of 97.7% (96.5-98.6%). The diagnostic performance after 30 m was similar. The TNIH 0 h/1 h algorithm ad modum Boeddinghaus performed excellently for rule-out of MI in a Danish cohort. The Boeddinghaus algorithm also performed excellently after only 30 m. NCT03634384. Rapid Use of High-Sensitive Cardiac Troponin I for Ruling-in and Ruling-out Acute Myocardial Infarction (RACING-MI), https://clinicaltrials.gov/ct2/show/NCT03634384.


Prevalence of Chronic Hepatitis B and C Infection in Mongolian Immigrants in the Washington, District of Columbia, Metropolitan Area, 2016-2017.
Mongolia has the highest liver cancer incidence in the world. Hepatocellular carcinoma is the most prevalent primary liver cancer, and the most common risk factors are hepatitis B virus (HBV) or hepatitis C virus (HCV) infection. Although viral hepatitis occurs mostly in the developing world, migration of people from high prevalence countries contributes to the health outcomes of the United States. Data on Mongolian Americans is limited. The objective of this study was to estimate HBV and HCV infection prevalence among Mongolia-born immigrants living in the Washington, District of Columbia, metropolitan area. We tested Mongolia-born immigrants for chronic hepatitis at community-based screening events from 2016 to 2017. Descriptive statistics were generated to describe the screening results. Bivariate analysis was conducted to examine the relationship between hepatitis prevalence and sociodemographic characteristics. Of 634 participants, most did not speak English primarily, were uninsured, and did not have a regular primary care provider. Eighty-two participants (12.9%) had chronic HBV or HCV infection after accounting for HBV and HCV co-infection. Thirty-nine (6.2%) were chronically infected with HBV, and 233 (36.8%) were susceptible to HBV. Sixty-three (9.9%) participants were positive for HCV exposure, and 45 (7.1%) had confirmed chronic HCV infection. While no sociodemographic characteristics were associated with HBV infection, age and primary spoken language (Mongolian) were significantly associated with HCV exposure. Foreign-born immigrants such as Mongolian Americans have a high prevalence of chronic viral hepatitis infection. Targeted screening, vaccination, and treatment programs can help decrease immigrant risk for developing hepatocellular carcinoma.


Roles of zinc-fingers and homeoboxes 1 during the proliferation, migration, and invasion of glioblastoma cells.
Zinc-fingers and homeoboxes 1 (ZHX1) is a nuclear transcription repressor and known to be involved in cell differentiation and tumorigenesis. However, the pathophysiological roles of ZHX1 have not been characterized in glioblastoma. We examined ZHX1 expression in glioblastoma patients' tissues and analyzed overall survival of the patients based on expression level of ZHX1. We also examined the effects of ZHX1 on proliferation and motility of glioblastoma cells. In silico analysis and immunohistochemical studies showed that the messenger RNA and protein expressions of ZHX1 were higher in the tissues of glioblastoma patients than in normal brain tissues, and that its overexpression was associated with reduced survival. In vitro, the downregulation of ZHX1 decreased the proliferation, migration, and invasion of glioblastoma cells, whereas its upregulation had the opposite effects. In addition, we showed ZHX1 could contribute to glioblastoma progression via the regulations of TWIST1 and SNAI2. Taken together, this study demonstrates that ZHX1 plays crucial roles in the progression of glioblastoma, and its findings suggest that ZHX1 be viewed as a potential prognostic maker and therapeutic target of glioblastoma.


Sexual aggression in the great apes.
Species-typical frequencies of copulation during the menstrual cycle differ among common chimpanzee, orang-utan, and gorilla, but all three species exhibit a midcycle enhancement associated with estrus. Thus, in the natural habitat, chimpanzees mate for 10-14 days, orang-utans for 5-6 days, and gorillas for 2-3 days. In traditional laboratory pair-tests, however, conducted in a single cage with both animals freely accessible to each other, all three species of great apes copulate more frequently than the species-typical pattern. In all three species, moreover, the increased copulation appears to result from increased male sexual initiative (aggression), male dominance over females, and the inability of the female to avoid or escape from the male within the limited spatial conditions of the free-access test. This interpretation is supported by studies using restricted-access tests in which females control sexual access. These data suggest that male sexual aggression in our closest biological affiliates commonly occurs when females are rendered vulnerable to the male by the absence of the normal social constraints and spatial prerogatives typical of the natural habitat. The possible implications of this interpretation for a biological perspective on human sexual aggression are considered.


Results of API-AI based regimen in osteosarcoma adult patients included in the French OS2006/Sarcome-09 study.
In the OS2006 study, patients younger than 18 years were treated with a methotrexate-based regimen (MTX), patients older than 25 years with a doxorubicin-cisplatin-ifosfamide-based regimen (API-AI), whereas patients aged 18-25 years received either API-AI or MTX. We herein report the prespecified subgroup analysis of the outcome of 106 patients treated with API-AI. Preoperative chemotherapy combined three doxorubicin-ifosfamide-cisplatin (API) and two doxorubicin-ifosfamide (AI) courses. Postoperative chemotherapy was assigned by risk group: localised patients with a good histological response (<10% viable cells) received two AI and two cisplatin-ifosfamide (PI) courses; patients with synchronous metastases, poor histological response or unresectable primary received five cycles of etoposide-ifosfamide (EI). Of the 106 patients, 61 were randomised to receive or not zoledronate. Median age was 30 years (range 18-67), 66 (62%) patients were >25 years. The primary tumours were axial in 28 patients (26%), and 28 (26%) presented with metastases. Ninety-six patients (91%) had surgery, conservative in 82 (85%); 36 patients (38%, 95% CI 28-48%) were good responders. Toxicity was manageable, with no significant difference in severe acute toxicity between patients aged >25 years and those younger. With a median follow-up of 4.8 years, the 5-year event-free survival and overall survival rates were 46% (95% CI 36-56) and 57% (95% CI 47-67), respectively. The primary tumour size and initial metastases correlated with a higher risk of event. In these 106 osteosarcoma adult patients, API-AI proved feasible with no excess of toxicity, and favourable activity despite poor-prognosis factors.


[Respirators in intensive care medicine. Fundamentals].
Microprocessor-controlled intensive care ventilators combine controls of pressure, flow, volume, and timing to generate various breathing modes and differentiated breathing patterns that will meet the respiratory needs of the patient. This is essential when respirator-supported ventilation is performed. Graphic representation of ventilatory parameters is another important feature, facilitating subtle adjustments. The future may bring even more desirable options to improve monitoring of respiratory mechanics and make management easier. Modern ventilators differ less in technical features than do the accessories with different options. Most of these options are costly without any corresponding benefit in terms of treatment or diagnosis; nevertheless, future upgrading possibilities should be borne in mind when hardware is purchased. There is no ideal ventilator, and the success of respiratory treatment will therefore continue to be dependent on the patient's underlying disease and the therapist's level of training and experience rather than on the choice of respirator.


[Effect of antibiotic therapy in the mother on the colonization of the newborn by enterobacteriaceae (author's transl)].
Two studies were undertaken to determine the effect of antibiotic therapy in the mother on the enterobacteriaceae of the newborn's fecal flora. In the first, mothers were given tetracycline after delivery. Although the effect on the maternal flora was important there was no noticeable effect on the enterobacteriaceae of the newborn although the organisms were predominantly susceptible. In the second, mothers were given ampicillin before delivery and resistant enterobacteriaceae were predominant in all the newborns. In the controls born to untreated mothers susceptible organism still predominate. Antibiotic treatment of the mother has an important effect on the newborn's flora if the treatment is given before delivery.


Extracellular Protein Microarray Technology for High Throughput Detection of Low Affinity Receptor-Ligand Interactions.
Secreted factors, membrane-tethered receptors, and their interacting partners are main regulators of cellular communication and initiation of signaling cascades during homeostasis and disease, and as such represent prime therapeutic targets. Despite their relevance, these interaction networks remain significantly underrepresented in current databases; therefore, most extracellular proteins have no documented binding partner. This discrepancy is primarily due to the challenges associated with the study of the extracellular proteins, including expression of functional proteins, and the weak, low affinity, protein interactions often established between cell surface receptors. The purpose of this method is to describe the printing of a library of extracellular proteins in a microarray format for screening of protein-protein interactions. To enable detection of weak interactions, a method based on multimerization of the query protein under study is described. Coupled to this microbead-based multimerization approach for increased multivalency, the protein microarray allows robust detection of transient protein-protein interactions in high throughput. This method offers a rapid and low sample consuming-approach for identification of new interactions applicable to any extracellular protein. Protein microarray printing and screening protocol are described. This technology will be useful for investigators seeking a robust method for discovery of protein interactions in the extracellular space.


Localization of the alpha 3 (V) chain of type V collagen in human skin.
Serum from goats immunized with human type V collagen chains that were cut out of polyacrylamide gels contained an antibody that recognized only type V collagen in an enzyme-linked immunoabsorbent assay and did not label laminin, fibronectin, or types I and IV collagen. Western blot analysis of the antibody showed that its determinant was the alpha 3 (V) chain of type V collagen. Indirect immunofluorescent staining of intact human skin with the antibody produced staining of the dermal blood vessels but not of the dermal-epidermal junction (DEJ). In contrast, both the dermal blood vessels and the DEJ were labeled by the antibody if the skin substrate was first split through the lamina lucida region of the DEJ by incubation in 1 M NaCl solution. Indirect immunoelectron microscopy confirmed the staining pattern found by immunofluorescence and defined the ultrastructural localization of type V collagen in skin. Type V collagen is localized within the DEJ to the lamina lucida region and polar aspects of the basal cell keratinocyte plasma membrane.


Compensation of a sensory deficit inflicted upon newborn and adult animals. A behavioural study.
Somatosensory deprivation (bilateral vibrissa clipping) was performed on newborn (P1) and adult (P80) rats and, on 10 successive days starting on day 81, the effect of sensory deprivation was tested in a rectangular maze versus controls. The maze performance (the time to reach the goal-box with food reward) of the P80 animals was significantly poorer than that of P1 animals. The tests repeatedly demonstrated, however, that the maze performance achieved by the P1 animals was better than that of the controls. This behavioural study clearly revealed that early sensory deprivation induced (probably cross-modal) compensatory changes in other sensory systems.


Co-located welfare advice in general practice: A realist qualitative study.
General practitioners (GPs) engage with patients about a variety of social issues distinct from direct clinical work ("non-health" issues), such as health-related benefits and debt. Co-located welfare advice services could provide support to practices but have usually been considered in terms of patient rather than practice outcomes. We aimed to develop an initial programme theory for how the provision of co-located advice supports specific practice outcomes, and to identify salient barriers and enabling factors. Twenty-four semi-structured interviews with general practice staff, advice staff and service funders in two UK urban localities were conducted between January and July 2016. Data were thematically analysed and a modified Realist Evaluation approach informed the topic guide, thematic analysis and interpretation. Two outcomes are described linked to participant accounts of the impact of such non-health work on practices: reduction of GP consultations linked to non-health issues and reduced practice time spent on non-health issues. We found that individual responses and actions influencing service awareness were key facilitators to each of the practice outcomes, including proactive engagement, communication, regular reminders and feedback between advice staff, practice managers and funders. Facilitating implementation factors were: not limiting access to GP referral, and offering booked appointments and advice on a broader range of issues responsive to local need. Key barriers included pre-existing sociocultural and organisational rules and norms largely outside of the control of service implementers, which maintained perceptions of the GP as the "go-to-location". We conclude that co-location of welfare advice services alone is unlikely to enable positive outcomes for practices and suggest several factors amenable to intervention that could enhance the potential for co-location to meet desired objectives.


Monte-Carlo simulation of noise in hard X-ray Transmission Crystal Spectrometers: identification of contributors to the background noise and shielding optimization.
Transmission crystal spectrometers (TCS) are used on many laser facilities to record hard X-ray spectra. During experiments, signal recorded on imaging plates is often degraded by a background noise. Monte-Carlo simulations made with the code GEANT4 show that this background noise is mainly generated by diffusion of MeV electrons and very hard X-rays. An experiment, carried out at LULI2000, confirmed that the use of magnets in front of the diagnostic, that bent the electron trajectories, reduces significantly this background. The new spectrometer SPECTIX (Spectromètre PETAL à Cristal en TransmIssion X), built for the LMJ/PETAL facility, will include this optimized shielding.


Effects of non-conservative changes to tyrosine 76, a key DNA binding residue of DNase I, on phosphodiester bond cleavage and DNA hydrolysis selectivity.
Non-conservative changes, consisting of Y76E, Y76L, Y76Q and Y76W, have been made to tyrosine 76, one of the key DNA binding residues in DNase I. Normally Y76 inserts into the minor groove of DNA and makes an unusual, hydrophobic, stacking interaction with one of the sugars. All four mutants bind to DNA more tightly than the wild type, but cut it more slowly as assessed by Kunitz assays. This gives a rather small decrease in the specificity constants (Vmax/K(m)) for the hydrolysis of DNA, which is roughly paralleled by the loss of activity towards the non-DNA small chromophoric substrate, thymidine-3',5'-di(p-nitrophenyl)phosphate. These non-conservative mutants, therefore, show different behaviour to Y76A and Y76G, studied previously [Doherty A.J., Worrall A.F. and Connolly B.A. (1995) J: Mol. Biol., 251, 366-377]. These two mutants both bind to and cut DNA poorly, resulting in large decreases in Vmax/K(m) values. However, they showed little reduction in rates with the chromophoric substrate. It is likely that the altered side chains in the non-conservative mutants are still able to interact productively with the DNA and contribute to the observed DNA distortion that is essential for efficient catalysis. However, these mutations disrupt the active site, most probably by interference with the hydrogen bonded Y76-E78-H134 triad. H134 is a critical hydrolytic residue of DNase I that is essential for catalysis. The DNA cleavage selectivity of the Y76E, Y76L, Y76Q and Y76W mutants were little altered as compared with the wild-type enzyme as measured using the cutting patterns of a 160 base-pair Escherichia coli Tyr T promoter DNA fragment. This confirms earlier observations, with Y76F, Y76A and Y76G, that showed that this tyrosine has little role in DNA cleavage specificity.


Enthalpic and entropic stages in alpha-helical peptide unfolding, from laser T-jump/UV Raman spectroscopy.
The alpha-helix is a ubiquitous structural element in proteins, and a number of studies have addressed the mechanism of helix formation and melting in simple peptides. However, fundamental issues remain to be resolved, particularly the temperature (T) dependence of the rate. In this work, we report application of a novel kHz repetition rate solid-state tunable NIR (pump) and deep UV Raman (probe) laser system to study the dynamics of helix unfolding in Ac-GSPEA3KA4KA4-CO-D-Arg-CONH2, a peptide designed for helix stabilization in aqueous solution. Its T-dependent UV resonance Raman (UVRR) spectra, excited at 197 nm for optimal enhancement of amide vibrations, were decomposed into variable contributions from helix and coil spectra. The helix fractions derived from the UVRR spectra and from far UV CD spectra were coincident at low T but deviated increasingly at high T, the UVRR curve giving higher helix content. This difference is consistent with the greater sensitivity of UVRR spectra to local conformation than CD. After a laser-induced T-jump, the UVRR-determined helix fractions defined monoexponential decays, with time-constants of approximately 120 ns, independent of the final T (Tf = 18-61 degrees C), provided the initial T (Ti) was held constant (6 degrees C). However, there was also a prompt loss of helicity, whose amplitude increased with increasing Tf, thereby defining an initial enthalpic phase, distinct from the subsequent entropic phase. These phases are attributed to disruption of H-bonds followed by reorientation of peptide links, as the chain is extended. When Ti was raised in parallel with Tf (10 degrees C T-jumps), the prompt phase merged into an accelerating slow phase, an effect attributable to the shifting distribution of initial helix lengths. Even greater acceleration with rising Ti has been reported in T-jump experiments monitored by IR and fluorescence spectroscopies. This difference is attributable to the longer range character of these probes, whose responses are therefore more strongly weighted toward the H-bond-breaking enthalpic process.


A Prospective Study Comparing Adolescent and Post-Adolescent Periods Regarding Effects of Activator Appliance in Patients with Class II Mandibular Retrognathia by Using 3dMDface Analysis and Cephalometry.
BACKGROUND The purpose of this prospective study was to compare adolescent and post-adolescent growth periods regarding the effectiveness of conventional activator appliance in patients with Class II mandibular retrognathia by using lateral cephalometric radiographs and three-dimensional photogrammetry (3dMDface). MATERIAL AND METHODS We enrolled 2 groups: 15 patients in the adolescent growth period and 17 patients in the post-adolescent growth period. All patients had Class II anomaly with mandibular retrognathia and were treated with conventional activator appliances. Lateral cephalometric radiographs and three-dimensional photogrammetric views were obtained at the beginning and end of the activator treatment of Class II patients. Maxillomandibular discrepancy, mandibular protrusion and lengths, convexity angles, facial heights, and dental measurements were evaluated cephalometrically. Projections of the lips and the chin and volumetric measurements of the lip and the mandibular area were assessed using three-dimensional photogrammetry. RESULTS Conventional activator therapy resulted in similar effects in both growth periods regarding improvements in the mandibular sagittal growth and maxillomandibular relationship (ANB° and the SNB° angles). Mandibular effective length was increased (Co-Gn length) and the maxillary horizontal growth was restricted (decreased SNA° angle) in both groups following the treatment. Treatment duration was significantly longer in the post-adolescent group. Increases in the projections of menton, pogonion, and sublabial points were observed in the three-dimensional photogrammetric views. Total lip volume was reduced while the mandibular volume was significantly increased in both groups. Lower gonial angle showed a greater increase in the post-adolescent group. CONCLUSIONS Correction of Class II anomaly with mandibular retrognathia was achieved with a combination of dental and skeletal changes in both growth periods. Conventional activator therapy may be an alternative treatment approach in the late growth period as it led to significant skeletal and dental changes.


Double-Headed 2'-Deoxynucleotides That Hybridize to DNA and RNA Targets via Normal and Reverse Watson-Crick Base Pairs.
Through the use of modified nucleotides, synthetic nucleic acids have found several fields of application within biotechnology and in the pharmaceutical industry. We have previously introduced nucleotides with an additional functional nucleobase linked to C2' of arabinonucleotides (BX). These double-headed nucleotides fit neatly into DNA·DNA duplexes, where they can replace the corresponding natural dinucleotides and thus condense the molecular information. Here, we introduce a 2'-deoxy version of the BX design with inversion of the C2' stereochemistry (dSBX) with the aim of obtaining improved RNA recognition. Specifically, dSBX analogues with cytosine or isocytosine attached to C2' of 2'-deoxyuridine (dSUC and dSUiC) were synthesized and evaluated in duplexes. Whereas the dSBX design did not outperform the BX design in terms of mimicking dinucleotides in nucleic acid duplexes, it was able to engage in reverse Watson-Crick pairing using its 2'-base. This was evident from the ability of the dSUC cytosine to form stable mis-matching base pairs with opposite cytosines identified as hemiprotonated C·C+ pairs. Furthermore, specific base-pairing with guanine was only observed for the isocytosine-bearing dSUiC monomer. Very stable duplexes were obtained with dSUC/iC monomers in each strand indicating that fully modified double-headed nucleic acid sequences could be based on the dSBX design.


Big roles for small GTPases in the control of directed cell movement.
Small GTPases are involved in the control of diverse cellular behaviours, including cellular growth, differentiation and motility. In addition, recent studies have revealed new roles for small GTPases in the regulation of eukaryotic chemotaxis. Efficient chemotaxis results from co-ordinated chemoattractant gradient sensing, cell polarization and cellular motility, and accumulating data suggest that small GTPase signalling plays a central role in each of these processes as well as in signal relay. The present review summarizes these recent findings, which shed light on the molecular mechanisms by which small GTPases control directed cell migration.


Feature selection and transformation by machine learning reduce variable numbers and improve prediction for heart failure readmission or death.
The prediction of readmission or death after a hospital discharge for heart failure (HF) remains a major challenge. Modern healthcare systems, electronic health records, and machine learning (ML) techniques allow us to mine data to select the most significant variables (allowing for reduction in the number of variables) without compromising the performance of models used for prediction of readmission and death. Moreover, ML methods based on transformation of variables may potentially further improve the performance. To use ML techniques to determine the most relevant and also transform variables for the prediction of 30-day readmission or death in HF patients. We identified all Western Australian patients aged 65 years and above admitted for HF between 2003-2008 in linked administrative data. We evaluated variables associated with HF readmission or death using standard statistical and ML based selection techniques. We also tested the new variables produced by transformation of the original variables. We developed multi-layer perceptron prediction models and compared their predictive performance using metrics such as Area Under the receiver operating characteristic Curve (AUC), sensitivity and specificity. Following hospital discharge, the proportion of 30-day readmissions or death was 23.7% in our cohort of 10,757 HF patients. The prediction model developed by us using a smaller set of variables (n = 8) had comparable performance (AUC 0.62) to the traditional model (n = 47, AUC 0.62). Transformation of the original 47 variables further improved (p<0.001) the performance of the predictive model (AUC 0.66). A small set of variables selected using ML matched the performance of the model that used the full set of 47 variables for predicting 30-day readmission or death in HF patients. Model performance can be further significantly improved by transforming the original variables using ML methods.


Reaction chemistry of complexes containing Pt--H, Pt--SH, or Pt--S fragments: from their apparent simplicity to the maze of reactions underlying their interconversion.
The relevance of platinum in the reaction of thiophene and derivatives with homogeneous transition-metal complexes as models for hydrodesulfurization has led us to the study of the reaction chemistry of complexes containing Pt--H, Pt--SH, and Pt--S fragments. Exploration of the reactions triggered by addition of controlled amounts of Na2S or NaSH to [Pt2(H)2(mu-H)(dppp)2]ClO4 (1) has provided evidence of the formation of complexes [Pt2(mu-H)(mu-S)(dppp)2]ClO4 (2), [Pt(H)(SH)(dppp)] (3), [Pt2(mu-S)2(dppp)2] (4), [Pt2(mu-S)(dppp)2] (5) and [Pt(SH)2(dppp)], in which dppp denotes 1,3-bis(diphenylphosphanyl)propane. Consequently, complexes 1, 2, and 5 as well as the already reported 3, 4, and [Pt(SH)2(dppp)] have been obtained and fully characterized spectroscopically. Also the crystal structures of 1 and 2 have been solved. Complexes 1-5 constitute the main framework of the network of reactions that account for the evolution of 1 under various experimental conditions as shown in Scheme 1. Apparently, this network has complexes 2 and 4 as dead-ends. However, their reciprocal interconversion by means of the replacement of one bridging hydride or sulfide ligand in the respective {Pt(mu-H)(mu-S)Pt} and {Pt(mu-S)2Pt} cores enables the closure of the reaction cycle involving complexes 1-5. Theoretical calculations support the existence of the undetected intermediates proposed for conversion from 1 to 2 and from 3 to 2 and also account for the fluxional behavior of 1 in solution. The intermediates proposed are consistent with the experimental results obtained in comparable reactions carried out with labeled reagents, which have provided evidence that complex 1 is the source of the hydride ligands in complexes 2 and 3. Overall, our results show the strong dependence on the experimental conditions for the formation of complexes 1-5 as well as for their further conversion in solution.


Aperiodic Copolymers.
Current polymer terminology only describes very simple copolymer structures such as block, graft, alternating periodic, or statistical copolymers. This restricted vocabulary implies that copolymers exhibit either segregated (i.e., block and graft), regular (i.e., alternating and periodic), or uncontrolled (i.e., statistical or random) comonomer sequence distributions. This standard classification does not include many new types of sequence-controlled copolymers that have been reported in recent years. In this context, the present viewpoint describes a new category of copolymers: aperiodic copolymers. Such structures can be defined as copolymers in which monomer sequence distribution is not regular but follows the same arrangement in all chains. The term aperiodic can be used to describe encoded comonomer sequences in monodisperse sequence-defined copolymers but also the block sequence of some multiblock copolymers. These new types of copolymers open up very interesting perspectives for the design of complex materials. Some recent relevant literature on the topic is discussed herein.


S-sulfocysteine synthase function in sensing chloroplast redox status.
The minor chloroplastic O-acetylserine(thiol)lyase isoform encoded by the CS26 gene in Arabidopsis thaliana has been described as an S-sulfocysteine synthase enzyme that plays an important role in chloroplast function. This enzyme is located in the thylakoid lumen, and its S-sulfocysteine activity is essential for the proper photosynthetic performance of the chloroplast under long-day growth conditions. Based on the present knowledge of this enzyme, we suggest that S-sulfocysteine synthase functions as a protein sensor to detect the accumulation of thiosulfate as a result of the inadequate detoxification of reactive oxygen species generated under conditions of excess light to produce the S-sulfocysteine molecule that triggers protection mechanisms of the photosynthetic apparatus.


Ferrokinetic studies in acute myocardial infarction.
Serum iron levels were determined in 16 patients with AMI at different days following the event and in five patients either treated with steroids or suffering from diseases acting as stress factors. Patients with AMI showed a marked decrease in serum iron concentrations, the lowest value being recorded at day 3 after the event; serum iron returned to normal level at day 12. These alterations in iron concentration were not accompanied by changes in the 24 hour urine excretion of iron. On the other hand, a significant shortening of the half-time 59Fe plasma clearance and an early increase in 59Fe incorporation into the red blood cells were found immediately after the event. These values returned to normal in all but one patient, who had in addition polycythemia. In the five patients comprising the control group, serum iron, iron excretion in urine, and ferrokinetics were within the normal limits at all times. Since in AMI patients the 11-OHCS values were found to be significantly higher on the day following the infarction than on day 15 after the event, it is suggested that the decrease in iron concentration in these patients may be connected with changes in plasma 11-OHCS levels.


Polyoxometalate-decorated nanoparticles.
Polyoxometalate cluster anions (POMs) control formation and morphology, and serve as protecting ligands, for structurally and compositionally diverse nanostructures. While numerous examples of POM-protected metal(0) nanoparticle syntheses and reactions can now be found in the literature, the use of POMs to prepare nano-scale analogs of binary inorganic materials, such as metal-oxides, sulfides and halides, is a relatively recent development. The first part of this critical review summarizes the use of POMs as protecting ligands for metal(0) nanoparticles, as well as their use as templates for the preparation of new inorganic materials. Here, key findings that reveal general trends are given additional emphasis. In the second part of the review, new information concerning the structure of POM-protected metal(0) nanoparticles is systematically developed. This information, obtained by the combined use of cryogenic transmission microscopy (cryo-TEM) and UV-vis spectroscopy, provides a new perspective on the formation and structure of POM-decorated nanoparticles, and on the rational design of catalytic and other functional POM-based nano-assemblies.