Efficacy of pulmonary surfactant combined with high-dose ambroxol hydrochloride in the treatment of neonatal respiratory distress syndrome.
Clinical efficacy of pulmonary surfactant combined with high-dose ambroxol hydrochloride in the treatment of neonatal respiratory distress syndrome (NRDS) was investigated. One hundred child patients with NRDS in Linyi Central Hospital were collected according to the diagnostic criteria for RDS in the Pediatrics, and randomly divided into the treatment group (n=50) and the control group (n=50) based on different therapeutic methods. Patients in the control group were treated with basic treatment and high-dose ambroxol hydrochloride injection, while those in the treatment group were additionally administered with pulmonary surfactant Curosurf based on conventional therapy in the control group. The chest X-rays were collected before the treatment and at 12 h after the drug administration, the degree of respiratory distress in child patients was observed and evaluated via Silverman grading, and changes in blood gas indexes were recorded before treatment and at 2, 6 and 12 h after the drug administration. The chest X-ray grade, Silverman grade and blood gas analysis results had no differences between the two groups before the treatment (P>0.05). In the treatment group, partial pressure of oxygen (PaO2) and PH were increased and partial pressure of carbon dioxide (PaCO2) was decreased compared with those in the control group at 2, 6 and 12 h after the drug administration (P<0.05). At 12 h after the drug administration, chest X-ray grade and Silverman grade in both groups were improved, which were significantly superior in the treatment group to those in the control group (P<0.01). Moreover, the efficacy in the treatment group was remarkably better than that in the control group at 12 h after drug administration (P<0.01). Pulmonary surfactant combined with high-dose ambroxol hydrochloride has definite efficacy in the treatment of NRDS, which can significantly improve the pulmonary infection, respiratory distress and blood gas indexes of child patients.


Graphene derivatives in bioplastic: A comprehensive review of properties and future perspectives.
The research and technological advancements observed in the latest years in the nanotechnology field translated into significant application developments in various areas. This is particularly true for the renewable polymers area, where the nano-reinforcement of biobased materials leads to an increase in their technique and economic competitiveness. The efforts were predominantly focused on materials development and energy consumption minimization. However, attention must also be given to the widespread commercialization and the full characterization of any particular potential toxicological and environmental impact. Some of the most important nanomaterials used in recent years as fillers in the bioplastic industry are graphene-based materials (GBMs). GBMs have high surface area and biocompatibility and have interesting characterizations such as strangeness and flexibility. In this paper, the current state of the art for these GBMs in the bioplastics area, their challenges, and the strategies to overcome them are analyzed.


Fish Pluripotent Stem-Like Cell Line Induced by Small-Molecule Compounds From Caudal Fin and its Developmental Potentiality.
The technique of induced pluripotent stem cells has significant application value in breeding and preserving the genetic integrity of fish species. However, it is still unclear whether the chemically induced pluripotent stem cells can be induced from non-mammalian cells or not. In this article, we first verify that fibroblasts of fish can be chemically reprogrammed into pluripotent stem cells. These induced pluripotent stem-like cells possess features of colony morphology, expression of pluripotent marker genes, formation of embryoid bodies, teratoma formation, and the potential to differentiate into germ cell-like cells in vitro. Our findings will offer a new way to generate induced pluripotent stem cells in teleost fish and a unique opportunity to breed commercial fish and even save endangered fish species.


Deflections from two types of human surrogates in oblique side impacts.
The objective of the study was to obtain time-dependent thoracic and abdominal deflections of an anthropomorphic test device, the WorldSID dummy, in oblique impact using sled tests, and compare with post mortem human subject (PMHS) data. To simulate the oblique loading vector, the load wall was configured such that the thorax and abdominal plates were offset by twenty or thirty degrees. Deflections were obtained from a chestband placed at the middle thoracic level and five internal deflection transducers. Data were compared from the chestband and the transducer located at the same level of the thorax. In addition, data were compared with deflections from similar PMHS tests obtained using chestbands placed at the level of the axilla, xyphoid process, and tenth rib, representing the upper thorax, middle thorax, and abdominal region of the biological specimen. Peak deflections ranged from 30 to 85 mm in the dummy tests. Peak deflections ranged from 60 to 115 mm in PMHS. Under both obliquities, dummy deflection-time histories at the location along the chestband in close proximity to the internal deflection transducer demonstrated similar profiles. However, the peak deflection magnitudes from the chestband were approximately 20 mm greater than those from the internal transducer. Acknowledging that the chestband measures external deflections in contrast to the transducer which records internal ribcage deformations, peak deflections match from the two sensors. Deflection time histories were also similar between the dummy and PMHS in terms of morphology, although thoracic deflection magnitudes from the dummy matched more closely with PMHS than abdominal deflection magnitudes. The dummy deformed in such a way that peak deflections occurred along the lateral vector. This was in contrast to PMHS tests wherein maximum deflections occurred along the antero-lateral direction, suggesting differing deformation responses in the two models. In addition, peak deflections occurred earlier in the dummy than in PMHS. These preliminary results are valuable in future crashworthiness studies.


Evaluation of the anxiolytic effect of Nepeta persica Boiss. in mice.
The aim of the present study was to evaluate the anxiolytic effects of hydroalcoholic extract (HE) of Nepeta persica Boiss. (Lamiaceae) on the elevated plus-maze (EPM) model of anxiety. The extract of arial parts of the plant was administered intraperitoneally to male NMRI mice, at various doses, 30 min before behavioural evaluation. The HE extract of N. persica at the dose of 50 mg kg(-1) significantly increased the percentage of time spent and percentage of arm entries in the open arms of the EPM. This dose of plant extract affected neither animal's locomotor activity nor ketamine-induced sleeping time. The 50 mg kg(-1) dose of the plant extract seemed to be the optimal dose in producing the anxiolytic effects, lower or higher doses of the plant produce either sedative or stimulant effects. At 100 mg kg(-1), the plant extract increased the locomotor activity. These results suggested that the extract of N. persica at dose of 50 mg kg(-1) possess anxiolytic effect with less sedative and hypnotic effects than that of diazepam and causes a non-specific stimulation at 100 mg kg(-1).


The associations of parental COVID-19 related worries, lifestyles, and insomnia with child insomnia during the COVID-19 outbreak.
The impacts of the Coronavirus Disease 2019 (COVID-19) pandemic on sleep health have been studied extensively. However, little is known about sleep problems within the family system during the pandemic. This study aimed to examine the influence of the COVID-19 pandemic on insomnia in both adults and children, and to explore whether parental COVID-19 related worries, lifestyles, and insomnia were associated with child insomnia. A total of 1355 parent-child dyads (39.2% fathers, mean age 38.37 years, SD = 5.34; 52.7% boys, mean age 12.47 years, SD = 1.67) were recruited from Jiangxi province in China from 4 to 18 February 2020. Data on insomnia, COVID-19 related worries, physical activity, and screen time were collected using online questionnaires. Path analysis showed that COVID-19 related worries and screen time were positively associated with insomnia in both parents and children; while children's physical activity was negatively related to children's insomnia. Parents' insomnia, COVID-19 related worries, physical activity, and screen time were positively associated with children's insomnia, COVID-19 related worries, physical activity, and screen time, respectively. Bootstrap tests showed that parents' worries were positively associated with children's insomnia via parents' insomnia and children's worries; parents' physical activity was negatively associated with children's insomnia via children's physical activity, parents' screen time was positively associated with children's insomnia via parents' insomnia and children's screen time. Both parental and child sleep are affected by the pandemic. Parental insomnia, stress reaction, and lifestyles contribute to child insomnia. Child sleep health may be maintained or improved by family bonds, home exercise, and sleep schedules.


Growth and Raman spectra of single-crystal trilayer graphene with different stacking orientations.
Understanding the growth mechanism of graphene layers in chemical vapor deposition (CVD) and their corresponding Raman properties is technologically relevant and of importance for the application of graphene in electronic and optoelectronic devices. Here, we report CVD growth of single-crystal trilayer graphene (TLG) grains on Cu and show that lattice defects at the center of each grain persist throughout the growth, indicating that the adlayers share the same nucleation site with the upper layers and these central defects could also act as a carbon pathway for the growth of a new layer. Statistics shows that ABA, 30-30, 30-AB, and AB-30 make up the major stacking orientations in the CVD-grown TLG, with distinctive Raman 2D characteristics. Surprisingly, a high level of lattice defects results whenever a layer with a twist angle of θ = 30° is found in the multiple stacks of graphene layers.


Carcinoma of the prostate. Treating disease that has metastasized.
Common manifestations of metastatic carcinoma of the prostate are bone pain, spinal cord compression, and disseminated intravascular coagulation. Prostate-specific antigen represents a useful marker to monitor tumor progression and response to therapy. Until recently, no therapy was available to prolong survival in these patients. Now, the use of a luteinizing hormone-releasing hormone agonist (leuprolide acetate [Lupron]) plus an antiandrogen (flutamide [Eulexin]) to provide total androgen blockade has demonstrated a 25% increase in survival time.


Hypercalcemia and Lytic Bone Lesions Masquerading Inflammatory Arthritis Treated as Rheumatoid Arthritis.
Hyperparathyroidism is a complex clinical syndrome characterized by dysfunction in the metabolism of bone, calcium and phosphorus. Rheumatologic manifestations are common amongst patients with hyperparathyroidism. We report a 50-year-old woman with hypercalcemia, lytic bone lesions and inflammatory arthritis of both hands that were not resolved after parathyroidectomy. Laboratory evidence of elevated erythrocyte sedimentation rate, positive C-reactive protein (CRP) and high titers of anti-CCP and rheumatoid factor was diagnostic of rheumatoid arthritis (RA) according to European League Against Rheumatism criteria. Eventually, with the concomitant diagnoses of hyperparathyroidism and RA, she was treated with methotrexate and hydroxychloroquin. Hyperparathyroidism may present with rheumatologic manifestations, leading to an initial misdiagnosis. Furthermore, attention to this fact that hypercalcemia is not commonly associated with RA, and rather suggestive of a concomitant disorder, is crucial to the diagnosis of hyperparathyroidism in RA patients with hypercalcemia.


Double C-H bond activation of hydrocarbons by a gas phase neutral oxide cluster: the importance of spin state.
The neutral cluster V2O5 is generated and detected in the gas phase. Its reactivity toward butane is studied both experimentally and theoretically. Experimental results show clearly that neutral V2O5 can react with n-butane (C4H10) to generate V2O5H2, indicating double hydrogen atom transfer from C4H10 to V2O5 to produce C4H8. Further experimental evidence indicates that V2O5 is only partially reacted even at very high concentrations of C4H10. Density functional theory (DFT) studies show that the lowest energy triplet state of V2O5 is reactive toward C4H10, whereas the ground state singlet V2O5 is inert. Calculated results are in agreement with experimental findings, and a detailed reaction mechanism is provided. Reactions of V2O5H2 with several oxidants are also studied theoretically to find a path to regenerate V2O5. Neutral (3)V2O5 can also react with C2H6 to form V2O5H2 and C2H4, but only as a minor reaction channel; the major product is the adsorption product V2O5(C2H6).


Expression of a high molecular weight cell surface glycoprotein (LETS protein) by preimplantation mouse embryos and teratocarcinoma stem cells.
The expression of a high molecular weight cell surface glycoprotein (LETS, fibronectin) by preimplantation mouse embryos as well as cultured teratocarcinoma stem cells was detected by using indirect immunofluorescent staining. When each stage of preimplantation embryonic development was tested for the presence of LETS protein, none was observed on two-cell, four-cell, or eight-cell embryos, or on the morula or the outer cell layer (trophectoderm) of the early or late blastocyst. However, when the inner cell mass was isolated by immunosurgery, positive staining was observed. The intensity of the staining was significantly greater on the inner cell mass isolated from the expanded (day 4) blastocyst than on that from the early (day 3) blastocyst. Certain established cell lines of teratocarcinoma stem cells (embryonal carcinoma cells) also express cell surface LETS protein. "Nullipotent" (Nulli-SCC-1) as well as pluripotent (PSA 1) embryonal carcinoma cell lines have deposits of LETS protein concentrated in areas of cell-cell contact. In addition, a teratocarcinoma-derived endodermal cell line (PYS) was found to be capable of depositing LETS onto the substratum in a fibrillar network.Taken together, our results indicate that LETS protein is synthesized at a specific stage of preimplantation mouse embryonic development. In particular, they suggest that LETS protein is a product of the embryonic ectoderm, and that some types of embryonic endoderm are also capable of synthesizing this protein.


Levels of vancomycin in cerebrospinal fluid of adult patients receiving adjunctive corticosteroids to treat pneumococcal meningitis: a prospective multicenter observational study.
Evidence from a recent randomized controlled trial suggests that dexamethasone as adjunct therapy in adult pneumococcal meningitis reduces mortality and neurological sequelae. However, adding dexamethasone has the potential to reduce penetration of vancomycin into the cerebrospinal fluid (CSF). We sought to determine concentrations of vancomycin in serum and CSF of patients with suspected or proven pneumococcal meningitis receiving dexamethasone to assess the penetration of vancomycin into the CSF during steroid therapy. In an observational open multicenter study, adult patients admitted to the intensive care unit because of suspected pneumococcal meningitis received recommended treatment for pneumococcal meningitis, comprising intravenous cefotaxime (200 mg per kg of body weight per day), vancomycin (administered as continuous infusion of 60 mg per kg of body weight per day after a loading dose of 15 mg per kg of body weight), and adjunctive therapy with dexamethasone (10 mg every 6 h). Vancomycin levels in CSF were measured on day 2 or day 3 of therapy and were correlated with protein levels in CSF and vancomycin levels in serum (determined at the same time as levels in CSF). Fourteen patients were included. Thirteen had proven pneumococcal meningitis; 1 patient, initially suspected of having pneumococcal meningitis, was finally determined to have meningitis due to Neisseria meningitidis. Mean levels of vancomycin in serum and CSF were 25.2 and 7.2 mg/L, respectively, and were positively correlated (r=0.6; P=.025). A positive correlation was also found between the ratio of vancomycin in CSF to vancomycin in serum and the level of protein in CSF (r=0.66; P=.01). Appropriate concentrations of vancomycin in CSF may be obtained even when concomitant steroids are used. Dexamethasone can, therefore, be used without fear of impeding vancomycin penetration into the CSF of patients with pneumococcal meningitis, provided that vancomycin dosage is adequate. This study is registered at http://www.ClinicalTrials.gov/ (registration number NCT00162578).


Fate of a Pseudomonas savastanoi pv. savastanoi type III secretion system mutant in olive plants (Olea europaea L.).
Pseudomonas savastanoi pv. savastanoi strain NCPPB 3335 is a model bacterial pathogen for studying the molecular basis of disease production in woody hosts. We report the sequencing of the hrpS-to-hrpZ region of NCPPB 3335, which has allowed us to determine the phylogenetic position of this pathogen with respect to previously sequenced Pseudomonas syringae hrp clusters. In addition, we constructed a mutant of NCPPB 3335, termed T3, which carries a deletion from the 3' end of the hrpS gene to the 5' end of the hrpZ operon. Despite its inability to multiply in olive tissues and to induce tumor formation in woody olive plants, P. savastanoi pv. savastanoi T3 can induce knot formation on young micropropagated olive plants. However, the necrosis and formation of internal open cavities previously reported in knots induced by the wild-type strain were not observed in those induced by P. savastanoi pv. savastanoi T3. Tagging of P. savastanoi pv. savastanoi T3 with green fluorescent protein (GFP) allowed real-time monitoring of its behavior on olive plants. In olive plant tissues, the wild-type strain formed aggregates that colonized the intercellular spaces and internal cavities of the hypertrophic knots, while the mutant T3 strain showed a disorganized distribution within the parenchyma of the knot. Ultrastructural analysis of knot sections revealed the release of extensive outer membrane vesicles from the bacterial cell surface of the P. savastanoi pv. savastanoi T3 mutant, while the wild-type strain exhibited very few vesicles. This phenomenon has not been described before for any other bacterial phytopathogen during host infection.


Poliovirus strain characterization: a WHO memorandum.
Reliable laboratory techniques for the intratypic characterization of poliovirus types 1, 2, and 3 isolates have an important role in the epidemiological surveillance of poliomyelitis and in studies of the safety and efficacy of poliovirus vaccines. Of the techniques available for poliovirus strain characterization, those potentially most useful are intratypic serodifferentiation and the biochemical techniques. The value of strain-specific (absorbed) antisera for antigenic characterization of strains has been clearly established for the identification of both vaccine-like viruses and different epidemic wild strains. Single-radial-diffusion techniques appear to be promising and should be further explored. Biochemical techniques involving studies of both virus polypeptides and nucleic acids are also capable of providing valuable information for strain characterization. Biological and physico-chemical tests are generally of limited value but their application may be useful in certain circumstances.


Heavy metal pollution of lakes along the mid-lower reaches of the Yangtze River in China: intensity, sources and spatial patterns.
Lakes in the middle and lower reaches of the Yangtze River form a shallow lake group unique in the World that is becoming increasingly polluted by heavy metals. Previous studies have largely focused on individual lakes, with limited exploration of the regional pattern of heavy metal pollution of the lake group in this area. This paper explores the sources, intensity and spatial patterns of heavy metal pollution of lake sediments. A total of 45 sample lakes were selected and the concentrations of key metal elements in the sediments of each lake were measured. The cluster analysis (CA), principal component analysis (PCA) and Geo-accumulation index (I(g)) analysis permitted analysis of the source and pollution intensity of the target lakes. Results suggested a notable spatial variation amongst the sample lakes. Lakes in the upper part of the lower reach of the Yangtze River surrounded by typical urban landscapes were strongly or extremely polluted, with high concentrations of Pb, Zn, Cu and Cd in their sediments. This was attributed to large amount of untreated industrial discharges and municipal sewage produced within the lake catchments. In contrast, the heavy-metal pollution of lakes in the Taihu Delta area was notably lower due to industrial restructuring and implementation of effective environmental protection measures. Lakes along the middle reach of Yangtze River surrounded by agricultural areas were unpolluted to moderately polluted by heavy metals overall. Our results suggested that lakes in the central part of China require immediate attention and efforts should be made to implement management plans to prevent further degradation of water quality in these lakes.


Does pethidine affect the cardiovascular and sedative effects of dexmedetomidine in dogs?
To investigate pethidine's effects on sedation and cardiovascular variables in dogs premedicated with dexmedetomidine. Sixty American Society of Anesthesiologists (ASA) I dogs were presented for routine neutering. Heart rate was measured at admission. Dogs were randomly assigned to one of the five groups to decide premedication; group D5+P (dexmedetomidine 5 microg/kg plus pethidine 5 mg/kg), D10+P (dexmedetomidine 10 microg/kg plus pethidine 5 mg/kg) with three control groups, D5 (dexmedetomidine 5 microg/kg), D10 (dexmedetomidine 10 microg/kg) or P (pethidine 5 mg/kg). Heart rate was measured at 3, 5, 10 and 20 minutes after preanaesthetic medication. Simple descriptive scores for sedation were assigned after 20 minutes. Anaesthesia was induced using propofol and maintained using isoflurane in oxygen. Heart rate was recorded throughout anaesthesia. Sedation scores after preanaesthetic medication were significantly higher (P<0.001) in groups D5+P and D10+P compared with the other three groups. D5+P and D10+P groups tended to have lower heart rates in dogs at all time points after premedication compared with groups containing only pethidine or dexmedetomidine at the relevant dose. Greater sedation is achieved using combinations of dexmedetomidine and pethidine compared with each drug alone. Pethidine does not attenuate the alpha-2 adrenergic-induced bradycardia.


[Novel Scale for Long-Term Prognostication of Risk of Death and Nonfatal Cardiovascular Complications in Patients From the PROGNOSIS-IHD Registry].
To elaborate a risk score for prognostication of long-term survival of patients with chronic ischemic heart disease (CIHD) using data of the PROGNOSIS-IHD Registry. Participants of the PROGNOSIS-IHD Registry (n=641, 500 men, 141 women) were inhabitants of Moscow region consecutively admitted for planned hospitalization with diagnosis of IHD to the clinic of the Center of Preventive Medicine from 01.01.2004 to 31.12.2007. During hospitalization all patients underwent coronary angiography. Diagnosis of IHD was not confirmed in 100 of 641 patients. In 2010 vital status was determined in 551 patients (86%). Mean duration of observation was 3.9 years. Uni- and multi-factorial analysis was used for assessment of prognostic value of clinical-anamnestic and instrumental parameters. The following parameters which were included into the risk score were most significant for prediction of occurrence of a primary end point (fatal and nonfatal cardiovascular complications [CVC]): feeling of shortness of breath (relative risk [RR] 1.86 and 1 point in risk score); history of unstable IHD course (acute coronary syndrome, myocardial infarction, unstable angina) (RR 1.76 and 1 point); need in diuretics before hospitalization (RR 1.92 and 1 point); stenosis of a cardiac valve (RR 2.95 and 2 points); zones of abnormal contractility of left ventricular myocardium at echocardiography (RR 2 and 1 point). Risk of death and nonfatal CVC in patients with suspected IHD was considered very low, low, medium, and high at score values 0, 1 (RR 1.6), 2 (RR 2.4), and more or equal 3 (RR 6.1), respectively. Novel scale has high prognostic significance relative to stratification of risk of death and nonfatal CVC in patients with suspected CIHD and can be used in wide clinical practice because of its informativeness, simplicity, and accessibility.


Prevalence of Escherichia coli O-types and Shiga toxin genes in fecal samples from feedlot cattle.
While efforts to control foodborne illness associated with the Shiga toxin-producing Escherichia coli (E. coli) O157 through processes and procedures implemented at harvest facilities have been very successful, there is concern about the burden of illness associated with other Shiga toxin-producing E. coli. The U.S. Department of Agriculture Food Safety and Inspection Service announced plans to classify an additional six non-O157 Shiga toxin-producing E. coli as adulterants. Little is known about the prevalence and distribution of these E. coli in the animal production environment. An investigation of the prevalence of O157 and the six major non-O157 E. coli serogroups was conducted in 21 feedlots over the period July 2011 to October 2011. Individual fecal swabs were collected from cattle approximately 60 days after their arrival in the feedlot and were pooled for evaluation using a polymerase chain reaction assay to identify the presence of seven E. coli O-types (O157, O45, O103, O121, O145, O26, and O111) and four virulence genes (stx1, stx2, eaeA, and ehxA). Overall, 1145 fecal pools were evaluated, with 506 (44.2%) being positive for one or more of the E. coli O-serogroups. The pool prevalences for E. coli O157, O45, O26, O103, O121, O145, and O111 were 19.7%, 13.8%, 9.9%, 9.3%, 5.5%, 1.1%, and 0.5%, respectively. Nearly all pools were positive for ehxA (99.7%) or stx2 (98.6%). The pool level prevalence for stx1 and eae was 65.5% and 69.3%, respectively. Pools that were positive for one or more of the other E. coli O-serogroups were 1.37 times more likely to be positive for E. coli O157. Conversely, pools that were positive for E. coli O157 were 1.43 times more likely to be positive for at least one of the other E. coli O-serogroups evaluated. These data will be useful to understand the expected prevalence of potential Shiga toxin-producing E. coli in cattle feedlots.


Reaction Center Excitation in Photosystem II: From Multiscale Modeling to Functional Principles.
Oxygenic photosynthesis is the fundamental energy-converting process that utilizes sunlight to generate molecular oxygen and the organic compounds that sustain life. Protein-pigment complexes harvest light and transfer excitation energy to specialized pigment assemblies, reaction centers (RC), where electron transfer cascades are initiated. A molecular-level understanding of the primary events is indispensable for elucidating the principles of natural photosynthesis and enabling development of bioinspired technologies. The primary enzyme in oxygenic photosynthesis is Photosystem II (PSII), a membrane-embedded multisubunit complex, that catalyzes the light-driven oxidation of water. The RC of PSII consists of four chlorophyll a and two pheophytin a pigments symmetrically arranged along two core polypeptides; only one branch participates in electron transfer. Despite decades of research, fundamental questions remain, including the origin of this functional asymmetry, the nature of primary charge-transfer states and the identity of the initial electron donor, the origin of the capability of PSII to enact charge separation with far-red photons, i.e., beyond the "red limit" where individual chlorophylls absorb, and the role of protein conformational dynamics in modulating charge-separation pathways.In this Account, we highlight developments in quantum-chemistry based excited-state computations for multipigment assemblies and the refinement of protocols for computing protein-induced electrochromic shifts and charge-transfer excitations calibrated with modern local correlation coupled cluster methods. We emphasize the importance of multiscale atomistic quantum-mechanics/molecular-mechanics and large-scale molecular dynamics simulations, which enabled direct and accurate modeling of primary processes in RC excitation at the quantum mechanical level.Our findings show how differential protein electrostatics enable spectral tuning of RC pigments and generate functional asymmetry in PSII. A chlorophyll pigment on the active branch (ChlD1) has the lowest site energy in PSII and is the primary electron donor. The complete absence of low-lying charge-transfer states within the central pair of chlorophylls excludes a long-held assumption about the initial charge separation. Instead, we identify two primary charge separation pathways, both with the same pheophytin acceptor (PheoD1): a fast pathway with ChlD1 as the primary electron donor (short-range charge-separation) and a slow pathway with PD1PD2 as the initial donor (long-range charge separation). The low-energy spectrum is dominated by two states with significant charge-transfer character, ChlD1δ+PheoD1δ- and PD1δ+PheoD1δ-. The conformational dynamics of PSII allows these charge-transfer states to span wide energy ranges, pushing oxygenic photosynthesis beyond the "red limit". These results provide a quantum mechanical picture of the primary events in the RC of oxygenic photosynthesis, forming a solid basis for interpreting experimental observations and for extending photosynthesis research in new directions.


Epidemiological survey on the relationship between different iodine intakes and the prevalence of hyperthyroidism.
To investigate the effect of different levels of iodine intake on the prevalence of hyperthyroidism and the impact of universal salt iodization on the incidence of hyperthyroidism. A comparative cross-sectional and longitudinal survey was conducted in three areas with borderline iodine deficiency, mild iodine excess (previously mild iodine deficiency) and severe iodine excess. Universal salt iodization had been introduced 3 years previously except in the area with borderline iodine deficiency. In total 16 287 inhabitants from three areas answered a questionnaire concerning the history of thyroid disease. Among them 3761 unselected subjects received further investigations including thyroid function, thyroid autoantibodies, thyroid ultrasonography and urinary iodine excretion. Among areas with median urinary iodine excretion of 103 microg/l, 375 microg/l and 615 microg/l (P<0.05), the prevalence of hyperthyroidism did not differ significantly (1.6%, 2% and 1.2%). The prevalence of subclinical hyperthyroidism was higher in areas with borderline iodine deficiency and mild iodine excess than in the area with severe excess iodine intake (3.7%, 3.9% and 1.1%, P<0.001). The prevalence of Graves' disease and its proportion in hyperthyroidism did not differ among areas. The incidence of hyperthyroidism did not significantly increase after the introduction of universal salt iodization. Different iodine intakes under a certain range do not affect the prevalence and type of hyperthyroidism. Subclinical hyperthyroidism is more prevalent in the iodine deficient area than in the severe iodine excessive area. In the area with mild iodine deficiency, the introduction of universal salt iodization may not be accompanied by an increased incidence of hyperthyroidism.


[Effect of shenqi fuzheng injection for assistance of chemotherapy in treating senile patients with non-small cell lung cancer].
To study the effect of chemotherapy assisted with shenqi fuzheng injection (SFI) on senile patients with non-small cell lung cancer (NSCLC). One hundred and twenty old patients with NSCLC were treated with NP chemotherapeutic protocol, to the 60 patients in the treated group among them, additional medication of SFI was started one week before the beginning of chemotherapy. The short-term therapeutic efficacy, long-term survival rate, changes on quality of life (QOL) and immune function of patients, and hematological toxicity of therapy were observed. Difference between the two groups on short-term therapeutic effect, 1- and 2-year survival rate showed no significance (P>0.05), but the 3-year survival rate in the treated group was 26.6%, while that in the control group was 11.7%, showed that the former was higher than the latter. After treatment QOL of the treated group was better than that of the control (P<0.05). Besides, the hematological toxicity and affection on immune function of chemotherapy after treatment in the treated group were all lower than those in the control group showing significant difference (P<0.05). SFI has definite toxicity relieving effect on chemotherapy in treating senile NSCLC.


Synthesis of Photolabile Caged Amino Acids for Measuring Amino Acid Transporters.
Photolabile precursors (caged compounds) of amino acids such as Ala, Leu, Lys, and Ser were prepared by some simple reactions. These compounds were designed for the rapid, photochemically initiated release of amino acids. These amino acid transporters were expressed in Xenopus oocyte by injecting mRNA prepared from rat kidney. The electrical response of each transporter was examined by applying the amino acids and caged compounds before and after photolysis. Photolysis of the caged amino acids increased the electrical response of the facilitated amino acid transporters expressed in the oocyte. Consequently, these synthesized caged amino acids would be applicable to kinetic investigations on the transporters when combined with a pulsed laser or xenon arc flash lamp.


Root apical meristem diversity in extant lycophytes and implications for root origins.
Root apical meristem (RAM) organization in lycophytes could be a key to understanding the early evolution of roots, but this topic has been insufficiently explored. We examined the RAM organization of lycophytes in terms of cell division activities and anatomies, and compared RAMs among vascular plants. RAMs of 13 species of lycophytes were semi-thin-sectioned and observed under a light microscope. Furthermore, the frequency of cell division in the RAM of species was analyzed using thymidine analogs. RAMs of lycophytes exhibited four organization types: type I (Lycopodium and Diphasiastrum), II (Huperzia and Lycopodiella), III (Isoetes) and RAM with apical cell (Selaginella). The type I RAM found in Lycopodium had a region with a very low cell division frequency, reminiscent of the quiescent center (QC) in angiosperm roots. This is the first clear indication that a QC-like region is present in nonseed plants. At least four types of RAM are present in extant lycophytes, suggesting that RAM organization is more diverse than expected. Our results support the paleobotanical hypothesis that roots evolved several times in lycophytes, as well as in euphyllophytes.


[350m heliox saturated diving test--dynamic observation on hearing threshold, brainstem evoked response and acoustic impedance].
Four divers were investigated simulating a diving of 350m with saturated heliox under compression, performed in Jan 1989 at Navy Medical Institute. Changes in hearing threshold, brainstem evoked response and acoustic impedance were observed. The 4 divers experienced no tinnitus, hard of hearing and earache during compression and decompression. Objective examination showed loss of lower frequency range of hearing, that was due to the masking effect of the noise in the chamber. Changes in the wave--form and latency of brainstem evoked response were due to a change in sound wave transmission effected by the chamber pressure and a poor signal to noise ratio in the hyperbaric chamber of helium oxygen environment. All the changes were transient, after leaving the chamber, the hearing threshold and brainstem evoked response all returned to normal. Besides, there were no changes in the tympanogram, acoustic compliance and stapedius reflex before and after the experiment. Therefore the profile of compression and decompression in the experiment brought no harm to the divers' acoustic system; their Eustachian tubes, middle and inner ears functioned normally.


Histologic follow-up of atypical endocervical cells. Liquid-based, thin-layer preparation vs. conventional Pap smear.
To review the histologic findings in patients diagnosed with "atypical glandular cells of uncertain significance, endocervical cell type" (AGUS-EC) by ThinPrep Pap Test (TPPT) or conventional Pap smear (CPS) and to evaluate the clinical value of subclassifying AGUS-EC as "favor reactive" or "favor neoplastic." All TPPT and CPS diagnosed as AGUS-EC (favor reactive, unspecified and favor neoplastic) from January 1998 through December 1999 and all available histologic follow-up (defined as endocervical curettage, cervical biopsy, cervical conization or hysterectomy obtained within six months of the time of an AGUS-EC diagnosis) were obtained from a computerized database. AGUS-EC was diagnosed in 0.77% of CPS (683 of 88,825) and 0.59% of TPPT (183 of 30,968) (P = NS). There was no statistically significant difference in any of the follow-up histologic diagnoses between the CPS and TPPT groups. The majority of the follow-up biopsies demonstrated benign processes in both groups. Patients with a diagnosis of AGUS-EC "favor neoplastic" had a greater proportion of true glandular pathology as compared with AGUS-EC "unspecified" or "favor reactive" (P < .001). None of the patients with a diagnosis of AGUS-EC "favor reactive" were found to have true glandular pathology; however, a minority of them proved to have squamous pathology. In this study there was no difference in CPS and TPPT in regard to the specificity of a diagnosis of AGUS-EC for true glandular pathology. Subclassifying AGUS-EC as "favor reactive" or "favor neoplastic" may provide valuable information for directing patient follow-up.


Lymphocytes and their subsets in the peripheral blood of hepatocellular carcinoma patients.
Using an automatic blood cell counter (Sysmex F500), the white blood cells of peripheral blood from patients can be accurately counted. The lymphocytes and their subsets can also be accurately counted and measured by the use of various fluorescent conjugated monoclonal antibodies and the flow cytometry (FACScan) method. This study disclosed a significant decrease in the lymphocyte, B cell, T cell and T-cell subsets of 45 hepatocellular carcinoma (HCC) patients as compared with those of 64 normal healthy individuals and those of 66 asymptomatic hepatitis B virus surface antigen carriers. The natural killer (NK) cells of HCC patients did not show any change as compared with that of the two normal control groups. A significant increase in the number of white blood cells of HCC patients was seen on the first and the seventh postoperative days as compared with the preoperative levels. However, the number of lymphocyte, T cell and NK cells of HCC patients decreased on the first postoperative day as compared with the preoperative levels. A temporary increase in B cells was observed on the seventh postoperative day. We conclude that the immunity of HCC patients is definitely reduced and is further aggravated after surgery.


A Non-Canonical Role for β-Secretase in the Retina.
It has long been established that β-Secretase (BACE) plays a critical role in the formation of amyloid plaques in Alzheimer's Disease patients, but it is only recently that the importance of β-secretases in retinal pathophysiology has been recognized. BACE expression is elevated in response to stress, and downregulation results in lysosomal abnormalities and mitochondrial changes. Inhibition of BACE can lead to reduced retinal function, retinal thinning, lipofuscin accumulation and vascular dysfunction in mice. Furthermore, BACE inhibition accelerates choroidal neovascularization (CNV) in mice. We propose that BACE plays an important role in retinal homeostasis and that BACE upregulation in response to stress is a protective measure.


Acquired immunodeficiency similar to Gulf War illness in a dead former serviceman.
A 38-year-old non-commissioned officer was certified unfit for military duty several months before his death. The forensic autopsy revealed a severe bone marrow aplasia and a pulmonary angioinvasive aspergillosis. Moreover, the presence of inorganic foreign particles in the pulmonary macrophages and intestinal endothelia was observed. The microanalysis implemented on these last selected specimens revealed the presence of silica particles microimpregnated by lanthanides and steel. The patient's acquired immunodeficiency appears comparable with that of Iraqi civilians suffering from Gulf War illness. This is the first report in the literature of the presence of intestinal endothelia engulfed by foreign war particulates; the silica particles may have entered the intestinal endothelia via the blood stream or by ingestion of impregnated fruit and vegetable foodstuffs. This finding provides new perspectives in the assessment of war-associated diseases and includes electron probe microanalysis among the new techniques of military and forensic medicine.


The association between renal function biomarkers and subclinical cardiovascular measures in African Caribbean families.
Risk of cardiovascular disease (CVD) and mortality are increased in people with subclinical CVD. The impact of ethnicity and race on subclinical CVD is substantial. Previous studies assessed the heritability of several renal function biomarkers and their relationship with subclinical CVD among populations of European ancestries, but, to our knowledge, no such data are available in African ancestry populations. Our aim was to investigate the relationships between renal function biomarkers and subclinical CVD among Afro-Caribbeans residing on the island of Tobago. 402 participants, aged 18 to 103 years, from seven large, multi-generation pedigrees (average family size: 50; range: 19 to 96; -3500 relative pairs) were included in this study. Subclinical cardiovascular disease (SCVD) was assessed by brachial-ankle pulse wave velocity (baPWV) and carotid intima-media thickness (IMT). Serum cystatin C, creatinine, and eGFR based on the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation were used to assess kidney function. The variance component approach, implemented in Sequential Oligogenic Linkage Analysis Routines (SOLAR), was used to assess heritability of these traits, and association with SCVD. Heritability of renal function biomarkers ranged from .19-.32 (all P < .001), and was highest for cystatin C (h2 = .32, P < .0001). Serum cystatin C was independently associated with arterial stiffness (P = .04). This association was not found with other renal function biomarkers. No significant association between renal function and IMT was found. Our data suggest that cystatin C is significantly heritable and associated with arterial stiffness among Afro-Caribbeans.


Generation of the germline peripheral B cell repertoire: VH81X-lambda B cells are unable to complete all developmental programs.
The generation of VH81X heavy chain lambda-light chain-expressing B cells (VH81X-lambda+ B cells) was studied in VH81X heavy chain transgenic mice as well as in VH81X JH (-/-) and VH81X JH (-/-) Ck (-/-) mice, in which competition resulting from expression of heavy and light chains from the endogenous heavy and kappa light chain loci was prevented. We show that although lambda light chain gene rearrangements occur normally and give rise to light chains that associate with the transgenic heavy chain to form surface and soluble IgM molecules, further B cell development is almost totally blocked. The few VH81X-lambda+ B cells that are generated progress into a mature compartment (expressing surface CD21, CD22, CD23, and low CD24 and having a relatively long life span) but they also have reduced levels of surface Ig receptor and express higher amounts of Fas Ag than VH81X-kappa+ B cells. These VH81X-lambda+ B cells reach the peripheral lymphoid organs and accumulate in the periarteriolar lymphoid sheath but are unable to generate primary B cell follicles. In other heavy chain transgenic mice (MD2, M167, and M54), lambda+ B cells are generated. However, they seem to be preferentially selected in the peripheral repertoire of some transgenic heavy chain mice (M54) but not in others (MD2, M167). These studies show that a crucial selection step is necessary for B cell survival and maintenance in which B cells, similar to T cells, receive signals depending on their clonal receptors.


Piezoelectric forceps actuator: theory and experiments.
This paper studies the characteristic performances of a novel piezoelectric forceps actuator (PFA) that has several potential applications for minimally invasive surgery and assembly lines of semiconductor industries. The first part of the paper treats the PFA model, which is comprised of a piezoelectric slightly curved composite beam derived using Hamilton's principle. In the latter part of the paper, the distributed transfer function method is applied to evaluate the transfer function formulation of the cantilevered PFA associated with its boundary conditions. This method will be used to resolve the radial displacements and natural frequencies of the PFA in an exact and closed-form solution, which is validated by in situ fiber optic curvature sensing measurements. The theoretical model predicted the natural frequencies of the first- and second-mode responses of the experimental quite accurately. For a cyclical low-field input, the field-induced displacement appears approximately linear, which seems comparable to the theoretical prediction and reflects primarily the converse piezoelectric effect. A cyclical high-field butterfly-shaped displacement behavior is also analogous to the behavior predicted by the model in that it demonstrates the range of validity of the linear converse piezoelectric effect without consideration of the ferroelectric domain switch effect.


Acute crude oil exposure alters mitochondrial function and ADP affinity in cardiac muscle fibers of young adult Mahi-mahi (Coryphaena hippurus).
Mitochondrial function is critical to support aerobic metabolism through the production of ATP, and deficiencies in mitochondrial bioenergetics will directly impact the performance capacity of highly aerobic tissues such as the myocardium. Cardiac function in fish has been shown to be negatively affected by crude oil exposure, however, the mechanism for this adverse response is largely unexplored. We hypothesized that lipophilic polycyclic aromatic hydrocarbons (PAHs) found in crude oil disrupt the electron transport system (ETS) ultimately leading to mitochondrial dysfunction. In this study, mitochondrial respiration and ADP affinity we measured using high resolution respirometery in permeabilized cardiac muscle fibers of young adult Mahi-mahi (Coryphaena hippurus) after an acute (24 h) whole animal crude oil exposure. Oil exposure reduced both complex I-fueled ADP stimulated respiration (OXPHOSCI) and complex I,II-fueled ADP stimulated respiration (OXPHOSCI, CII) by 33%,while complex II-fueled ADP stimulated respiration (OXPHOSCII) was reduced by 25%. These changes were found without changes in enzyme activity or mitochondrial density between control and oil exposed Mahi. Additionally, mitochondrial affinity for ADP was decreased three-fold after acute exposure to crude oil. We purpose that acute crude oil exposure selectively impairs mitochondrial complexes of the electron transport system and ATP supply to the cell. This limited ATP supply could present several challenges to a predatory animal like the mahi; including a reliance on anaerobic metabolism and ultimately cell or tissue death as metabolic substrates are rapidly depleted. However, the impact of this impairment may only be evident under periods of increased aerobic metabolic demand.


Assessing Self-reported Medication Adherence in Inflammatory Bowel Disease: A Comparison of Tools.
Capturing (non)-adherence to medical prescriptions in patients with inflammatory bowel disease (IBD) is challenging. We aimed to compare 3 different tools to measure self-assessed medication adherence of patients with IBD. Adult patients with Crohn's disease and ulcerative colitis were prospectively followed. IBD-specific medication use was collected by 3-monthly questionnaires. At 2.5 years of follow-up, medication adherence was assessed using 3 tools: (1) the 8-item Morisky Medication Adherence Scale (MMAS-8), (2) the single question how well patients take their daily medication using a Visual Analogue Scale (VAS), and (3) the Forget Medicine scale (FM), assessing how often patients forget their medication. Cross-sectional agreement among measures was visualized with scatterplots and quantified with Spearman's rank correlations. In total, 913 patients with IBD were analyzed, 697 of whom received IBD-specific medication. High adherence on the MMAS-8 was consistent with high scores on the VAS and low scores on the FM. Disagreement between tools increased when patients were less adherent. A correlation of 0.44 was found between the MMAS-8 and VAS; -0.59 between the MMAS-8 and FM, and -0.55 between the VAS and FM (all P < 0.01). The VAS most optimally represented the quantitative variability of adherence, whereas the MMAS-8 and the FM might have resulted in overestimation or underestimation of adherence due to unequal differences in outcome possibilities. In patients with IBD, a VAS seems the most appropriate tool for quantifying medication adherence in clinical practice. The MMAS-8 may be used additionally to provide insight in specific reasons for non-adherence.


Convenient synthesis of pyrimidine 2'-deoxyribonucleoside monophosphates with important epigenetic marks at the 5-position.
Methyl groups of thymine and 5-methylcytosine (5mC) bases in DNA undergo endogenous oxidation damage. Additionally, 5mC residues can be enzymatically deaminated or oxidized through either genetic alterations or the newly identified epigenetic reprogramming pathway. Several methods have been developed to measure the formation of modified DNA nucleobases including 32P-postlabeling. However, the postlabeling method is often limited by the absence of authentic chemical standards. The synthesis of monophosphate standards of nucleotide oxidation products is complicated by the presence of additional functional groups on the modified bases that require complex protection and deprotection strategies. Due to the emerging interest in the pyrimidine oxidation products, the corresponding protected 3'-phosphoramidites needed for solid-phase oligonucleotide synthesis have been reported, and several are commercially available. We report here an efficient synthesis of 3'-monophosphates from 3'-phosphoramidites and the subsequent enzymatic conversion of 3'-monophosphates to the corresponding 5'-monophosphates using commercially available enzymes.


GENETIC VARIABILITY AND POPULATION DIFFERENTIATION INFERRED FROM DNA FINGERPRINTING IN SILVEREYES (AVES: ZOSTEROPIDAE).
This study evaluated DNA fingerprinting as a tool for estimating population genetic diversity and differentiation by comparing minisatellite variation in island and mainland populations of silvereyes (Aves: Zosterops lateralis). Three populations with different recent histories were compared: (1) Heron Island and neighboring islands, colonized 3000 to 4000 yr ago; (2) Lady Elliot Island, colonized within the past two decades; and (3) an adjacent mainland population, which presumably has existed for thousands of years. The degree of genetic variability within the three populations reflected both their size and the time since their colonization. Minisatellite diversity was highest in the mainland population, intermediate in the Capricorn Island group (which was shown to represent a single admixture), and lowest in the Lady Elliot Island population, possibly because of a recent population bottleneck during colonization. Mean band sharing between any two populations was less than the mean within either of those populations, and four fingerprint bands common to island birds were rare or absent in the fingerprints of mainland birds. In the absence of significant gene flow between the mainland and the islands, the populations have apparently become distinct at minisatellite loci, as evidenced by differences in both allelic diversity and in the frequencies of specific fragments. Within the Heron Island population, cohort analyses demonstrated the temporal stability of the fingerprint profile over 6 yr. This study demonstrates that length polymorphisms at minisatellite loci may be stable enough over time to retain information about recent historical and demographic effects on the relative genetic variability and differentiation of small, closely related populations.


Lack of tocopherol in peripheral nerves of vitamin E-deficient patients with peripheral neuropathy.
Vitamin E deficiency is often associated with symptoms of a peripheral neuropathy. To evaluate whether vitamin E deficiency affects the vitamin E content of the peripheral nervous system, we measured the alpha-tocopherol content in biopsy specimens of sural nerve and adipose tissue from 5 patients with symptomatic vitamin E deficiency (2 with homozygous hypobetalipoproteinemia and 3 with familial isolated vitamin E deficiency) and 34 control patients with neurologic diseases without vitamin E deficiency. A significant reduction in tissue tocopherol content was present in the vitamin E-deficient patients, as compared with the controls, both in sural nerves (1.8 +/- 1.2 vs. 20 +/- 16 ng per microgram of cholesterol [P less than 0.001], or 7.7 +/- 5.4 vs. 64 +/- 44 ng per milligram of wet weight [P less than 0.01]) and in adipose tissue (46 +/- 43 vs. 222 +/- 111 ng per milligram of triglyceride [P less than 0.001]). Levels of tocopherol in adipose tissue were significantly correlated (P less than 0.001) with levels in peripheral nerves. The low tocopherol content of the nerves preceded histologic degeneration in three vitamin E-deficient patients, suggesting that the nerve injury resulted from the low nerve tocopherol content.


Lymphocyte surface antigen L25 is a member of the integrin receptor superfamily.
Monoclonal antibody (mAb) anti-L25 identifies an antigen on the surface of human lymphocytes. This mAb immunoprecipitated three distinct polypeptides of Mr 150,000, 85,000, and 75,000 from Nonidet P-40 lysates of surface radioiodinated lymphocytes. The three polypeptides were found under both nonreducing and reducing conditions. An additional polypeptide of Mr 130,000 was detected in mAb anti-L25 immuno-precipitates when cells were lysed with CHAPS (3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate). Epitope localization experiments indicated that both the Mr 150,000 and 85,000 polypeptides contained antibody reactive sites. Peptide mapping studies demonstrated structural similarities in the Mr 150,000 and 85,000 components. The analysis of L25 subunits from lysates of antigen-stimulated T lymphocytes revealed a loss of the Mr 150,000 polypeptides in mAb anti-L25 immunoprecipitates. Solid phase double determinant binding assays demonstrated that L25 is similar and probably identical to lymphocyte surface antigen very late activation-4. This relationship placed L25 as a member of the integrin receptor superfamily.


Unilateral Bilevel Erector Spinae Plane Catheters for Flail Chest: A Case Report.
Providing effective analgesia for acute rib fractures is crucial in avoiding pulmonary complications. Erector spinae plane (ESP) block is an alternative treatment option to neuraxial techniques. ESP blocks have demonstrated pain relief in patients with rib fractures. However, the utilization of unilateral bilevel ESP catheters has not been described. We present a case of unilateral bilevel ESP catheters placed in a patient with flail chest secondary to a motor vehicle accident.


In vitro and in vivo antitumor effects of vitamin K5 on hepatocellular carcinoma.
Although a number of studies have shown that vitamins K1, K2 and K3 exerted antitumor effects on various types of rodent- and human-derived neoplastic cell lines, it has not been examined whether or not vitamin K5 also possesses antitumor activity. In the present study, we examined the antitumor effects of vitamin K5 on PLC/PRF/5 human hepatocellular carcinoma (HCC) cells in vitro and in vivo. Furthermore, we examined the mechanisms of antitumor actions of vitamin K5 not only in vitro but also in vivo. Vitamin K5 was shown to suppress the proliferation of PLC/PRF/5 cells at a concentration of 30 microM. By a flow cytometric analysis, it was shown that although vitamin K5 did not induce apoptosis on PLC/PRF/5 cells, it did induce G1 arrest on PLC/PRF/5 cells. Subsequent in vivo study using subcutaneous HCC-bearing athymic nude mice demonstrated that vitamin K5 markedly suppressed the growth of HCC tumors. Although protein expression levels of cyclin D1 and p16INK4a cyclin-dependent kinase (Cdk) inhibitor in HCC tumors were not decreased by vitamin K5 treatment, those of Cdk4 were reduced significantly by the treatment. Taken collectively, vitamin K5 could induce potent antitumor effects on HCC not only in vitro but also in vivo, at least in part by inducing G1 arrest of cell cycle through downregulation of Cdk4 expression. The results demonstrated here indicate that vitamin K5 may be a useful agent for the treatment of patients with HCC.


A Magneto-Optical Nanoplatform for Multimodality Imaging of Tumors in Mice.
Multimodality imaging involves the use of more imaging modes to image the same living subjects and is now generally preferred in clinics for cancer imaging. Here we present multimodality-Magnetic Particle Imaging (MPI), Magnetic Resonance Imaging (MRI), Photoacoustic, Fluorescent-nanoparticles (termed MMPF NPs) for imaging tumor xenografts in living mice. MMPF NPs provide long-term (more than 2 months), dynamic, and accurate quantification, in vivo, of NPs and in real time by MPI. Moreover, MMPF NPs offer ultrasensitive MPI imaging of tumors (the tumor ROI increased by 30.6 times over that of preinjection). Moreover, the nanoparticle possessed a long-term blood circulation time (half-life at 49 h) and high tumor uptake (18% ID/g). MMPF NPs have been demonstrated for imaging breast and brain tumor xenografts in both subcutaneous and orthotopic models in mice via simultaneous MPI, MRI, fluorescence, and photoacoustic imaging with excellent tumor contrast to normal tissues.


Reducing rates of Clostridium difficile infection by switching to a stand-alone NAAT with clear sampling criteria.
Clostridium difficile infection is an important cause of morbidity and mortality but the optimal method of diagnosis for both patient management and infection prevention remains controversial. Our hospital made a decision to switch from the use of toxin immunoassay to a stand-alone nucleic acid test. This change was accompanied by the provision of clear sampling guidance and rejection criteria and this study aimed to assess the impact of that change. We analysed sample numbers, numbers of positive results, and the proportion of cases assessed as healthcare acquired over a 6-year period during which the testing method was changed from a toxin A/B immunoassay to a stand-alone commercial nucleic acid test after the first two years. Sample numbers and numbers of cases assessed as healthcare acquired fell following the introduction of the nucleic acid test and sampling guidance, while infection rates in other hospitals in the same region remained relatively stable. It is our opinion that the use of a highly sensitive assay together with clear sampling guidance offers the optimal approach to patient management and best use of isolation facilities.


Appropriateness of Surgical Antibiotic Prophylaxis in Pediatric Patients in Italy.
OBJECTIVES Appropriate use of surgical antibiotic prophylaxis (SAP) reduces intraoperative wound contamination in pediatric surgery, thus minimizing the risk of surgical site infection (SSIs). Conversely, inappropriate use of SAP exposes patients to the risk of antibiotic side effects and contributes to the emergence of antimicrobial resistance. Our aims were to describe SAP administration and to analyze factors associated with nonadherence in pediatric patients. DESIGN Descriptive study. SETTING Overall, 955 pediatric patients underwent 1,038 surgical procedures. METHODS We assessed adherence to SAP international guidelines for surgical procedures performed on children aged <18 years in 2015 in 4 randomly selected hospitals in Calabria (Italy). The clinical records of these patients were retrospectively reviewed. RESULTS Appropriate SAP administration or nonadministration pertained to 754 surgical procedures (72.6%). Surgical antibiotic prophylaxis was administered in 88.5% of 358 procedures with an SAP indication. Adherence to guidelines for appropriate drug choice were followed in 5.7% of cases, for route of administration in 76.7% of cases, for timing in 48.6% of cases, for duration in 14.5% of cases, and for dose in 91.5% of cases, and for all components in only 5 cases (1.6%). Among 680 procedures without SAP indication, 35.7% case patients received antibiotics. Inappropriate administration of antibiotics in procedures without SAP indication was associated with surgical specialty wards (P=.008), ordinary admission (P<.001), head and neck surgical procedures (P=.020), clean surgery (P=.017), and surgical duration (P=.010). CONCLUSIONS Discrepancies between SAP guidelines and actual practice behavior more frequently indicate excessive use of antibiotics than underuse. Increased awareness of SAP guidelines is required. Infect Control Hosp Epidemiol 2017;38:823-831.


Neurologic complications of pancreas transplants.
A review of 15 cases of pancreas transplantation at the Presbyterian University Hospital in Pittsburgh showed that all of the neurologic complications occurred outside of the pancreas transplantation surgery itself. Major CNS complications included hypoxic encephalopathy (20 per cent), cerebral and spinal-cord infarction (7 per cent), and seizures (13 per cent). These appeared to be closely associated with cardiovascular collapse or cardiac arrest that often occurred following septic, hemorrhagic, or additional surgical-anesthetic stresses, removed in time from the transplantation. When patients who died of sudden cardiorespiratory arrest were included, the overall frequency of global cerebral ischemia was 33 per cent. The occurrence of herpes zoster neuritis (13 per cent) was contrasted with the lack of CNS infections. The possible associations of visual hallucinations with cyclosporine therapy (7 per cent), CSF pleocytosis with OKT3 therapy (7 per cent), and compressive neuropathy with operative-anesthetic monitoring (7 per cent) were discussed in relation to previous reports in the literature. Randomized controlled clinical studies were suggested to distinguish more clearly the complications due to pancreas transplantation from those due to the natural history of the underlying diabetes and to distinguish the beneficial and adverse effects of pancreas transplants from those of coexisting renal transplants.


N3,N7-diaminophenothiazinium derivatives as antagonists of α7-nicotinic acetylcholine receptors expressed in Xenopus oocytes.
Derivatization of phenothiazine (PTZ, 1) has been a commonly used method to develop drugs with various pharmacological properties. In the present study, a series of PTZ derivatives 1-11 were investigated on the inhibition of the cloned α7 subunit of the human nicotinic acetylcholine receptor (α7-nAChR) expressed in Xenopus oocytes by using the two-electrode voltage-clamp technique. In the first series of experiments, the effect of unsubstituted phenothiazine 1 on α7-nAChRs was compared with that of the N3,N7-diaminophenothiazin-5-ium derivative 2, and of sequentially methylated derivatives 3-6. In the second set of experiments, the effects of N3,N7-tetra-ethyl- to n-hexylphenothiazin-5-ium derivatives 7-11 were tested. Despite the lack of activity found for 1, a reversible inhibition of α7-nAChRs, ranging from moderate to potent, was observed as a result of a sequential amine- and methylamine substitution of 1. The inhibition of ACh (100 μM)-induced currents was concentration-dependent with IC(50) values ranging from 0.4 to 16.8 μM. However, an optimal inhibitory activity was achieved by prolongation of alkyl chains up to propyl size, as found in PTZ derivative 8, whereas further lengthening of alkyl chains to n-butyl-, n-pentyl-, or n-hexyl groups resulted in inactive derivatives 9-11. The results evidently suggest the presence of a lipophilic binding pocket of narrow tolerability on the receptor protein. These results emphasize the importance of amine and/or alkylamine moieties for the inhibitory effect of PTZ derivatives and provide further insights for the development of novel antagonists targeting α7-nAChRs.


Effect of physical property of supporting media and variable hydraulic loading on hydraulic characteristics of advanced onsite wastewater treatment system.
A laboratory-scale study was carried out to investigate the effects of physical properties of the supporting media and variable hydraulic shock loads on the hydraulic characteristics of an advanced onsite wastewater treatment system. The system consisted of two upflow anaerobic reactors (a septic tank and an anaerobic filter) accommodated within a single unit. The study was divided into three phases on the basis of three different supporting media (Aqwise carriers, corrugated ring and baked clay) used in the anaerobic filter. Hydraulic loadings were based on peak flow factor (PFF), varying from one to six, to simulate the actual conditions during onsite wastewater treatment. Hydraulic characteristics of the system were identified on the basis of residence time distribution analyses. The system showed a very good hydraulic efficiency, between 0.86 and 0.93, with the media of highest porosity at the hydraulic loading of PFF≤4. At the higher hydraulic loading of PFF 6 also, an appreciable hydraulic efficiency of 0.74 was observed. The system also showed good chemical oxygen demand and total suspended solids removal efficiency of 80.5% and 82.3%, respectively at the higher hydraulic loading of PFF 6. Plug-flow dispersion model was found to be the most appropriate one to describe the mixing pattern of the system, with different supporting media at variable loading, during the tracer study.


Evaluation of the expressed miR-129 and miR-549a in patients with multiple sclerosis.
The expression of microRNAs (miRNAs) as circulating biomarkers has been underlined in multiple sclerosis (MS) in the last decade. Due to the presence of a possible relationship between expressed miRNAs and heterogeneous appearances of the pathological processes in MS, the present study attempts to evaluate the expression of miR-129 and miR-549a in patients with MS in comparison with healthy control (HC) group. Peripheral blood mononuclear cells were separated from fifty patients with MS (subtypes including relapsing-remitting MS and secondary progressive MS) in the Kashani Hospital, Isfahan, Iran, and fifty people as HC group. After RNA extraction and complementary DNA synthesis, the expression of miR-129 and miR-549a was evaluated in patients with MS in comparison with the HC group using a quantitative real-time polymerase chain reaction assay. The data were analyzed using the Kolmogorov-Smirnov and Mann-Whitney tests. Spearman's correlation coefficient was used to examine the relationship between miR-129 and miR-549a with age. The results showed that the expression of miR-129 and miR-549a was not significant in patients with MS in comparison with the HC group. Furthermore, the relationship between such miRNAs and age and gender was not significant. We suggest the expression of miR-129 and miR-549a as circulating miRNAs in peripheral blood mononuclear cells could not be considered a biomarker for diagnosis and Para clinical.


Impact of host factors on susceptibility to antifungal agents.
An obstacle to drug development, particularly in this era of multiple drug resistance, is the under-appreciation for the role the host environment plays in microbial response to drugs. With the rise in fungal infection and drug resistance, particularly in individuals with co-morbidities, the influence serum and its components have on antimicrobial susceptibility requires assessment. This study examined the impact of physiologically relevant glucose and insulin levels in the presence and absence of 50 % human plasma on MICs for clinical isolates of Candida lusitaniae, Candida parapsilosis, Candida albicans, Candida tropicalis, Candida glabrata, Candida krusei and Cryptococcus neoformans. The addition of insulin or glucose at physiologic levels in RPMI medium alone altered the MIC in either a positive or negative fashion, depending on the organisms and drug tested, with C. glabrata most significantly altered with a 40, >32- and 46-fold increase in MIC for amphotericin B, itraconazole and miconazole, respectively. The addition of candida-antibody negative plasma also affected MIC, with the addition of glucose and insulin having a tandem effect on MIC. These findings indicate that phenotypic resistance of Candida and Cryptococcus can vary depending on the presence of insulin with glucose and plasma. This modulation of resistance may help explain treatment failures in the diabetic population and facilitate the development of stable drug-resistant strains. Furthermore, these findings indicate the need for a precision approach in the choice of drug treatment and drug development.


Failure of oral tyrosine supplementation to improve exercise performance in the heat.
Acute oral tyrosine administration has been associated with increased constant-load, submaximal exercise capacity in the heat. This study sought to determine whether self-paced exercise performance in the heat is enhanced with the same tyrosine dosage. After familiarization, seven male endurance-trained volunteers, unacclimated to exercise in the heat, performed two experimental trials in 30°C (60% relative humidity) in a crossover fashion separated by at least 7 d. Subjects ingested 150 mg·kg(-1) body mass tyrosine (TYR) or an isocaloric quantity of whey powder (PLA) in 500 mL of sugar-free flavored water in a randomized, double-blind fashion. Sixty minutes after drink ingestion, the subjects cycled for 60 min at 57% ± 4% peak oxygen uptake (VO2peak) and then performed a simulated cycling time trial requiring completion of an individualized target work quantity (393.1 ± 39.8 kJ). The ratio of plasma tyrosine plus phenylalanine (tyrosine precursor) to amino acids competing for brain uptake (free-tryptophan, leucine, isoleucine, valine, methionine, threonine, and lysine) increased 2.5-fold from rest in TYR and remained elevated throughout exercise (P < 0.001), whereas it declined in PLA from rest to preexercise (P = 0.004). Time-trial power output (P = 0.869) and performance (34.8 ± 6.5 and 35.2 ± 8.3 min in TYR and PLA, respectively; P = 0.4167) were similar between trials. Thermal sensation (P > 0.05), RPE (P > 0.05), core temperature (P = 0.860), skin temperature (P = 0.822), and heart rate (P = 0.314) did not differ between trials. These data indicate that acute tyrosine administration did not influence self-paced endurance exercise performance in the heat. Plasma tyrosine availability is apparently not a key determinant of fatigue processes under these conditions.


[Psychoeducative ambulatory group in bulimia nervosa. Evaluation of a short-term approach].
This study examined the relative efficacy of a brief-psychoeducational treatment approaches for bulimia nervosa. Our sample comprised 26 women who sought consecutively treatment at the Eating Disorders Outpatient Unit. All subjects met DSM-IV criteria for Bulimia nervosa. For the assessment were used commonly applied questionnaires in the fiel of eating disorders such as: Eating Attitudes Test (EAT-40), Eating Disorders Inventory (EDI) and the Beck Depression Inventory (BDI). Outcome measures included also change in vomiting and binge-eating episodes per week. Each patient was assessed before and after a 6 weeks brief psychoeducational group therapy. At posttreatment, 30% of the patients were abstinent from binge eating-purging and 62% reduced their weekly frequency in binge eating and 56% reduced their weekly frequency in vomiting. Good-outcome (EAT scores < 30) was observed in more than 35% of our patients. The authors sought to identify factors that differentiate bulimic patients who improve while receiving treatment from those who do not.


Magnetocrystalline two-fold symmetry in CaFe2O4 single crystal.
Understanding of magnetocrystalline anisotropy in CaFe2O4 is a matter of importance for its future applications. A high quality single crystal CaFe2O4 sample is studied by using synchrotron x-ray diffraction, a magnetometer and the electron spin resonance (ESR) technique. A broad feature of the susceptibility curve around room temperature is observed, indicating the development of 1D spin interactions above the on-set of antiferromagnetic transition. The angular dependency of ESR reveals an in-plane two-fold symmetry, suggesting a strong correlation between the room temperature spin structure and magnetocrystalline anisotropy. This finding opens an opportunity for the device utilizing the anisotropy field of CaFe2O4.


Silicon-silica nanowires, nanotubes, and biaxial nanowires: inside, outside, and side-by-side growth of silicon versus silica on zeolite.
It was demonstrated that zeolite can be used as a pseudo-template to grow very fine and uniform silicon nanostructures via disproportionation reaction of SiO by thermal evaporation. Three distinct types of composite nanowires and nanotubes of silicon and silica were grown on the surfaces of zeolite Y pellets. The first type is formed by an ultrafine crystalline silicon nanowire sheathed by an amorphous silica tube (a silicon nanowire inside a silica nanotube). The second type is formed by a crystalline silicon nanotube filled with amorphous silica (a silicon nanotube outside a silica nanowire). The third type is a biaxial silicon-silica nanowire structure with side-by-side growth of crystalline silicon and amorphous silica. These silicon nanostructures exhibit unusually intense photoluminescence (in comparison to ordinary silicon nanowires).


Investigating K+ Storage Behavior of Highly Graphitized Carbon Fibers as Anodes for a Potassium-Ion Battery.
Many problems of potassium-ion batteries (PIBs) are hidden under a low mass load of the active material. However, developing research based on areal capacity is challenging for PIBs, due to the lack of an anode capable of delivering a stable capacity of more than 1 mAh cm-2. This work investigates the K+ storage behavior of highly graphitized carbon fibers (HG-CF), which exhibit automatic structural adjustments to mitigate voltage polarization. The created defects and residual K+ in the structure favor the reversible insertion/deinsertion of K+. HG-GF after structural adjustment realizes a capacity of 2 mAh (1.13 cm-2) without K deposition and a stable cyclic stability (>500 h). In situ X-ray diffraction and in situ Raman spectra were used to detect defect formation and structural evolution during cycles. This work demonstrates the feasibility of HG-GF as an anode for PIBs and provides a suitable anode for further research of PIBs based on areal capacity.


Magneto-optic microscope for visually detecting subsurface defects.
A visual test method for detecting microdefects under fine surfaces is described. A new MO microscope that has a laser source, a CCD camera, and an exciting coil is developed for this work. A pulse generator supplies an intermittent square pulse to the exciting coil, which can intensify eddy currents yet reduce the working temperature of the exciting coil and sample. The magnetic field variation produced by the imbedded defect causes a rotation of the polarization plane of the reflected beam. Therefore the reflected beam carries an image of the defect, which is received by a CCD camera. The optical arrangement guarantees that no light is reflected back to the laser. The system was tested with a calibrator, which has an artificial subsurface defect; such a test attains a visual detected image. To our knowledge this is the first time an image of a subsurface defect has been distinctly detected with a MO sensor system.


Neutering is associated with developing hemangiosarcoma in dogs in the Veterinary Medical Database: An age and time-period matched case-control study (1964-2003).
The hypothesis that neutered dogs in the Veterinary Medical Database (VMDB) are at increased risk for developing hemangiosarcoma (HSA) was tested. Dogs (n = 5736) were diagnosed with HSA from a population of 2 106 324 dogs in the VMDB from 1964 to 2003. A case-control design matched on age and time period was created for general, cardiac, and splenic HSAs. A logistic regression analysis was performed including breed. Spayed females had an odds ratio (OR) of 1.59 for splenic, 1.47 for cardiac, and 1.72 for HSA in general. Castrated males had an OR of 1.26 for splenic and 1.14 for HSA in general compared to intact males. Controlled for historical time period and patient age, VMDB data support that neutering is associated with development of splenic HSA and HSA in general in both male and female dogs, but not cardiac HSA with an apparently lower than previously described magnitude of association. Key clinical message: This case-control design confirms an association between neutering and development of HSA and splenic HSA, but not cardiac HSA, in both male and female dogs. By controlling for time period at diagnosis, the bias of recent early neuter practices is eliminated, suggesting early neuter is not a principal driver of this effect.


Spinal cord compression and bilateral sensory neural hearing loss: an unusual manifestation of neurocysticercosis.
Neurocysticercosis is the most common parasitic infestation involving the central nervous system in tropical countries. Common presentations are seizure, meningitis and increased intracranial pressure. The authors report a case of a 52-year-old woman with racemose neurocysticercosis in the subarachnoid space at the cistern of the brain through the lumbar cistern. She presented with progressive paraparesis due to spinal cord compression and finally had progressive bilateral sensori-neural hearing loss. MRI brain and the whole spinal cord revealed numerous rim-enhancing cystic lesions at the basal cistern, prepontine cistern, bilateral cerebellopontine angle, internal acoustic canals, intramedullary lesion at the 5th cervical spinal level, lumbar cistern lesions and secondary syringomyelia at the thoracic spinal cord. The histopathologic examination confirmed cysticercosis. After treatment by albendazole and surgical removal, she still developed recurrent spinal compression at a higher level and obstructive hydrocephalus. Finally, she died from status epilepticus and septic shock.


Imaging analysis of subcellular correlation of androgen receptor and estrogen receptor alpha in single living cells using green fluorescent protein color variants.
Androgen and estrogen act not only in a sex-specific manner but also interactively and synergistically. In the present study, to examine the possible interaction between androgen receptor (AR) and estrogen receptor-alpha (ERalpha), we investigated the subcellular dynamics of AR and ERalpha fused with green fluorescent protein color variants in single living cells using time-lapse microscopy and the technique of fluorescence recovery after photobleaching. AR and ERalpha showed punctate colocalization in the nucleus with estrogen, but not androgen. N-terminal AR deletion mutant did not form a nuclear punctate pattern with either androgen or estrogen. In the presence of AR, but not ERalpha, N-terminal AR deletion mutant formed a punctate nuclear pattern with androgen. AR had different mobility depending on the ligand and the presence of ERalpha. On the other hand, AR had little effect on the stability of ERalpha. ERalpha mutant that does not bind coactivators did not alter the mobility of AR. Taken together, using an imaging technique, we clarified that possible homo/hetero dimerization between AR and ERalpha could be attributed to androgen-estrogen interaction in living cells.


Drug-induced cholestasis.
Acute, drug-induced hepatocellular cholestasis (either pure or cholestatic hepatitis) is a common manifestation of drug-induced hepatic injury. The drugs most frequently responsible are hormonal steroids and psychopharmacological agents (in particular phenothiazines and some antidepressants). Cholestasis usually subsides without sequelae in less than six months. Acute, drug-induced ductular cholestasis is uncommon and can resemble biliary tract obstruction. Complete recovery occurs promptly after the withdrawal of the causative drug in most cases. The pathogenetic mechanism may be immunoallergic. Prolonged ductular or ductal cholestasis can follow drug-induced acute hepatitis despite prompt withdrawal of the offending drug. This syndrome, observed mainly with chlorpromazine and uncommonly with twenty other drugs, is characterized by the progressive disappearance of small bile ducts and by manifestations mimicking primary biliary cirrhosis. However, its prognosis appears to be better than that of primary biliary cirrhosis, the condition being reversible in the majority of cases or even subsiding completely. The mechanism is still unknown, but several features suggest some form of autoimmunity. Extrahepatic cholestasis related to sclerosing cholangitis is a frequent and long-term complication of intra-arterial infusion of floxuridine in patients treated for hepatic metastases from colorectal carcinoma. Although it may be reversible, floxuridine-induced sclerosing cholangitis has a poor prognosis and can lead to death in a few patients. The mechanism is probably related to the vascular supply of the common hepatic duct and its relationship to the perfusion territory of floxuridine.


Age- and menopause-related differences in subcutaneous adipose tissue estrogen receptor mRNA expression.
Changes in estrogen receptor (ER) expression likely underlie differential metabolic effects of estrogen in pre- and postmenopausal women. The aim of the current study was to determine whether ER gene expression in abdominal and femoral subcutaneous adipose tissue (SAT) was associated with age, menopause, or regional adiposity. We studied pre- and post-menopausal (n=23 and 22, respectively; age 35-65y) normal weight (mean±SD; BMI 23.7±2.5kg/m2) women with similar total fat mass. Abdominal and femoral SAT ERα (ESR1) and ERβ (ESR2) mRNA expression was determined by qPCR. Total fat mass did not differ between pre- and postmenopausal women (22.7±5.3vs. 21.7±5.3kg). Compared to premenopausal women, ESR1 and the ratio of ESR1 to ESR2 were lower (p≤0.05) in postmenopausal abdominal and femoral SAT. ESR1 and ESR1:ESR2 were inversely associated with age in abdominal SAT (r=-0.380 and r=-0.463, respectively; p<0.05) and femoral SAT (r=-0.353 and r=-0.472, respectively; p<0.05). ESR2 was not related to age or menopause. The inverse association between ESR1 and age persisted after adjusting for trunk fat mass, estradiol, or leptin. Among healthy pre- and postmenopausal women, increased age was associated with a decreased balance of ERα to ERβ in abdominal and femoral subcutaneous adipose tissue.


Leptin and plasminogen activator inhibitor-1 levels in children on chronic dialysis.
In this study, it is aimed to compare the serum leptin and PAI-1 levels and evaluate their relationship in children on hemodialysis (HD) and peritoneal dialysis (PD). Thirty-six patients on HD (mean age: 15.0 ± 2.8 years), 19 patients on PD (mean age: 13.0 ± 3.5 years) and 15 healthy subjects (mean age: 14.5 ± 2.7 years) were included in the study. Laboratory investigations included blood count, biochemical parameters, serum iron, iron binding capacity, parathormone, erythrocyte sedimentation rate, C-reactive protein (CRP), prothrombin time (PT), partial thromboplastin time (PTT), fibrinogen, serum leptin and PAI-1 levels. Serum leptin levels were significantly higher in HD group than in control group when the effects of BMI and sex were controlled, while PD and control groups had similar leptin levels. PAI-1 levels were also significantly higher in HD group than in control group, while there was no statistically significant difference in PAI-1 levels of PD and control group. PAI-1 levels and leptin levels were significantly correlated, which was independent of the effect of BMI in both HD and PD groups when they are evaluated separately. Results of our study showed that HD patients had higher leptin and PAI-1 levels and leptin and PAI-1 levels were correlated significantly in both patient groups. The effect of elevated serum leptin and PAI-1 levels on the cardiovascular complications remains to be established.


Multimode hybrid gold-silicon nanoantennas for tailored nanoscale optical confinement.
High-index dielectric nanoantennas, which provide an interplay between electric and magnetic modes, have been widely used as building blocks for a variety of devices and metasurfaces, both in linear and nonlinear regimes. Here, we investigate hybrid metal-semiconductor nanoantennas, consisting of a multimode silicon nanopillar core coated with a gold layer, that offer an enhanced degree of control over the mode selection and confinement, and emission of light on the nanoscale exploiting high-order electric and magnetic resonances. Cathodoluminescence spectra revealed a multitude of resonant modes supported by the nanoantennas due to hybridization of the Mie resonances of the core and the plasmonic resonances of the shell. Eigenmode analysis revealed the modes that exhibit enhanced field localization at the gold interface, together with high confinement within the nanopillar volume. Consequently, this architecture provides a flexible means of engineering nanoscale components with tailored optical modes and field confinement for a plethora of applications, including sensing, hot-electron photodetection and nanophotonics with cylindrical vector beams.


Design, synthesis, and optoelectronic properties of dendrimeric Pt(II) complexes and their ability to inhibit intermolecular interaction.
Dendrimeric Pt(II) complexes [(C(∧)N)Pt(dpm)] and [Pt(C(∧)N)2] (Hdpm = dipivaloylmethane, HC(∧)N = 1,2-diphenylbenzoimidazole and its derivatives containing the carbazole dendrons) have been synthesized and characterized systematically. All of the complexes display green emission in the range of 495-535 nm that originated from the 360-440 nm absorption bands, which are assigned to dπ(Pt)→π*(L) metal-to-ligand charge transfer (MLCT) mixed with intraligand π(L)→π*(L) transition. Solution photoluminescence quantum yield (φp 0.26-0.31) of the heteroleptic complexes [(C(∧)N)Pt(dpm)] obviously increases when compared with that of complex [(C(∧)N)Pt(acac)]. Organic light-emitting diode devices based on these Pt(II) complexes with a multilayer configuration were fabricated and gave desirable electroluminescent (EL) performances, such as non- or less red-shifted EL spectra, in comparison with the photoluminescence spectra and slow efficiency roll-off with increasing brightness or current density. Complex [(t-BuCzCzPBI)Pt(dpm)] (where t-BuCzCzPBI = 1-(4-(3,6-di-(3,6-di-t-butyl-carbazol-9-yl))carbazol-9-yl)phenyl-2-phenylbenzoimidazole) showed the best performance, with a maximum current efficiency of 29.31 cd/A and a maximum external quantum efficiency (EQE) of 9.04% among the fabricated devices. Likewise, for homoleptic [Pt(t-BuCzCzPBI)2] dendrimer, the powder φp (0.14) and maximum EQE (0.74%) improve by 7 and 7.4 times, respectively, as high as they do for nondendrimeric [Pt(1,2-diphenylbenzoimidazole)2] (0.02, 0.10%), although its efficiency is still lower than that of the heteroleptic counterpart due to the severely distorted square-planar geometry of the emitting core. These results reveal that large steric hindrance from ancillary ligand (dpm) or the homoleptic conformation can effectively inhibit intermolecular interaction for these dendrimeric Pt(II) complexes.


Severe Systemic Lead Toxicity Resulting From Extra-Articular Retained Shrapnel Presenting as Jaundice and Hepatitis: A Case Report and Review of the Literature.
Despite greater than 60,000 nonfatal firearm injuries per year in the United States, retained shrapnel is a relatively rare cause of systemic lead toxicity with less than 100 cases reported in the medical literature since 1867. While intra-articular retained shrapnel as a cause of lead toxicity is well-described, extra-articular fragments are less well known to cause symptomatic disease. A 31-year-old man initially presented with abdominal pain, constipation, jaundice, and elevated liver transaminases approximately 3 weeks after suffering a left lower extremity injury during athletic activity. The patient was found to have steatohepatitis after extensive inpatient and outpatient gastroenterological workup to include upper and lower endoscopy, liver ultrasound, and biopsy of the liver to confirm the diagnosis. Imaging was incidentally notable for retained gunshot in the left flank and large shell fragment containing seroma in the left thigh. The patient was initially discharged with improved pain, but later presented to a primary care clinic with weight loss and continued pain. This was followed by a subsequent progression to diffuse weakness, ultimately resulting in an inability to ambulate. The patient was readmitted to a tertiary care medical center, 3 months after the initial presentation. Physical exam was then notable for 70-lb weight loss from initial admission and diffuse peripheral weakness with global muscle atrophy. Following a broad differential workup, he was found to have a blood lead level of 129 μg/dL, and hemoglobin of 7.7 g/dL with basophilic stippling on peripheral smear. The patient was transferred to the intensive care unit for chelation therapy with dimercaprol and calcium ethylenediaminetetraacetic acid. Lead levels initially decreased, but rose when patient was transitioned to oral therapy with succimer. Surgery was consulted for removal of multiple retained fragments, which were analyzed by the Joint Pathology Center and found to contain lead. The patient's motor function gradually improved on oral chelation and he was discharged to a subacute rehabilitation facility. This complex case describes a rare cause for a relatively common clinical presentation, jaundice and hepatitis, and reinforces the importance of longitudinal follow up and reassessment of a patient with an unknown illness and worsening clinical condition. Diagnosis of systemic lead toxicity is challenging because of its protean clinical manifestations, and relative rarity with the advent of strict environmental lead controls and decrease in lead-based paint and industrial products. Furthermore, extra-articular lead remains a rare cause of systemic toxicity, and the surgical standard of care has been to not remove these fragments in gunshot victims. This case adds to a small amount of evidence that lead screening may be of value in selected patients with extra-articular retained shrapnel, especially those with seroma and osteophyte formation in the wound.


Associated autoimmune thyroid diseases in children and adolescents with type one diabetes in Jordan.
To investigate the prevalence of thyroid autoimmunity and related thyroid disorders among children and adolescents with type 1 diabetes in Jordan. In a retrospective study, thyroid stimulating hormone and thyroid hormone (Free T4) levels were measured in 684 children with type 1 diabetes who presented to Jordan University Hospital between January 2012 and February 2021. Anti-thyroid peroxidase (TPOAb) and anti-thyroglobulin (TGAb) antibodies were measured in 526 and 438 subjects with type 1 diabetes, respectively. 681 children were included in the study (52.4 % females, average current age 14.3 years, average age at diagnosis 8.0 years, and average diabetes duration 6.2 years). Of the whole group, 18 children (2.6 %) were diagnosed with subclinical hypothyroidism and 31 children (4.4 %) had overt hypothyroidism. Of those who were tested for TPOAb and TGAb, 22.6 and 23.1 % were positive respectively. Predictors for developing hypothyroidism were female sex and positive antibodies to glutamic acid decarboxylase. Screening for associated thyroid autoimmunity in children and adolescents with type one diabetes from Jordan is advised with a special focus on females and those with positive antibodies to glutamic acid decarboxylase.


Manganese intoxication decreases the expression of manganoproteins in the rat basal ganglia: an immunohistochemical study.
Manganese (Mn) is a cofactor for some metalloprotein enzymes, including Mn-superoxide dismutase (Mn-SOD), a mitochondrial enzyme predominantly localized in neurons, and glutamine synthetase (GS), which is selectively expressed in astroglial cells. The detoxifying effects of GS and Mn-SOD in the brain, involve catabolizing glutamate and scavenging superoxide anions, respectively. Mn intoxication is characterized by impaired function of the basal ganglia. However, it is unclear whether regional central nervous system expression of manganoproteins is also affected. Here, we use immunocytochemistry in the adult rat brain, to examine whether Mn overload selectively affects the expression of GS, Mn-SOD, Cu/Zn-SOD, another component of the SOD family, and glial fibrillary acid protein (GFAP), a specific marker of astrocytes. After chronic Mn overload in drinking water for 13 weeks, we found that the number and immunostaining intensity of GS- and Mn-SOD-positive cells was significantly decreased in the striatum and globus pallidus, but not in the cerebral frontal cortex. In addition, we found that GS enzymatic activity was decreased in the strio-pallidal regions but not in the cerebral cortex of Mn-treated animals. In contrast, Cu/Zn-SOD- and GFAP-immunoreactivity was unchanged in both the cerebral cortex and basal ganglia of Mn-treated rats. Thus, we conclude that in response to chronic Mn overload, a down-regulation of some manganoproteins occurs in neurons and astrocytes of the striatum and globus pallidus, probably reflecting the vulnerability of these regions to Mn toxicity.


Pausing guides RNA folding to populate transiently stable RNA structures for riboswitch-based transcription regulation.
In bacteria, the regulation of gene expression by cis-acting transcriptional riboswitches located in the 5'-untranslated regions of messenger RNA requires the temporal synchronization of RNA synthesis and ligand binding-dependent conformational refolding. Ligand binding to the aptamer domain of the riboswitch induces premature termination of the mRNA synthesis of ligand-associated genes due to the coupled formation of 3'-structural elements acting as terminators. To date, there has been no high resolution structural description of the concerted process of synthesis and ligand-induced restructuring of the regulatory RNA element. Here, we show that for the guanine-sensing xpt-pbuX riboswitch from Bacillus subtilis, the conformation of the full-length transcripts is static: it exclusively populates the functional off-state but cannot switch to the on-state, regardless of the presence or absence of ligand. We show that only the combined matching of transcription rates and ligand binding enables transcription intermediates to undergo ligand-dependent conformational refolding.


Population behavioral scenarios influencing radiological disaster preparedness and planning.
Considerable attention is focused on plans for sheltering or evacuating the population of the US national capital region in response to a regional emergency such as a terrorist attack or natural disaster. Such planning engages multiple disciplines spanning infrastructure engineering, emergency management, health care, mass communication, water and food supply, logistics, and others. Knowledge of population behaviors should influence the many dimensions of protection, prevention, response, and recovery. Of particular interest are the behaviors and needs of the resident and non-resident populations in the aftermath of a regional disaster, including those at home, at work, and traveling. The authors deployed a 30-min telephone survey to 2700 residents of the region to gain knowledge of their intended behaviors in the event of a variety of potential dirty bomb attacks. The survey provides a unique foundation for the current paper. The paper will identify and model the assumptions of population behaviors that most affect agency priorities for emergency planning including regional sheltering and evacuation following a radiological disaster such as a dirty bomb. The technical approach assessed several planning initiatives across performance criteria derived from strategic plans and applied combinations of behavioral assumptions to vary the relative importance of each criterion. The results reveal the behavioral scenarios that are most significant to the prioritization of planning initiatives and identify the highest and lowest priority initiatives across the criteria used.