The neural basis of shared preference learning.
During our daily lives, we often learn about the similarity of the traits and preferences of others to our own and use that information during our social interactions. However, it is unclear how the brain represents similarity between the self and others. One possible mechanism is to track similarity to oneself regardless of the identity of the other (Similarity account); an alternative is to track each other person in terms of consistency of their choice similarity with respect to the choices they have made before (consistency account). Our study combined functional Magnetic Resonance Imaging (fMRI) and computational modelling of reinforcement learning (RL) to investigate the neural processes that underlie learning about preference similarity. Participants chose which of two pieces of artwork they preferred and saw the choices of one agent who usually shared their preference and another agent who usually did not. We modelled neural activation with RL models based on the similarity and consistency accounts. Our results showed that activity in brain areas linked to reward and social cognition followed the consistency account. Our findings suggest that impressions of other people can be calculated in a person-specific manner, which assumes that each individual behaves consistently with their past choices.


Comparison of zebrafish and mice knockouts for Megalencephalic Leukoencephalopathy proteins indicates that GlialCAM/MLC1 forms a functional unit.
Megalencephalic Leukoencephalopathy with subcortical Cysts (MLC) is a rare type of leukodystrophy characterized by astrocyte and myelin vacuolization, epilepsy and early-onset macrocephaly. MLC is caused by mutations in MLC1 or GLIALCAM, coding for two membrane proteins with an unknown function that form a complex specifically expressed in astrocytes at cell-cell junctions. Recent studies in Mlc1-/- or Glialcam-/- mice and mlc1-/- zebrafish have shown that MLC1 regulates glial surface levels of GlialCAM in vivo and that GlialCAM is also required for MLC1 expression and localization at cell-cell junctions. We have generated and analysed glialcama-/- zebrafish. We also generated zebrafish glialcama-/- mlc1-/- and mice double KO for both genes and performed magnetic resonance imaging, histological studies and biochemical analyses. glialcama-/- shows megalencephaly and increased fluid accumulation. In both zebrafish and mice, this phenotype is not aggravated by additional elimination of mlc1. Unlike mice, mlc1 protein expression and localization are unaltered in glialcama-/- zebrafish, possibly because there is an up-regulation of mlc1 mRNA. In line with these results, MLC1 overexpressed in Glialcam-/- mouse primary astrocytes is located at cell-cell junctions. This work indicates that the two proteins involved in the pathogenesis of MLC, GlialCAM and MLC1, form a functional unit, and thus, that loss-of-function mutations in these genes cause leukodystrophy through a common pathway.


Synthesis, characterization, DFT calculations and biological activity of new Schiff base complexes.
Schiff bases ligand (HL) was produced by condensing 4-aminobenzohydrazide with N-(4-chlorophenyl)-2-(4-formylphenoxy)acetamide. Cobalt (II), nickel (II), and copper (II) acetate and ligand are reacted to form 1:1 complexes. By using electronic spectra, magnetic susceptibility measurements, infrared data from 1H NMR, and XRD studies, the ligand and its metal complexes have been characterized. According to the spectrum data, the ligand functions as a monobasic bidentate, coordinating with the nitrogen atom of azomethine (-C[bond, double bond]N-) group and the oxygen atom of carbonyl group in enol form. An octahedral structure has been proposed for Co(II), Ni(II), and Cu(II) complexes according to magnetic and electronic spectrum analysis. Using the DFT method, the computational investigations of the ligand and its metal complexes showed the bond lengths, bond angles, and quantum chemical parameters. To determine the thermal stability and mode of thermal degradation of hydrazone ligand and its complexes, thermogravimetric analysis was approved out on the samples. Two calculated method, Horowitz-Metzger and Coats-Redfern, were used to calculate the characteristics of the composites' thermal degradation mechanisms at each step, including their breakdown kinetics. The ligand and its complexes were investigated for their cytotoxicity in vitro compared to human amnion (WISH) and epitheliod carcinoma (Hela). The Ni(II) complex showed highly inhibition against (WISH) growth (IC50 = 18.28±1.8 μM) with relationship to the produced chemicals and other common medications. The interaction between the ligand and its complexes with the genetic tumor (3hb5) receptor was examined using docking experiments.


Antiinflammatory, analgesic, and antipyretic activities of methyl 7-butyl-4,5,6,7-tetrahydro-3-methylamino-4,6-dioxo-5-propyl-2H-pyrazol o[3, 4-d]pyrimidine-2-carboxylate (AA-2379), a novel non-acidic agent.
The antiinflammatory, analgesic, and antipyretic activities of methyl 7-butyl-4,5,6,7-tetrahydro-3-methylamino-4,6-dioxo-5-propyl-2H-pyrazolo[ 3, 4-d]pyrimidine-2-carboxylate (AA-2379), a novel non-acidic agent, were examined. 1. AA-2379 had a potent antiinflammatory activity; 3-25 mg/kg, p.o. of the compound inhibited rat carrageenin-, bradykinin-, trypsin-, formalin-, dextran-, and nystatin-induced paw edema; mouse traumatic edema; and rat croton oil pouch inflammation by about 30%. The compound at 25-50 mg/kg, p.o. also inhibited the vascular permeability induced by histamine, serotonin, and bradykinin. 2. AA-2379 had an analgesic activity; the ID50 values in mouse phenylquinone-induced writhing were 10.1 mg/kg, p.o. and the compound at 12.5 mg/kg, p.o. inhibited dog urate arthritis. 3. AA-2379 at 3-10 mg/kg, p.o. showed antipyretic activity in febrile rats and rabbits. 4. AA-2379, at 500 mg/kg, p.o. was not ulcerogenic in rats. 5. These data show that AA-2379 is more active than non-acidic antiinflammatory agents, such as tiaramide and aminopyrine.


Prediction of Ovarian Hyperstimulation Syndrome in Patients Treated with Corifollitropin alfa or rFSH in a GnRH Antagonist Protocol.
What is the threshold for the prediction of moderate to severe or severe ovarian hyperstimulation syndrome (OHSS) based on the number of growing follicles ≥ 11 mm and/or estradiol (E2) levels? The optimal threshold of follicles ≥11 mm on the day of hCG to identify those at risk was 19 for both moderate to severe OHSS and for severe OHSS. Estradiol (E2) levels were less prognostic of OHSS than the number of follicles ≥ 11 mm. In comparison to long gonadotropin-releasing hormone (GnRH) agonist protocols, the risk of severe OHSS is reduced by approximately 50% in a GnRH antagonist protocol for ovarian stimulation prior to in vitro fertilisation (IVF), while the two protocols provide equal chances of pregnancy per initiated cycle. Nevertheless, moderate to severe OHSS may still occur in GnRH antagonist protocols if human chorionic gonadotropin (hCG) is administered to trigger final oocyte maturation, especially in high responder patients. Severe OHSS following hCG trigger may occur with an incidence of 1-2% in a relatively young (aged 18 to 36 years) IVF population treated in a GnRH-antagonist protocol. From the Engage, Ensure and Trust trials, in total, 2,433 women who received hCG for oocyte maturation and for whom the number of follicles ≥ 11 mm and the level of E2 on the day of hCG administration were known were included in the analyses. The threshold for OHSS prediction of moderate and severe OHSS was assessed in women treated with corifollitropin alfa or daily recombinant follicle stimulation hormone (rFSH) in a gonadotropin-releasing hormone (GnRH)-antagonist protocol. Receiver operating characteristics curve analyses for moderate to severe OHSS and severe OHSS were performed on the combined dataset and the sensitivity and specificity for the optimal threshold of number of follicles ≥ 11 mm, E2 levels on the day of (hCG), and a combination of both, were determined. The optimal threshold of follicles ≥ 11 mm on the day of hCG to identify those at risk of moderate to severe OHSS was 19 (sensitivity and specificity 62.3% and 75.6%, respectively) and for severe OHSS was also 19 (sensitivity and specificity 74.3% and 75.3%, respectively). The positive and negative predictive values were 6.9% and 98.6%, respectively, for moderate to severe OHSS, and 4.2% and 99.5% for severe OHSS. This was a retrospective analysis of combined data from three trials following ovarian stimulation with two different gonadotropins. For patients with 19 follicles or more ≥11 mm on the day of hCG, measures to prevent the development of OHSS should be considered. Secondary preventive measures include cycle cancellation or coasting, use of a GnRH agonist to trigger final oocyte maturation in place of hCG and a freeze all strategy. ClinicalTrials.gov NCT00702845 NCT00696800 NCT00696878.


The Ax21 protein influences virulence and biofilm formation in Stenotrophomonas maltophilia.
Stenotrophomonas maltophilia is an antibiotic-resistant Gram-negative pathogen, which is associated with hospital-acquired infection. The genome encodes a protein highly related to the Ax21 protein of Xanthomonas oryzae that is implicated in interactions of this plant pathogen with rice. Here, we report on the pleiotropic nature of ax21 mutation in S. maltophilia and the effects of addition of the Ax21 protein on the restoration of the wild-type phenotype. We show that loss by mutation of Ax21 leads to reduced motility, reduced biofilm formation, reduced tolerance to the antibiotic tobramycin and reduced virulence to larvae of Galleria mellonella, as well as alteration in the expression of specific genes associated with virulence or antibiotic resistance. Addition of the Ax21protein restored motility and the level of gene expression towards wild type. These findings are consistent with the notion that the Ax21 protein is involved in intraspecies communication, although other interpretations cannot be discounted.


Characterization of the bisintercalative DNA binding mode of a bifunctional platinum-acridine agent.
The DNA interactions of PT-BIS(ACRAMTU) ([Pt(en)(ACRAMTU)2](NO3)4; ACRAMTU = 1-[2-(acridin-9-ylamino)ethyl]-1,3-dimethylthiourea, en = ethylenediamine), a bifunctional platinum-acridine conjugate, have been studied in native and synthetic double-stranded DNAs and model duplexes using various biophysical techniques. These include ethidium-DNA fluorescence quenching and thermal melting experiments, circular dichroism (CD) spectroscopy and plasmid unwinding assays. In addition, the binding mode was studied in a short octamer by NMR spectroscopy in conjunction with molecular modeling. In alternating copolymers, PT-BIS(ACRAMTU) shows a distinct preference for poly(dA-dT)2, which is approximately 3-fold higher than that of ACRAMTU. In the ligand-oligomer complex, d(GCTATAGC)2.PT-BIS(ACRAMTU) (complex I*), PT-BIS(ACRAMTU) increases the thermal stability of the B-form host duplex by DeltaT(m) > 30 K (CD and UV melting experiments). The agent unwinds pSP73 plasmid DNA by 44(+/-2) degrees per bound molecule, indicating bisintercalative binding. A 2-D NMR study unequivocally demonstrates that PT-BIS(ACRAMTU)'s chromophores deeply bisintercalate into the 5'-TA/TA base pair steps in I*, while the platinum linker lies in the minor groove. An AMBER model reflecting the NMR results shows that bracketing of the central AT base pairs in a classical nearest neighbor excluded fashion is feasible. PT-BIS(ACRAMTU) inhibits DNA hydrolysis by BstZ17 I at the enzyme's restriction site, GTA downward arrowTAC. Possible consequences for other relevant DNA-protein interactions, such as those involved in TATA-box-mediated transcription initiation and the utility of the platinum-intercalator technology for the design of sequence-specific agents are discussed.


Shape-dependent catalytic activity of CuO/MgO nanocatalysts.
CuO/MgO catalysts with various shapes have been obtained by using morphology-controlled synthesis technology. It is demonstrated that there is a remarkable difference in catalytic activity for CO oxidation among these samples. However, when all these catalysts react with water before calcination, their shapes become irregular and similar, consequently, the difference of their catalytic activities disappears.


Naphthyl- and quinolylluciferin: green and red light emitting firefly luciferin analogues.
In the course of investigations on the possible involvement of the CIEEL (chemically initiated electron-exchange luminescence) mechanism in firefly bioluminescence, we have synthesized two novel firefly luciferin substrate analogues. D-Naphthylluciferin and D-quinolylluciferin were prepared by condensing D-cysteine with 2-cyano-6-hydroxynaphthalene and 2-cyano-6-hydroxyquinoline, respectively. These analogues are the first examples of bioluminescent substrates for firefly luciferase that do not contain a benzothiazole moiety. Firefly luciferase-catalyzed bioluminescence emission spectra revealed that compared to the normal yellow-green light of luciferin (lambda max = 559 nm), the emission from naphthylluciferin is significantly blue-shifted (lambda max = 524 nm); whereas quinolylluciferin emits orange-red light (lambda max = 608 nm). The fluorescence emission spectra, reaction pH optima, relative light yields, light emission kinetics and KM values of the analogues also were measured and compared to those of luciferin. Neither of the analogues produced the characteristic flash kinetics observed for the natural substrate. Instead, slower rise times to peak emission intensity were recorded. It appears that the formation of an intermediate from the analogue adenylates prior to the addition of oxygen is responsible for the slow rise times. The synthetic substrate analogues described here should be useful for future mechanistic studies.


Topographic distribution of brain iron deposition and small cerebrovascular lesions in amyotrophic lateral sclerosis and in frontotemporal lobar degeneration: a post-mortem 7.0-tesla magnetic resonance imaging study with neuropathological correlates.
Amyotrophic lateral sclerosis (ALS) is associated with frontotemporal lobar degeneration (FTLD) in 15% of the cases. A neuropathological continuity between ALS and FTLD-TDP is suspected. The present post-mortem 7.0-tesla magnetic resonance imaging (MRI) study compares the topographic distribution of iron (Fe) deposition and the incidence of small cerebrovascular lesions in ALS and in FTLD brains. Seventy-eight post-mortem brains underwent 7.0-tesla MRI. The patients consisted of 12 with ALS, 38 with FTLD, and 28 controls. Three ALS brains had minor FTLD features. Three coronal sections of a cerebral hemisphere were submitted to T2 and T2* MRI sequences. The amount of Fe deposition in the deep brain structures and the number of small cerebrovascular lesions was determined in ALS and the subtypes of FTLD compared to control brains, with neuropathological correlates. A significant increase of Fe deposition was observed in the claustrum, caudate nucleus, globus pallidus, thalamus, and subthalamic nucleus of the FTLD-FUS and FTLD-TDP groups, while in the ALS one, the Fe increase was only observed in the caudate and the subthalamic nuclei. White matter changes were only significantly more severe in the FTLD compared to those in ALS and in controls brains. Cortical micro-bleeds were increased in the frontal and temporal lobes of FTLD as well as of ALS brains compared to controls. Cortical micro-infarcts were, on the other hand, more frequent in the control compared to the ALS and FTLD groups. The present study supports the assumption of a neuropathological continuity between ALS and FTLD and illustrates the favourable vascular risk profile in these diseases.


DNA methylation marker to estimate the breast cancer cell fraction in DNA samples.
Estimation of the cancer cell fraction in breast cancer tissue is important for exclusion of samples unsuitable for multigene prognostic assays and a variety of molecular analyses for research. Here, we aimed to establish a breast cancer cell fraction marker based on DNA methylation. First, we screened genes unmethylated in non-cancerous mammary tissues and methylated in breast cancer tissues using microarray data from the TCGA database, and isolated 12 genes. Among them, four genes were selected as candidate marker genes without a high incidence of copy number alterations and with broad coverage across patients. Bisulfite pyrosequencing analysis of additional breast cancer biopsy specimens purified by laser capture microdissection (LCM) excluded two genes, and a combination of SIM1 and CCDC181 was finally selected as a fraction marker. In further additional specimens without LCM purification, the fraction marker was substantially methylated (≥ 20%) with high incidence (50/51). The cancer cell fraction estimated by the fraction marker was significantly correlated with that estimated by microscopic examination (p < 0.0001). Performance of a previously established marker, HSD17B4 methylation, which predicts therapeutic response of HER2-positive breast cancer to trastuzumab, was improved after the correction of cancer cell fraction by the fraction marker. In conclusion, we successfully established a breast cancer cell fraction marker based on DNA methylation.


Mechanisms of Antiphospholipid Syndrome Induction: Role of NKT Cells.
The review discusses the mechanisms of participation of natural killer T cells (NKT cells) in the induction of antiphospholipid antibodies (APA) that play a major pathogenetic role in the formation of antiphospholipid syndrome (APS), summarizes the data on APS pathogenesis, and presents modern concepts on the antibody formation involving follicular helper type II NK cells.


Development of a three-dimensional topographic map display for capillary electrophoresis/mass spectrometry with an ion trap/reflectron time-of-flight mass spectrometer detector: applications to tryptic digests of isoforms of myelin basic protein.
A three-dimensional (3-D) contour map format has been developed to display the large amount of data continuously collected throughout an on-line capillary separation using an ion trap storage/reflectron time-of-flight detector (IT/reTOF). The resulting data are displayed on a single computer screen with a mass-to-charge ratio value-elution time-intensity representation. The intensity of various components is represented by 16 different colors so that the mass-to-charge ratio value, the elution time, and the intensity can be conveniently determined for each component. In addition, the mass spectrum and total ion chromatogram or total ion electropherogram (TIE) are shown on the same screen as the 3-D map that enables the correlation of a single spot in the 3-D map to the peaks in the TIE and the corresponding mass spectrum. The 3-D map has been used to identify various posttranslational modification sites of bovine myelin basic protein charge isomers, where the datafiles of tryptic digests of proteins analyzed by capillary electrophoresis/mass spectrometry were processed by this software and a comparison could be performed among the isoforms. The feature of in-screen integration over both the separation domain and the mass domain makes the acquisition of the selected ion chromatogram very convenient and greatly improves the ability to detect modified components present in low amounts.


Late results after mitral valve replacement with bileaflet mechanical prosthesis in children: evaluation of prosthesis-patient mismatch.
Mechanical prosthesis is the choice of valve at the mitral position in children, although re-replacement of prostheses because of prosthesis-patient mismatch is almost inevitable when prostheses were implanted in small children. The methods to predict prosthesis-patient mismatch as a result of patients' somatic growth or pannus formation in children by noninvasive methods have not been well established. Thirty-two children underwent mitral valve replacement with 37 bileaflet mechanical prostheses (26 St. Jude Medical prosthetic valves, and 11 CarboMedics prosthetic valves) and were followed up a mean of 6.8 years (maximum 18.3 years) with a complete follow-up rate of 94%. There were no operative deaths and 5 late deaths. Re-replacement of mitral valve because of prosthesis-patient mismatch was required in 5 patients. Freedom from valve-related events and re-replacement of mitral valve at 15 years were 32% +/- 23% and 54% +/- 18%, respectively. Actuarial survival rate was 63% +/- 19% at 15 years. Prosthetic valve orifice area index (manufactured geometric prosthetic valve area divided by patient's body surface area) was well correlated with maximum transprosthesis flow velocity estimated by Doppler echocardiography during follow-up, whereas valve orifice area index had no significant correlation with pulmonary artery wedge pressure assessed by cardiac catheterization. Maximum transprosthesis flow velocity had a significant correlation with pulmonary artery wedge pressure. Valve orifice area index itself was not a reliable index to predict prosthesis-patient mismatch. Maximum transprosthesis flow velocity was a useful index to predict pulmonary artery wedge. Invasive cardiac catheterization to determine re-replacement of the prosthesis should be considered when maximum transprosthesis flow velocity exceeds 270 cm/s.


Prevention of diet-induced fatty liver in experimental animals by the oral administration of a fatty acid bile acid conjugate (FABAC).
Fatty acid bile acid conjugates (FABACs) are a new family of synthetic molecules designed to solubilize biliary cholesterol. They were shown to prevent and dissolve cholesterol gallstones in inbred C57L/J mice fed a lithogenic, high-fat diet (HFD). In these mice, fatty liver was observed in the controls but not in the FABAC-treated ones. The present study was designed to study the effect of FABAC (arachidyl-amido-cholanoic acid) on diet-induced fatty liver in rats, hamsters, and mice. The fatty liver score (on a scale of 0-4 by light microscopy) was 4.0 in control hamsters and 0.3 in the FABAC-fed hamsters (P <.001). In mice it was 1.5 and 0.4, respectively (P <.01). The lipid/protein ratio in the liver was 1.3 +/- 0.44 (mg lipid/mg protein) in control rats and 0.66 +/- 0.04 in the FABAC group (P =.001) after 14 days. In hamsters it was 1.41 +/- 0.27 and 1.11 +/- 0.20, respectively (P =.03), after 21 days. In Imperial Charles River (ICR) mice the ratio was 0.34 +/- 0.10 and 0.17 +/- 0.07 (P =.03), respectively, after 24 days. Liver fat concentration, measured as mg lipid/g liver tissue, decreased similarly by FABAC feeding. The decrease in liver fat affected mainly the triglyceride levels. FABAC-fed animals gained weight similarly to the controls. Triglyceride absorption was unaffected by FABAC supplementation. In conclusion, oral FABAC therapy prevents/reduces the development of fatty liver in animals consuming a HFD.


Hysteroscopic Endometrial Resection in Women Treated With Tamoxifen for Breast Cancer Provides Definitive Diagnosis and Effective Long-Term Therapy.
We evaluated resectoscopic surgery for definitive diagnosis and long-term therapy in 16 symptomatic tamoxifen-treated women with breast cancer who presented with abnormal uterine bleeding and/or intrauterine anomalies. Seven pre-menopausal women had benign pre- and post-operative endometrial biopsy, and 4 had benign polyps. At a median of 7 years of follow-up (range 2-8 y), all remained amenorrheic. Of 9 post-menopausal women, pre-operative biopsy was inadequate in 4, benign endometrium was found in 4, and non-atypical endometrial hyperplasia was found in 1. Post-operatively, all had benign pathology, 8 having polyp and 1 leiomyoma. At a median follow-up of 7 years (range 2-13 y), all were amenorrheic, with no recurrence of breast cancer or uterine pathology.


Single and multiple dose pharmacokinetics of tenoxicam in the elderly.
Fourteen elderly subjects (10 women, 4 men) with a mean age of 81 (SD 6.7) years and in need of anti-inflammatory drug treatment were given a single dose of 20 mg tenoxicam. After a drug-free interval of 5 weeks, multiple dose treatment with 20 mg tenoxicam once daily for 56 days was initiated. The single and multiple dose kinetics of tenoxicam were investigated after HPLC determination of tenoxicam in the plasma. The elimination half-life of tenoxicam ranged from 44 to 132 h (mean 71.9 h) with no significant difference between the single and multiple dosage regimens. Tenoxicam reached maximum plasma concentrations after 1.4 and 1.1 h, with values of 3.6 and 15.5 micrograms.ml-1, for the single and multiple dosage regimen respectively. The corresponding trough values (24-h values) were 1.8 and 11.7 micrograms.ml-1. A mean accumulation ratio of 5.1 was calculated. The mean increase in the area under the plasma concentration time curves at steady-state was 21% more than predicted from the initial single dose. This deviation from linearity was considered to be of minor clinical significance. The kinetics of tenoxicam in elderly were similar to that published for young healthy volunteers.


Diverse regulation of atrial natriuretic peptide secretion by serotonin receptor subtypes.
Serotonin (5-hydroxytryptamine [5-HT]) receptors are located in peripheral tissues as well as in the central nervous system. Serotonin receptors mediate positive inotropic and chronotropic effects in atria. The aim of this study was to investigate physiological role of endogenous serotonin on the regulation of atrial natriuretic peptide (ANP) secretion from the atria. An isolated perfused nonbeating rat atrial model was used. Changes in atrial volume induced by increasing intra-atrial pressure were measured. The concentration of ANP was measured by radioimmunoassay and the translocation of ECF was measured by [3H]-inulin clearance. Serotonin, an endogenous 5-HT receptor agonist, caused concentration-dependent suppressions of stretch-induced ANP secretion, which were less pronounced than those caused by alpha-methyl-5-HT maleate, a 5-HT(2) receptor selective agonist. The suppression of stretch-induced ANP secretion due to serotonin and alpha-methyl-5-HT maleate was attenuated by ketanserin, a 5-HT(2) receptor antagonist, and accentuated by RS23597-190, a 5-HT(4) receptor antagonist. The suppressive effect of serotonin on ANP secretion was attenuated by neomycin, staurosporine, and chelerythrine. In contrast, 2-[1-(4-piperonyl)piperazinyl]benzothiazole, a 5-HT(4) receptor selective agonist, caused an accentuation of stretch-induced ANP secretion, which was completely blocked by RS23597-190 and SB203186 HCl but not by ketanserin. This effect was not affected by MDL12330, KT-5720, or H-89. The intracellular Ca(2+) concentration in single atrial myocytes was not changed by serotonin and agonist for either 5-HT(2) or 5-HT(4) receptor. These results suggest that atrial 5-HT(2) and 5-HT(4) receptor agonists have opposite actions on the regulation of ANP secretion and the suppressive effect of serotonin on the ANP secretion may act through 5-HT(2) receptor and phospholipase C pathway.


Imaging the fetal spine using in utero MR: diagnostic accuracy and impact on management.
In-utero MR imaging (iuMR) has entered the clinical arena during the last decade. It is used mainly for imaging fetal brain abnormalities. To report our experience of imaging the fetal spine and spinal cord in fetuses with known or suspected abnormalities diagnosed on US imaging. Prospective imaging and retrospective analysis of the possible impact on management of 50 consecutive fetuses with spinal abnormalities detected by antenatal US imaging. In 40 (80%) of 50 fetuses, iuMR and US imaging were in complete agreement. In the other 10 fetuses (20%), iuMR provided additional information or changed the diagnosis, including 8 fetuses where the iuMR could find no abnormality and was found to be correct by later follow-up. IuMR is useful in fetuses with a suspected spinal abnormality. The clinical impact of iuMR may be numerically less than with brain abnormalities, but is still sufficient to warrant its use, especially if there is any uncertainty about the US imaging, and particularly as a relatively high proportion of diagnoses on US imaging are false-positives.


Association between low-density lipoprotein receptor-related protein gene, butyrylcholinesterase gene and Alzheimer' s disease in Chinese.
To research the relations between low-density lipoprotein receptor-related protein gene (LRP) polymorphism, butyrylcholinesterase gene (BchE) polymorphism and Alzheimer's disease (AD) in Chinese. The gene polymorphisms of LRP and BchE were genotyped in 38 AD cases and 40 controls with polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methods. AD groups were classified according to the LRP C/C genotype and compared with matched controls. AD group had higher frequencies of C/C homozygote (81.69% vs 60.0%, P < 0.05) and of C allele (89.5% vs 76.3%, P < 0.05), with no significant difference between any of these LRP genotypes classified AD groups and their respective control groups. A positive correlation was found between LRP gene polymorphism and AD, but not between BchE gene polymorphism and AD in Chinese AD cases.


Effects of pharmacological manipulation on neurotransmitter and other amino acid levels in the CSF of the Senegalese baboon Papio papio.
The concentrations of GABA, glutamate, aspartate, glycine, taurine, glutamine, asparagine and alanine were determined in the CSF of 10 Senegalese baboons (Papio papio) following initial ketamine anaesthesia and subsequent administration (4 h later) of different compounds known to alter either inhibitory or excitatory neurotransmission. Ketamine itself was apparently without effect as the administration of a second dose of ketamine did not significantly alter the levels of any of the amino acids studied, although GABA levels tended to decrease. The presence of haemolysed material in occasional samples was associated with high GABA, glutamate, aspartate, taurine and asparagine levels. Therefore only haemolysate-free samples were included for analysis. Of the compounds administered, gamma-vinyl GABA had the most evident effect on CSF amino acid levels, increasing GABA (greater than 5-fold) and decreasing glutamate (greater than 50%), aspartate (40-50%), asparagine (20%) and alanine (30-35%) levels. The changes in GABA, glutamate and aspartate were still apparent 24 h post-gamma-vinyl GABA administration. In contrast, sodium valproate did not significantly alter the CSF levels of any of the amino acids studied. Upon acute administration allylglycine decreased the CSF concentrations of GABA and alanine, but not glutamate. These alterations are unlikely related to the occurrence of allylglycine-induced convulsions (in 2 of 4 experiments) as electroconvulsive shock did not alter CSF amino acid levels. During the experimental period encompassing the allylglycine injection (8 weeks), basal (initial post-ketamine, pre-drug sample) amino acid levels were abnormal with large increases in glutamate, GABA, aspartate and taurine whereas asparagine levels were below the limit of detection. Diazepam administration was followed by a significant increase in taurine and a decrease in aspartate levels.(ABSTRACT TRUNCATED AT 250 WORDS)


A personalised approach to antibiotic pharmacokinetics and pharmacodynamics in critically ill patients.
Critically ill patients admitted to intensive care unit (ICU) with severe infections, or those who develop nosocomial infections, have poor outcomes with substantial morbidity and mortality. Such patients commonly have suboptimal antibiotic exposures at routinely used antibiotic doses related to an increased volume of distribution and altered clearance due to their underlying altered physiology. Furthermore, the use of extracorporeal devices such as renal replacement therapy and extracorporeal membrane oxygenation in these group of patients also has the potential to alter in vivo drug concentrations. Moreover, ICU patients are likely to be infected with less-susceptible pathogens. Therefore, one potential contributing cause to the poor outcomes observed in critically ill patients may be related to subtherapeutic antibiotic exposures. Newer concepts include the clinician considering optimised dosing based on a blood antibiotic exposure defined by pharmacokinetic modelling and therapeutic drug monitoring, combined with a knowledge of the antibiotic penetration into the site of infection, thereby achieving optimal bacterial killing. Such optimised dosing is likely to improve patient outcomes. The aim of this review is to highlight key aspects of antibiotic pharmacokinetics and pharmacodynamics (PK/PD) in critically ill patients and provide a PK/PD approach to tailor antibiotic dosing to the individual patient.


Effect of Cuscuta chinensis on renal function in ischemia/reperfusion-induced acute renal failure rats.
The kidneys play a central role in regulating water, ion composition and excretion of metabolic waste products in the urine. Cuscuta chinensis has been known as an important traditional Oriental medicine for the treatment of liver and kidney disorders. Thus, we studied whether an aqueous extract of Cuscuta chinensis (ACC) seeds has an effect on renal function parameters in ischemia/reperfusion-induced acute renal failure (ARF) rats. Administration of 250 mg/kg/day ACC showed that renal functional parameters including urinary excretion rate, osmolality, Na(+), K(+), Cl(-), creatinine clearance, solute-free water reabsorption were significantly recovered in ischemia/reperfusion-induced ARF. Periodic acid Schiff staining showed that administration of ACC improved tubular damage in ischemia/reperfusion-induced ARF. In immunoblot and immunohistological examinations, ischemia/reperfusion-induced ARF decreased the expressions of water channel AQP 2, 3 and sodium potassium pump Na,K-ATPase in the renal medulla. However, administration of ACC markedly incremented AQP 2, 3 and Na,K-ATPase expressions. Therefore, these data indicate that administration of ACC ameliorates regulation of the urine concentration and renal functions in rats with ischemia/reperfusion-induced ARF.


Complement C4 allotype association with and serum C4 concentration in an autoimmune disease in the dog.
Serum C4 concentrations and C4 allotypes were determined wherever possible on eight dogs with an autoimmune disorder characterized by antinuclear antibody (ANA) positivity, pyrexia, and seronegative arthritis. Three of the six dogs tested serially showed hypocomplementemia at disease onset with return to normal concentrations with clinical remission following steroid therapy. All five dogs C4 allotyped were phenotypically identical. The phenotype (C4-4) was significantly increased in the diseased dogs. Thus C4 allotype may provide a marker for susceptibility to development of an autoimmune disorder in the dog. Serum C4 concentrations may help in disease diagnosis and monitoring the effectiveness of therapy.


A review of the mechanism for poor placentation in early-onset preeclampsia: the role of autophagy in trophoblast invasion and vascular remodeling.
Shallow trophoblast invasion and impaired vascular remodeling of spiral arteries have been recognized in early-onset preeclampsia. Placentation and vascular remodeling are multistep processes, and hypoxia, placental oxidative stress, excessive or atypical maternal immune response to trophoblasts, exaggerated inflammation, and increased production of anti-angiogenic factors such as the soluble form of the vascular endothelial growth factor (VEGF) receptor (sFlt-1) and soluble endoglin (sENG) may play a role in poor placentation in preeclampsia. Recent findings suggest that autophagy plays an important role in extravillous trophoblast (EVT) invasion and vascular remodeling under hypoxia, and sENG inhibits EVT invasion and vascular remodeling by the inhibition of autophagy under hypoxic conditions. In this review, we discuss the relationship between inadequate autophagy and poor placentation in preeclampsia.


Ureteroscopy in children: is there a need for ureteral dilation and postoperative stenting?
Ureteroscopic stone manipulation and extraction is the standard of care for distal stone disease in the adult population. Recently, with refinements in instrumentation, these standards have been applied in pediatrics. Here, we investigate the role of ureteral dilation and the need for postoperative stenting after ureteroscopy. Twenty-nine children (21 male, eight female) with a mean age of 11.0 (2.5-17.5) years underwent 34 ureterscopic procedures (21 right, 13 left) to address ureteral stones in 27 (23 distal, 3 mid and 1 proximal), surveillance of the upper tract in six and a retained stent in one. Active ureteral dilation was not required in any of these patients. A Wolfe 4.5-F or 6.5-F tapered semi-rigid ureterescope was passed alongside a previously placed guidewire to access the upper collecting system. Proximal ureteral surveillance was performed after completion of the procedure; all but two patients had a diagnostic ureterogram. Four patients had preoperative placement of a JJ stent. Postoperative stents were placed in six patients, two had stents placed preoperatively for infection associated with either autonomic dysreflexia or stone impaction, two for extravasation or perforation, one for edema and one for subsequent ESWL. Mean follow up after ureteroscopy was 16.2 (0.3-48) months. Of the 27 procedures for stone disease, 15 (55%) stones required laser litholipaxy and 12 (45%) were managed with stone basket extraction. The overall re-treatment rate for stone disease was 4%. Diagnostic ureteroscopy was normal in six procedures. None of the procedures managed without a post-ureteroscopy stent required subsequent intervention. Ureteroscopy is a safe, effective method to manage ureteral stones. Refinements in instrumentation allow its application to the pediatric population. Ureteroscopy including laser lithotripsy can be performed without ureteral dilation or postoperative stenting.


[Coagulation problems associated with massive blood transfusions. An experimental study (author's transl)].
During storage banked blood show changes as far as function and concentration of their corpuscular and plasmatic ingredients are concerned. Antihaemophilic globulin (factor VIII) and pro-accelerin (factor V) in particular lose their activities so quickly that only very few activities still remain after a storage period of 3-5 days. In connection with existing primary diseases but also in trauma and shock a dilution-coagulopathy caused by insufficient supply of factors VIII and V can develop during massive transfusion, and this especially with banked blood already stored over a longer period of time. Therapy of this disturbance of coagulation consists of substituting the missing coagulation factors under heparin protection.


Optimization with artificial intelligence of the machinability of Hardox steel, which is exposed to different processes.
In this study, different process types were processed on Hardox 400 steel. These processes were carried out with five different samples as heat treatment, cold forging, plasma welding, mig-mag welding and commercial sample. The aim here is to determine the changes in properties such as microstructure, microhardness and conductivity that occur in the structure of hardox 400 steel when exposed to different processes. Then, the samples affected by these changes were processed in WEDM with the box-behnken experimental design. Ra, Kerf, MRR and WWR results were analyzed in Minitab 21 program. In the continuation of the study, using these data, a prediction models were created for Ra, Kerf, MRR and WWR with Deep Learning (DL) and Extreme Learning Machine (ELM). Anaconda program Python 3.9 version was used as a program in the optimization study. In addition, a linear regression models are presented to comparison the results. According to the results the lowest Ra values were obtained in heat-treated, cold forged, master sample, plasma welded and mig-mag welded processes, respectively. The best Ra (surface roughness) value of 1.92 µm was obtained in the heat treated sample and in the experiment with a time off of 250 µs. Model F value in ANOVA analysis for Ra is 86.04. Model for Ra r2 value was obtained as 0.9534. The lowest kerf values were obtained in heat-treated, cold forged, master sample, plasma welded and mig-mag welded processes, respectively. The best kerf value of 200 µ was obtained in the heat treated sample and in the experiment with a time off of 200 µs. Model F value in ANOVA analysis for Kerf is 90.21. Model for Kerf r2 value was obtained as 0.9555. Contrary to Ra and Kerf, it is desirable to have high MRR values. On average, the highest MRR values were obtained in mig-mag welded, plasma welded, cold forged, master sample and heat-treated processes, respectively. The best mrr value of 200 g min-1 was obtained in the mig-mag welded sample and in the experiment with a time off of 300 µs. Model for MRR r2 value was obtained as 0.9563. The lowest WWR values were obtained in heat-treated, cold forged, master sample, plasma welded and mig-mag welded processes, respectively. The best wwr value of 0.098 g was obtained in the heat treated sample and in the experiment with a time off of 200 µs. Model F value in ANOVA analysis for WWR is 92.12. Model for wwr r2 value was obtained as 0.09561. In the analysis made with artificial intelligence systems; The best test MSE value for Ra was obtained as 0.012 in DL and the r squared value 0.9274. The best test MSE value for kerf was obtained as 248.28 in ELM and r squared value 0.8676. The best MSE value for MRR was obtained as 0.000101 in DL and the r squared value 0.9444. The best MSE value for WWR was obtained as 0.000037 in DL and the r squared value 0.9184. As a result, it was concluded that different optimization methods can be applied according to different outputs (Ra, Kerf, MRR, WWR). It also shows that artificial intelligence-based optimization methods give successful estimation results about Ra, Kerf, MRR, WWR values. According to these results, ideal DL and ELM models have been presented for future studies.


Tensile properties of human knee joint cartilage. II. Correlations between weight bearing and tissue pathology and the kinetics of swelling.
The nonequilibrium or kinetic swelling behavior of normal, fibrillated, and osteoarthritic (OA) (removed from total knee joint replacements) human knee joint cartilage has been measured using our isometric tensile apparatus (ITA). We found that large local variations exist in the manner with which human knee joint cartilage swells, including anisotropic effects, inhomogeneities, and dependence on local biochemical composition and pathological condition. The ITA provides three convenient biomechanical parameters--peak stress (sigma p), stress relaxation (sigma R), and diffusion coefficient (D)--to quantify the kinetics of swelling. We used these parameters to quantify and differentiate the kinetic swelling behavior of normal, fibrillated, and osteoarthritic cartilage, as well as the swelling behavior of cartilage from high and low weight-bearing areas. Also, these kinetic swelling parameters correlated very well, though by varying degrees, with such biochemical measures as collagen/proteoglycan ratio, hexosamine content/wet weight, and hydroxyproline content/dry weight, providing important insight into the mechanisms and processes involved during the course of swelling. Hence, the kinetic swelling behavior of cartilage should be used to provide important information not obtainable from equilibrium swelling studies.


Multidimensional Assessment of Subjective Well-Being and Risk of Dementia: Findings from the UK Biobank Study.
This study aimed to examine the associations between subjective well-being (SWB) and risk of all-cause dementia, Alzheimer's disease (AD), and vascular dementia (VD). We adopted a multidimensional approach to SWB that included the level and breadth of SWB, the latter indicating the extent to which SWB spreads across life domains. Participants (N=171,197; mean age=56.78; SD=8.16 years) were part of the UK Biobank and were followed up to 8.78 years. Domain-general and domain-specific SWB were measured by single items, and the breadth of SWB was indexed with a cumulative score of satisfaction across domains. Dementia incidence was ascertained through hospital and death records. Cox regression was used to examine the association between SWB indicators and risk of all-cause dementia, AD, and VD. General happiness, health and family satisfaction, and satisfaction breadth (satisfaction in multiple domains) were associated with lower risk of all-cause dementia. The associations held after accounting for socio-demographics, health, behavioral, and economic covariates, and depressive symptoms. Health satisfaction and the breadth of satisfaction were also associated with lower risk of AD and VD, with a pattern of slightly stronger associations for VD compared to AD. Some life domains (e.g., health) may be more fruitfully targeted to promote well-being and help protect against dementia, but it is also important to enhance well-being across multiple domains to maximize the protective effects.


Patients' quality of life improves after surgical intervention of stage III medication-related osteonecrosis of the jaw.
The treatment of advanced stages of medication-related osteonecrosis of the jaw (MRONJ) remains challenging. In order to improve decision making concerning the therapy, we examined the change of patients' quality of life (QoL) after surgical treatment of MRONJ stage III. The primary outcome variable was patients' QoL. It was preoperative (T0), 6 weeks postoperative (T1) and 6 months postoperative (T2) assessed by the European Organisation for Research and Treatment of Cancer QoL-H&N35 (EORTC QoL-H&N35) and the Oral Health Impact Factor-G14 (OHIP-G14) questionnaire in a prospective cohort study. Other variables included location, age, sex, risk factors, and recurrence. Descriptive statistics and general multivariate regression models were calculated. Forty-three patients with stage III MRONJ underwent surgery. OHIP-G14 scores decreased (improvement) statistically significant (p = .001) by 52.02% (T0-T1) and 56.45% (T1-T2). EORTC QoL-H&N35 showed statistical improvement for "swallowing" (p = .007), "opening mouth" (p = .045), "painkiller" (.005), "weight loss" (.004), "pain" (p = .001), "trouble with social eating" (p = .001), "trouble with social contact" (p = .001), and "teeth" (p = .001). Patients who developed a recurrence did not show any significant higher (worse) scores in OHIP G14 or EORTC QoL-H&N35 scores compared with patients without recurrence. Twenty-nine out of 36 patients showed full mucosal healing (T2). For patients with no full mucosal healing, a downgrade to stage I was achieved. In terms of QoL patients with stage III MRONJ do benefit from surgical treatment. The incident of a recurrence seems to have no significant impact on patients QoL.


A Novel Biflavonoid from Rhus leptodictya.
An investigation of the leaves of Rhus leptodictya led to the isolation of the new biflavonoid: 5,5",6",7,8-pentahydroxy-2,2"-bis(p-hydroxyphenyl)-4H,4"H- 3,7"-bichromene-4,4"-dione the structure of which was established by NMR spectroscopy and mass spectrometry.


Peroral Endoscopic Myotomy for Achalasia in a Thoracic Surgical Practice.
Peroral endoscopic myotomy (POEM) is a new option in the treatment of achalasia. It has typically been performed by general surgeons and gastroenterologists familiar with advanced endoscopic procedures. Our objective was to assess the initial experience and outcomes with POEM by a thoracic surgeon. A retrospective chart review was performed of all patients who underwent POEM from October 2012 until December 2014. Pre- and post-POEM evaluation included upper endoscopy, high-resolution manometry, and a timed barium swallow. There were 35 patients (18 men and 17 women), with a median age of 53 years. Based on high-resolution manometry, there were 8 patients (23%) with type I, 21 (60%) with type II, and 5 (14%) with type III achalasia, and 1 patient had hypertensive lower esophageal sphincter. Prior therapy had been performed in 18 patients (51%). The POEM procedure was completed in all but 1 patient. On follow-up, dysphagia was improved in all patients. The Eckardt score was significantly reduced from 7 before POEM to 0 after POEM (p < 0.0001), and improved similarly for all manometric types of achalasia. Post-POEM upper endoscopy showed esophagitis in 55% of patients, but this condition resolved in all with acid suppression. Timed barium swallow showed a reduction of esophageal retention at 5 minutes from 63% before POEM to 5% after POEM. Ten patients had follow-up at 12 months or greater after POEM and the improvements persisted. Peroral endoscopic myotomy is a safe and effective therapy for achalasia. It provides reliable and persistent palliation of dysphagia and objective improvement in esophageal emptying. Esophagitis is common but resolves with acid suppression therapy. Thoracic surgeons with an interest in esophageal diseases and experience with endoscopy are encouraged to adopt the procedure.


Patient Willingness to Accept Antibiotic Side Effects to Reduce Surgical Site Infection After Colorectal Surgery.
Mechanical bowel preparation with antibiotics is associated with decreased surgical site infections (SSI) after colorectal surgery. However, antibiotics have side effects, such as vomiting. It is unknown how patient willingness to take antibiotics is affected by side effect severity. This was a single-center study of 86 patients (37 undergoing colorectal surgery) using a modified standard gamble technique. We presented patients with four hypothetical scenarios, holding SSI reduction constant and varying antibiotic side effect severity. Patients reported willingness to take antibiotics using a scale from 0 to 100. Patients also reported the maximum level of side effects they would accept. We examined the association between side effect severity and willingness to take antibiotics with a multivariable mixed-effects regression model and investigated differences in surgical and nonsurgical patients. After adjusting for age, sex, and patient type, willingness scores decreased with increasing side effect severity. No side effects: 92 (CI 86,99), mild: 83 (CI 76,90), moderate: 76 (CI 69,83), and severe: 46 (CI 38,52), P < 0.001. Surgical patients were more willing to take antibiotics at all severity levels compared with nonsurgical patients, P < 0.001. Surgical (57%) and nonsurgical (58%) patients reported that they would accept moderate side effects. Patients with prior SSI (n = 5) would take antibiotics regardless of side effect severity. Increasing antibiotic side effect severity is associated with decreased willingness to take antibiotics during bowel preparation, despite a reduction in SSI. Adherence may be improved with strategies that increase patient education and decrease side effects during bowel preparation.


Virus-specific T-cell responses associated with hepatitis C virus (HCV) persistence in the liver after apparent recovery from HCV infection.
Hepatitis C virus (HCV) RNA persistence in the liver has been described even after apparent resolution of HCV infection. Because T-cell reactivity plays a role in recovery from HCV infection, virus-specific T-cell responses were investigated in apparently recovered individuals in whom hepatic HCV RNA persistence was documented: 15 sustained virological responders to interferon (IFN)-treatment and 9 asymptomatic aviremic anti-HCV carriers. HCV-specific CD4(+) T-cell proliferative responses were detected significantly more often in apparently recovered individuals (sustained virological responders: 60%; asymptomatic anti-HCV carriers: 66%) compared with 50 chronic hepatitis C patients (28%; P < 0.05). However, T-cell frequencies and numbers tended to decline over time and the number of HCV proteins targeted by CD4(+) T-cell proliferative responses was limited. Interestingly, liver viral load correlated inversely with virus-specific immune responses. Thus, CD4(+) T-cell responders showed significantly lower hepatic HCV RNA levels (P < 0.05). HCV-specific IFN-gamma-secreting CD4(+) T-cells were not detected in all the apparently recovered patients although they were found significantly more often compared with chronic hepatitis C patients (P < 0.05). Also, HCV NS3-specific CD8(+) T-cells were detected in 11 HLA-A2-positive apparently recovered individuals (8 sustained virological responders and 3 asymptomatic anti-HCV carriers); T-cell frequencies tended to be greater in those patients who had lower hepatic viral levels. In conclusion, HCV-specific T-cells are detectable in apparently recovered individuals in whom HCV RNA can persist in the liver indicating that HCV replication may be prolonged in the face of an insufficient or inadequate virus-specific CD4(+) and CD8(+) T-cell response.


High Short-Term Failure Rate Associated With Decellularized Osteochondral Allograft for Treatment of Knee Cartilage Lesions.
To report the short-term clinical and radiographic outcomes following the use of decellularized osteochondral (OC) allograft plugs in the treatment of distal femoral OC lesions. An Institutional Review Board-approved database with prospectively collected data was used to identify patients treated with the decellularized OC allograft plugs implant. Demographic information, patient-reported outcomes, magnetic resonance imaging (MRI), and the number and type of reoperations were assessed. Failure was defined as revision surgery with removal of the implant. Patients were evaluated pre- and postoperatively using the Short Form-36, Activity of Daily Living Score, International Knee Documentation Committee Subjective Evaluation, Cincinnati Knee Rating System, and Marx Activity Scale. MRIs were evaluated using the OsteoChondral Allograft MRI Scoring System. Thirty-four patients were identified, with a mean age of 45 (±11.9) years; 71% were male. Fifteen (44%) patients had undergone prior ipsilateral surgical intervention. Mean defect size was 4 (±1.5) cm2, and median number of allografts per knee was 2 (range, 1-5). Mean follow-up duration was 15.5 months (range, 6-24). Ten patients (29%) required revision surgery with removal of the implant. Implant survivorship was 61% at 2 years. Female gender was independently predictive of failure, with a hazard ratio of 9.4 (95% confidence interval [CI], 2.0-58.9; P = .005). Defect size was also independently predictive of failure, with a hazard ratio of 1.9 per 1 cm2 increase (95% CI, 1.2-3.1; P = .005). MRIs obtained at 1 year postoperatively demonstrated significantly improved osseous integration (P = .0086) and opposing cartilage (P = .019) in the nonfailure group as compared with the failure group. Based on the high short-term failure rate observed in this study, the authors advise that a decellularized OC allograft plugs implant should be used with caution in the treatment of OC lesions of the knee, as similar outcomes have not been noted with other cartilage restoration techniques. LEVEL OF EVIDENCE: Level IV, therapeutic case series.


A uniformly convergent numerical scheme for solving singularly perturbed differential equations with large spatial delay.
In this study, a parameter-uniform numerical scheme is built and analyzed to treat a singularly perturbed parabolic differential equation involving large spatial delay. The solution of the considered problem has two strong boundary layers due to the effect of the perturbation parameter, and the large delay causes a strong interior layer. The behavior of the layers makes it difficult to solve such problem analytically. To treat the problem, we developed a numerical scheme using the weighted average ( θ -method) difference approximation on a uniform time mesh and the central difference method on a piece-wise uniform spatial mesh. We established the Stability and convergence analysis for the proposed scheme and obtained that the method is uniformly convergent of order two in the temporal direction and almost second order in the spatial direction. To validate the applicability of the proposed numerical scheme, two model examples are treated and confirmed with the theoretical findings.


Minimally invasive percutaneous new designed transpedicular lag-screw fixation for the management of Hangman fracture using O-arm-based navigation: a clinical study.
To investigate the outcomes and safety of using minimally invasive percutaneous new transpedicular lag-screw fixation with intraoperative, full rotation, three-dimensional image (O-arm)-based navigation for the management of Hangman fracture. Twenty-two patients with Hangman fracture were treated with minimally invasive percutaneous new transpedicular lag-screws using intraoperative, full rotation, and three-dimensional image (O-arm)-based navigation. The preoperative and postoperative conditions of the patients were evaluated according to the ASIA (American Spinal Injury Association) scale. The patient's VAS (visual analog scale) scores before and after surgery, operation time, cervical vertebral activity, intervertebral angle and bone healing were recorded and collected, and repeated measures analysis of variance was used for statistical analysis. All patients were satisfactorily repositioned after surgery, and the VAS scores for neck pain were significantly lower than those before surgery on the first day and at 1 month, 3 months and the last follow-up (P < 0.001). According to the ASIA scale, four patients recovered from preoperative grade D to postoperative grade E. Bony fusion was achieved for all cases, and the range of neck rotation was restored to normal at the last follow-up. The post-surgery angular displacement (AD) demonstrated the stability of C2-3 after our new screw fixation for the treatment of Hangman fracture. Minimally invasive percutaneous new transpedicular lag-screw fixation using intraoperative, full rotation, three-dimensional image (O-arm)-based navigation achieved satisfactory clinical results with the advantages of immediate stability, safety and effectivity. We suggest that it is a reliable and advanced technique for the management of Hangman fracture.


Reconstructing the anterolateral ligament does not decrease rotational knee laxity in ACL-reconstructed knees.
Little is known about the anterolateral ligament's (ALL) influence on knee laxity. The purpose of this study was to investigate rotational knee laxity against a pure axial rotational stress using radiostereometric analysis (RSA) after cutting and reconstructing both the anterior cruciate ligament (ACL) and the ALL. Eight human donor legs were positioned and stereoradiographically recorded at 0°, 30° and 60° of knee flexion using a motorised fixture, while an internally rotating force of 4 Nm was applied to the foot. Anterior-posterior and rotational laxity were investigated for knees with intact ligaments and compared with those observed after successive ACL and ALL resection and reconstruction. After cutting the ALL in ACL-deficient knees, the internal rotation was increased in all three knee flexion angles, 0° (p = 0.04), 30° (p = 0.03) and 60° (p < 0.01) by 1.0°, 1.6° and 2.5°, respectively. However, no decrease in laxity was found after reconstructing the ALL in ACL-reconstructed knees. The ALL was confirmed as a stabiliser of internal rotation in ACL-deficient knees. However, reconstructing the ALL using a gracilis autograft tendon did not decrease the internal rotation laxity in the ACL-reconstructed knee. Based on the results of this study, we do not recommend reconstructing the ALL in ACL-reconstructed knees to decrease internal knee laxity.


Intestinal microbiota-mediated biotransformations alter the pharmacokinetics of the major metabolites of azathioprine in rats after oral administration.
Adverse reactions to azathioprine (AZA) vary greatly among individuals, which is associated with the variable levels of its major metabolites 6-thioguanine nucleotides (6-TGN) and 6-methylmercaptopurine (6-MMP). The intestinal microbiota has been proven to contain AZA-metabolizing enzymes, although the explicit role of the intestinal microbiota in AZA metabolism in vivo remains poorly comprehended. In this study, the pharmacokinetic behaviours of 6-TGN and 6-MMP were assessed in the pseudo germ-free (PGF) group and control group following oral administration of AZA. The AUC0-t and Cmax of 6-TGN in the PGF group were significantly decreased by 34.0% and 35.0% (P < 0.05) compared with those in the control group. Additionally, the AUC0-t and Cmax of 6-MMP were reduced by 27.9% and 34.2% in the PGF group, although the differences were not significant. The TPMT and NUDT15 genotypes of rats in the two groups were genetically identical. The expression levels of key AZA-metabolizing enzymes in liver were not different between two groups. Furthermore, the major metabolites of AZA in the incubation system with intestinal microbial enzymes were identified. In summary, shifts in the composition of the intestinal microbiota may regulate the exposure of 6-TGN in vivo by altering the gut microbial metabolism of AZA.


Easing vasomotor symptoms: Besides HRT, what works?
Prescription HRT is the most effective therapy for vasomotor symptoms, but some patients may find the risks unacceptable. Treatment with lower doses or alternative dosage forms for short periods may reduce risk. Soy isoflavones and black cohosh have a proven ability to reduce hot flashes, but they should not be used when estrogen is contraindicated. Bioidentical HRT may offer no benefits over conventional HRT. Neuroendocrine agents may reduce hot flashes effectively and can be used when estrogen is contraindicated, but these agents may cause significant CNS side effects. Lifestyle modifications are the foundation of vasomotor symptom therapy and are safe to recommend for all women. Clinicians and patients should carefully discuss the expectations for therapy, and the clinician should be prepared to customize the treatment regimen.


Xanthone additives for blood storage that maintain its potential for oxygen delivery. I. 2-Hydroxyethoxy- and 2-ethoxy-6-(5-tetrazoyl) xanthones in citrate-phosphate-dextrose-adenine (CPDA-1) blood.
Two xanthones, 2-hydroxyethoxy-6-(5-tetrazoyl) (BW A440C) and 2-ethoxy-6-(5-tetraozyl) (BW A827C), are members of a chemical series tested in vitro as potential additives to citrate-phosphate-dextrose-adenine (CPDA-1) medium for blood storage. P50 was maintained in the presence of these compounds during 42 days' storage by a partial maintenance of 2,3 diphosphoglycerate (2,3 DPG) and by a direct effect on hemoglobin previously reported for BW A827C. Red cell 2,3 DPG levels for BW A440C (n = 5), BW A827C (n = 5), and control (n = 6), respectively, were 3.38 +/- 0.47, 3.44 +/- 0.25, and 1.20 +/- 0.10 mM +/- SEM on day 7; 1.16 +/- 0.13, 1.52 +/- 0.37, and 0.16 +/- 0.02 mM on day 21; and 0.67 +/- 0.09, 0.61 +/- 0.08, and 0.06 +/- 0.006 mM on day 42. Red cell adenine triphosphate levels at the same time intervals were 1.84 +/- 0.09, 1.46 +/- 0.18, and 2.11 +/- 0.04 mM; 2.10 +/- 0.05, 2.07 +/- 0.17, and 2.13 +/- 0.05 mM; and 1.42 +/- 0.13, 1.37 +/- 0.13, and 1.38 +/- 0.06 mM, respectively. The degree of hemolysis was less with the addition of the compounds, and the methemoglobin formation, plasma Na+ and K+, and lactate production were unaffected by the compounds.


A review on fake news detection 3T's: typology, time of detection, taxonomies.
Fake news has become an industry on its own, where users paid to write fake news and create clickbait content to allure the audience. Apparently, the detection of fake news is a crucial problem and several studies have proposed machine-learning-based techniques to combat fake news. Existing surveys present the review of proposed solutions, while this survey presents several aspects that are required to be considered before designing an effective solution. To this aim, we provide a comprehensive overview of false news detection. The survey presents (1) a clarity to problem definition by explaining different types of false information (like fake news, rumor, clickbait, satire, and hoax) with real-life examples, (2) a list of actors involved in spreading false information, (3) actions taken by service providers, (4) a list of publicly available datasets for fake news in three different formats, i.e., texts, images, and videos, (5) a novel three-phase detection model based on the time of detection, (6) four different taxonomies to classify research based on new-fangled viewpoints in order to provide a succinct roadmap for future, and (7) key bibliometric indicators. In a nutshell, the survey focuses on three key aspects represented as the three T's: Typology of false information, Time of detection, and Taxonomies to classify research. Finally, by reviewing and summarizing several studies on fake news, we outline some potential research directions.


Effects of repeated tiapride administration on anterior pituitary dopamine receptors and prolactin release in the rat.
The substituted benzamides tiapride and sulpiride, and the classic neuroleptic haloperidol, were studied in the rat to assess their interaction with the anterior pituitary (AP) dopamine (DA) receptors both in vitro ([3H]spiperone binding) and in vivo prolactin-PRL-release). Tiapride weakly inhibited [3H]spiperone binding in both pituitary and striatal membranes with affinity 5-7 times lower than sulpiride and 400-300 times lower than haloperidol. All three drugs were more potent in displacing [3H]spiperone from striatum than from AP. In vivo, tiapride produced weak and transient stimulation of PRL release reaching a full effect at 2 mg/kg i.p. Similar doses of sulpiride produced longer-lasting effects. Haloperidol was more potent than both benzamides. In prolonged treatments (15 or 60 days), tiapride, given twice daily at 0.5 mg/kg i.p., did not modify [3H]spiperone binding in either AP or striatum, nor did it induce significant changes of basal PRL levels. The challenge with a low threshold dose of TIA (0.2 mg/kg ip) produced similar increases of PRL release in the group either treated with TIA or saline. The data indicate that the benzamides examined have low potency for interaction with DA receptors in pituitary and striatum. In particular, tiapride displayed weaker affinity for AP-DA receptors than the other drugs and induced only slight stimulation of PRL levels. Results from repeated tiapride administration indicate that the drug, at a clinically relevant dose, is unable to modify either kinetic characteristics of DA receptors in the pituitary or plasma PRL levels.


A curriculum in health systems and public health for internal medicine residents.
Medical educators and accreditation organizations recognize that healthcare professionals in the future will depend on working knowledge of the larger contexts and systems of health care, including population and public health. Little published guidance on medical education in health systems and public health exists, particularly for graduate medical education. This study describes the evaluation of a curriculum in health systems and public health which was successfully implemented in an internal medicine residency training program. A pilot program consisting of a week-long didactic curriculum for senior residents, including ten half-day seminars. Two cycles of the pilot curriculum were implemented in September and November, 2007. The participants were third-year residents in an internal medicine training program at a large, urban academic medical center. The 1-week curriculum was fully implemented and evaluated in the academic years 2008-2010. It included seminars on health policy and economics, health insurance, technology and cost assessment, legal medicine, public health, community-oriented primary care, and local health department initiatives. Residents evaluated the quality and impact of the seminars and overall curriculum, retrospectively assessed their knowledge of topics presented before and after the seminars, and rated the seminars that were most valuable to them. The seminars were highly rated by the participating residents, and the curriculum was judged by them to be valuable in their clinical activities and professional development. Key lessons learned included the importance of accessing resources external to the residency program and the challenge of making learning in health systems and public health active and relevant to clinical practice.


The potential of antifungal peptide Sesquin as natural food preservative.
Sesquin is a wide spectrum antimicrobial peptide displaying a remarkable activity on fungi. Contrarily to most antimicrobial peptides, it presents an overall negative charge. In the present study, we elucidate the molecular basis of its mode of action towards biomimetic membranes by NMR and MD experiments. While a specific recognition of phosphatidylethanolamine (PE) might explain its activity in a variety of different organisms (including bacteria), a further interaction with ergosterol accounts for its strong antifungal activity. NMR data reveal a charge gradient along its amide protons allowing the peptide to reach the membrane phosphate groups despite its negative charge. Subsequently, the peptide gets structured inside the bilayer, reducing its order. MD simulations predict that its activity is retained in conditions commonly used for food preservation: low temperatures, high pressure, or the presence of electric field pulses, making Sesquin a good candidate as food preservative.


Randomization in a substance abuse treatment study: participants who consent vs those who do not.
A mixed research design study compared patients who consented to treatment randomization with patients who opted for usual care. Patients in substance abuse rehabilitation who consented to randomization (that is, consenting group [CG]) were compared with those unwilling to undergo randomization (that is, nonconsenting group [NG]) but who, nevertheless, underwent the experimental assessment sessions, which spanned from intake to 6-month follow-up. Patients in the CG exhibited a longer history of drug abuse, less occupational stability at intake, and following intensive treatment, tended not to do as well in terms of recovery, compared with those in the NG. Inclusion of data from partial participants in research protocols may offer a viable strategy to better appraise data generalizability.


Immunohistochemical and behaviour pharmacological analysis of rats inoculated intranasally with vesicular stomatitis virus.
A temperature-sensitive mutant of vesicular stomatitis virus was inoculated intranasally into infant Sprague-Dawley rats aged 9 to 17 days. Rats receiving the virus at 9 days of age had an extensive spread of infection throughout the brain and the animals died after a few days. Rats inoculated at day 11 postnatally survived and the infection was limited to the olfactory pathways, hypothalamus, diagonal bands and the anterior raphe nuclei. Stereological measurements showed that the volume of infected neurons constituted 67 +/- 10% of the total neuronal volume in the dorsal raphe nucleus. Double-labelling experiments revealed that both 5-hydroxytryptamine- and substance P-immunoreactive neurons contained the virus antigen. The motor stimulant effect of amphetamine was studied at 3 months post infection. The increase in amphetamine-induced frequency and duration of rearing was significantly attenuated in infected rats and the amphetamine-induced locomotion was slightly reduced.


Renal denervation preserves renal function in patients with chronic kidney disease and resistant hypertension.
Arterial hypertension and increased sympathetic activity are underlying pathogenetic mechanisms of the progressive loss of renal function in patients with chronic kidney disease (CKD). Meta-analyses have shown that impaired renal function is an independent cardiovascular risk factor. We hypothesized that renal denervation (RDN) decreases the decline of renal function in patients with CKD stages 3 and 4 and treatment-resistant hypertension. We performed an observational study of 27 patients with CKD stages 3 and 4, office blood pressure (BP) ≥ 140/90 mmHg, while on at least three antihypertensive drug classes including diuretic, and diagnosis confirmed by 24-h ambulatory BP measurement ≥ 130/80 mmHg. All patients underwent catheter-based RDN using the Symplicity Flex RDN System (Medtronic Inc., Santa Rosa, California, USA). Renal function was evaluated for up to 3 years prior and 1 year after RDN. The change in estimated glomerular filtration rate (eGFR) was calculated by regression slope individually for each patient before and after RDN. The study was registered at http://www.clinicaltrials.gov (ID: NCT01442883). Mean baseline BP was 156 ± 12/82 ± 13 mmHg, despite treatment with 6.2 ± 1.1 antihypertensive drugs. One year after RDN, office BP was reduced by 20 ± 20 (P < 0.001)/8 ± 14 mmHg (P = 0.005) and average 24-h ambulatory BP by 9 ± 14 (P = 0.009)/4 ± 7 mmHg (P = 0.019). Before RDN, eGFR declined by -4.8 ± 3.8 ml/min per 1.73 m per year, and after RDN eGFR improved by +1.5 ± 10 ml/min per 1.73 m at 12 months (P = 0.009). Our observational pilot study in patients with CKD stages 3 and 4 indicates that treatment of hypertension with RDN decreases BP and slows or even halts the decline of renal function.


Cost-utility analysis of cast compared to removable brace in the management of adult patients with ankle fractures.
To compare the cost-utility of removable brace compared with cast in the management of adult patients with ankle fracture. A within-trial economic evaluation conducted from the UK NHS and personnel social services (PSS) perspective. Health resources and quality-of-life data were collected as part of the Ankle Injury Rehabilitation (AIR) multicentre, randomized controlled trial over a 12-month period using trial case report forms and patient-completed questionnaires. Cost-utility analysis was estimated in terms of the incremental cost per quality adjusted life year (QALY) gained. Estimate uncertainty was explored by bootstrapping, visualized on the incremental cost-effectiveness ratio plane. Net monetary benefit and probability of cost-effectiveness were evaluated at a range of willingness-to-pay thresholds and visualized graphically. The incremental cost and QALYs of using brace over a 12-month period were £46.73 (95% confidence interval (CI) £-9 to £147) and 0.0141 (95% CI -0.005 to 0.033), respectively. The cost per QALY gained was £3,318. The probability of brace being cost-effective at a £30,000 per QALY willingness-to-pay threshold was 88%. The results remained robust to a range of sensitivity analyses. This within-trial economic evaluation found that it is probable that using a removable brace provides good value to the NHS when compared to cast, in the management of adults with ankle fracture. Cite this article: Bone Jt Open 2022;3(6):455-462.


A new quantitative structure-property relationship model to predict bioconcentration factors of polychlorinated biphenyls (PCBs) in fishes using E-state index and topological descriptors.
A quantitative structure-property relationship (QSPR) study for predicting the logarithm of bioconcentration factors (LogBCF) of polychlorinated biphenyls (PCBs) is presented in this work. For this, the descriptors were obtained using only the Simplified Molecular Input Line Entry System (SMILES) strings in the free web server Parameter Client. The model was built using the Partial Least Squares (PLS) regression method. The best model presented five descriptors (one E-state index and four topological descriptors) and a high quality for fit, internal, and external predictions. The leave-N-out (LNO) cross validation and the y-randomization test showed the model is robust and has no shown chance correlation. With a second test set, the model was compared to other models and presented a root mean square error (RMSE) very close to the best model. The mechanistic interpretation was corroborated by other works in the literature and by the descriptors' theory. Thus, the results meet the five Organization for Economic Co-operation and Development (OECD) principles for validation of QSA(P)R models, and it is expected the model can effectively predict the BCF values in fishes of the PCB congeners without highly reliable experimental BCF.


Changes in serum KL-6 after intravenous fosfomycin administration in idiopathic interstitial pneumonia.
Changes in serum KL-6 levels after intravenous fosfomycin (FOM) administration in idiopathic interstitial pneumonia (IIP) were studied. Seventeen patients who were diagnosed with usual interstitial pneumonia by surgical lung biopsy were selected as subjects. In these patients, FOM was administered intravenously, at a dose of 2 g twice daily, for 14 days, and serum KL-6 was determined before and after its administration. FOM administration resulted in a reduction of serum KL-6 in all 17 patients (1273 +/- 132 U/ml [mean +/- SEM] to 1023 +/- 101 U/ml; P < 0.01). FOM may reduce serum KL-6 in IIP and may be an appropriate therapeutic drug for this condition.


WITHDRAWN: Erratum to "Derivation and presentation of formulas for drug concentrations in two-, three- and four-compartment pharmacokinetic models" [Journal of Pharmacological and Toxicological Methods 100 (2019), 106621].
The Publisher regrets that this article is an accidental duplication of an article that has already been published, http://dx.doi.org/10.1016/j.vascn.2019.106648. The duplicate article has therefore been withdrawn. The full Elsevier Policy on Article Withdrawal can be found at https://www.elsevier.com/about/our-business/policies/article-withdrawal.


Biophysical studies on molecular mechanisms of abortifacient action of prostaglandins. V. CNDO/2 estimation of the relative affinities of the cations Na+, Mg2+ and Ca2+ to the carboxylic group.
The paper describes the study of relative affinities of the cations Na+, Mg2+ and Ca2+ to the carboxylic group, their electronic structure and optimum binding positions on the basis of the CNDO/2 technique, using the well known supramolecular approach. The cation for this purpose was made to approach the carboxylic group in various possible directions in and out of the plane C1O1AO1B and the final parameters were evaluated for the optimum planar as well as nonplanar geometries. With the exception of Ca2+ the nonplanar geometries were always favoured over the planar ones for binding at O1A and O1B, whereas for symmetric binding between O1A and O1B planar geometries were favoured for Mg2+ and Ca2+. The distance between the cation and oxygen was slightly larger for this geometry and Etot which followed the order Mg2+ less than Ca2+ less than Na+ had the lowest value.


Influence of age and scanning system on the learning curve of experienced and novel intraoral scanner operators: A multi-centric clinical trial.
To evaluate the effect of age and intra-oral scanner (IOS) on the learning curve of inexperienced operators. Thirty-four operators pertaining to 1 of 3 groups: (G1) students ≤ 25 years (y), (G2) dentists ≥ 40y, and (G3) a control group of experienced IOS operators (no age limitation), were included. All participants performed baseline and final quadrant scans on a volunteer subject, before and after a training program of 3 sessions, with two different IOS: TRIOS 3 (S1) and True Definition (S2). Baseline and final scanning times were registered in seconds. A Pearson correlation was applied to evaluate the correlation between age and scanning time. An ANOVA of repeated measures test was applied to evaluate inter-group (G1, G2, G3) and inter-system performance. Significance level was set at a = 0.05. Age and scanning time for inexperienced operators showed a weak positive correlation for final scanning time (r = 0.29, p < 0.05). When comparing groups and filtering by IOS, S1 failed to show differences between groups (p > 0.05). With S2, the control group demonstrated a better performance than G2 (p < 0.05), while G1 only demonstrated a better performance than G2 at final scanning time (p = 0.005). Overall, the type of IOS had a significant impact on the scanning time (p < 0.001). Results from this study indicate that age and type of IOS have an impact on the performance and learning curve of inexperienced IOS operators. Gaining knowledge on how different aspects, such as age, experience or IOS system, influence the learning curve to IOSs is relevant due to the financial and strategical impact associated with the acquisition of an IOS.


Orientational influences of layer V of visual area 18 upon cells in layer V of area 17 in the cat cortex.
We examined the orientation tuning curves of 86 cells located in layer V of area 17, before, during, and after focal blockade of a small (300-microns diameter) region of near-retinotopic register in layer V of area 18 of quantitatively established orientation preference. Such focal blockade revealed three distinct populations of area 17 layer V cells-cells with decreased responses to stimuli of some orientations (21%), cells with increased responses to stimuli of some orientations (43%), and cells unaffected by the focal blockade (36%). These effects were clearcut, reproducible, and generally directly related to the known receptive field properties of the cell recorded in area 18 at the center of the zone of blockade. These effects were also analyzed in terms of alterations in orientation bandwidth in the cells in area 17 as a result of the blockade-bandwidth increases (22%) and decreases (24%) were found; however, these changes were essentially unrelated to the measured receptive field properties. Inhibitory and excitatory effects were most pronounced when the regions in areas 17 and 18 were of like ocular dominance and were of similar orientation preference. Inhibitory effects (suggesting a normally excitatory input) were most dependent upon the similarity of receptive fields; excitatory effects (suggesting a normally inhibitory input) were less heavily dependent.


Inactivation of Salmonella enterica on post-harvest cantaloupe and lettuce by a lytic bacteriophage cocktail.
Salmonella enterica (S. enterica) is a causative agent of multiple outbreaks of foodborne illness associated with fresh produce, including pre-cut melon and leafy vegetables. Current industrial antimicrobial interventions have been shown to reduce microbial populations by <90%. Consequently, bacteriophages have been suggested as an alternative to chemical sanitizers. Seven S. enterica strains from four serovars (105 CFU/mL) were separately inoculated onto excised pieces of Romaine lettuce leaf and cantaloupe flesh treated with a five-strain bacteriophage cocktail 24 h before S. enterica inoculation. S. enterica, total aerobic populations and water activity were measured immediately after inoculation and after 1 and 2 days of incubation at 8 °C. The efficacy of the bacteriophage cocktail varied between strains. Populations of S. enterica Enteritidis strain S3, S. Javiana S203, S. Javiana S200 were reduced by > 3 log CFU/g and S. Newport S2 by 1 log CFU/g on both lettuce and cantaloupe tissues at all sampling times. In contrast, populations of strains S. Thompson S193 and S194 were reduced by 2 log CFU/g on day 0 on lettuce, but were not significantly different (P > 0.05) from the controls thereafter, S. Newport S195 populations were reduced on lettuce by 1 log CFU/g on day 0 and no reductions were found on cantaloupe tissue. Both aerobic populations and water activity were higher on cantaloupe than on lettuce. The water activity of lettuce decreased significantly (P < 0.05) from 0.845 ± 0.027 on day 0-0.494 ± 0.022 on day 1, but that of cantaloupe remained between 0.977 and 0.993 from day 0-2. The results of this study showed that bacteriophages can reduce S. enterica populations on lettuce and cantaloupe tissues but that the magnitude of the effect was strain-dependent.


COVID-19 Anti-Chinese Discrimination, Current Pandemic Stress, And Adolescents' Mental Health.
The current study investigated adolescents' experiences of COVID-19 anti-Chinese discrimination (i.e., vicariously witnessed, directly experienced), the consequences for mental health, and the moderating role of general pandemic stress. During Summer 2020, 106 adolescents (43% Latino/a/x, 19% Asian American, 13% Black/African American, 26% biracial/multiracial/other; 58% female) participated in a 14-day daily diary study. Path analyses revealed that more experiences of vicarious COVID-19 anti-Chinese discrimination were associated with greater anxious mood, depressed mood, and mental health stress, while direct COVID-19 anti-Chinese discrimination was unrelated to mental health outcomes. The interaction between vicarious COVID-19 anti-Chinese discrimination and general COVID-19 stress was significant for depressed mood; simple slope analyses showed that for adolescents reporting high levels of COVID-19 stress, more frequent experiences of vicarious COVID-19 anti-Chinese discrimination were associated with greater severity in depressed mood, but this link was nonsignificant for those reporting low levels of general pandemic stress. Findings from the current study underscore the pernicious effects of vicarious COVID-19 anti-Chinese discrimination on the mental health of minoritized youth beyond solely Asian Americans. Additionally, the results evince the need for future pandemic-response efforts to craft public health messaging that avoids the racialization of disease and subsequent stigmatization of ethnic-minority communities.


Active avoidance in rats with unilateral hypothalamic and optic nerve lesions.
During the height of the contralateral sensorimotor deficit that follows unilateral hypothalamic lesions, rats demonstrate severe performance deficits when tested on a two-way active avoidance task which utilizes a visual conditioned stimulus. This deficit is observed whether or not the ipsilateral or contralateral optic nerve is sectioned in conjunction with the unilateral hypothalamic lesion. With the return of sensorimotor function contralateral to the lesion, animals that had been unable to avoid shock during their debillitated phase demonstrated significant savings when tested on the original task.


Neural circuit mechanisms encoding motivational states in Drosophila.
Animals engage in motivated behaviors, such as feeding and mating behaviors, to ensure their own survival and the survival of their species. However, the neural circuits mediating the generation and persistence of these motivational drives remain poorly understood. Here we review recent studies on the circuit mechanisms underlying motivational states in Drosophila, with a focus on feeding, courtship, and aggression. These studies shed light on the molecular and cellular mechanisms by, which key drive neurons receive relevant input signals, integrate information, and decide on a specific behavioral output. We also discuss conceptual models for integrating these circuit mechanisms, distinguishing between those for homeostatically-regulated versus non-homeostatically-regulated motivated behaviors. We suggest that the ability to trigger persistence of a motivated behavior may be a feature of integrator or apex/command neurons.


The role, duties and responsibilities of technologists in the clinical laboratory.
Within the United Kingdom, the job functions of the technologist are carried out by Biomedical Scientists who account for the greater proportion of staff employed within clinical laboratories. Their traditional responsibilities have involved providing a quality service through their scientific, technical and clinical skills. During the 1990s, a number of factors combined, leading to a change in the way which quality was viewed within the National Health Service (NHS). This has changed the role of the technologist, encouraging them to broaden their knowledge and take on new skills and responsibility.


Differentiating the symptoms of posttraumatic stress disorder and bipolar disorders in adults: Utilizing a trauma-informed assessment approach.
In adult populations, bipolar disorders (BDs) and posttraumatic stress disorder (PTSD) have overlapping symptoms, potentially leading to misdiagnosis. This misdiagnosis or failure to diagnose both co-occurring disorders can result in individuals not receiving the proper treatment to address their symptoms. This article highlights how trauma-informed psychological assessment can assist in differential diagnosis and improve the timely delivery of appropriate treatments. The overlapping symptoms of PTSD and BD are discussed to assist in differential diagnosis, and we suggest guidelines for conducting trauma-informed, evidence-based assessments to help clarify these diagnoses.


Socioeconomic disparities in sexually transmitted infections among young adults in the United States: examining the interaction between income and race/ethnicity.
There is considerable evidence of racial/ethnic patterning of sexually transmitted infection (STI) risk in the United States. There is also evidence that poorer persons are at increased STI risk. Evidence regarding the interaction of race/ethnicity and income is limited, particularly nationally at the individual level. We examined the pattern of socioeconomic gradients in STI infection among young people in a nationwide US study and determined how these gradients varied by race/ethnicity. We estimated the cumulative diagnosis prevalence of chlamydia, gonorrhea, or trichomoniasis (via self-report or laboratory confirmation) for young adults (ages, 18-26 years old) Hispanics and non-Hispanic whites, blacks, and others across income quintiles in the Add Health data set. We ran regression models to evaluate these relationships adjusting for individual- and school-level covariates. Sexually transmitted infection diagnosis was independently associated with both racial/ethnic identity and with low income, although the racial/ethnic disparities were much larger than income-based ones. A negative gradient of STI risk with increasing income was present within all racial/ethnic categories, but was stronger for nonwhites. Both economic and racial/ethnic factors should be considered in deciding how to target STI prevention efforts in the United States. Particular focus may be warranted for poor, racial/ethnic minority women.


Biomonitoring of non-persistent pesticides in urine from lactating mothers: Exposure and risk assessment.
The aim of the present study was to assess the exposure to pesticides in urine from Spanish lactating mothers (n = 116). Six nonspecific (dialkyl phosphates) and 20 specific metabolites of organophosphate pesticides (OPs), herbicides and pyrethroids were analyzed. The most frequently detected biomarkers were diethyl phosphate, p-nitrophenol, 3,5,6-trichloro-2-pyridinol and 3-phenoxybenzoic acid, whose geometric means were 1.9 ng·mL-1, 0.8 ng·mL-1, 1.5 ng·mL-1 and 1.4 ng·mL-1, respectively. Herbicide metabolites were the least frequently detected biomarkers with detection frequencies between 0% (2,4,5-Trichlorophenoxyacetic acid) and 22% (2,4-Dichlorophenoxyacetic acid). Multiple regression analyses showed that the closeness to a farming activity, the place of residence and the presence of garden/plants at home were some of the most important contributors to urinary levels of pesticide metabolites. Estimated daily intake (EDI), hazard quotient (HQ) and hazard index (HI) were obtained in order to interpret urinary levels of the most frequently detected pesticide metabolites in a risk assessment context. The highest EDIs were obtained for chlorpyrifos (0.40-1.14 μg·kg bw-1·day-1) and deltamethrin (0.34-4.73 μg·kg bw-1·day-1). The calculated HQ for chlorpyrifos, dimethoate, parathion and deltamethrin ranged from 0.01 to 0.47, and HI for OPs ranged from 0.09 to 0.33 showing that apparently there were low health risks due to the exposure to these pesticides in this group of Spanish breastfeeding women.


Assessment of causes of early death after twenty years of liver transplantation.
Postoperative poor graft function is a serious complication that can lead to graft loss requiring retransplantation or even death. The postoperative complications of primary nonfunction (PNF), early graft dysfunction (EGD), bleeding due to coagulopathy, and hepatic artery thrombosis (HAT) can lead to graft loss requiring retransplantation or even death. We determined the causes of death after liver transplantation. This was an observational descriptive study on adult liver transplant recipients from September 1991 to December 2011. The cutoff for the definition of death was 30 days after surgery. We included patients older than 18 years of age who underwent liver grafts using the piggyback technique, excluding those who had retransplantations or liver-kidney transplantations. We analyzed 561 liver transplantations through chart review. After application of exclusion criteria we had 81 patients for analysis. Overall mortality was classified into 3 main causes: PNF (34/81; 42%), EGD (10/81; 12%), and abdominal bleeding due to coagulopathy (9/81; 11%). Despite advances, mortality in the first 30 days after surgery is still high, mainly related to the occurrence of PNF and EGD, whose causality was associated with red blood cell transfusion (>5 U).


The role of remote flavin adenine dinucleotide pieces in the oxidative decarboxylation catalyzed by salicylate hydroxylase.
Salicylate hydroxylase (NahG) has a single redox site in which FAD is reduced by NADH, the O2 is activated by the reduced flavin, and salicylate undergoes an oxidative decarboxylation by a C(4a)-hydroperoxyflavin intermediate to give catechol. We report experimental results that show the contribution of individual pieces of the FAD cofactor to the observed enzymatic activity for turnover of the whole cofactor. A comparison of the kinetic parameters and products for the NahG-catalyzed reactions of FMN and riboflavin cofactor fragments reveal that the adenosine monophosphate (AMP) and ribitol phosphate pieces of FAD act to anchor the flavin to the enzyme and to direct the partitioning of the C(4a)-hydroperoxyflavin reaction intermediate towards hydroxylation of salicylate. The addition of AMP or ribitol phosphate pieces to solutions of the truncated flavins results in a partial restoration of the enzymatic activity lost upon truncation of FAD, and the pieces direct the reaction of the C(4a)-hydroperoxyflavin intermediate towards hydroxylation of salicylate.


New data on the rare Afrotropical scarab beetles Orphnus drumonti Frolov and Delopleurus naviauxi Frolov et Cambefort (Coleoptera, Scarabaeidae, Orphninae and Scarabaeinae).
The scarab beetle genera Orphnus Macleay and Delopleurus Boheman are most speciose in the Afrotropical region. However, a number of species are only known from type specimens, sometimes only from one sex. New locality records of Orphnus drumonti Frolov (Orphninae) and Delopleurus naviauxi Frolov et Cambefort (Scarabaeinae) are given. The previously unknown female of the former and male of the latter species are described.


Carotid-radial pulse wave velocity as a discriminator of intrinsic wall alterations during evaluation of endothelial function by flow-mediated dilatation.
Flow-mediated dilatation (FMD) is the most accepted technique for the evaluation of endothelial function. However, it has been show a great inter-subject variability limiting its clinical use. Carotid-radial pulse wave velocity (PWVcr) was proposed as an alternative tool for the evaluation of endothelial function. At the present, there is no doubt that PWVcr reduces its values in response to reactive hyperemia test (RHT) in healthy subjects. a) to determine simultaneously the temporal profile of FMD, PWVcr and shear rate in response to RHT and b) to describe and analyze how subjects "FMD responders" or "non-responders" behave regards to PWVcr changes. 34 Healthy young subjects were included. The PWVcr (strain gauge mechanotransducers), brachial diameter (B-Mode ultrasound and blood flow velocity (Doppler ultrasound) were measured before (baseline) the cuff was inflated and after its deflation (5 minutes). 10(th) percentiles FMD and PWVcr changes in the population were used for the definition of the subjects ("responders and non-responders"). Changes in PWVcr, brachial arterial diameter and shear rate were evidenced after the cuff release (p<0.05). There were differences in the PWV and FMD temporal profiles. Within "FMD responders" there were "PWV responders and non-responders". Assessing RHT-related changes in PWVcr in the context of a FMD evaluation, could be useful as a discriminator of intrinsic wall alterations giving additional information of vascular dynamics.


Exogenous DCPTA Ameliorates Simulated Drought Conditions by Improving the Growth and Photosynthetic Capacity of Maize Seedlings.
Previous reports have indicated that 2-(3,4-dichlorophenoxy)triethylamine (DCPTA) can promote the growth and photosynthetic capacity of plants. However, only a small number of these studies have focused on crops, and few reports have focused on whether DCPTA affects stress tolerance. In this study, maize (Zea mays L.) seedlings were pretreated with or without DCPTA and then exposed to drought stress in a controlled growth room for 7 days, and the growth and photosynthesis indexes of the seedlings were investigated. The DCPTA treatment partly counteracted the observed decreases in biomass, net photosynthetic rate (Pn), stomatal conductance (Gs), transpiration rate (Tr), effective photochemical efficiency of photosystem II (ΦPSII), maximum photochemical efficiency of PSII (Fv/Fm), non-photochemical quenching (NPQ), and photosynthetic pigment content and increased the minimal fluorescence (Fo) induced by drought stress. The DCPTA treatment also alleviated the damage induced by drought stress in the photosynthetic apparatus. In addition, DCPTA pretreatment simultaneously increased the root size (e.g., the length, surface area, and volume) and root hydraulic conductivity, which promoted the maintenance of higher relative leaf water contents (RLWCs) under stress conditions. These results indicate that exogenous DCPTA ameliorates simulated drought conditions by improving the growth and photosynthetic capacity of maize seedlings.