Activation of type 4 dopaminergic receptors in the prelimbic area of medial prefrontal cortex is necessary for the expression of innate fear behavior.
The prelimbic area (PL) of the medial Prefrontal cortex (mPFC) is involved in the acquisition and expression of conditioned and innate fear. Both types of fear share several neuronal pathways. It has been documented that dopamine (DA) plays an important role in the regulation of aversive memories in the mPFC. The exposure to an aversive stimulus, such as the smell of a predator odor or the exposure to footshock stress is accompanied by an increase in mPFC DA release. Evidence suggests that the type 4 dopaminergic receptor (D4R) is the molecular target through which DA modulates fear expression. In fact, the mPFC is the brain region with the highest expression of D4R; however, the role of D4R in the expression of innate fear has not been fully elucidated. Therefore, the principal objective of this work was to evaluate the participation of mPFC D4R in the expression of innate fear. Rats were exposed to the elevated plus-maze (EPM) and to the cat odor paradigm after the intra PL injection of L-745,870, selective D4R antagonist, to measure the expression of fear-related behaviors. Intra PL injection of L-745,870 increased the time spent in the EPM open arms and decreased freezing behavior in the cat odor paradigm. Our results also showed that D4R is expressed in GABAergic and pyramidal neurons in the PL region of PFC. Thus, D4R antagonism in the PL decreases the expression of innate fear-behavior indicating that the activation of D4R in the PL is necessary for the expression of innate fear-behavior.


Perturbation of a prehension movement in Parkinson's disease.
Movement kinematics of the transport and manipulation components of a double-step prehension task were studied in eight Parkinson patients and eight control subjects. The aims were to (a) assess the effects of a spatial perturbation upon the movement for the two groups and (b) add data to the controversy about the damage/preservation of predictive behaviour in Parkinson patients. The results showed: (a) Both groups are able to preprogram a movement. (b) In both groups, the perturbation results in an anticipation of all kinematic parameters, both of the transport and manipulation components. (c) Parkinson patients, when adopting a predictive behavior, show a delay between the beginning of the two components, and thus activate them in sequence rather than simultaneously. This delay is significantly reduced by the perturbation, indicating that Parkinson patients, when using a responsive behavior, can recouple the two motor components.


Importance of identifying the overweight patient who will benefit the most by losing weight.
Because being overweight increases the risk for type 2 diabetes, hypertension, and coronary heart disease, the rapid increase in the prevalence of overweight and obesity in the United States represents a major health problem. The relationship between overweight and obesity and these conditions is probably due to insulin resistance and compensatory hyperinsulinemia. However, although it is known that weight loss in insulin-resistant and hyperinsulinemic persons will be of substantial metabolic benefit, it is equally well established that many overweight and obese persons are not insulin resistant. In the absence of insulin resistance and its manifestations, the risk for type 2 diabetes, hypertension, and coronary heart disease is reduced and the metabolic benefit of weight loss in the substantial number of overweight persons who are insulin sensitive is relatively minimal. Consequently, it is important to identify which overweight persons are most likely to be insulin resistant by considering their family history; blood pressure; and plasma glucose, triglyceride, and high-density lipoprotein cholesterol concentrations. Thoughtful use of this information will help identify the subset of persons who will benefit the most from intense therapeutic efforts to lose weight.


Strategic manipulations for associative memory and the role of verbal processing abilities in schizophrenia.
Individuals with schizophrenia demonstrate episodic memory (EM) deficits and abnormal EM-related brain activity. Experimental encoding manipulations significantly benefit memory performance in schizophrenia, suggesting that a strategic processing deficit may contribute to memory impairment. However, few studies have investigated the combined effects of encoding and retrieval strategies on EM in schizophrenia. The current study examined the impact of encoding and retrieval strategies on associative memory and brain activity in schizophrenia. We also assessed the role of verbal processing ability in response to strategic memory interventions in schizophrenia. Behavioral and functional neuroimaging data were collected from 23 participants with schizophrenia and 24 comparison subjects while performing associative memory encoding and recall tasks. Behaviorally, both schizophrenia participants and controls benefited from memory strategies and showed significant associations between verbal processing ability and recall. Additionally, among schizophrenia participants, encoding strategy use was associated with enhanced brain activity in multiple brain areas. Schizophrenia participants also demonstrated significant associations between verbal processing ability and encoding-related brain activity in prefrontal cortex. Findings suggest that memory performance and brain activity in schizophrenia can be enhanced via strategic manipulations, and individual differences in cognitive abilities in schizophrenia can affect behavioral and neurobiological responses to strategic memory interventions.


Black Hole Scrambling from Hydrodynamics.
We argue that the gravitational shock wave computation used to extract the scrambling rate in strongly coupled quantum theories with a holographic dual is directly related to probing the system's hydrodynamic sound modes. The information recovered from the shock wave can be reconstructed in terms of purely diffusionlike, linearized gravitational waves at the horizon of a single-sided black hole with specific regularity-enforced imaginary values of frequency and momentum. In two-derivative bulk theories, this horizon "diffusion" can be related to late-time momentum diffusion via a simple relation, which ceases to hold in higher-derivative theories. We then show that the same values of imaginary frequency and momentum follow from a dispersion relation of a hydrodynamic sound mode. The frequency, momentum, and group velocity give the holographic Lyapunov exponent and the butterfly velocity. Moreover, at this special point along the sound dispersion relation curve, the residue of the retarded longitudinal stress-energy tensor two-point function vanishes. This establishes a direct link between a hydrodynamic sound mode at an analytically continued, imaginary momentum and the holographic butterfly effect. Furthermore, our results imply that infinitely strongly coupled, large-N_{c} holographic theories exhibit properties similar to classical dilute gases; there, late-time equilibration and early-time scrambling are also controlled by the same dynamics.


New antibiotics in the management of acute bacterial skin and skin structure infections.
Acute bacterial skin and skin-structure infections (ABSSSIs), often caused by aerobic gram-positive cocci, are most often mild-tomoderate infections that can easily be treated in an outpatient setting. With the rates of these infections substantially increasing in the past decade, owing in part to the emergence of community acquired methicillin-resistant Staphylococcus aureus (CA-MRSA), alternative options for the treatment of ABSSSIs are necessary. This editorial reviews the mechanism of action, efficacy, bacterial coverage, and potential side effect profiles for dalbavancin and oritavancin, both semisynthetic lipoglycopeptide antibiotics, and tedizolid, an oxazolidinone. Dalbavancin, oritavancin, and tedizolid have been extremely valuable additions to treatment options for ABSSSIs due to the convenient dosing regimen and the fact that there are fewer resistant organisms to these therapies at this time.


Syntheses and structures of magnesium and zinc boraamidinates: EPR and DFT investigations of Li, Mg, Zn, B, and In complexes of the [PhB(NtBu)2].- anion radical.
The first magnesium and zinc boraamidinate (bam) complexes have been synthesized via metathetical reactions between dilithio bams and Grignard reagents or MCl2 (M = Mg, Zn). The following new classes of bam complexes have been structurally characterized: heterobimetallic spirocycles {(L)mu-Li[PhB(mu-NtBu)2]}2M (6a,b, M = Mg, L = Et2O, THF; 6c, M = Zn, L = Et(2)O); bis(organomagnesium) complexes {[PhB(mu3-NtBu)2](MgtBu)2(mu3-Cl)Li(OEt2)3} (8) and {[PhB(mu3-NtBu)2](MgR)2(THF)2} (9a, R = iPr; 9b, R = Ph); mononuclear complex {[PhB(mu-NDipp)2]Mg(OEt2)2} (10). Oxidation of 6a or 6c with iodine produces persistent pink (16a, M = Mg) or purple (16b, M = Zn) neutral radicals {Lx-mu-Li[PhB(mu-NtBu)2]2M}. (L = solvent molecule), which are shown by EPR spectra supported by DFT calculations to be Cs-symmetric species with spin density localized on one of the bam ligands. In contrast, characterization of the intensely colored neutral radicals {[PhB(mu-NtBu)2]2M}. (5c, M = In, dark green; 5d, M = B, dark purple) reveals that the spin density is equally delocalized over all four nitrogen atoms in these D2d-symmetric spirocyclic systems. Oxidation of the dimeric dilithio complex {Li2[PhB(mu4-NtBu)2]}2 with iodine produces the monomeric neutral radical {[PhB(mu-NtBu)2]Li(OEt2)x}. (17), characterized by EPR spectra and DFT calculations. These findings establish that the bam anionic radical [PhB(NtBu)2].- can be stabilized by coordination to a variety of early main-group metal centers to give neutral radicals whose relative stabilities are compared and discussed.


Xenobiotic kidney organogenesis from human mesenchymal stem cells using a growing rodent embryo.
Given the limits of allogenic organ transplantation, an ultimate therapeutic solution is to establish a self-organ from autologous stem cells and transplant them as syngrafts back into donor patients. It was reported previously that human mesenchymal stem cells (hMSC) that are cultivated in growing rodent embryos can differentiate within a spatially and temporally appropriate developmental milieu, facilitating the first step of nephrogenesis. As another step toward clinical application, the system was modified for progression to complete functional organogenesis. Rat embryos (E11.5) were isolated from uteri, and bone marrow-derived hMSC, which were transfected adenovirally with glial cell line-derived neurotrophic factor and retrovirally with LacZ, were implanted into the nephrogenic site. Forty-eight hours later, ureteric buds were elongated and initial branching was completed. The metanephroi were dissected out, developed further using in vitro organ culture for 24 h, transplanted into the omentum of a uninephrectomized rat, and grown for 2 wk. They enlarged and exhibited normal kidney structure and ultrastructure. hMSC-derived LacZ-positive cells were identified throughout the regenerated kidney and were morphologically identical to resident renal cells. Transplantation of developing metanephroi into the LacZ transgenic rat revealed that neo-kidney vasculature originated from the host circulation. Finally, fluid was collected from expanded ureters, and urea nitrogen and creatinine were measured. Levels were much higher in these fluids compared with transplanted rat sera (840.3 +/- 184.6 versus 30.4 +/- 10.8 and 10.1 +/- 3.1 versus 0.3 +/- 0.2 mg, respectively), suggesting that the neo-kidney may produce urine. Taken together, these findings suggest that hMSC can differentiate into a mature renal structure with the potential to replace lost kidney function.


Developing techniques in blood transfusion.
Expansion of transfusion medicine has led to an increasing awareness of the importance of its practice. Specialists in this branch of haematology whose main aim is to provide adequate and safe supplies of blood (and blood products) and to ensure these are used appropriately, are increasingly aware that to do this efficiently requires the development and utilization of new laboratory and technical procedures. Review of cross-matching techniques has led to the introduction of more rapid methods using low ionic strength saline. Use of monoclonal antibodies for blood grouping has made use of new technology, whilst allowing scarce human plasma to be used more appropriately for therapeutic purposes. Similarly, the implementation of a more rational approach to blood ordering, as in a maximum surgical blood-order schedule, allows for the more efficient use of donor blood. The use of microtitre plates for grouping and cross-matching techniques allows for speed and economy in the transfusion laboratory. Their use is also associated with increased automation and computer use. The possibility of using solid-phase techniques, monocyte-macrophage assays and antibody-dependent cellular cytotoxicity assays introduces new techniques differing markedly from time-honoured liquid-phase serology methods. The application of flow cytometry, which has already been shown to be useful in many aspects of haematology, is also of benefit in the field of blood transfusion science. Safety of blood transfusion is an important aspect of its practice and has led to the introduction and development of screening tests for donor blood to exclude infection risks from such organisms as HIV-1, hepatitis B and non-A, non-B hepatitis. Another approach to ensure the safety of transfused blood has been increased usage of autologous transfusion by means of both predeposit donation and intraoperative cell salvage.


Intestinal transport and absorption of bioactive phenolic compounds from a chemically characterized aqueous extract of Athrixia phylicoides.
Athrixia phylicoides, popularly known as "bush tea", is an indigenous aromatic shrub found in mountainous and grassland areas of the northern and eastern parts of southern Africa. The plant is traditionally used for the treatment of several ailments, including coughing, treating infected wounds, treating boils and sore throat, hypertension and heart disease. Potential anti-diabetic effects have also been demonstrated in vitro. To investigate the intestinal transport of prominent phenolic constituents, across a fully differentiated Caco-2 monolayer, using a characterized aqueous extract of A. phylicoides, previously shown to have bioactivity. HPLC-DAD and LC/MS analyses were used to identify the major phenolic compounds within the extract. Intestinal transport of the phenolic compounds was assessed using a differentiated Caco-2 monolayer model in order to predict bioavailability and identify metabolite formation. Rate of transport, efflux and percentage cross-over were calculated for the respective phenolic compounds. Nine prominent compounds, present in the aqueous extract of A. phylicoides, were identified. Of these, three phenolic acids (protocatechuic acid, caffeic acid and para-coumaric acid), crossed the Caco-2 cell monolayer in significant amounts, with Papp values of 4.52, 4.35 (×10-6cm/s) and 2.38 (×10-5cm/s), respectively. para-Coumaric acid was shown to have the highest predicted bioavailability. Para-Coumaric acid, identified for the first time in A. phylicoides, was shown to have the highest predicted bioavailability suggesting that it could play a major role in the bioactivity of A. phylicoides.


Predictive models of CYP3A4 Heteroactivation: in vitro-in vivo scaling and pharmacophore modeling.
Although activation of CYP3A4 is frequently observed in vitro, predictive computational-based models and methods for in vitro-in vivo scaling are scarce. It has been previously shown that in vitro CYP3A4 heteroactivation of carbamazepine (CBZ)-epoxide (ep) formation can be associated with the clinical drug interaction between felbatame and CBZ. The previously reported prediction methodology is applied here to an additional set of in vitro CYP3A4 heteroactivators, some exerting this effect at concentrations relevant in vivo. The antimalarial artemisinin potently increases CBZ-ep formation by a maximum of 500% at 300 microM. Testosterone and progesterone activates by a maximum of 1680 and 920%, respectively, at 150 microM, and quinidine causes a 130% increase at 300 microM. The predicted maximum in vivo decrease in steady-state concentration of carbamazepine (Css(CBZ)) at saturating effector concentrations is 85 to 90% for testosterone and progesterone, 75% for artemisinin, and 45% for quinidine. The corresponding predicted in vivo increase in Css(CBZ-ep) is 50, 60, 55, and 30% for artemisinin, testosterone, progesterone, and quinidine, respectively. At effector concentrations relevant in vivo, the Css(CBZ) change is predicted to </=20% for testosterone, artemisinin, and quinidine and </=10% for progesterone, with a concomitant Css(CBZ-ep) increase of 12% for testosterone and </=10% for progesterone, artemisinin, and quinidine. Structure-heteroactivation relationships were evaluated by generating a pharmacophore. The model includes two hydrogen bond acceptor features separated by hydrophobic features. Internal predictivity is high, and heteroactivation of an external test set correlate to observed in vitro heteroactivation.


Analysis of basic pentacysteine6 transcription factor involved in abiotic stress response in Arabidopsis thaliana.
Background: Abiotic stress is a significant environmental factor that limits plant growth. Plants have complex and diverse mechanisms for dealing with abiotic stress, and different response mechanisms are interconnected. Our research aims to find key transcription factors that can respond to multiple non -biological stress. Methods: We used gene expression profile data of Arabidopsis in response to abiotic stress, constructed a weighted gene co-expression network, to obtain key modules in the network. The functions and pathways involved in these modules were further explored by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. Through the enrichment analysis of transcription factor, the transcription factor that plays an important regulatory role in the key module. Through gene difference expression analysis and building protein interaction networks, the important role of key transcription factors is verified. Result: In weighted gene co-expression network, identified three gene modules that are primarily associated with cold stress, heat stress, and salt stress. Functional enrichment analysis indicated that the genes in these modules participate in biological processes such as protein binding, stress response, and others. Transcription factor enrichment analysis revealed that the transcription factor Basic Pentacysteine6 (BPC6) plays a crucial regulatory role in these three modules. The expression of the BPC6 gene is dramatically affected under a variety of abiotic stress treatments, according to an analysis of Arabidopsis gene expression data under abiotic stress treatments. Differential expression analysis showed that there were 57 differentially expressed genes in bpc4 bpc6 double mutant Arabidopsis relative to normal Arabidopsis samples, including 14 BPC6 target genes. Protein interaction network analysis indicated that the differentially expressed genes had strong interactions with BPC6 target genes within the key modules. Conclusion: Our findings reveal that the BPC6 transcription factor plays a key regulatory function in Arabidopsis coping with a variety of abiotic stresses, which opens up new ideas and perspectives for us to understand the mechanism of plants coping with abiotic stresses.


Important risk factors in melanoma from the Dermato-Oncologic Unit of Brescia, Italy.
One of the most significant risk factors for melanoma is a positive family history of the disease. It is estimated that approximately 10 percent of melanoma cases report a first-or second-degree relative with melanoma. We reported the experience of the Dermato-Oncologic Unit of Brescia, Italy.


Prediction of in vivo bone forming potency of bone marrow-derived human mesenchymal stem cells.
Human mesenchymal stem cells (MSC) have attracted much attention for tissue regeneration including repair of non-healing bone defects. Heterogeneity of MSC cultures and considerable donor variability however, still preclude standardised production of MSC and point on functional deficits for some human MSC populations. We aimed to identify functional correlates of donor-dependency of bone formation in order to develop a potency assay predicting the therapeutic capacity of human MSC before clinical transplantation. MSC from 29 donors were characterised in vitro and results were correlated to bone formation potency in a beta-tricalcium-phosphate (β-TCP)-scaffold after subcutaneous implantation into immunocompromised mice. In contrast to osteogenic in vitro differentiation parameters, a doubling time below 43.23 hours allowed to predict ectopic bone formation at high sensitivity (81.8%) and specificity (100%). Enriched conditions adapted from embryonic stem cell expansion rescued bone formation of inferior MSC populations while growth arrest of potent MSC by mitomycin C abolished bone formation, establishing a causal relationship between neo-bone formation and growth. Gene expression profiling confirmed a key role for proliferation status for the bone forming ability suggesting that a rate limiting anabolism and open chromatin determined and predicted the therapeutic potency of culture-expanded MSC. Proliferation-based potency testing and switch to enriched expansion conditions may pave the way for standardised production of MSC for bone repair.


Stereocomplexation Assisted Assembly of Poly(γ-glutamic Acid)-graft-polylactide Nano-micelles and Their Efficacy as Anticancer Drug Carrier.
Micelles as drug carriers are characterized by their inherent instability due to the weak physical interactions that facilitate the self-assembly of amphiphilic block copolymers. As one of the strong physical interactions, the stereocomplexation between the equal molar of enantiomeric polylactides, i.e., the poly(L-lactide) (PLLA) and poly(D-lactide) (PDLA), may be harnessed to obtain micelles with enhanced stability and drug loading capacity and consequent sustained release. In this paper, stereocomplexed micelles gama-PGA-g-PLA micelles) were fabricated from the stereocomplexation between poly(gama-glutamic acid)-graft-PLLA gama-PGA-g-PLA) and poly(gamaglutamic acid)-graft-PDLA gama-PGA-g-PLA). These stereocomplexed micelles exhibited a lower CMC than the corresponding enantiomeric micelles. Furthermore, they showed higher drug loading content and drug loading efficiency in addition to more sustained drug release profile in vitro. In vivo imaging confirmed that the DiR-encapsulated stereocomplexed gama-PGA-g-PLA micelles can deliver anti-cancer drug to tumors with enhanced tissue penetration. Overall, gama-PGA-g-PLA micelles exhibited greater anti-cancer effects as compared with the free drug and the stereocomplexation may be a promising strategy for fabrication of anti-cancer drug carriers with significantly enhanced efficacy.


Pathogenesis of Renal Injury and Gene Expression Changes in the Male CD-1 Mouse Associated with Exposure to Empagliflozin.
An increased incidence of renal tubular adenomas and carcinomas was identified in the 2-year CD-1 mouse carcinogenicity study with empagliflozin (sodium-glucose transporter 2 inhibitor) in high dose (1,000 mg/kg/day) male mice. A 13-week mouse renal investigative pathogenesis study was conducted with empagliflozin to evaluate dose dependency and temporal onset of nonneoplastic degenerative/regenerative renal tubular and molecular (genes, pathways) changes which precede neoplasia. Male and female CD-1 mice were given daily oral doses of 0, 100, 300, or 1,000 mg/kg/day (corresponding carcinogenicity study dose levels) for 1, 2, 4, 8, or 13 weeks. The maximum expected pharmacology with secondary osmotic diuresis was observed by week 1 at ≥100 mg/kg/day in both genders. Histopathologic kidney changes were first detected after 4 weeks of dosing in the male 1,000 mg/kg/day dose group, with progressive increases in the incidence and/or number of findings in this dose group so that they were more readily detected during weeks 8 and 13. Changes detected starting on week 4 consisted of minimal single-cell necrosis and minimal increases in mitotic figures. These changes persisted at an increased incidence at weeks 8 and 13 and were accompanied by minimal to mild tubular epithelial karyomegaly, minimal proximal convoluted tubular epithelial cell hyperplasia, and a corresponding increase in Ki-67-positive nuclei in epithelial cells of the proximal convoluted tubules. There were no corresponding changes in serum chemistry or urinalysis parameters indicative of any physiologically meaningful effect on renal function and thus these findings were not considered to be adverse. Similar changes were not identified in lower-dose groups in males nor were they present in females of any dose group. RNA-sequencing analysis revealed male mouse-specific changes in kidney over 13 weeks of dosing at 1,000 mg/kg/day. Treatment-related changes included genes and pathways related to p53-regulated cell cycle and proliferation, transforming growth factor β, oxidative stress, and renal injury and the number of genes with significant expression change dramatically increased at week 13. These treatment-related changes in genes and pathways were predominant in high-dose males and complemented the observed temporal renal tubular changes. Overall, these mouse investigative study results support the role of early empagliflozin-related degenerative/regenerative changes only observed in high-dose male CD-1 mice as a key contributing feature to a nongenotoxic mode of renal tumor pathogenesis.


Causal attribution of drinking antecedents in American Indian and Caucasian social drinkers.
Sixty-five American Indian and 100 Caucasian college students were tested with Beckman's rating scale for antecedents of drinking. Subjects were social drinkers who had had no previous alcohol-related problems (arrests, accidents, etc.). They were matched on age, education, and drinking history. The scale addresses beliefs about drinking and its related causes--internal and external. Results indicate only one major difference between Indians and Caucasians (alcoholism as an illness was rated higher by Indians), while similarities in rating patterns were found in comparing our college sample to college students from the Los Angeles area tested by Beckman. American Indian college students were significantly different in their causal attribution of drinking problems from white college students in Los Angeles.


[Lichenoid pityriasis. Immunologic study of 10 children].
Ten children clinically and histologically diagnosed as having pityriasis lichenoides (PL), have been studied by direct immunofluorescence (DIF). Circulating immune complexes (CI) have also been studied in four children. Granular deposits of IgM, located in the walls of the dermal vessels have been observed in two cases, but they have never been found at the dermo-epidermal junction. Granular deposits of C3 have been observed in three children, both in the walls of the dermal vessels and at the dermo-epidermal junction. The search for immune complexes gave negative results in all cases. The hypothesis of some authors that PL is an immune complex disease cannot be confirmed by our findings.


Percutaneous transjejunal approaches to the biliary system.
The authors report 10 cases in which various retrograde manipulations in the biliary tract were performed via percutaneous access from the jejunum in patients who had previously undergone Roux-Y biliary surgery. The first cases involved attempted retrograde cholangiography through the jejunal limb in children who had undergone Roux-Y portoenterostomies, followed by cases of percutaneous placement of U tubes and an attempt at percutaneous creation of an hepaticojejunostomy. When a limb from the Roux-Y has been brought to the skin and marked with clips, jejunal puncture is easily performed, is well tolerated by patients, and may be repeated frequently. It also appears that after Roux-Y choledochojejunostomy, the Roux-Y limb is fixed and may be punctured with relative safety. Since access from below is more favorable for intrabiliary manipulations, the transjejunal approach expands the armamentarium of the interventional radiologist in the combined radiologic and surgical management of complex biliary disease.


Catastrophic antiphospholipid syndrome and heparin-induced thrombocytopenia-related diseases or chance association?
Antiphospholipid syndrome (APS) and heparin-induced thrombocytopenia (HIT) are thrombotic disorders due to specific autoimmune-mediated antibodies. Catastrophic APS (CAPS), also known as Asherman's syndrome, is a life-threatening severe form of APS. Diagnostic criteria for CAPS include the development of a thrombotic event of three or more organs in less than a week with the presence of antiphospholipid antibodies and microvascular thrombosis on histology. Thrombocytopenia is seen in more than 60% of cases of CAPS. HIT is a life-threatening disorder with the clinical presentation of thrombocytopenia and arterial or venous thrombosis in patients who develop antibodies to heparin and platelet factor 4 typically within 10 days after starting heparin treatment. Due to the multiple similarities in clinical features and pathophysiology of CAPS and HIT, it has been postulated that these two antibody-mediated disorders may be related. We report two cases in which patients diagnosed with CAPS developed HIT very soon during the same admission as well as a case of a patient initially diagnosed with HIT who presented with CAPS years later.


The PhoQ-activating potential of antimicrobial peptides contributes to antimicrobial efficacy and is predictive of the induction of bacterial resistance.
Antimicrobial peptides (AMPs) are among the leading candidates to replace antibiotics which have been rendered ineffective by the evolution of resistant bacterial strains. Concerns do exist, however, that the therapeutic administration of AMPs may also select for resistant strains but with much more dire consequences, as these peptides represent an endogenous and essential component of host immune defense. The recent demonstration that AMPs function as ligands for the bacterial sensory kinase PhoQ for the initiation of virulence and adaptive responses lends credence to these concerns. While the ability to serve as PhoQ ligands suggests that the therapeutic administration of AMPs could (i) exacerbate infections by promoting bacterial virulence and (ii) select resistant mutants by encouraging adaptive behaviors, it also provides a rational basis for AMP selection and optimization. Here, we demonstrate that derivatives of a representative AMP have differential abilities to serve as PhoQ ligands and that this correlates with the ability to induce bacterial adaptive responses. We propose that PhoQ-activating potential is a logical parameter for AMP optimization and introduce a novel strategy for the treatment of minimal bactericidal concentration data that permits the discrimination and quantification of the contributions of PhoQ-activating potential and direct antimicrobial activity to net antimicrobial efficiency.


Resting-state brain activity in schizophrenia and major depression: a quantitative meta-analysis.
Intrinsic activity of the brain during resting-state is not random and is currently discussed as a neural reflection of self-referential processing. Self-reference is typically reduced in schizophrenia as a disorder of the self while extensive self-attribution of, eg, negative thoughts is characteristic for major depression. However, a quantitative meta-analysis targeting the resting-state brain activity in both disorders is lacking. Here, we predict primarily abnormal resting-state activity in brain regions related to self-referential processing. By means of activation likelihood estimation (ALE) on functional magnetic resonance imaging and positron emission tomography studies, we investigated concurrence of hyperactivation and hypoactivation in resting-state measurements of schizophrenic and depressed patients compared with healthy controls. We found hypoactivation in ventromedial prefrontal cortex (vmPFC), left hippocampus, posterior cingulate cortex, lower precueus and the precuneus, and hyperactivation in bilateral lingual gyrus of schizophrenic patients. In major depression, we found hyperactivation in vmPFC, left ventral striatum, and left thalamus and hypoactivation in left postcentral gyrus, left fusiform gyrus, and left insula. An overall ALE analysis confirmed the proximity of hypoactivation in schizophrenia and hyperactivation in major depression in the vmPFC.The opposing resting-state activity in vmPFC for the 2 disorders is in line with the different expression of dysfunctional self-reference as core characteristics of schizophrenia and major depression. The vmPFC has previously been identified as a crucial area for self-referential processing and may represent a target to increase the diagnostic validity of resting-state activity for disorders with dysfunctions of the self.


Phase I study of fixed dose gemcitabine plus epirubicin in patients with advanced solid malignancies.
A Phase I study was initiated to investigate fixed dose rate gemcitabine (GEM) combined with epirubicin (EPI) given weekly or every other week, since, GEM given as a standard 30 minute infusion has modest activity. The study was designed based on the hypothesis that prolonged exposure (over 90 minutes) may improve response rates and combination with epirubicin (EPI) is synergistic. Eligible patients had measurable refractory solid malignancies with adequate bone marrow, renal, and liver functions. Patients received GEM 800, 1000, 1250 mg/m(2) over 90 minutes followed by EPI 10 or 15 mg/m(2) as a 30 minutes infusion on days 1, 8, and 15 or days 1 and 15 of a 28 day cycle. Twenty-eight patients were enrolled and 24 are evaluable for overall toxicities and response rate. Toxicities include neutropenia (Gr 3 of Gr 4, 9 pts), thrombocytopenia (Gr 3 of Gr 4, 3 pts), fatigue (Gr 3 of Gr 4, 4 pts), and myalgia (Gr 3 of Gr 4, 1 pt). Dose limiting toxicity was grade 4 neutropenia. Seven patients experienced stable disease for >16 weeks and 3 patients with pancreatic cancer had partial responses. The maximum tolerated dose is GEM 800 mg/m(2)/EPI 10 mg/m(2) days 1, 8, 15 or GEM 1000 mg/m(2)/EPI 15 mg/m(2) days 1, 15 given every 4 weeks. Further studies are warranted with targeted therapies to define the efficacy of this doublet.


Thoracic spinal injuries: operative treatments and neurologic outcomes.
Between January 1983 and December 1997, 29 patients with either a fracture (11 patients) or a fracture-dislocation (18 patients) of the thoracic spine were treated operatively. All patients underwent posterior decompression and stabilization within a mean time of 4 days after injury (range, 0-45 days). Patients with complete paraplegia had no postoperative improvement in neurologic status, whereas all patients with incomplete spinal cord lesions improved in neurologic status after surgery. There was no significant association between time from injury to operation and final neurologic outcome. For thoracic fractures, the procedure of surgical decompression and stabilization is safe, and neurologic recovery may be anticipated in patients with incomplete spinal cord lesions.


Purification, characterization and immuno-modulating properties of polysaccharides isolated from Flammulina velutipes mycelium.
To investigate the immuno-modulating activity of Flammulina velutipes mycelium, three different Flammulina velutipes polysaccharides (FVPs) were isolated by fractionation using gel filtration and were identified as the immunomodulators of murine peritoneal macrophages. Based on the results of fourier transform infrared spectroscopy (FTIR), high performance liquid chromatography (HPLC), NMR spectroscopy, methylation analysis and gas chromatography-mass spectrogram (GC-MS), FVP2C was identified as glucose, galactose, mannose and fucose in molar ratio of 100: 14: 7: 4. FVP2C, molecular weight of 27.3 x 10(3) Da, was characterized as alpha-D-(1-->4)-glucan which was highly branched with alpha-D-(1-->6)-glucosyl residues, a single galactose or small amounts of mannoses and fucose at the C-6 position every twelve residues, on average, along the main chain. In the present study, it was found that three FVPs induced a significant increase in cellular nitric oxide formation, interleukin-1 production and tumor necrosis factor-alpha secretion in macrophages in vitro. The immuno-modulating activity of FVP2A, FVP2B and FVP2C was dose-dependent.


[Functional mechanism of glucocorticoid in bone turnover and bone structure].
The functional mechanism of glucocorticoid (GC)-induced osteoporosis is not fully understood. We examined to the effects of GC on bone turnover, minerals, structure, and bone strength in growing minipigs. GC administration caused prolongation of the period of bone tissue turnover in both trabecular and cortical bone and imbalance in bone formation and resorption, consequently leading to osteoporosis in growing minipigs. Bone structure were deteriorated both trabeculare and cortex. Deterioration of cortical bone rather than trabecular bone could play a role as main factor of bone fragilities in GC-induced osteoporosis.


Development and Testing of a Novel Arm Cranking-Powered Watercraft.
There is a lack of human-powered watercrafts for people with lower-body disabilities. The purpose of this study was therefore to develop a watercraft for disabled people and investigate the metabolic cost and efficiency when pedaling. The watercraft was designed by combining parts of a waterbike and a handbike. Nine able-bodied subjects pedaled the watercraft at different speeds on a lake to provide steady-state metabolic measurements, and a deceleration test was performed to measure the hydrodynamic resistance of the watercraft. The results showed a linear correlation between metabolic power and mechanical power (r2 = 0.93). Metabolic expenditure when pedaling the watercraft was similar to other physical activities performed by people with lower-body disabilities. Moreover, the efficiency of the watercraft showed to be comparable to other human-powered watercraft and could, as a result, be an alternative fitness tool especially for people with lower-body disabilities, who seek water activities. A number of suggestions are proposed however, to improve the efficiency and ergonomics of the watercraft.


[Acceleration of the metabolism of carcinogens in the maternal body and embryos].
Outbred mice on the 19th-21st day of pregnancy were injected intravenously 3,4-benzpyrene (BP) in the dosage of 15 mg/kg or 9,10-dimethyl-1,2-benzanthracene (DMBA) in the dosage of 40 mg/Kg in control groups, and moreover preliminary injected BP (24 hours before) in experimental groups. The BP concentration of embryos and the maternal liver 15 minutes following the injection of the basic dose of the carcinogen in increased dosage of preliminary exposure first would decrease, reach the minimum, in preliminary dosage equal to 0.75 mg/Kg, and then would increase up to values observed in control experiments with the dosage of 30 mg/Kr 7.5-15 mg/Kg, and then it would fall again in the dosage of 30 mg/Kg. The preliminary injection of BP in the dosage of 0.75 mg/Kg produced a sharp fall in the carcinogen concentration in embryos and the maternal organism during the first moment of observation (after 5 minutes), but it failed to influence the rate of subsequent decrease of the substance level. An explanation of the two effects observed is suggested based on the assumption that there exist two enzymatic systems metabolizing BP: one-premanently present in the liver and the other-induced by the carcinogen. The preliminary BP injection did not influence the concentration of DMBA.


[Peripheral neuropathy produced by cisplatin].
The authors tell about one case of peripheral neuropathy of the upper limbs as a complication of cis-diaminedichloroplatinum. It is a rare complication that has to be diagnosed early to prevent invalidating damage.


A novel combined conjugate vaccine: enhanced immunogenicity of bFGF with CRM197 as a carrier protein.
Tumor growth is partly dependent on tumor-associated angiogenesis, which is regulated by angiogenic growth factors. As the first angiogenic growth factor to be identified, basic fibroblast growth factor (bFGF) plays a major role in angiogensis and tumor growth and has been an effective target for anti-tumor therapy. However, due to its low immunogenicity, injection with bFGF alone cannot stimulate the body to produce a strong immune response. In this study, we investigated the role of CF (containing bFGF and CRM197) assisted by CpG and alum in enhancing antigen-specific immune response and suppressing the growth of murine colon carcinoma. The results revealed that compared to bFGF, CF could not stimulate NIH-3T3 fibroblast proliferation even at a concentration of 10 µg/ml in vitro. In vivo, the CF-CpG-alum produced a stronger antigen-specific immune response and inhibited tumor growth. The anti-tumor activity was associated with generating antigen-specific antibody, suppressing angiogenesis, promoting the apoptosis of tumor cells and inducing the mixed Th1 and Th2 responses. This indicates that CRM197 may be an innovative intramolecular adjuvant and provides a rational preservation for mouse CT26 colon carcinoma.


Children's Internet use in a family context: influence on family relationships and parental mediation.
We conducted a survey of 222 fourth-, fifth-, and sixth-grade Korean children to examine (a) whether children's Internet use influences declines in family time and family communication and (b) how parental mediation techniques are related to children's online activities. According to the findings, total time using the Internet was related to perceived declines in family time but not related to family communication. The influence of the Internet on family time and family communication differed by the type of children's online activities. The analysis of the relationship between parental mediation techniques and children's online activities indicated that parents' recommendation of useful Web sites and co-using were positively related to frequency of children's educational online activities. However, parental restrictions on time and Web sites did not alter children's actual Internet usage.


Effects of an oral health promotion program in people with mental illness.
More knowledge is needed regarding what works to prevent oral health problems and reduce disparities in oral health. Motivational interviewing (MI) has demonstrated utility for improving health behavior, including among those with severe mental illness. This study tests whether MI enhances the efficacy of an oral health education intervention in individuals with severe mental illness. Sixty individuals were randomly assigned to MI plus oral health education or oral health education alone. Plaque scores, oral health knowledge, and self-regulation were assessed at baseline and at 4 and 8 weeks. Repeated-measures ANOVA showed improvement (p < 0.05) in plaque, autonomous regulation, and oral health knowledge across time for both groups; however, individuals receiving MI improved significantly more when compared with those receiving oral health education alone. Results suggest that MI is effective for enhancing short-term oral health behavior change for people with severe mental illness and may be useful for the general population.


Collyrium names attested on stone tablets: the example of the Helvetian corpus.
Collyrium-stamps are usually parallelepipedic stones that might have been used in the Roman world, between the second part of the first century and the fourth century A.D., to stamp eye medicine. On their four narrow sides, those seals contain instructions engraved in retrograde characters, of varying drawing quality, sometimes in Greek, mostly in Latin and in an abbreviated form. These markings represent some sort of medical prescriptions since they contain one or more of the following information: a personal name in the genitive case, a collyrium name, therapeutic instructions, and a method of administration. Like personal names and therapeutic instructions, collyrium names suggest that Roman eye medicine was inscribed in the Greek medical tradition. A comparison between the collyrium names engraved on the seals unearthed in Switzerland and the collyrium names known through our reading the Greek medical texts allows for an estimation of the influence of Greek ophthalmology on Roman eye medicine.


Characterization of tea cultivated at four different altitudes using 1H NMR analysis coupled with multivariate statistics.
The taste of black tea differs according to the different areas in which the tea is grown, even for the same species of tea. A combination of (1)H NMR spectroscopy and partial least-squares discriminate analysis (PLS-DA) was used to assess the quality differences of tea leaves from four cultivation areas with different elevations, RAN > 1800 m, UDA = 1200 m, MEDA = 600 m, and YATA < 300 m, in Sri Lanka. As a result of a statistical analysis, PLS-DA showed a separation between high- and low-quality black teas derived from the four different tea cultivation areas. RAN from the highest elevation showed characteristic trends in the levels of theaflavin and theaflavin 3,3'-digallate that were found only in RAN, and the levels of theanine and caffeine were higher, and the levels of thearubigins, especially thearubigin 3,3'-digallate, were lower in RAN than in UDA, MEDA, and YATA. The structures of these components were determined by 1D and 2D NMR analyses. These results demonstrate that this method can be used to evaluate black tea quality according to the chemical composition or metabolites, which are characteristic of the tea leaves cultivated in four regions with different elevations in Sri Lanka.


Ultrafast study of 9-diazofluorene: direct observation of the first two singlet states of fluorenylidene.
Ultrafast photolysis of 9-diazofluorene (DAF) produces a broadly absorbing transient within the instrument time resolution (300 fs), which is assigned to an excited state of the diazo compound. The diazo excited state fragments to form fluorenylidene (Fl) in both its lowest energy singlet state (1Fl, 405-430 nm, depending on the solvent) and a higher energy singlet state (370 nm, 1Fl*). The excited singlet carbene has a lifetime of 20.9 ps in acetonitrile and decays to the lower energy singlet state (1Fl), which relaxes to the triplet ground state (3Fl) in acetonitrile, cyclohexane, benzene, and hexafluorobenzene. The equilibrium mixture of singlet and triplet fluorenylidene reacts with these solvents. Singlet fluorenylidene reacts with methanol and cyclohexene in competition with relaxation to 3Fl. One of the reaction products in methanol is the 9-fluorenyl cation. The rate of intersystem crossing (ISC) in hexafluorobenzene and other halogenated solvents is remarkably slow given that carbene ISC rates are generally fastest in nonpolar solvents. An explanation of this effect is advanced.


Non-otogenic lateral sinus thrombosis: a complication of acute sphenoid sinusitis.
The consequences of intracranial spread of sinus infection can be dismal. The subtle presentation of sphenoid sinusitis often leads to a delay in diagnosis. The disease may go unrecognized until complications are severe enough to cause more localizing symptoms. Often infections in the head and neck spread into the cranial cavity, leading to a localized effect. For example, otogenic infections can spread to the mastoid or lateral venous sinus. We report a case of sphenoid sinusitis complicated by lateral and sigmoid venous sinus thrombosis.


A theoretical study on the formation mechanism of carboxylic sulfuric anhydride and its potential role in new particle formation.
New particle formation (NPF) is the major source of atmospheric aerosol particles. However, the chemical species involved and the exact mechanism are still unclear. Cycloaddition reaction of SO3 to carboxylic acids bas been identified as a possible formation mechanism of carboxylic sulfuric anhydrides which may be involved in NPF. Herein, energy profiles for forming diaterpenylic acetate sulfuric anhydride (DTASA) through cycloaddition of SO3 to diaterpenylic acid acetate (DTAA) and the potential role of DTASA in NPF were studied through computational methods combined with atmospheric cluster dynamics code (ACDC). Gas phase reaction barriers for the two carboxyl groups of DTAA are 0.4 and 0.6 kcal mol-1, respectively, illustrating a feasible formation mechanism for DTASA. According to thermodynamical analysis and dynamical simulations, atmospheric clusters containing DTASA and atmospheric nucleation precursors sulfuric acid (SA), ammonia (NH3) and dimethylamine (DMA) possess both thermodynamically and dynamically higher stabilities than those of DTAA-contained clusters. Furthermore, DTASA-NH3 and DTASA-DMA are more stable than SA-NH3 and SA-DMA, enabling DTASA, even carboxylic sulfuric anhydrides, to become potential participants in the atmospheric NPF process which may hence promote a better understanding of NPF.


Prophylactic SSRI treatment for women suffering from mood and anxiety symptoms undergoing in vitro fertilization-a prospective placebo-controlled study.
To explore the mood protective effect of prophylactic SSRI treatment on women undergoing IVF suffering from moderate affective and anxiety symptoms. In a randomized double blind, placebo-controlled, parallel design study, 41 women diagnosed with an Adjustment Disorder, who were undergoing IVF treatments, were randomized into two groups; a study group (n = 22) administered escitalopram 10 mg/day, and a control group (n = 19) administered placebo for a total of 8 weeks before and during the IVF treatment cycle. Patients were assessed at the onset of drug treatment and at embryo transfer. The main outcome measure was the difference in mean score severity rating of depression and anxiety symptoms on the CES-D and Zung questionnaires between groups at the time of embryo transfer. Secondary outcome measures included the MHI rating subscales addressing aspects of psychological distress and coping. At the day of embryo transfer (6 weeks of drug treatment), the CES-D average score for the treatment group was 6.40 (6.71) and 27.47 (4.29) on the Zung Self-Rating Anxiety Scale, while the placebo group scored an average of 15.83 (8.69) and 33.17 (6.95) receptively. These findings were significant (p = .004, p = .015 receptively) and were endorsed by the scoring on the MHI questionnaire subscales. Short-term treatment with SSRI may serve as a prophylactic treatment against the perpetuation and possible worsening of depressive and anxiety symptoms in women undergoing IVF treatments. Further studies concerning pharmacological interventions in larger samples and studies addressing screening for psychological stress indicators in this population are warranted.


Race, socioeconomic resources, and late-life mobility and decline: findings from the Health, Aging, and Body Composition study.
This study examines the relationship between race and mobility over 5 years in initially well-functioning older adults and evaluates how a broad set of socioeconomic status indicators affect this relationship. Data were from 2,969 black and white participants aged 70-79 from the Health, Aging, and Body Composition study. Mobility parameters included self-reported capacity to walk a quarter mile and climb 10 steps and usual gait speed. Incident mobility limitation was defined as reported difficulty walking a quarter mile or climbing 10 steps at two consecutive semiannual assessments. Gait speed decline was defined as a 4% reduction in speed per year. At baseline, even though all participants were free of mobility limitation, blacks had slower walking speed than their white counterparts, which was not explained by poverty, education, reading level, or income adequacy. After 5 years, accounting for age, site, and baseline mobility, blacks were more likely to develop mobility limitation than whites. Adjusting for prevalent conditions at baseline eliminated this difference in women; controlling for education eliminated this difference in men. No differences in gait speed decline were identified. Higher rates of mobility loss observed in older blacks relative to older whites appear to be a function of both poorer initial mobility status and existing health conditions particularly for women. Education may also play a role especially for men.


The anticorrosion ability of titanium nitride (TiN) plating on an orthodontic metal bracket and its biocompatibility.
Typically, an orthodontic metal bracket is made from stainless steel. It has been shown that such metal may corrode in an acid- and chloride-rich environment. The purpose of the current study was to investigate a titanium nitride (TiN) ion-plated stainless steel orthodontic bracket's anticorrosion properties and compare its biocompatibility with that of non-TiN-plated brackets. The stainless-steel brackets studied here were tested in acidic artificial saliva. The plated metal bracket was produced by the titanium nitride (TiN) ion-plating method. The TiN-plating on the bracket surface was demonstrated to be successful by EDX analysis. The quantity of metallic-ion release under test immersion solutions was analyzed by atomic absorption spectrophotometry. Both TiN- and non-TiN-plated brackets may release detectable ions into the test solution, including nickel, chromium, manganese, copper, and iron (ferric). The anticorrosion ability of the plated bracket was analyzed by means of inductively coupled plasma atomic emission spectroscopy. The results revealed that the TiN-plated metal bracket did not increase the anticorrosion ability of the standard bracket. The biocompatibility of the TiN plating versus the standard bracket material resulting from bracket immersion in the test solution revealed no toxicity on U2OS cells using a methylthiazole tetrazolium (MTT) colorimetric assay. Clearly, the search for an improved technique for enhancing the anticorrosion ability of the normal metal orthodontic bracket should be continued.


Giant Room-Temperature Electrocaloric Effect of Polymer-Ceramic Composites with Orientated BaSrTiO3 Nanofibers.
Cooling based on the electrocaloric effect (ECE) is a promising solution to environmental and energy efficiency problems of vapor-compression refrigeration. Ferroelectric polymer-ceramics nanocomposites, integrating high electric breakdown of organic ferroelectrics and large EC strength of ceramics, are attractive EC materials. Here, we tuned the orientation of Ba0.67Sr0.33TiO3 nanofibers (BST nfs) in the P(VDF-TrFE-CFE) polymer. When the nfs were aligned parallel to the field, a ΔT of 11.3 K with an EC strength of 0.16 K·m/MV was achieved in the blends. The EC strength not only surpasses advanced nanocomposites but also is comparable to ferroelectric ceramics. The simulation indicates that a significantly higher electric field is concentrated in polymer regions around the ends of the orientated nfs, contributing to easier flipping of polymer chains for large ECE. This work provides a new method to obtain large ECE in composites for next-generation refrigeration.


Composition and local strain mapping in Au-catalyzed axial Si/Ge nanowires.
For most applications, heterostructures in nanowires (NWs) with lattice mismatched materials are required and promise certain advantages thanks to lateral strain relaxation. The formation of Si/Ge axial heterojunctions is a challenging task to obtain straight, defect free and extended NWs. And the control of the interface will determine the future device properties. This paper reports the growth and analysis of NWs consisting of an axial Si/Ge heterostructure grown by a vapor-liquid-solid process. The composition gradient and the strain distribution at the heterointerface were measured by advanced quantitative electron microscopy methods with a resolution at the nanometer scale. The transition from pure Ge to pure Si shows an exponential slope with a transition width of 21 nm for a NW diameter of 31 nm. Although diffuse, the heterointerface makes possible strain engineering along the axis of the NW. The interface is dislocation-free and a tensile out-of-plane strain is noticeable in the Ge section of the NW, indicating a lattice accommodation. Experimental results were compared to finite element calculations.


[Study on chronic toxicity to rats of implantation of super-high molecular weight polylactate].
To make sure whether super-high molecular weight polylactate is toxic to the body after it has been implanted into the body for a long period. We implanted super-high molecular weight polylactate into the rats and took the specimens of blood at 3, 6, 9, 12 months after the operation. The changes of proteins, electrolyte, enzyme and other indices were observed. At the same time, the tissue around the implants were taken out to carry out the histological observation. At 3, 6, 9, 12 months after the operation, the levels of albumin, globulin, total bilirubin, direct bilirubin, triglyceride, glucose, K+, Na+, Cl-, Ca2+, alkaline phosphatase, glutamic-pyruvic transaminase in the blood plasma were all in the normal range; there were no significant differences between the experimental group and the control group. The level of lactate dehydrogenase increased slightly, but there was no statistically significant difference between the experimental group and the control group. There were no non-reversible immune rejection around the implants in the histological observation. Super-high molecular weight polylactate is not toxic to the body after it has been implanted into the animals for a long period.


Development of Coronary Vasospasm during Adenosine-Stress Myocardial Perfusion CT Imaging.
Adenosine is a short-acting coronary vasodilator, and it is widely used during pharmacological stress myocardial perfusion imaging. It has a well-established safety profile, and most of its side effects are known to be mild and transient. Until now, coronary vasospasm has been rarely reported as a side effect of adenosine during or after adenosine stress test. This study reports a case of coronary vasospasm which was documented on stress myocardial perfusion CT imaging during adenosine stress test.


Digital image correlation assisted absolute phase unwrapping.
This paper presents an absolute phase unwrapping method for high-speed three-dimensional (3D) shape measurement. This method uses three phase-shifted patterns and one binary random pattern on a single-camera, single-projector structured light system. We calculate the wrapped phase from phase-shifted images and determine the coarse correspondence through the digital image correlation (DIC) between the captured binary random pattern of the object and the pre-captured binary random pattern of a flat surface. We then developed a computational framework to determine fringe order number pixel by pixel using the coarse correspondence information. Since only one additional pattern is used, the proposed method can be used for high-speed 3D shape measurement. Experimental results successfully demonstrated that the proposed method can achieve high-speed and high-quality measurement of complex scenes.


[Investigations of influential factors of acute renal injury after coronary artery bypass grafting].
To investigate the incidence, correlate factors and effect on convalescent of acute kidney injury (AKI) after coronary artery bypass grafting (CABG). Sixty-eight consecutive patients who underwent scheduled CABG were included. AKI was diagnosed according to the diagnostic criteria from expert group of AKI. The patients were divided into AKI group with AKI and control group without AKI. Difference of clinic features was contrasted between the two groups. And multivariable logistic regression modeling was used to identify the risk factors of AKI. AKI occurred in 27.94% patients (19/68). There was significant difference between the two groups in gender, hypertension, hyperlipemia, number of grafts, the duration of mechanic ventilation, the time of ICU and the length of stay post operation. Hypertension(Wald 3.27, P=0.07, 95% CI 0.85-53.59), number of grafts(Wald 7.67, P=0.01, 95%CI 1.48-9.73), the duration of mechanic ventilation(Wald 4.94, P=0.03, 95%CI 1.00-1.18) were risk factors of AKI in multivariable logistic regression modeling. The incidence of AKI was high (27.94%). Female, hypertension, hyperlipemia, number of grafts, the duration of mechanic ventilation were risk factors in monovariance analysis, and AKI may increase the time of ICU and the length of stay post operation. Hypertension, number of grafts, duration of mechanic ventilation were independent risk factors of AKI in multivariable logistic regression model.


Cytotoxic, embryotoxic, insecticidal and anti-microbial activities of standardized Areca catechu nut.
The study was aimed at evaluating various biological actions of widely consumed Areca catechu nut. The nut's ethanolic extract exhibited cytotoxicity (lung cancer cell line), embryotoxicity (chick embryo), phytotoxicity (Lemna minor), insecticidal (Rhyzopertha dominica), anti-bacterial (Pseudomonas aeruginosa), anti-fungal (Microsporum canis) and mitogenic (human blood lymphocytes) actions. The standardization results revealed presence of 1.7 μ g arecoline per mg of extract. In conclusion, the Areca nut is endowed with both harmful and beneficial biological actions. Keeping in view its wide consumption and ease of availability, the aforesaid information should be channelized for health and agricultural benefits.


Composite intestinal adenoma-microcarcinoid.
Composite intestinal adenoma and microcarcinoid is a rare intestinal neoplasm consisting of intermingled adenomatous and well-differentiated neuroendocrine components. A few case reports and small series have suggested an indolent clinical course for this entity. We reported 7 cases of composite intestinal adenoma-microcarcinoid, including their morphologic features and clinical follow-up, both in biopsy and resection specimens. We identified 7 cases of composite intestinal adenoma-microcarcinoid from our pathology database. Five were from the large intestine, and 2 were in the duodenum. Morphologically, all microcarcinoids exhibited low-grade cytologic atypia and were devoid of significant pleomorphism, necrosis, and mitotic activity. Among the 7 lesions, 6 had a lobular architecture with smooth borders and mucosa-confined microcarcinoids; none had neuroendocrine carcinoma in subsequent resections. However, 1 colonic case had carcinoid cells penetrating the muscularis mucosae into the submucosa with an infiltrative border, and the resection showed metastatic high-grade neuroendocrine carcinoma in 1 lymph node. Composite intestinal adenoma-microcarcinoid is extremely rare. Although composite mucosa-confined adenoma-microcarcinoid is likely to have an indolent behavior, submucosal invasion by the neuroendocrine component may be associated with aggressive behavior.


Spinal intradural hematoma and permanent paraparesis after a lumboperitoneal shunt operation: an unusual complication.
Pseudotumor cerebri is a condition of increased intracranial pressure in the absence of clinical, laboratory or radiological pathology. Spinal intradural hematoma formation after lumboperitoneal shunt (LPS) implantation is very rare, but it can cause sudden and serious deterioration. In this report, we present a patient who developed an intradural hematoma following LPS operation. A 27-year-old male patient suffering from headaches and progressive vision loss was diagnosed with pseudotumor cerebri. He underwent LPS operation in January 2009. Four hours after the operation, he developed urinary and fecal incontinence with paraparesis (1/5). Lumbar magnetic resonance imaging identified an intradural hematoma at the level of L2-L3, and he was reoperated. The intradural hematoma was removed. Physical therapy was started because of paraparesis. Two months later, the patient's muscle strength had increased to 3/5. Surgeons must remember that, LPS implantation can cause a spinal intradural hematoma in a small percentage of patients, with catastrophic results.


Development and evaluation of a microemulsion formulation for transdermal delivery of terbinafine.
The aim of the present study is to develop and evaluate microemulsion formulations for Terbinafine (TB) with a view to enhance its permeability through the skin and provide release for 24 h. Various o/w microemulsions were prepared by the spontaneous emulsification method. Oleic acid was chosen as the oil phase, Caprylo caproyl macrogol-8- glyceride (Labrasol S) and purified diethylene glycol monoethyl ether (Transcutol P) were used as surfactant and cosurfactant, respectively, on the basis of solubility studies. Pseudoternary phase diagrams were constructed to obtain the concentration range of oil, surfactant, cosurfactant, and water for microemulsion formulation. The optimized microemulsion consisted of 2% w/w TB, 8% w/w oleic acid, 31% w/w labrasol S, 31% w/w transcutol P, and 30% w/w distilled water. Permeability parameters like Jss and Kp were found to be significantly higher for formulation F4 as compared to other formulations (P < 0.05). Microbiological studies of TB in microemulsion showed better anti-fungal activity against Candida albicans and Aspergillus flavus as compared to marketed product (P < 0.05).


Heterogeneous Graph Propagation for Large-Scale Web Image Search.
State-of-the-art web image search frameworks are often based on the bag-of-visual-words (BoVWs) model and the inverted index structure. Despite the simplicity, efficiency, and scalability, they often suffer from low precision and/or recall, due to the limited stability of local features and the considerable information loss on the quantization stage. To refine the quality of retrieved images, various postprocessing methods have been adopted after the initial search process. In this paper, we investigate the online querying process from a graph-based perspective. We introduce a heterogeneous graph model containing both image and feature nodes explicitly, and propose an efficient reranking approach consisting of two successive modules, i.e., incremental query expansion and image-feature voting, to improve the recall and precision, respectively. Compared with the conventional reranking algorithms, our method does not require using geometric information of visual words, therefore enjoys low consumptions of both time and memory. Moreover, our method is independent of the initial search process, and could cooperate with many BoVW-based image search pipelines, or adopted after other postprocessing algorithms. We evaluate our approach on large-scale image search tasks and verify its competitive search performance.


Results of resting and ambulatory electrocardiograms in patients with hypothyroidism and after return to euthyroid status.
Hypothyroidism is not infrequently associated with an abnormally long QTc interval (> or = 450 msec). Rarely, marked prolongation of the QTc interval and malignant ventricular arrhythmias have been reported. In this study, QTc intervals on resting electrocardiograms (ECGs) were compared in 10 patients before and after treatment of hypothyroidism. The QTc interval increased in seven patients during euthyroidism compared with hypothyroidism, and decreased in three patients. During hypothyroidism, the QTc interval was mildly prolonged in 2 of the 14 patients; both had mild decreases in triiodothyronine (T3) or thyroxine (T4). The 24-hour ambulatory ECGs measured during hypothyroidism and after restoration of biochemical euthyroidism also were compared in 9 patients. There was no significant difference in ventricular ectopy. None of the 13 patients assessed during hypothyroidism had > or = 4 beats of ventricular tachycardia. There was no relationship between thyroid-stimulating hormone (TSH) or T3 levels and QTc intervals during hypothyroidism. A moderate correlation between lesser degrees of T4 depression and increasing QTc interval was present. Mild QTc prolongations are relatively common in patients with hypothyroidism and are usually associated with milder degrees of thyroid underactivity, but are not associated with clinically significant ventricular tachyarrhythmias.


Frequency of burn-trauma patients in an urban setting.
Burn-trauma patient encounters constitute 5% of the emergency department population. A large urban hospital will treat twice as many (ie, 10%) burn-trauma patients. Retrospective 44-month study. Metropolitan county hospital. Population-based sample of burn-only (n = 1102), burn-trauma (n = 120), and assault burn-trauma (n = 43) patients. Frequency and demographics. Just under 10% (n = 120) of the burn population had burn-trauma injuries. The mean +/- SD Injury Severity Score was 12 +/- 12 in these burn-trauma patients: 4 +/- 2 in outpatients and 14 +/- 13 in inpatients. The burn-only and burn-trauma groups had similar age ranges, ethnic distribution, frequency of inhalation injury, substance abuse, malnutrition, sepsis, pneumonia, diabetes mellitus, percentage total burn surface area, number of procedures, grafted areas, and mortality. Forty-three burn-trauma patients (35.8%) sustained injuries due to assault, compared with 123 (11.2%) in the burn-only group (P<.001). Burn-trauma patients who were assaulted had a mean +/- SD Injury Severity Score of 11 +/- 10. There was a significantly increased male-female ratio among the assault burn-trauma patients (6:1) compared with the burn-trauma (3:1) and burn-only (2.3:1) groups (P<.04). Most of these injuries were caused by an unknown assailant, in connection with an automobile, a motorcycle, a bicycle, or pedestrians intentionally struck by moving vehicles, or by child abuse. The main mechanism of injury was contact in 57 burn-trauma patients (47.5%), compared with 127 (11.5%) in the burn-only group (P<.001). A large urban population will have an increased frequency (2-fold in our center) of burn-trauma injuries. Assault and child abuse are significant contributory factors to burn-trauma injuries in this population.


Digital healthcare: the future.
Digital healthcare offers a huge range of possibilities and may improve the quality of patient care. The traditional paradigm of clinical history, examination, differential diagnosis and treatment may be improved by tools such as machine learning, mobile applications and sensors, wearables, and telehealth. The recent pandemic has accelerated the move towards this future, however, important concerns remain. These include ensuring that new technologies are assessed effectively and are introduced thoughtfully, data are unified into care records, and, ultimately, digital tools are underpinned with appropriate clinical support. Patients must benefit without worsening workload for the clinician. Old barriers may be overcome but new challenges will be faced, in particular, ensuring the promise of better care for those who lack access to smart phones and the internet will be crucial. Clinicians must continue to advocate for patients and their colleagues as we embrace the future of digital healthcare.


Alkane Coiling in Perfluoroalkane Solutions: A New Primitive Solvophobic Effect.
In this work, we demonstrate that n-alkanes coil when mixed with perfluoroalkanes, changing their conformational equilibria to more globular states, with a higher number of gauche conformations. The new coiling effect is here observed in fluids governed exclusively by dispersion interactions, contrary to other examples in which hydrogen bonding and polarity play important roles. FTIR spectra of liquid mixtures of n-hexane and perfluorohexane unambiguously reveal that the population of n-hexane molecules in all-trans conformation reduces from 32% in the pure n-alkane to practically zero. The spectra of perfluorohexane remain unchanged, suggesting nanosegregation of the hydrogenated and fluorinated chains. Molecular dynamics simulations support this analysis. The new solvophobic effect is prone to have a major impact on the structure, organization, and therefore thermodynamic properties and phase equilibria of fluids involving mixed hydrogenated and fluorinated chains.


Design of noncovalent inhibitors of human cathepsin L. From the 96-residue proregion to optimized tripeptides.
A novel series of noncovalent inhibitors of cathepsin L have been designed to mimic the mode of autoinhibition of procathepsin L. Just like the propeptide, these peptide-based inhibitors have a reverse-binding mode relative to a substrate and span both the S' and S subsites of the enzyme active site. In contrast to previous studies in which even moderate truncation of the full-length propeptide led to rapid reduction in potency, these blocked tripeptide-sized inhibitors maintain nanomolar potency. Moreover, these short peptides show higher selectivity (up to 310-fold) for inhibiting cathepsin L over K versus only 2-fold selectivity of the 96-residue propeptide of cathepsin L. A 1.9 A X-ray crystallographic structure of the complex of cathepsin L with one of the inhibitors confirms the designed reverse-binding mode of the inhibitor as well as its noncovalent nature. Enzymatic analysis also shows the inhibitors to be resistant to hydrolysis at elevated concentrations of the enzyme. The mode of inhibition of these molecules provides a general strategy for inhibiting other cathepsins as well as other proteases.


Insertion/Deletion Within the KDM6A Gene Is Significantly Associated With Litter Size in Goat.
A previous whole-genome association analysis identified lysine demethylase 6A (KDM6A), which encodes a type of histone demethylase, as a candidate gene associated to goat fecundity. KDM6A gene knockout mouse disrupts gametophyte development, suggesting that it has a critical role in reproduction. In this study, goat KDM6A mRNA expression profiles were determined, insertion/deletion (indel) variants in the gene identified, indel variants effect on KDM6A gene expression assessed, and their association with first-born litter size analyzed in 2326 healthy female Shaanbei white cashmere goats. KDM6A mRNA was expressed in all tissues tested (heart, liver, spleen, lung, kidney, muscle, brain, skin and testis); the expression levels in testes at different developmental stages [1-week-old (wk), 2, 3 wk, 1-month-old (mo), 1.5 and 2 mo] indicated a potential association with the mitosis-to-meiosis transition, implying that KDM6A may have an essential role in goat fertility. Meanwhile, two novel intronic indels of 16 bp and 5 bp were identified. Statistical analysis revealed that only the 16 bp indel was associated with first-born litter size (P < 0.01), and the average first-born litter size of individuals with an insertion/insertion genotype higher than that of those with the deletion/deletion genotype (P < 0.05). There was also a significant difference in genotype distributions of the 16 bp indel between mothers of single-lamb and multi-lamb litters in the studied goat population (P = 0.001). Consistently, the 16 bp indel also had a significant effect on KDM6A gene expression. Additionally, there was no significant linkage disequilibrium (LD) between these two indel loci, consistent with the association analysis results. Together, these findings suggest that the 16 bp indel in KDM6A may be useful for marker-assisted selection (MAS) of goats.


Association of Cullin1 haplotype variants with rheumatoid arthritis and response to methotrexate.
Aberrations in ubiquitin pathway have been implicated in many diseases and drug response. In a previous study on rheumatoid arthritis (RA) in Japanese population, significant association of Cullin1 gene (CUL1), an ubiquitin E3 ligase, was observed. CUL1 also mediates degradation of IκBα and p27, levels of which has been associated with RA etiology and drug response, respectively. We carried out a replication study of association of CUL1 polymorphisms with RA in a north Indian population. Allelic, genotypic, and haplotypic associations of a promoter and two intronic polymorphisms of CUL1 with RA and with methotrexate response in patients with RA, were tested. A significant association (P=0.00056, adjusted) of a haplotype A-T-T with RA (odds ratio=3.68; 95% confidence interval=1.86-7.27) and in patients with RA poorly responding to methotrexate treatment (P=0.04, adjusted) was observed. Association with CUL1 haplotype indicates a possible role of CUL1 variation(s) in RA and its response to methotrexate.


On the self-affinity of heparan sulfates from quiescent or proliferating normal 3T3 cells and from SV40-transformed cells.
35S-Labelled heparan sulfates derived from the culture medium (extracellular), a trypsinate of the cells (pericellular) and the cell residue (intracellular) of quiescent normal, proliferating normal or SV40-transformed 3T3 cells were analyzed for charge heterogeneity, by ion exchange chromatography and for self-affinity, by chromatography on heparan sulfate-agarose gels. Quiescent normal cells retained most of their heparan sulphate intra- or pericellularly. The surface-exposed material was charge heterogeneous and had a strong affinity for heparan sulfate. In cultures of growing cells and transformed cells most of the heparan sulfate was found in the medium. The heparan sulfate retained on the surface or growing cells had a lower self-affinity than did the corresponding material from normal and transformed cells. Although cell surface heparan sulfates from transformed cells showed affinity for a matrix substituted with the total heparan sulfate pool, the affinity for one particular subtype was much less pronounced or non-existent.


Increasing the cancer screening of the medically underserved in south Florida.
Diagnosis and treatment of cancers at advanced stages have contributed to a significantly lower survival rate among individuals of low socioeconomic status compared with those in higher brackets. In an effort to increase the accessibility and acceptability of cancer screening among such individuals in Dade County, Florida, the Cancer Control Division of the Sylvester Comprehensive Cancer Center at the University of Miami School of Medicine initiated a pilot early detection program in 1987. The program initially provided breast cancer screening for women, aged 40 and older, who attended ten community health care centers located in low-income neighborhoods. With the selection of Miami by the American Cancer Society as one of three sites for conducting a screening demonstration project for the socioeconomically disadvantaged, this program has recently been expanded to include pelvic screening for women, aged 40 and older, and prostate screening for men, aged 65 and older.


Beta-binomial modeling of CRISPR pooled screen data identifies target genes with greater sensitivity and fewer false negatives.
The simplicity and cost-effectiveness of CRISPR technology have made high-throughput pooled screening approaches accessible to virtually any laboratory. Analyzing the large sequencing data derived from these studies, however, still demands considerable bioinformatics expertise. Various methods have been developed to lessen this requirement, but there are still three tasks for accurate CRISPR screen analysis that involve bioinformatic know-how, if not prowess: designing a proper statistical hypothesis test for robust target identification, developing an accurate mapping algorithm to quantify sgRNA levels, and minimizing the parameters that need to be fine-tuned. To make CRISPR screen analysis more reliable as well as more readily accessible, we have developed a new algorithm, called CRISPRBetaBinomial or CB2 Based on the beta-binomial distribution, which is better suited to sgRNA data, CB2 outperforms the eight most commonly used methods (HiTSelect, MAGeCK, PBNPA, PinAPL-Py, RIGER, RSA, ScreenBEAM, and sgRSEA) in both accurately quantifying sgRNAs and identifying target genes, with greater sensitivity and a much lower false discovery rate. It also accommodates staggered sgRNA sequences. In conjunction with CRISPRcloud, CB2 brings CRISPR screen analysis within reach for a wider community of researchers.


Restoring the Mauri of Oruarangi Creek.
In recognition of the societal and cultural values of ecological restoration several community-based programs have been developed throughout the world. In particular those with interests in the field of freshwater and riparian management have developed numerous programs to encourage community involvement in their management. While each of these programs gives de facto recognition to an ethos typically espoused by indigenous peoples, the concerns, values and localised knowledge of indigenous peoples continues to remain excluded from the management process. In documenting key aspects of the proposed restoration of Oruarangi Creek this paper aims to provide an example of how the concerns, values and knowledge of local indigenous communities can form a major component of the restoration process.


Sexual intercourse and high-risk sexual behaviours among a national sample of urban adolescents in China.
To describe the characteristics of a population with high-risk sexual behaviours and associations between sexual intercourse, high-risk sexual behaviours and socio-demographic characteristics among Chinese urban adolescents. In 2005, 109,754 students in grades 10-12 and 33,653 college students were anonymously surveyed using a Chinese Youth Risk Behaviour Survey. Demographic variables and indicators of forced sex, condom use and unintended pregnancy were analysed with multiple logistic regressions. Of students surveyed, median age was 17.6 (range 14-24 years) and 76,233 were female (53.2%); 4.8% of high school students reported had experienced sexual intercourse; of these, 32.8% reported had forced sex; 11.3% of college students reported had experienced sexual intercourse and of these, the prevalence of forced sex, condom use and unintended pregnancy were 23.5, 49.7 and 24.2%, respectively. School type and socioeconomic status were found to be independently associated with sexual intercourse and forced sex for high school students. For college students, educational level, school type, family structure, maternal education and socioeconomic status were independently associated with high-risk sexual behaviours. This study highlights the association between high-risk sexual behaviours and school type and socioeconomic status. These results strongly suggest the importance of providing sex education in high schools and lower socioeconomic areas.


A 2,2',6,6'-tetraphosphinobiphenyl.
The first example of a 2,2',6,6'-tetraphosphinobiphenyl was prepared and used as a ligand in a dinuclear palladium(II) complex. The close proximity of the two complex fragments induces a coupling pathway allowing the allosteric communication between the two palladium complex fragments.


Depression and Hand-Grip: Unraveling the Association.
This review article explores the association between hand-grip strength and depression. A total of 14 studies were carefully considered to provide a comprehensive analysis of the topic. The studies reveal a consistent association between low hand-grip strength and depressive symptoms, independent of age, gender, and chronic disease status. The evidence suggests that hand-grip strength assessment could be a useful tool for identifying individuals at risk of depression, particularly older adults and those with chronic diseases. Incorporating physical activity and strength training into treatment plans can contribute to better mental health outcomes. Hand-grip strength assessment can also be used as a monitoring tool to track changes in physical and mental health over time in individuals with depression. Healthcare professionals should consider the relationship between hand-grip strength and depression when evaluating patients and developing treatment plans. The findings from this comprehensive clinical review have important clinical implications and highlight the importance of considering physical health factors in the context of mental health.


Evaluation of new MR invisible silicon carbide based dielectric pads for 7 T MRI.
The use of dielectric pads to redistribute the radiofrequency fields is currently a popular solution for 7 T MRI practical applications, especially in brain imaging. In this work, we tackle several downsides of the previous generation of dielectric pads. This new silicon carbide recipe makes them MR invisible and greatly extends the performance lifespan. We produce a set of two 10x10x1cm3 dielectric pads based on silicon carbide (SiC) powder dispersed in 4-Fluoro 1, 3-dioxalan-2-one (FEC) and polyethylene Glycol (PEG). The stability of the complex permittivity and the invisibility of the pads are characterized experimentally. Numerical simulations are done to evaluate global and local SAR over the head in presence of the pads. B0, B1+ and standard imaging sequences are performed on healthy volunteers. SiC pads are compared to state-of-the-art perovskite based dielectric pads with similar dielectric properties (barium titanate). Numerical simulations confirm that head and local SAR are similar. MRI measurements confirm that the pads do not induce susceptibility artefacts and improve B1+ amplitude in the temporal lobe regions by 25% on average. We demonstrate the long-term performance and invisibility of these new pads in order to increase the contrast in the brain temporal lobes in a commercial 7 T MRI head coil.


Large area smoothing of surfaces by ion bombardment: fundamentals and applications.
Ion beam erosion can be used as a process for achieving surface smoothing at microscopic length scales and for the preparation of ultrasmooth surfaces, as an alternative to nanostructuring of various surfaces via self-organization. This requires that in the evolution of the surface topography different relaxation mechanisms dominate over the roughening, and smoothing of initially rough surfaces can occur. This contribution focuses on the basic mechanisms as well as potential applications of surface smoothing using low energy ion beams. In the first part, the fundamentals for the smoothing of III/V semiconductors, Si and quartz glass surfaces using low energy ion beams (ion energy: ≤2000 eV) are reviewed using examples. The topography evolution of these surfaces with respect to different process parameters (ion energy, ion incidence angle, erosion time, sample rotation) has been investigated. On the basis of the time evolution of different roughness parameters, the relevant surface relaxation mechanisms responsible for surface smoothing are discussed. In this context, physical constraints as regards the effectiveness of surface smoothing by direct ion bombardment will also be addressed and furthermore ion beam assisted smoothing techniques are introduced. In the second application-orientated part, recent technological developments related to ion beam assisted smoothing of optically relevant surfaces are summarized. It will be demonstrated that smoothing by direct ion bombardment in combination with the use of sacrificial smoothing layers and the utilization of appropriate broad beam ion sources enables the polishing of various technologically important surfaces down to 0.1 nm root mean square roughness level, showing great promise for large area surface processing. Specific examples are given for ion beam smoothing of different optical surfaces, especially for substrates used for advanced optical applications (e.g., in x-ray optics and components for extreme ultraviolet lithography).


Reviving ethics in sports time for physicians to act.
When will we face the fact that we're producing some really ugly, violent young men?" observed my friend, an internationally prominent basketball coach, who is given neither to hand-wringing nor to strident overstatement. His disquieting words cast a pall over an already disheartening conversation about the state of contemporary sports.


Immunogenicity of retransplanted rat kidney allografts. Effect of inducing chimerism in the first recipient and quantitative studies on immunosuppression of the second recipient.
It has been previously shown that long surviving, enhanced (AS X AUG)F1 rat kidneys residing in a primary AS recipient are not acutely rejected if transferred into a second AS recipient. The reduced immunogenicity of the retransplanted graft was attributed to a depletion of incompatible passenger cells. It is shown here that if the primary AS recipient is made chimeric by x irradiation and injection of (AS X AUG)F1 bone marrow cells, transfer of the long surviving, enhanced graft into a second AS recipient provokes acute graft rejection comparable to that observed when normal (AS X AUG)F1 kidneys are transplanted into untreated AS recipients. Transplantation of passenger cell-depleted AUG kidneys into AS recipients leads to graft rejection, with a median survival time of 22 d. Treatment of these recipients with as little as 1.5 mg/kg cyclophosphamide for 14 d induces prolonged graft survival. By contrast, five times as much cyclophosphamide treatment is required to induce prolonged survival of normal AUG kidneys (i.e., containing incompatible passenger cells) transplanted to AS recipients. These results confirm that the major alloimmunogenic stimulus of rat kidney grafts is provided by the incompatible passenger cells.


The 100 Most-Cited Articles in COVID-19 Vaccine Hesitancy Based on Web of Science: A Bibliometric Analysis.
To perform a bibliometric analysis of the 100 most-cited articles (T100 articles) on COVID-19 vaccine hesitancy to characterize current trends. The data of the bibliometric analysis were retrieved from the Web of Science Core Collection (WoSCC) database on January 29, 2023, and the results were sorted in descending order by citations. Two researchers independently extracted the characteristics of the top 100 cited articles, including title, author, citations, publication year, institution, country, author keywords, Journal Cited Rank, and impact factor. Excel and VOSviewer were used to analyze the data. The T100 articles ranged from 79 to 1125 citations, with a mean of 208.75. The T100 articles were contributed by 29 countries worldwide, of which the USA ranked first with 28 articles and 5417 citations. The T100 articles were published in 61 journals; the top three citations were VACCINES, NATURE MEDICINE, and EUROPEAN JOURNAL OF EPIDEMIOLOGY, and the number of citations was 2690, 1712, and 1644, respectively. Professor Sallam, M(n=4) from Jordan, is the author who participated in the most published articles. Catholic University of the Sacred Heart (n=8) had the most T100 articles. It is the first bibliometric analysis of the T100 articles in the field of COVID-19 vaccine hesitancy. We carefully analyzed and described the characteristics of these T100 articles, which provide ideas for further strengthening COVID-19 vaccination and fighting against the epidemic in the future.


Effect of buformin on the regulation of glycogen metabolism in the skeletal muscle of normal rats.
In view of the experience that after short- or long-term oral administration of biguanides to rats no glycogenolysis in the muscle tissue occurs or even an increase of the muscle glycogen content and a high rate of incorporation of radioglucose into the muscle glycogen, the glycogen synthetase activity of skeletal muscle in a concentrated muscle homogenate and the effect of isoproterenol on glycogenolysis were investigated in normal rats after short-term oral administration of 1-butylbiguanide (buformin). The basal synthetase activity and the ATP inhibition of the enzyme were not affected by buformin, but the cyclic AMP mediated inactivation was significantly inhibited after buformin pretreatment. This inhibition was reversed by running the assay in the presence of Mg2+. Buformin also inhibited the isoproterenol induced glycogenolysis of the skeletal muscle tissue. From our results we suppose that biguanides may influence the regulation of glycogen metabolism by inhibiting the inactivating synthetase kinase and the activating phosphorylase kinase. It is possible that divalent cations like Mg2+ as an activator of kinase reactions are concerned.


Bladder urethral dysfunction after abdominoperineal resection of the rectum for ano-rectal cancer.
We prospectively studied bladder and urethral function in 44 patients before and after abdominoperineal resection of the rectum for ano-rectal cancer. The patients were investigated with the following examinations: combined cystometry and electromyography, urethral pressure profile measurement, urecholine denervation test, urine culture, urethrogram and residual urine measurement after voiding. Urodynamic results after surgery demonstrated the partial or total denervation of the detrusor muscle with bladder areflexia in the 54% of the cases, the decrease in the urethral pressure profile in the 48% of the cases, and the absence of detrusor sphincter dyssynergia in all cases. Urethrogram results showed a high incidence of bladder dislocation into the presacral space (36%). Urine cultures were frequently positive in 52% of the patients. Most patients (52%) had difficulty in voiding with high residual urine and/or stress incontinence (4.5%). All the patients received an early rehabilitative treatment with kinesitherapy and/or pharmacologic therapy after bladder catheter removal and after urodynamic results. The patients with neurogenic bladder with residual urine volume had satisfactory functional recovery of the activity.


Rural-Urban Differences in Behavioral Outcomes among Adults with Lifetime History of Traumatic Brain Injury with Loss of Consciousness: 2016-2019 Ohio BRFSS.
This study examined if the associations between lifetime history of traumatic brain injury (TBI) with loss of consciousness (LOC) and unhealthy alcohol use or mental health problems differ by location of living (rural vs. urban). The lifetime history data of TBI with LOC, location of living, unhealthy alcohol use (binge drinking, heavy drinking), and mental health problems (depression diagnosis, number of poor mental health days) were sourced from the 2016, 2017, 2018, and 2019 Ohio Behavioral Risk Factory Surveillance Surveys, and the final sample included 16,941 respondents. We conducted multivariable logistic regressions to determine the odds ratios for each of the five outcomes between individuals living in rural vs. urban areas and between individuals with vs. without a lifetime history of TBI with LOC. No interaction between location of living and lifetime history of TBI with LOC was observed for any outcomes, indicating rurality did not modify these relationships. Living in a rural area was associated with decreased binge drinking or heavy drinking but not mental health outcomes. Lifetime history of TBI with LOC was associated with an increased risk of binge drinking, heavy drinking, depression diagnoses, and poor general mental health, regardless of location of living. Our findings support the need for TBI screenings as part of mental health intake evaluations and behavioral health screenings. Though rurality was not associated with mental health outcomes, rural areas may have limited access to quality mental health care. Therefore, future research should address access to mental health services following TBI among rural residents.


Optimisation of methadone treatment in a group of patients on a mephedrone binge and dependent on many psychoactive substances.
Objectives: In recent years, an increase in the frequency of hospitalisations of patients on a mephedrone binge has been observed. The literature lacks data on the optimisation of methadone treatment in this group of people.Methods: The study included 601 patients who took mephedrone on a regular basis between 2010 and 2018. Based on the pharmacological database created, it was verified which methadone interaction contributed to subsequent hospitalisations in the group of people studied and which of them had the best therapeutic effect.Results: During the study, 62.4% of patients received methadone (p < .001). The higher the number of drugs taken together with methadone, the higher the frequency of hospitalisations (p < .001). The highest frequency of re-hospitalisations was recorded in patients who combined mephedrone with at least two other psychoactive substances, as well as those who used methadone with chlorprothixene (p < .001). The most optimal therapeutic effect is characteristic for the intake of methadone with thiazolidine carboxylic acid, namely 95% of people using this type of treatment were hospitalised once (p < .001).Conclusions: Therapy with methadone and thiazolidine carboxylic acid seems to be the most optimal therapy for patients taking mephedrone.Key pointsThe number of hospitalisations of patients receiving mephedrone on a regular basis grows from year to year.The multiple use of poly-pharmacotherapy increased in a group of patients on a mephedrone binge.There is a statistically significant correlation between the number of hospitalisations of patients on a mephedrone binge and the total number of drugs taken together with methadone.Administration of methadone with thiazolidine carboxylic acid was the most effective therapy for patients regularly combining mephedrone with at least two other psychoactive substances.