Applying Radiomics to Predict Pathology of Postchemotherapy Retroperitoneal Nodal Masses in Germ Cell Tumors.
After chemotherapy, approximately 50% of patients with metastatic testicular germ cell tumors (GCTs) who undergo retroperitoneal lymph node dissections (RPNLDs) for residual masses have fibrosis. Radiomics uses image processing techniques to extract quantitative textures/features from regions of interest (ROIs) to train a classifier that predicts outcomes. We hypothesized that radiomics would identify patients with a high likelihood of fibrosis who may avoid RPLND. Patients with GCT who had an RPLND for nodal masses > 1 cm after first-line platinum chemotherapy were included. Preoperative contrast-enhanced axial computed tomography images of retroperitoneal ROIs were manually contoured. Radiomics features (n = 153) were used to train a radial basis function support vector machine classifier to discriminate between viable GCT/mature teratoma versus fibrosis. A nested 10-fold cross-validation protocol was used to determine classifier accuracy. Clinical variables/restricted size criteria were used to optimize the classifier. Seventy-seven patients with 102 ROIs were analyzed (GCT, 21; teratoma, 41; fibrosis, 40). The discriminative accuracy of radiomics to identify GCT/teratoma versus fibrosis was 72 ± 2.2% (area under the curve [AUC], 0.74 ± 0.028); sensitivity was 56.2 ± 15.0%, and specificity was 81.9 ± 9.0% ( P = .001). No major predictive differences were identified when data were restricted by varying maximal axial diameters (AUC range, 0.58 ± 0.05 to 0.74 ± 0.03). The prediction algorithm using clinical variables alone identified an AUC of 0.76. When these variables were added to the radiomics signature, the best performing classifier was identified when axial masses were limited to diameter < 2 cm (accuracy, 88.2 ± 4.4; AUC, 0.80 ± 0.05; P = .02). A predictive radiomics algorithm had a discriminative accuracy of 72% that improved to 88% when combined with clinical predictors. Additional independent validation is required to assess whether radiomics allows patients with a high predicted likelihood of fibrosis to avoid RPLND.


Angiotensin blockade and matrix synthesis by glomerular epithelial cells in high glucose: a further experimental insight into the pathophysiology of diabetic nephropathy.
Angiotensin converting enzyme inhibitors (ACEIs) and angiotensin II receptor-1 (AT-1) antagonists are used in the treatment of proteinuria of diabetic nephropathy. One of the major pathogenic events in this condition is represented by the alteration of the extracellular matrix protein synthesis by glomerular epithelial cells. We evaluated the effects of the angiotensin converting enzyme inhibitor, Enalaprilat, and the AT-1 receptor antagonist, Losartan, on mRNA fibronectin and laminin synthesis by glomerular epithelial cells, in conditions mimicking hyperglycemia. In high glucose conditions, Enalaprilat reduced significantly the mRNA expression of fibronectin (p 0.03), but not significantly that of laminin. Losartan addition to high glucose incubated cells reduced (-30%) mRNA expression of fibronectin, and significantly (p 0.05) the mRNA expression of laminin. In addition to the known hemodynamic effects, the improvement of renal function in diabetic patients treated with these compounds may also be due to a modulator effect on extracellular matrix content and composition.


Phonological abilities of hearing-impaired Cantonese-speaking children with cochlear implants or hearing AIDS.
This article examined the phonological skills of 2 groups of Cantonese-speaking children with prelingual, profound bilateral hearing loss. The phonological abilities of 7 children fitted with hearing aids were compared with the abilities of 7 children who wore cochlear implants. Participants in each group ranged in age from 5;1 to 6;4 years. The participants were asked to name 57 pictures and retell 2 stories. Phonological abilities were described in terms of the participants' phonological units and the phonological processes used. The participants' perception of single words was assessed using a Cantonese phonology test that includes tonal, segmental, and semantic distracters. All except 1 participant had incomplete phonetic repertories. All participants showed complete vowel and tone inventories. The study group used both developmental rules and nondevelopmental phonological rules. For perception of single words, participants chose the target word most often. The cochlear implant users had a significantly higher percentage correct score for consonant production than hearing aid users. The prediction that Cantonese children wearing cochlear implants would have better phonological skills than children having hearing aids with a similar degree of hearing loss was confirmed. Cochlear implant usage appeared to promote consonant feature production development to a greater degree than did the use of a hearing aid.


[The use of CT in the treatment of lung cancer with radiation therapy].
In this study, the extent to which CT accuracy in the diagnosis of regional lymph node metastasis of non-small cell lung cancer contributed to treatment results with radiation therapy was examined. The long-termed survival rate of 133 cases examined by CT scanning was superior to that of 154 cases diagnosed by conventional radiological method alone. The difference was statistically significant in N2 cases. When the mediastinal lymph node metastasis was detected on the ipsilateral side of the primary tumor or when the mediastinal lymph node swelling was smaller than 3 cm in diameter, the prognosis became better.


Removal of toxic elements from aqueous solution using bentonite modified with L-histidine.
This study proposes the use of bentonite modified with L-histidine for the removal of Cu, Co, Cr, Fe, Hg, Ni, U and Zn from aqueous solutions such as those impacted by acidic drainage. The surface areas of natural bentonite and bentonite-histidine were 73.8 and 61.2 m(2) g(-1), respectively. Elemental analysis showed an increase in the amount of carbon (0.258%) and nitrogen (0.066%) for the bentonite-histidine. At a fixed solid/solution ratio, the operating variables affecting the adsorption of metal ions from aqueous solution such as pH, initial concentration, contact time and temperature were studied in batch mode. The Freundlich isotherm model yielded a better fit than the Langmuir for the adsorption of Cu, Co, Ni and Zn, implying adsorption on a heterogeneous surface. Adsorption kinetics followed a pseudo-second-order model, suggesting chemisorption as the rate-limiting step. The apparent activation energy was greater than 40 kJ mol(-1) for Cu, Zn, Ni, Co and U, which is characteristic of a chemically controlled reaction. Thermodynamic constants ΔG and ΔH showed that the adsorption of metals was endothermic and spontaneous. Adsorption of heavy metals onto bentonite-histidine was efficient at low pH values, meaning that the adsorbent could be useful for remediating acid mine water.


Signs and symptoms of mandibular dysfunction in shortened dental arches.
In this study subjects with shortened dental arches (SDA, n = 60), characterized by the absence of molar support, are compared with subjects with a complete dentition (n = 72) with respect to signs and symptoms of mandibular dysfunction. The subjective examination consisted of questions related to pain, noises within the joints and mobility of the lower jaw. The objective examination consisted of the registration of clicking of the temporomandibular joint (TMJ) by bilateral palpation and measuring the maximal mouth opening. In spite of the finding that significantly more subjects of the SDA group under 40 years of age reported pain in or around the TMJ, it is concluded that in the population studied no convincing evidence was found that a SDA provokes signs and symptoms of mandibular dysfunction.


Osteoprotegerin levels in ST-elevation myocardial infarction: Temporal profile and association with myocardial injury and left ventricular function.
Elevated levels of osteoprotegerin (OPG) have been associated with adverse outcomes in ST-elevation myocardial infarction (STEMI). However, the role of OPG in myocardial injury and adverse remodeling in STEMI patients remains unclear. The aims of this observational cohort study were to evaluate: 1) the temporal profile of OPG during STEMI, 2) possible associations between OPG measured acutely and after 4 months, with infarct size, adverse left ventricular (LV) remodeling, microvascular obstruction (MVO) and myocardial salvage and 3) the effect of heparin administration on OPG levels. Blood samples were drawn repeatedly from 272 STEMI patients treated with primary percutaneous coronary intervention (PCI). Cardiac magnetic resonance imaging (CMR) was performed in the acute phase and after 4 months. The effect of heparin administration on OPG levels was studied in 20 patients referred to elective coronary angiography. OPG levels measured acutely were significantly higher than Day 1 and during follow-up. OPG levels were correlated with age. No association was found between early OPG levels and CMR measurements at 4 months. Patients with >median OPG levels measured at Day 1 had larger final infarct size, lower LV ejection fraction (LVEF) at 4 months and higher frequency of MVO. There were no associations between OPG and change in end-diastolic volume or myocardial salvage. OPG remained associated with infarct size and LVEF after adjustment for relevant covariates, except peak troponin T and CRP. A 77% increase in OPG levels following heparin administration was found in patients undergoing elective coronary angiography. OPG was found to be associated with myocardial injury, but not with LV remodeling or myocardial salvage. The use of OPG as a biomarker in STEMI patients seems to be limited by a strong association with age, confounding effect of heparin administration, and little additive value to established biomarkers.


Imatinib attenuates cardiac fibrosis by inhibiting platelet-derived growth factor receptors activation in isoproterenol induced model.
Cardiac fibrosis is a significant global health problem with limited treatment choices. Although previous studies have shown that imatinib (IMA) inhibited cardiac fibrosis, the anti-fibrotic mechanisms have not been clearly uncovered. The aim of this study is to evaluate whether IMA attenuates cardiac fibrosis by inhibiting platelet-derived growth factor receptors (PDGFR) on isoproterenol (ISO)-induced mice. Adult male C57BL/6 mice were treated with vehicle or ISO ± IMA for one week. After echocardiography examination, the hearts of mice were used for histopathologic, RT-qPCR, and western blot analyses. We found that the ventricular wall thickness, cardiac hypertrophy, and apoptosis were enhanced following ISO treatment. IMA decreased the left ventricular wall thickness, prevented hypertrophy, and inhibited apoptosis induced by ISO. In addition, IMA attenuated the accumulation of collagens and α-smooth muscle actin (α-SMA) (the markers of fibrosis) caused by ISO treatment. Moreover, the expression of fibrosis related genes, and the phosphorylation of PDGFRs in ISO-treated mice hearts were inhibited by IMA as well. However, IMA did not change the expression of the matrix metalloproteinase-9 (MMP-9) in ISO-treated hearts. Furthermore, IMA reduced the expressions of collagens as well as α-SMA caused by activation of PDGFRα in cardiac fibroblasts. Taken together, our data demonstrate that IMA attenuated the cardiac fibrosis by blocking the phosphorylation of PDGFRs in the ISO-induced mice model. This study indicates that IMA could be a potentially therapeutic option for cardiac fibrosis in clinical application.


Complications of lung transplantation on computed tomography: pictorial essay.
Lung transplantation is becoming increasingly more common as an alternative treatment for end-stage lung disease. Despite advances in laboratory testing, surgical technique, and donor/recipient selection, lung transplantation is still associated with significant mortality, due to postoperative complications. This paper consists of a brief review of postoperative complications in lung transplant recipients, illustrating those complications with computed tomography images.


Effector Repertoire of Phytophthora betacei: In Search of Possible Virulence Factors Responsible for Its Host Specificity.
Phytophthora betacei is an oomycete plant pathogen closely related to Phytophthora infestans. It infects tree tomato (Solanum betaceum) in northern South America, but is, under natural conditions, unable to infect potatoes or tomatoes, the main hosts of its sister species P. infestans. We characterized, and compared the effector repertoires of P. betacei and other Phytophthora species. To this end, we used in silico approaches to predict and describe the repertoire of secreted proteins in Phytophthora species and determine unique and core effectors. P. betacei has the largest proteome and secretome of all Phytophthora species evaluated. We identified between 450 and 1933 candidate effector genes in Phytophthora ramorum, Phytophthora sojae, Phytophthora cactorum, Phytophthora parasitica, Phytophthora palmivora, P. infestans, and P. betacei genomes. The P. betacei predicted secretome contains 5653 proteins, 1126 of which are apoplastic effectors and 807cytoplasmic effectors. Genes encoding cytoplasmic effectors include 791 genes with an RxLR domain (the largest number known so far in a Phytophthora species) and 16 with a Crinkler (CRN) domain. We detected homologs of previously described avirulence gene (Avr) present in Phytophthora spp., such as Avr1, Avr3b, Avr4, and Avrblb1, suggesting a high level of effector gene conservation among Phytophthora species. Nonetheless, fewer CRN effectors were obtained in P. betacei compared to all other Phytophthora species analyzed. The comparison between P. infestans and P. betacei effector profiles shows unique features in P. betacei that might be involved in pathogenesis and host preference. Indeed, 402 unique predicted effector genes were detected in P. betacei, corresponding to 197 apoplastic effector genes, 203 RxLR cytoplasmic effector genes, and 2 effector genes with CRN domain. This is the first characterization of the effector profile of P. betacei and the broadest comparison of predicted effector repertoires in the genus Phytophthora following a standardized prediction pipeline. The resultant P. betacei putative effector repertoire provides a reasonable set of proteins whose experimental validation could lead to understand the specific virulence factors responsible for the host specificity of this species.


Epidemiology of acute mountain sickness on Jade Mountain, Taiwan: an annual prospective observational study.
Acute mountain sickness (AMS) is a pathophysiological symptom complex that occurs in high altitude areas. The AMS prevalence is reportedly 28% on Jade Mountain, the highest mountain (3952 m) in Taiwan. We conducted this study owing to the lack of annual epidemiological data on AMS in Taiwan. Between April 2007 and March 2008, 1066 questionnaires were completed by trekkers visiting Paiyun Lodge on Jade Mountain. Information in the questionnaire included demographic data, mountaineering experience, AMS history, and trekking schedule. Weather data were obtained from the Central Weather Bureau of Taiwan. The Lake Louise AMS score was used to record symptoms and diagnose AMS. The chi-square test or the Student t test was used to evaluate associations between variables and AMS. In our study, the AMS prevalence was 36%. It increased significantly at different rates at different locations on the Jade Mountain trail and varied significantly in different months. Rainy weather tended to slightly increase the incidence of AMS. A lower incidence of AMS was correlated with hig-altitude trekking experience or preexposure (p < 0.05), whereas a higher incidence of AMS was correlated with a prior history of AMS (p < 0.05). The trekkers with AMS were significantly younger, ascended faster from their residence to the entrance or to Paiyun Lodge, and ascended slower from the entrance to the Paiyun Lodge (p < 0.05), but the differences lacked clinical significance. No differences in the incidence of AMS based on blood type, gender, or obesity were observed. The most common symptom among all trekkers was headache, followed by difficulty sleeping, fatigue or weakness, gastrointestinal (GI) symptoms, and dizziness or lightheadedness. In conclusion, the AMS prevalence on Jade Mountain was 36%, varied by month, and correlated with trekking experience, preexposure, and a prior history of AMS. The overall presentation of AMS was similar to that on other major world mountains.


Application of computed tomography for the evaluation of obstetrically relevant measurements in German Holstein-Friesian calves.
The aim of this study was to measure obstetrically relevant dimensions in calves manually and via computed tomography and to investigate their relationship with the dimensions of fetal body parts that are accessible to the obstetrician during early stages of vaginal delivery. Twenty Holstein-Friesian stillborn calves (Bos taurus) weighing 41.1 ± 3.7 kg (33.6-46.5 kg) were examined and the maximum height (H), width (W), circumference (C) and cross-sectional area (A) of their body was determined. The largest (P < 0.05) one-dimensional variable was the height of the thorax in the region of cranial sternum (H-Thorax; 29.3 ± 1.3 cm), and the largest (P < 0.05) two-dimensional variables were the cross-sectional area of the shoulder region at greater tubercles of the humeri (A-Shoulder; 307 ± 27 cm²) and of the thorax in the region of cranial sternum (A-Thorax; 306 ± 25 cm²). The dimensions of the front legs, which included the circumference of the canon bone and width of the fetlock joint, did not correlate (P > 0.05) with H-Thorax, A-Shoulder and A-Thorax. There were moderate significant correlations between the perpendicular height of the head (H-Head) and A-Thorax (r = 0.65, P < 0.05) and between the circumference of the head (C-Head) and A-Shoulder (r = 0.64, P < 0.05) and A-Thorax (r = 0.52, P < 0.05), but other relationships (P > 0.05) between the dimensions at the level of the head and H-Thorax, A-Shoulder and A-Thorax were not significant (P > 0.05). The results of this study show that the shoulders and thorax are the obstetrically most relevant calf dimensions, but the size of these variables cannot be reliably predicted by evaluating the dimensions of the forelimbs and head of calves during delivery.


Radiation-induced cerebral meningiomas. Case reports.
Two cases are presented of meningiomas following external cranial irradiation in which several features clearly indicate a causal relationship between radiotherapy and tumour development. In one patient multiple recurred meningioma was diagnosed 30 years after low-dose X-ray treatment of Tinea capitis; in the other patient the meningioma was diagnosed approximately 18 years after high-dose radiation therapy for astrocytoma. The features distinguishing radiation-induced meningiomas from other meningiomas are reviewed. The use of radiation therapy only in those cases in which there is clear evidence that it will have beneficial effects and that these effects will outweigh the risks is emphasized.


Outcomes of secondary trapeziectomy after revision of trapeziometacarpal implants: a retrospective comparative matched study.
We evaluated secondary trapeziectomy for revision of trapeziometacarpal implants and compared this to primary trapeziectomy with a matched retrospective single centre study performed between October 2003 and February 2015. Thirty-one patients with trapeziometacarpal prosthesis failure who had a secondary trapeziectomy were matched with a primary trapeziectomy regarding sex, date of the operation and age. We evaluated function, mobility, autonomy, pain, strength, complications and shortening of the thumb on radiographs. The median time until removal of the implant was 37 months. The median age in both groups was similar. Median follow-up was more than 7 years in both groups. There was no statistically significant difference in terms of function, mobility, autonomy, pain, strength, complications and shortening of the thumb. Secondary trapeziectomy after revision of trapeziometacarpal implants provides results comparable with primary trapeziectomy.Level of evidence: III.


[Single-voxel proton spectroscopy using a press sequence with a 135 ms echotime: normal values].
The clinical value of MR spectroscopy is now well established and this technique has been added to the current French classification of medical acts (CCAM). This paper presents a set of normal control values for 3 metabolite ratios obtained using a PRESS sequence with a TE of 135 ms at 1.5T: NAA/Cho, NAA/Cr and Cho/CR. Spectroscopy data acquisition were obtained from the following 12 anatomical regions: parieto-occipital white matter, centrum semiovale, frontal white matter, thalamus, basal ganglia, cerebellum (hemisphere, including dentate nucleus), brain stem (including pons, medulla and midbrain), anterior and posterior temporal lobe, parietal, occipital and pre-frontal cortices. The presented data allow radiologists equipped with a similar MR system to implement a clinical spectroscopy program without undergoing research protocols in order to obtain control values.


1H nuclear magnetic resonance spectroscopy-based studies of the metabolism of food-borne carcinogen 2-amino-3-methylimidazo[4,5-f]quinoline by human intestinal microbiota.
2-Amino-3-methylimidazo[4,5-f]quinoline (IQ) is a mutagenic/carcinogenic compound formed from meat and fish during cooking. Following ingestion, IQ is metabolized mainly by liver xenobiotic-metabolizing enzymes, but intestinal bacteria may also contribute to its biotransformation. The aim of this study was to investigate the metabolism of IQ by the human intestinal microbiota. Following incubation of IQ (200 microM) under anoxic conditions with 100-fold dilutions of stools freshly collected from three healthy volunteers, we quantified residual IQ by high-pressure liquid chromatography (HPLC) analysis and characterized the production of IQ metabolites by in situ (1)H nuclear magnetic resonance ((1)H-NMR) spectroscopic analysis of crude incubation media. In addition, we looked for IQ-degrading bacteria by screening collection strains and by isolating new strains from the cecal contents of human-microbiota-associated rats gavaged with IQ on a regular basis. HPLC and (1)H-NMR analyses showed that the three human microbiota degraded IQ with different efficiencies (range, 50 to 91% after 72 h of incubation) and converted it into a unique derivative, namely, 7-hydroxy-IQ. We found 10 bacterial strains that were able to perform this reaction: Bacteroides thetaiotaomicron (n = 2), Clostridium clostridiiforme (n = 3), Clostridium perfringens (n = 1), and Escherichia coli (n = 4). On the whole, our results indicate that bacteria belonging to the predominant communities of the human intestine are able to produce 7-hydroxy-IQ from IQ. They also suggest interindividual differences in the ability to perform this reaction. Whether it is a metabolic activation is still a matter of debate, since 7-hydroxy-IQ has been shown to be a direct-acting mutagen in the Ames assay but not carcinogenic in laboratory rodents.


Coping, social support and medical factors on psychosocial impact in couples experiencing infertility.
This study assessed dyadically the relationship between psychosocial impact of infertility experienced by 87 couples and individual coping strategies, perceived social support and some medical factors. Although problem-focused strategies emerged as positive, certain side effects on partner were revealed. Social support was related to psychosocial outcomes in a positive way, cognitive component of coping strategies resulted as a prominent factor on individual's adjustment as well as the partner's role. Findings suggest the convenience of promoting the awareness about the effects of each partner's feelings, behaviors and beliefs on his/her individual's well-being in this field due to the interdependent context in which they are. Infertility counselors may foster this process by evaluating and educating to them about the functionality of these factors.


Expression of c-myc oncoprotein in laryngeal squamous cell carcinoma.
c-myc seems to play a pivotal role in normal growth and development as well in cellular transformation and carcinogenesis. Overexpression of the c-myc oncogene has been observed in many hematopoetic and solid tumors. The role of c-myc protein in squamous cell carcinoma of the head and neck in general and laryngeal squamous cell carcinomas (LSCCs) in particular is far from clear. The aim of this study was to evaluate the relations between the level of c-myc protein in LSCCs and the clinicopathological data of patients, DNA ploidy and the SG2M phase index (PI). The c-myc protein level was evaluated immunohistochemically in tumor specimens from 50 patients with LSCC. The DNA index and SG2M PI were determined by means of flow cytometry. We found c-myc protein in 34 (68%) tumors. Expression of c-myc protein was demonstrated to be frequent in nonmetastatic cases (p = 0.016). There was no association between c-myc protein level and age, primary tumor size, histological grading or type of cancer. In 13 (26%) cases we observed DNA aneuploid tumors. The mean value of the SG2M PI was 22.5%. Expression of c-myc protein was not related to SG2M PI or DNA ploidy. We have shown that c-myc oncoprotein may be involved in the genesis of LSCC. Our findings suggest that the detectability of c-myc protein is associated with a lower metastatic potential. The c-myc oncogene is probably not as important in laryngeal cancers compared to other cancers. Further investigations must be performed to establish the value of predicting nodal metastases in LSCC.


Complex Consisting of β-Glucan and Antigenic Peptides with Cleavage Site for Glutathione and Aminopeptidases Induces Potent Cytotoxic T Lymphocytes.
The efficient induction of antigen-specific immune responses requires not only promotion of the uptake of antigens and adjuvant molecules into antigen-presenting cells but also control of their intracellular behavior. We previously demonstrated that the β-glucan schizophyllan (SPG) can form complexes with CpG oligonucleotides with attached dA40 (CpG-dA/SPG), which can accumulate in macrophages in the draining inguinal lymph nodes and induce strong immune responses. In this study, we prepared various conjugates composed of antigenic peptide (OVA257-264) and dA40 and made complexes with SPG. The conjugates with a disulfide bond between OVA257-264 and dA40 were easily cleaved by glutathione. The resultant peptides with a hydrophobic amino acid at the C-terminal end was recognized by puromycin-insensitive leucine aminopeptidase (PILS-AP), which trims antigenic peptide precursors and prepares peptides of eight or nine amino acids in length, which is the optimal length for binding to major histocompatibility complex (MHC)-I. The conjugate exposed to such enzymes induced a high antigen presentation level. The antigen presentation level was almost the same before and after the complexation with SPG. Immunization with a mixture of dA-OVA257-264/SPG and CpG-dA/SPG induced high antigen-specific cytotoxic T-lymphocyte activity at a much lower peptide dose than in previous studies. These results can be strongly ascribed to not only the cell-specific delivery by SPG but also the control of the intracellular behavior by the introduction of cleavage sites. Therefore, peptide-dA/SPG complexes could be used as potent vaccine antigens for the treatment of cancers and infectious diseases.


Tritium-labelled isovaleryl-RYYRIK-NH2 as potential antagonist probe for ORL1 nociceptin receptor.
IsoVa-RYYRIK-NH2 is a highly specific antagonist ligand of the opioid receptor-like 1 (ORL1) receptor, an endogenous ligand of which is 17-mer peptide nociceptin. ORL1 antagonists have potential for clinical use as analgesic and antineuropathic drugs, and thus information on the receptor-binding characteristics of antagonists is very important for rational drug design. In the present study, we prepared tritium-labelled isova-RYYRIK-NH2 from its precursor with the 3-methylcrotonyl (CH3)2CCHCO group by a catalytic reduction using tritium gas. The resulting [(3)H]isoVa-RYYRIK-NH2 was evaluated in a saturation binding assay using the COS-7 cell membrane preparations of transiently expressed ORL1. It exhibited more than 90% specific binding with a dissociation constant of 1.21±0.03nM. From the mutual heterologous binding assays using [(3)H]isoVa-RYYRIK-NH2 and [(3)H]nociceptin, isoVa-RYYRIK-NH2 and nociceptin were found to share the receptor-binding site, but each also had a separate specific binding site of its own. They differentiated the two different binding states or conformations of ORL1, which might represent the agonist-active and antagonist-inactive conformations of ORL1. [(3)H]isoVa-RYYRIK-NH2 is thus a key tracer to uncover the amino acid residues important for receptor inactivation.


Electrochemical oxidation of sugars at moderate potentials catalyzed by Rh porphyrins.
In this communication, we demonstrate that certain kinds of Rh porphyrins on carbon black can electrochemically oxidize aldose at low potentials. The onset potential was much lower than those with the other complex-based catalysts. A product analysis suggested that this reaction involves 2-electron oxidation of the aldehyde group.


Are entry criteria for cataract surgery justified?
The German Ophthalmological Society (GOS) recently proposed surgical entry criteria, i.e. 300 cataract surgeries. We herein correlate the surgical hands-on experience with the risk of posterior capsule ruptures in order to assess whether this number is appropriate. We identified all cataract operations that had been performed at the University Eye Hospital Freiburg since 1995. For each surgeon, we assigned a running number to his/her procedures in the order they had been performed. Thereafter, we excluded all combined procedures and the second eyes. We then selected the 5475 surgical reports between November 2008 and November 2012 for detailed review. We additionally classified each surgery into low- vs. high- à priori risk for posterior capsule ruptures. We fitted a multifactorial logistic regression model to assess the GOS recommendation of 300 surgeries under supervision. In the low-risk group, we additionally visualized the 'typical' learning curve by plotting the posterior capsule ruptures against the respective rank numbers. The odds ratio for posterior capsule ruptures of 'learning-mode' (one of the respective surgeon's 300 first procedures) vs. the non-learning-mode was 3.8 (p<0.0001). By contrast, classification into the low-risk group lowered the risk of posterior capsule ruptures three fold (p<0.0001). According to the low-risk plot, the surgeons started with a complication rate of 4% and continuously improved towards 0.5% after 1500 operations. Thereafter, the rate increased again and stabilized around one percent. The learning curve with respect to posterior capsule ruptures is surprisingly flat. The GOS entry criterion of 300 cataract procedures is therefore most likely justified. Careful selection of low-risk patients for the training surgeons may help in reducing the rate of posterior capsule ruptures during training.


Gold-Catalyzed Oxidative [2+2+1] Annulations of Aryldiazo Nitriles with Imines To Yield Polyarylated Imidazolium Salts.
Gold-catalyzed oxidative [2+2+1] annulations between two imines and one α-cyano arylgold carbene afforded polyarylated imidazolium salts and molecular hydrogen efficiently. Control experiments suggest that the gold catalyst alone facilitates the main annulation, whereas Ag+ avoids the formation of inactive LAuCN. DFT calculations suggest that the success of this annulation relies on a 6 π-electrocyclization of cyano-free intermediates with cis-configured imines as initial reagents.


Tracheal damage.
Tracheal damage. Blunt/penetrating trauma and inhalation injuries to the trachea can result in acute airway compromise, with life-threatening implications. Early assessment, identification, and prompt and appropriate management are of paramount importance in order to reduce patient morbidity and mortality. Signs and symptoms of these injuries are specific and sometimes subtle, and their seriousness may be obscured by other injuries. Diagnosis can therefore be challenging, requiring a high index of suspicion. Indeed, diagnosis and treatment are often delayed, resulting in attempted surgical repair months or even years after injury. Laryngoscopy, flexible and/or rigid bronchoscopy and computed tomography of the chest are the procedures of choice for a definitive diagnosis. Airway control and appropriate ventilation represent the key aspects of emergency management. Definitive treatment depends on the site and the extent of injury. Surgery, involving primary repair with direct suture or resection and end-to-end anastomosis, is the treatment of choice for patients suffering from tracheal injuries. A conservative approach must be considered for the paediatric population and selected patients with mainly iatrogenic damage. We present a review of the incidence, mechanisms of injury, clinical presentations, diagnosis, initial airway management, anaesthetic considerations and definitive treatment in the case of tracheal damage from blunt/penetrating trauma and inhalation injuries.


Appraisal of self-collected cervical specimens in cytologic screening of uterine cancer.
Cytologic specimens were collected simultaneously by three methods on 122 patients with cervical neoplastic lesions: self-irrigated collection, self-scraped collection and physician-scraped collection. In invasive epidermoid carcinoma, the accuracy with the self-collected specimens approached the physician-scraped specimens. There was a serious defect in the detection of cervical intraepithelial neoplasia by the self-irrigation method. In carcinoma in situ and dysplasia, the self-scraping method was considerably better than the self-irrigation method. In mass screening of 89,206 females, the self-scraping positive detection rates were closer to the physican-scraping results than the self-irrigation method.


Identification of the linear ligand epitope on classical swine fever virus that interacts with porcine kidney 15 cells.
Binding of the viral ligand to a specific receptor is the first step of virus entry into target cells. The envelope proteins Erns, E1, and E2 of classical swine fever virus (CSFV) are involved in the interaction with host cell receptors to mediate CSFV infection. The aim of this investigation was to identify epitopes that bind to porcine kidney (PK)-15 cells to prevent CSFV infection. Ten peptides representing Erns, E1, and E2 were synthesized. Immunohistochemical study showed that the SE24 peptide, which is derived from the E2 amino acid sequence, could effectively bind to PK-15 cells. Similarly, a flow cytometry assay demonstrated that SE24 binding to PK-15 cells could be blocked by CSFV. The binding of SE24 with PK-15 cells leads to decreased CSFV infection of PK-15 cells in a dose-dependent manner. These results suggest a potential new strategy for the prevention and control of CSFV infection that requires further investigation.


[Impact and clinical outcome of intra-aortic balloon pump use during percutaneous coronary intervention].
Objective: To observe the impact and clinical outcome of intra-aortic balloon pump(IABP) use in patients underwent percutaneous coronary intervention (PCI). Methods: From January 2013 to December 2013, 10 724 consecutive patients undergoing PCI were enrolled.After 2 years' follow-up, the incidence of major adverse cardiovascular and cerebrovascular events such as death, myocardial infarction, stent thrombosis, revascularization, recurrent stroke were recorded, propensity score was used to match baseline data, and the clinical outcomes in patients with IABP and non-IABP were compared. Results: The overall use of IABP was 1.3%(143/10 724), clinical and angiographic risks were significantly higher in IABP group than non-IABP group.The rate of cardiac shock was significantly higher (9.8%(14/143) vs. 0.2%(16/10 581), P<0.01) and left ventricular ejection fraction was significantly lower (54.3%±11.0% vs. 62.9%±7.2%, P<0.01) in the IABP group than in the non-IABP group.Patients in IABP group had a significantly higher rate of left main or triple-vessel disease (P<0.01), and their SYNTAX score, target lesion number, stent number were also significantly higher compared with non-IABP patients (all P<0.01). During the 2-year follow-up, all-cause mortality was significantly higher in IABP group than in non-IABP group (10.5%(15/142) vs. 1.1%(116/10 581), P<0.001). Multivariable analyses indicated that IABP was associated with increased mortality (HR=3.51, 95%CI 1.71-7.17, P=0.001). However, after propensity score matched analyses (137 pairs), IABP use was no longer an independent predictor of all-cause mortality (HR=2.09, 95%CI 0.72-6.13, P=0.177). Conclusions: In this single large center of coronary heart disease in China, the IABP usage was about 1.3%.Propensity score matched analyses showed that during the 2 years' follow-up, adverse effect including similar long-term mortality is similar between PCI patients with or without IABP after adjusting for confounders.


Femtosecond-laser-written, stress-induced Nd:YVO4 waveguides preserving fluorescence and Raman gain.
We report the formation of optical waveguides in the self-Raman Nd:YVO(4) laser crystal by femtosecond laser inscription. The confocal fluorescence and Raman images have revealed that the waveguide is constituted by a locally compressed area in which the original fluorescence and Raman gains of the Nd:YVO(4) system are preserved. Thus the obtained structures emerge as promising candidates for highly efficient self-Raman integrated laser sources.


Selectable Markers and Reporter Genes for Engineering the Chloroplast of Chlamydomonas reinhardtii.
Chlamydomonas reinhardtii is a model alga of increasing interest as a cell factory for the production of valuable compounds, including therapeutic proteins and bioactive metabolites. Expression of foreign genes in the chloroplast is particularly advantageous as: (i) accumulation of product in this sub-cellular compartment minimises potential toxicity to the rest of the cell; (ii) genes can integrate at specific loci of the chloroplast genome (plastome) by homologous recombination; (iii) the high ploidy of the plastome and the high-level expression of chloroplast genes can be exploited to achieve levels of recombinant protein as high as 5% total cell protein; (iv) the lack of any gene silencing mechanisms in the chloroplast ensures stable expression of transgenes. However, the generation of C. reinhardtii chloroplast transformants requires efficient methods of selection, and ideally methods for subsequent marker removal. Additionally, the use of reporter genes is critical to achieving a comprehensive understanding of gene expression, thereby informing experimental design for recombinant applications. This review discusses currently available selection and reporter systems for chloroplast engineering in C. reinhardtii, as well as those used for chloroplast engineering in higher plants and other microalgae, and looks to the future in terms of possible new markers and reporters that will further advance the C. reinhardtii chloroplast as an expression platform.


Wideband numerical modeling for vertical-cavity surface-emitting laser Bragg reflectors.
We present a novel, to our knowledge, scheme for vertical-cavity surface-emitting laser Bragg reflectors modeling in wideband systems, which notably improves accuracy and numerical efficiency. These Bragg reflectors are characterized as digital filters and then are approximated by use of autoregressive moving-average models. The features of the models are analyzed in terms of the predicted error in the frequency domain, keeping it below 0.1% over a 85-nm range. The numerical structure allows the Bragg reflectors to be integrated accurately into dynamic models of tunable lasers and amplifiers.


Behavioral consequences of repeated nicotine during adolescence in alcohol-preferring AA and alcohol-avoiding ANA rats.
Epidemiological studies suggest that exposure to nicotine at adolescent age is associated with increased potential to use alcohol and that genetic predisposition may further increase the risk. The present study addressed adolescent vulnerability to repeated nicotine exposure and its influence on subsequent ethanol self-administration by investigating interactions between nicotine-induced behavioral sensitization and voluntary ethanol consumption in alcohol preferring AA (Alko Alcohol) and alcohol nonpreferring ANA (Alko Non-Alcohol) rat lines selected for differential ethanol intake. Adolescent and adult rats received 10 injections of nicotine (0.5 mg/kg s.c.), given every second day from postnatal day (Pnd) 27 and 75, respectively. Nicotine-induced (0.5 mg/kg) locomotor activity was measured acutely after the first injection, and after the repeated treatment with nicotine on Pnds 52 and 86 in the adolescent groups and on Pnd 99 in the adult groups. After this, acquisition of voluntary ethanol (10% v/v) consumption as well as nicotine-induced (0.5 mg/kg) ethanol intake was measured in the AA rats. Adolescent AA rats were more sensitive than adolescent ANA rats to the locomotor effects of nicotine. They were also stimulated more than adult AA rats, but such a difference was not found among ANA rats. Adolescent and adult rats did not differ in their susceptibility to nicotine-induced behavioral sensitization. Genetic predisposition to ethanol self-administration did not interact with development of behavioral sensitization in either adolescents or adults. Acquisition of ethanol intake was enhanced in the adolescent groups relative to the adult groups in a manner that was independent of the nicotine treatment. An increase in ethanol intake was found after challenging animals with nicotine, and this effect was enhanced in the nicotine-treated adolescent group. These findings provide no or little support for the views that adolescent animals are more sensitive to the neurobehavioral effects of repeated exposure to nicotine and that exposure to nicotine in adolescence may contribute to enhanced vulnerability to ethanol abuse. Furthermore, genetic predisposition to high or low ethanol self-administration does not seem to be a factor that influences individual vulnerability to the neurobehavioral effects of repeated administration of nicotine.


Both systemic Calcitonin Gene Related Peptide (CGRP) and a vestibular challenge promote anxiety-related behaviors and dynamic imbalance in mice.
Motion-induced anxiety and agoraphobia are more frequent symptoms in patients with vestibular migraine than migraine without vertigo. The neuropeptide calcitonin gene-related peptide (CGRP) is a therapeutic target for migraine and vestibular migraine, but the link between motion hypersensitivity, anxiety, and CGRP is relatively unexplored, especially in preclinical mouse models. To further examine this link, we tested the effects of systemic CGRP and off-vertical axis rotation (OVAR) on elevated plus maze (EPM) and rotarod performance in male and female C57BL/6J mice. Rotarod ability was assessed using two different dowel diameters: mouse dowel (r = 1.5 cm) versus rat dowel (r = 3.5 cm). EPM results indicate CGRP increased anxiety indexes and time spent in the closed arms in females but not males, while OVAR increased anxiety indexes and time spent in the closed arms in both sexes. The combination of CGRP and OVAR elicited even greater anxiety-like behavior. On the rotarod, CGRP reduced performance in both sexes on a mouse dowel but had no effect on a rat dowel, whereas OVAR had a significant effect on the rat dowel. Rotarod performance is influenced by dowel diameter, with larger dowels presenting greater challenges on balance function. These results suggest that both CGRP and vestibular stimulation induce anxiety-like behavior and that CGRP affects dynamic balance function in mice depending on the type of challenge presented. Findings highlight the potential translation of anti-CGRP receptor signaling therapeutics for treating motion hypersensitivity and motion-induced anxiety that manifests in vestibular migraine. Anxiety is very common in patients with dizziness and vestibular migraine (VM). Elevated CGRP levels have been linked to migraine symptoms of increased light and touch sensitivity in mice and humans and we wondered if a systemic injection of CGRP into mice would increase anxiety and imbalance; and if mice further exposed to a vestibular stimulus would have their anxiety measures sharpened. We observed a female preponderance in both CGRP and motion-induced anxiety-like behaviors, suggesting that the role of CGRP in migraine's anxiety symptoms can be recapitulated in the mouse. Our findings suggest that CGRP signaling has a pertinent role in motion-induced anxiety and dynamic imbalance, and warrants the potential use of anti-CGRP therapies for the treatment of these symptoms.


A Nanocluster [Ag307Cl62(SPhtBu)110]: Chloride Intercalation, Specific Electronic State, and Superstability.
The controlling synthesis of novel nanoclusters of noble metals (Au, Ag) and the determination of their atomically precise structures provide opportunities for investigating their specific properties and applications. Here we report a novel silver nanocluster [Ag307Cl62(SPhtBu)110] (Ag307) whose structure is determined by X-ray single crystal diffraction. The structure analysis shows that nanocluster Ag307 contains a Ag167 core, a surface shell of [Ag140Cl2S110], and a Cl60 intermediate layer located between Ag167 and [Ag140Cl2S110]. It is a first example that such many chlorides are intercalated into a Ag nanocluster. Chlorides are released in situ from solvent CHCl3. Nanocluster Ag307 exhibits superstability. Differential pulse voltammetry experiment reveals that Ag307 has continuous charging/discharging behavior with a capacitance value of 1.39 aF, while the Ag307 has a surface plasmonic feature. These characteristics show that Ag307 is of metallic behavior. However, its electron paramagnetic resonance (EPR) spectra display a spin magnetic behavior which could be originated from the unpassivated dangling bonds of surface atoms. The direct capture of EPR signals can be attributed to the Cl- intercalating layer which partly suppresses the electronic interactions between core and surface atoms, resulting in the relatively independent electronic states for core and surface atoms.


Stereoselective hydroxylation of norcamphor by cytochrome P450cam. Experimental verification of molecular dynamics simulations.
The stereoselectivity of cytochrome P450cam hydroxylation has been investigated with the enantiomerically pure substrate analog norcamphor. (1R)- and (1S)-norcamphor (> 92 enantiomeric excess) were characterized in the hydroxylation reaction with cytochrome P450cam with respect to the product profile, steady state kinetics, coupling efficiency, and free energy of substrate dissociation. The experimental results demonstrate regiospecificity that is enantiomer-specific and confirm our previously reported prediction that (1R)-norcamphor is hydroxylated preferentially at the 5-carbon and (1S)-norcamphor at the 6-carbon (Bass, M. B., and Ornstein, R. L. (1993) J. Comput. Chem. 14, 541-548); these simulation results are now compared with simulations involving a ferryl oxygen intermediate. Hydroxylation of (1R)-norcamphor was found at the 5-, 6-, and 3-carbons in a ratio of 65:30:5 (respectively), whereas (1S)-norcamphor was oxidized to produce a 28:62:10 ratio of the same products. With the exception of the regiospecificity, all of the reaction and physical parameters are similar for each enantiomer of norcamphor. These results show that the position of the carbonyl group on the hydrocarbon skeleton of norcamphor plays a role in determining the average orientation of this substrate in the active site and suggests that hydrogen bonding interactions can aid in directing the regiospecificity and stereospecificity of the hydroxylation reaction catalyzed by cytochrome P450cam.


Temperature Dependence of the Anomalous Hall Effect from Electron Interactions.
We consider the impact of electron-electron interactions on the temperature dependence of the anomalous Hall effect in disordered conductors. The microscopic analysis is carried out within the diagrammatic approach of the linear response Kubo-Streda formula with an account of both extrinsic skew-scattering and side-jump mechanisms of the anomalous Hall effect arising in the presence of spin-orbit coupling. We demonstrate the importance of electron interactions in the Cooper channel even for nominally non-superconducting materials and find that the corresponding low-temperature dependence of the anomalous Hall conductivity is asymptotically of the form sqrt[T]/ln(T_{0}/T) in three dimensions and ln[ln(T_{0}/T)] in two dimensions, where the scale of T_{0} is parametrically of the order of Fermi energy. These results, in particular, may provide a possible explanation for the recently observed unconventional temperature dependence of the anomalous Hall effect in HgCr_{2}Se_{4}.


DNA damage tolerance in stem cells, ageing, mutagenesis, disease and cancer therapy.
The DNA damage response network guards the stability of the genome from a plethora of exogenous and endogenous insults. An essential feature of the DNA damage response network is its capacity to tolerate DNA damage and structural impediments during DNA synthesis. This capacity, referred to as DNA damage tolerance (DDT), contributes to replication fork progression and stability in the presence of blocking structures or DNA lesions. Defective DDT can lead to a prolonged fork arrest and eventually cumulate in a fork collapse that involves the formation of DNA double strand breaks. Four principal modes of DDT have been distinguished: translesion synthesis, fork reversal, template switching and repriming. All DDT modes warrant continuation of replication through bypassing the fork stalling impediment or repriming downstream of the impediment in combination with filling of the single-stranded DNA gaps. In this way, DDT prevents secondary DNA damage and critically contributes to genome stability and cellular fitness. DDT plays a key role in mutagenesis, stem cell maintenance, ageing and the prevention of cancer. This review provides an overview of the role of DDT in these aspects.


Cyclic AMP delays G2 progression and prevents efficient accumulation of cyclin B1 proteins in mouse macrophage cells.
In mouse macrophage cells, the increase of the intracellular cAMP level activates protein kinase A (PKA) and results in inhibition of cell cycle progression in both G1 and G2/M phases. G1 arrest is mediated by a cdk inhibitor, p27Kip1, which prevents G1 cyclin/cdk complexes from being activated in response to colony stimulating factor-1, whereas inhibition of G2/M progression has not been fully elucidated. In this report we analyzed the effect of cAMP on G2/M progression in a mouse macrophage cell line, BAC1.2F5A. Flow cytometric analysis and mitotic index measurement using both synchronized and asynchronized cells revealed that addition of cAMP-elevating agents (8-bromoadenosine 3':5'-cyclic monophosphate and 3-isobutyl-methyl-xanthine), although they did not affect S phase progression or M/G1 transition, temporarily arrested cells in G2 but eventually the cells proceeded to M phase, resulting in about 4 hours delay of G2 progression. Timing of cyclin B1/Cdc2 kinase activation was also retarded by about 4 hours, which was accompanied by inhibition of efficient accumulation of cyclin B1 proteins. Initial induction and accumulation of cyclin B1 mRNA were not hampered, but the half life of cyclin B1 proteins was significantly shorter during G2 phase in the presence of cAMP-elevating agents compared with that of the cells blocked from progressing through M phase by nocodazole. These results imply that the cAMP/PKA pathway regulates G2 phase progression by altering the stability of a crucial cell cycle regulator.


Dietary Phosphorus Reduced Hepatic Lipid Deposition by Activating Ampk Pathway and Beclin1 Phosphorylation Levels to Activate Lipophagy in Tilapia Oreochromis niloticus.
High-phosphorus diet (HPD) reduces lipid deposition and significantly influences lipid metabolism. However, the relevant mechanism is unknown. Herein, using widely-cultured teleost tilapia Oreochromis niloticus as the experimental animals, we found that HPD and Pi incubation reduced triglyceride (TG) content (P ≤ 0.05), suppressed lipogenesis, activated AMP-activated protein kinase (AMPK) pathway and autophagy (P ≤ 0.05), and increased fatty acid β-oxidation and lipolysis in tilapia liver and hepatocytes (P ≤ 0.05). Our further investigation indicated that Pi treatments activated the lipophagy and facilitated mitochondrial fatty acid β-oxidation, and according reduced TG deposition (P ≤ 0.05). Mechanistically, phosphorus increased the AMPKα1 phosphorylation level at S496 and Beclin1 phosphorylation at S90, and Beclin1 phosphorylation by AMPKα1 was required for phosphorus-induced lipophagy and lipolysis. Our study revealed a mechanism for Beclin1 regulation and autophagy induction in response to high-phosphorus diet, and provided novel evidences for the link between dietary phosphorus addition and lipolytic metabolism via the AMPK/Beclin1 pathway. Our results also suggested that AMPK should be the potential target for the prevention and control of lipid metabolic disorders. Overall, these results suggested that HPD reduced hepatic lipid deposition by activating AMPK pathway and Beclin1 phosphorylation levels to activate lipophagy, which provided potential targets for the prevention and control of fatty liver in fish.


Donepezil-tacrine hybrid related derivatives as new dual binding site inhibitors of AChE.
A new series of donepezil-tacrine hybrid related derivatives have been synthesised as dual acetylcholinesterase inhibitors that could bind simultaneously to the peripheral and catalytic sites of the enzyme. These new hybrids combined a tacrine, 6-chlorotacrine or acridine unit as catalytic binding site and indanone (the heterocycle present in donepezil) or phthalimide moiety as peripheral binding site of the enzyme, connected through a different linker tether length. One of the synthesised compounds emerged as a potent and selective AChE inhibitor, which is able to displace propidium in a competition assay. These results seem to confirm the ability of this inhibitor to bind simultaneously to both sites of the enzyme and make it a promising lead for developing disease-modifying drugs for the future treatment of Alzheimer's disease. To gain insight into the molecular determinants that modulate the inhibitory activity of these compounds, a molecular modelling study was performed to explore their binding to the enzyme.


Evolution of tricuspid regurgitation after mitral valve surgery for patients with moderate-or-less functional tricuspid regurgitation.
The purpose of this study was to evaluate the impact of moderate-or-less functional tricuspid regurgitation (TR) treatment on the clinical outcome of patients with mitral valve (MV) surgery. From October 2001 to January 2005, 167 patients in our hospital with MV surgery and without organic tricuspid valve (TV) disease or pulmonary hypertension (PH) showed moderate-or-less functional TR preoperatively, and 41.9% of these patients were treated with TR (group T), compared with 58.1% untreated with TR (group no-T). According to tricuspid annulus dimension (TAD)/body surface area (BSA), these 167 patients were further divided into another 2 groups (A and B): group A (70 patients) represented TAD/BSA ≤ 21 mm/m2 with 32 patients from group T and 38 from group no-T, and group B (97 patients) represented TAD/BSA > 21 mm/m2 with 38 patients from group T and 59 patients from group no-T. There was no statistical difference in preoperative and operative variables between the 2 groups. Meanwhile, among the 167 patients with MV surgery, 157 patients were replaced with MV and 10 patients were repaired with MV, and De Vega technique was constantly used for TR treatment. All the results were estimated by multivariate analysis. The median follow-up time was 63 months (25th and 75th percentiles are 53 and 94 months, respectively); 30-day mortality was 3% (1.4% in group T versus 4.1% in group no-T; P = .31). Adjusted 5-year survival was 70.7% (66.6%-80.4%) with 85.3% (83.0%-93.4%) in group T and 64.7% (33.7%-58.3%) in group no-T, P = .001. Among the 70 patients with TAD/BSA ≤ 21 mm/m2, patients who received treatment of moderate-or-less TR and those who did not showed similar secondary TR grade at postoperative period (0.5 ± 0.6 in group T versus 0.9 ± 0.9 in group no-T; P = .2) and follow-up (1.3 ± 1.1 in group T versus 1.8 ± 1.1 in group no-T; P = .06). In subgroup B (TAD/BSA > 21 mm/m2), patients who received tricuspid valvoplasty manifested more significantly improved outcome than patients without functional TR at postoperative period (0.8 ± 0.8 in group T versus 1.6 ± 1.3 in group no-T; P = .03) and follow-up (2.0 ± 1.2 in group T versus 3.0 ± 1.1 in group no-T; P = .005). The multivariate analysis identified TAD/BSA > 21 mm/m2 and preoperative atrial fibrillation (AF) as the risk factors for lower survival at follow-up period. Patients with MV surgery have better midterm outcome when they receive either more aggressive and effective surgical treatment for functional TR or moderate-or-less TR preoperatively. Indexed TAD (TAD/BSA > 21 mm/m2) is a more reliable surgical guideline for the treatment of TR. Preoperative tricuspid annulus dilation and AF might be predictors of late lower survival.


Oligoclonal T cell expansion in blood but not in the thymus from a patient with thymoma-associated pure red cell aplasia.
Despite the well-known association between thymoma and PRCA, the role of thymoma remains uncertain. There is accumulating evidence that clonal T cells are involved in acquired PRCA. We examined T cell receptor repertoires in blood and thymus from a patient with PRCA associated with thymoma and myasthenia gravis. Oligoclonal expansions of Vdelta1- and Vbeta1-expressing T cells were found in peripheral blood, whereas the repertoires of Vdelta1+ and Vbeta1+ T cells in thymoma were not skewed. Oligoclonal expansion of Vdelta1-expressing T cells remained unchanged after thymectomy. Thymus may not be the site of clonal T cell expansion in thymoma-associated PRCA.


The Neuroscience of Growth Mindset and Intrinsic Motivation.
Our actions can be triggered by intentions, incentives or intrinsic values. Recent neuroscientific research has yielded some results about the growth mindset and intrinsic motivation. With the advances in neuroscience and motivational studies, there is a global need to utilize this information to inform educational practice and research. Yet, little is known about the neuroscientific interplay between growth mindset and intrinsic motivation. This paper attempts to draw on the theories of growth mindset and intrinsic motivation, together with contemporary ideas in neuroscience, outline the potential for neuroscientific research in education. It aims to shed light on the relationship between growth mindset and intrinsic motivation in terms of supporting a growth mindset to facilitate intrinsic motivation through neural responses. Recent empirical research from the educational neuroscience perspective that provides insights into the interplay between growth mindset and intrinsic motivation will also be discussed.


Acylphloroglucinol Derivatives from Garcinia multiflora with Anti-Inflammatory Effect in LPS-Induced RAW264.7 Macrophages.
Two new acylphloroglucinol derivatives, 13,14-didehydroxygarcicowin C (1) and 13,14-didehydroxyisoxanthochymol (2), have been isolated from the stems of Garcinia multiflora, together with seven known compounds (3⁻9). The structures of new compounds 1 and 2 were elucidated by MS and extensive 1D/2D NMR spectroscopic analyses. Among the isolates, 13,14-didehydroxy-isoxanthochymol (2) and sampsonione B (3) exhibited inhibition against lipopolysaccharide (LPS)-induced NF-κB activation in macrophages at 30 μM with relative luciferase activity values (inhibitory %) of 0.75 ± 0.03 (24 ± 4%) and 0.12 ± 0.03 (88 ± 4%), respectively. Additionally, sampsonione B (3) reduced LPS-induced nitric oxide (NO) production in murine RAW264.7 macrophages and did not induce cytotoxicity against RAW 264.7 cells after 24 h treatment. Compound 3 is worth further investigation and may be expectantly developed as an anti-inflammatory drug candidate.


Effects of 2,4-D on the germination of megaspores and initial development of Regnellidium diphyllum Lindman (Monilophyta, Marsileaceae).
Regnellidium diphyllum is considered as endangered, occurring in the State of Rio Grande do Sul, Brazil, and a few adjoining localities in Uruguay, Argentina and the State of Santa Catarina. It grows in wetlands frequently altered for agricultural activities. Herbicides based on 2,4-dichlorophenoxyacetic acid (2,4-D) are widely used in these fields. The effects of 2,4-D on the germination of megaspores and initial sporophytic development of R. diphyllum were investigated. Six concentrations of 2,4-D (0.32; 0.64; 1.92; 4.80; 9.60 and 19.20 mg.L-1), and the control (0.00 mg.L-1), were tested in vitro, using Meyer's medium. Cultures were maintained in a growth chamber at 24 +/- 1 degrees C, under artificial light with nominal irradiance of 110 micromol.m-2/s and 16 hours photoperiod. Megaspore germination was lower at 9.60 and 19.20 mg.L-1 of 2,4-D (56 and 48%, respectively), compared with the control (68%). Herbicide concentrations of up to 1.92 mg.L-1 did not significantly decrease the number of sporophytes formed. At 19.20 mg.L-1, no sporophytes were formed. The lengths of the primary root, primary and secondary leaves were greater at concentrations of 0.32 and 0.64 mg.L-1 of 2,4-D. Low concentrations of 2,4-D do not affect germination rates and initial development of R. diphyllum in a significant way. However, higher concentrations (9.60 and 19.20 mg.L-1) affect substantially the germination of the megaspores and interfere with the establishment of the species.


Interobserver concordance for endoscopic ultrasonography-guided fine-needle aspiration on-site cytopathology.
Endoscopic ultrasonography-guided fine-needle aspiration (EUS-FNA) is an accurate method of diagnosing and staging gastrointestinal and thoracic malignancy. A key issue in maximizing FNA accuracy is to ensure that an adequate specimen is obtained. On-site cytopathology increases the diagnostic yield of EUS-FNA. However, this increases the time and costs. Physicians trained in EUS and in pathology are capable of interpreting cytologic adequacy from EUS-FNA specimens. Furthermore, on-site interpretation by the endoscopist could reduce cost and procedure duration. The learning curve of endossonographers in on-site cytopathology and how they could contribute in EUS-FNA accuracy increase is unknown. To determine the interobserver concordance of on-site cytopathology interpretation of EUS-FNA specimens by comparing endosonographers trained in cytology with a physician cytopathologist. A prospective blinded study comparing one endossonographer with one physician cytopathologist. The study was developed in the Santa Casa Medical School, Brazil from February to November 2012. Fifteen different cases of EUS-FNA were analysed, in a total of 50 slides. Each observer described the slides for the adequate or not of tissue sampling, and classified as benign, suspicious, malign or undefined. The analyses were then matched. We analyzed the concordance of 50 slides description made by the endossonographer and physician cytopathologist, according to enough material, cellular group identification and final diagnosis. Kappa (κ) indexes were: Presence of material κ = 0.480 (P < 0.001); presence of malignance κ = 0.808 (P < 0.001); in subepithelial lesions κ = 0.615 (P = 0.06); in pancreatic lesions κ = 0.675 (P < 0.001); in mediastinal lesions κ = 0.243 (P = 0.128). Our study showed that endosonographers and cytopathologists had good concordance in EUS-FNA specimens on-site cytopathology interpretation, except in mediastinal/pulmonary cases.


Psychodynamic psychiatry's green shoots.
Psychodynamic psychiatry makes a significant educational, scientific and therapeutic contribution to contemporary psychiatry. Recent developments in gene-environment interaction, neuropsychoanalysis and the accumulating evidence base for psychoanalytic therapies and their implications for practice are reviewed.


Tripodal nitro-imidazolium receptor for anion binding driven by (C-H)+- - -X- hydrogen bonds.
[structure: see text] A positively charged tripodal receptor with nitro groups in the imidazolium rings was designed, synthesized, and characterized for its anion binding strength. The receptor shows strong affinity and high selectivity for Cl- through (C-H)+- - -X(-) hydrogen bonds wherein charge-charge and charge-dipole electrostatic interactions dominate. The association constant with chloride anion in a 9:1 mixture of acetonitrile-d3 and DMSO-d6 is measured to be 1.1 x 10(6) M(-1). The receptor also shows reasonably high affinity toward H2PO4-.


Isolation and molecular characterization of an ethylene response factor NtERF1-1 in Nicotiana tabacum cv. Xanthi.
Apetala2/Ethylene Response Factors (AP2/ERF) play important roles in regulating gene expression under abiotic and biotic stress in the plant kingdom. Here, we isolated a member of the AP2/ERF transcription factors, NtERF1-1, from Nicotiana tabcum cv. Xanthi NN carrying the N gene, which is resistant to Tobacco mosaic virus (TMV). NtERF1-1 encoded a putative protein of 229 amino acids with a predicted molecular mass of 24.58 kDa. Nucleotide sequence analysis showed that NtERF1-1 contained a conserved DNA-binding domain at the N-terminal. Comparison of amino acid sequences revealed that NtERF1-1 possessed high similarities to ERFs from diverse plants. Semi-quantitative and real-time quantitative RT-PCR analyses indicated that NtERF1-1 was up-regulated following TMV infection. In addition, we speculated that NtERF1-1 might participate in the signal transduction pathway of defence response inducted by the interaction between the N gene and TMV.


The temporal effect of Category II fetal monitoring on neonatal outcomes.
To correlate the duration of Category II cardiotocograms (CTG) with adverse neonatal outcomes associated with perinatal asphyxia and determine the duration before fetal compromise. This retrospective, observational study used electronic medical record data from a cohort of 271 patients, delivered by C-section due to non-reassuring fetal heart rate, at a tertiary medical center, from 2015 through 2017. Duration of Category II CTG, variability, tachycardia and deceleration frequency were analyzed and correlated to immediate postnatal outcomes. including cord pH ≤ 7, cord base excess >12, 1- and 5-min Apgar scores ≤7, need for ventilation, need for chest compressions, NICU admission, hypoglycemia and convulsions. Intrapartum fever and meconium stained amniotic fluid were correlated to the same outcomes. Categorical and continuous variables were analyzed using chi-square and t-tests, respectively. P < 0.05 was considered significant. The mean duration of Category II CTG was 146 min (range 17-553). Longer duration did not result in increased rates of adverse neonatal outcomes. In contrast, reduced fetal heart rate (FHR) variability, fetal tachycardia and intrapartum fever did show increased rates of adverse neonatal outcomes, as follows: patients exhibiting reduced vs. normal (FHR) variability had 12.9% vs. 1.4% cord pH ≤ 7, P = 0.006 and 12.5% vs. 1.3% cord BE > 12, P = 0.004: patients with fetal tachycardia vs. normal baseline FHR exhibited 48% vs. 17.9% 1-minute Apgar score ≤7, P = 0.0004; 8% vs. 0.8% 5-minute Apgar score ≤7, P = 0.04; and 48% vs. 18.7% ventilation support, P < 0.001; patients with intrapartum fever vs. normal temperature, cord BE > 12 was seen in 9.7% vs. 1.7%, P = 0.035; 1-minute Apgar score was ≤7 in 35.5% vs. 18.7%, P = 0.03; 5-minute Apgar score ≤7 in 9.7% vs. 0.4%, P = 0.005; need for ventilation in 35.5% vs. 19.6%, P = 0.042; need for chest compressions in 6.45% vs. none, P = 0.013; and NICU admission in 12.9% vs. 2.5%, P = 0.018. Our results suggest that the duration of Category II CTG alone does not appear to predict perinatal asphyxia. Parameters associated with perinatal asphyxia are reduced FHR variability, fetal tachycardia and intrapartum fever. Therefore, when contemplating intervention during labor to avoid fetal asphyxia, these parameters should be strongly considered.


A Study on the Influencing Factors of Continued Intention to Use MOOCs: UTAUT Model and CCC Moderating Effect.
Massive Open Online Courses (MOOCs) is the product of "internet + education," which offer the open educational resources to global students. This study analyzed the factors influencing the continued intention to use the MOOCs by students. To achieve research objectives, this study integrated the unified theory of acceptance and use of technology (UTAUT) and connected classroom climate (CCC). In this study, 312 valid samples were used to verify the hypothesis proposed with the help of structural equation modeling and PROCESS. The results showed that the factors of UTAUT model (performance expectancy, effort expectancy, social influence, and facilitating conditions) had significant positive effects on continued intention to use MOOCs. More importantly, there was a significant moderating effect of CCC between UTAUT and the continued intention to use MOOCs. Based on this research the findings, implications and limitations are discussed.


Major group-specific protein of rat type C viruses.
The major internal protein of a rat type C virus pseudotype of murine sarcoma virus, MSV(RaLV), was purified by isoelectric focusing (pI = 8.6) and used to prepare antibody in guinea pigs. The protein was identified by its reaction with antisera reactive with the mammalian type C virus group-specific (gs) antigenic determinant, gs-3. The guinea pig antisera mainly contained species-specific (gs-1) antibody for reactions in gel diffusion with other type C viruses were limited to those of rat origin, whereas in complement fixation tests heterologous reactions could be eliminated by use of appropriate antiserum concentrations without affecting homologous reactions. Guinea pig antisera against mouse, hamster, or cat gs-1 determinants did not react with MSV(RaLV) purified gs protein or with any of several other rat type C viruses.


Proteomic analysis of the acidocalcisome, an organelle conserved from bacteria to human cells.
Acidocalcisomes are acidic organelles present in a diverse range of organisms from bacteria to human cells. In this study acidocalcisomes were purified from the model organism Trypanosoma brucei, and their protein composition was determined by mass spectrometry. The results, along with those that we previously reported, show that acidocalcisomes are rich in pumps and transporters, involved in phosphate and cation homeostasis, and calcium signaling. We validated the acidocalcisome localization of seven new, putative, acidocalcisome proteins (phosphate transporter, vacuolar H+-ATPase subunits a and d, vacuolar iron transporter, zinc transporter, polyamine transporter, and acid phosphatase), confirmed the presence of six previously characterized acidocalcisome proteins, and validated the localization of five novel proteins to different subcellular compartments by expressing them fused to epitope tags in their endogenous loci or by immunofluorescence microscopy with specific antibodies. Knockdown of several newly identified acidocalcisome proteins by RNA interference (RNAi) revealed that they are essential for the survival of the parasites. These results provide a comprehensive insight into the unique composition of acidocalcisomes of T. brucei, an important eukaryotic pathogen, and direct evidence that acidocalcisomes are especially adapted for the accumulation of polyphosphate.


Human amniotic epithelial cells are reprogrammed more efficiently by induced pluripotency than adult fibroblasts.
Cellular reprogramming from adult somatic cells into an embryonic cell-like state, termed induced pluripotency, has been achieved in several cell types. However, the ability to reprogram human amniotic epithelial cells (hAECs), an abundant cell source derived from discarded placental tissue, has only recently been investigated. Here we show that not only are hAECs easily reprogrammed into induced pluripotent stem cells (AE-iPSCs), but hAECs reprogram faster and more efficiently than adult and neonatal somatic dermal fibroblasts. Furthermore, AE-iPSCs express higher levels of NANOG and OCT4 compared to human foreskin fibroblast iPSCs (HFF1-iPSCs) and express decreased levels of genes associated with differentiation, including NEUROD1 and SOX17, markers of neuronal differentiation. To elucidate the mechanism behind the higher reprogramming efficiency of hAECs, we analyzed global DNA methylation, global histone acetylation, and the mitochondrial DNA A3243G point mutation. Whereas hAECs show no differences in global histone acetylation or mitochondrial point mutation accumulation compared to adult and neonatal dermal fibroblasts, hAECs demonstrate a decreased global DNA methylation compared to dermal fibroblasts. Likewise, quantitative gene expression analyses show that hAECs endogenously express OCT4, SOX2, KLF4, and c-MYC, all four factors used in cellular reprogramming. Thus, hAECs represent an ideal cell type for testing novel approaches for generating clinically viable iPSCs and offer significant advantages over postnatal cells that more likely may be contaminated by environmental exposures and infectious agents.


Interferon-gamma acts directly on CD8+ T cells to increase their abundance during virus infection.
Interferon-gamma (IFNgamma) is important in regulating the adaptive immune response, and most current evidence suggests that it exerts a negative (proapoptotic) effect on CD8(+) T cell responses. We have developed a novel technique of dual adoptive transfer, which allowed us to precisely compare, in normal mice, the in vivo antiviral responses of two T cell populations that differ only in their expression of the IFNgamma receptor. We use this technique to show that, contrary to expectations, IFNgamma strongly stimulates the development of CD8(+) T cell responses during an acute viral infection. The stimulatory effect is abrogated in T cells lacking the IFNgamma receptor, indicating that the cytokine acts directly upon CD8(+) T cells to increase their abundance during acute viral infection.


Meta-analysis and systematic review of contrast-enhanced ultrasound in evaluating the treatment response after locoregional therapy of hepatocellular carcinoma.
Contrast-enhanced ultrasound (CEUS) is a useful tool to assess treatment response after percutaneous ablation or transarterial chemoembolization (TACE) of hepatocellular carcinoma (HCC). Here, we performed a systematic review and meta-analysis to evaluate the usefulness of CEUS in identifying residual tumor after locoregional therapy. PubMed, Scopus, and Cochrane library databases were searched from their inception until March 8, 2021, for diagnostic test accuracy studies comparing CEUS to a reference standard for identifying residual tumors after locoregional therapy of HCC. The pooled sensitivity, specificity, accuracy, and diagnostic odds ratio (DOR) were obtained using a bivariate random effects model. Subgroup analyses were performed by stratifying the studies based on study design, type of locoregional therapy, CEUS criteria for residual tumor, timing of CEUS follow up, and type of standard reference. Two reviewers independently evaluated 1479 publications. After full-text review, 142 studies were found to be relevant, and 43 publications (50 cohorts) were finally included. The overall sensitivity of CEUS in detection of residual disease estimated from the bivariate random effects model was 0.85 (95% CI 0.80-0.89). Similarly, the overall specificity was 0.94 (95% CI 0.91-0.96). The diagnostic accuracy was 93.5%. The DOR was 70.1 (95% CI 62.2-148), and the AUROC was 0.95. Importantly, subgroup analysis showed no apparent differences in the diagnostic performance between locoregional therapy (TACE vs. ablation) and criteria used to define residual enhancement, timing of performing CEUS, study design, or type of reference standard. CEUS is a highly accurate method to identify HCC residual tumor after TACE or percutaneous ablation.


Dental Quality Measurement--A Practitioner Perspective.
This article reviews the HealthPartners Dental Group's experience with clinical quality measurement and provides information on the administrative infrastructure that supports measurement within the group. Some examples of the role measurement plays in operations and clinical practice are also reviewed.


Behcet's disease and IgA nephropathy: report of this association in a patient from Brazil and literature review.
Behcet's disease (BD) is associated with renal involvement in about one-third of the cases and a variety of renal lesions have been reported. A 27-year-old man presented a history of recurrent oral and genital ulcers, associated with pseudofoliculitis and arthritis in his left knee. The first laboratory tests revealed: urea = 53mg/dL, creatinine = 1.8 mg/dL. The urinalysis showed leukocyturia. Initial treatment with ceftriaxone, thalidomide and prednisone was instituted. He became clinically stable, with normal renal function, but presenting hematuria and proteinuria. One year later the patient presented dark urine. The new laboratory tests showed urea=58 mg/dL, creatinine = 1.4 mg/dL, and mild proteinuria (500-1000 mg/24h). Two years later the proteinuria was 2230 mg/day. The renal biopsy showed one glomerulus with severe glomerular sclerosis, mild tubular atrophy, mild interstitial fibrosis and thickening of arterial walls. Treatment with captopril was started to decrease proteinuria. Two years later, the patient presented creatinine = 1.7 mg/dL and proteinuria = 2509 mg/day. A new renal biopsy evidenced proliferative crescentic glomerulonephritis, with diffuse granullary deposits of IgA, IgM and C3. It was instituted pulsotherapy with metilprednisolone, monthly endovenous cyclophosphamide and maintenance prednisone. The patient became clinically stable, with creatinine of 1.3 mg/dL and proteinuria of 500 mg/day. BD could be one of the various causes of secondary IgA nephritis. It is important to periodically perform renal function evaluation in patients with BD, through urinalysis and measurement of serum creatinine and its clearance, in order to detect any abnormality and provide an early adequate treatment.


Intramural coronary arteriosclerosis of normal and dwarfed swine.
Dwarfing of swine maintained in large groups with relatively little space per animal may be attributed to psychosocial factors. Intramural coronary arteriosclerosis developed at approximately the same rate in dwarfed and normally developing animals. Lesions in arteries of the left posterior papillary muscle were more advanced than in the left anterior papillary muscle of the same animal, irrespective of its growth rate, and often were more advanced than in swine twice as old.


Effects of inference on dopaminergic prediction errors depend on orbitofrontal processing.
Dopaminergic reward prediction errors in monkeys reflect inferential reward predictions that well-trained animals can make when associative rules change. Here, in a new analysis of previously described data, we test whether dopaminergic error signals in rats are influenced by inferential predictions and whether such effects depend on the orbitofrontal cortex (OFC). Dopamine neurons were recorded from controls or rats with ipsilateral OFC lesions during performance of a choice task in which odor cues signaled the availability of sucrose reward in 2 wells. To induce prediction errors, we manipulated either the timing or number of rewards delivered in each well across blocks of trials. Of importance, a change in reward at 1 well predicted a change in reward at the other on later trials. We compared behavior and neural activity on trials when such inference was possible versus trials involving the same reward change when inference was not possible. Rats responded faster when they could infer an increase in reward compared to when the same reward was coming but they could not infer a change. This inferential prediction was reflected in the firing of dopamine neurons in controls, which changed less to unexpected delivery (or omission) of reward and more to the new high-value cue on inference versus noninference trials. These effects were absent in dopamine neurons recorded in rats with ipsilateral OFC lesions. Thus, dopaminergic error signals recorded in rats are influenced by both experiential and inferential reward predictions, and the effects of inferential predictions depend on OFC. (PsycINFO Database Record


The effect of heterologous anti-lymphocyte serum on lymphocytes of thymus and marrow origin.
When CY-treated mice were given sheep red blood cells the serum hemagglutinin titers produced were significantly lower than those found when mice received SRBC but not CY. Titers could be raised to the levels found in the latter group if, in addition to SRBC, the CY-treated mice received 2 x 10(7) normal syngeneic spleen cells or a mixture containing 1.2 x 10(8) normal thymus and 1.2 x 10(8) normal marrow cells. Inocula which contained fewer cells produced correspondingly smaller amounts of antibody. A synergistic interaction between normal thymus and marrow cells was always demonstrable in these experiments. Hemagglutinin titers produced by CY-treated mice given SRBC and 2 x 10(7) normal syngeneic spleen cells were always much higher than those found when the spleen cells were obtained from animals previously given ALS. Titers could be raised to normal levels if the animals in this latter group received additional injections containing mixtures of normal syngeneic thymus and marrow cells. Marrow cells alone were completely ineffective, while inocula which only contained thymus cells were much less effective than mixtures of thymus and marrow cells. These results suggest that immunosuppression by ALS is associated with the inactivation of both thymus and marrow-derived lymphocytes. In other experiments CY-treated mice received SRBC and mixtures of thymus and marrow cells from both untreated and ALS-treated donors. No decrease in the immunological competence of cells located within the thymus of ALS-treated donors was demonstrable in these experiments. Marrow cells were slightly affected but to a markedly lesser degree than were spleen cells of ALS-treated animals. In a final experiment, it was possible to show that the thymus and marrow cells of ALS-treated animals could repair the immunological defects which were present in their own spleen cell populations.


Knowledge of hepatitis C screening and management by internal medicine residents: trends over 2 years.
Over 2 million people in the United States are infected with hepatitis C, and there has been an explosion in knowledge regarding this disease in the last decade. Internal medicine residents must be able to identify patients at risk for hepatitis C and institute appropriate diagnostic testing and referral of these patients. A survey regarding hepatitis C risk factors and the management of hepatitis C patients was administered on three occasions over 15 months (time 0, 1 month, and 15 months) to members of a large university-based internal medicine residency. During the study period 59 residents completed all three surveys. Less than half of the residents (39%) ask patients about hepatitis C risk factors. Only 58% reported that they would refer a hepatitis C antibody positive patient with elevated liver enzymes to a subspecialist on the initial survey. The residents who did not refer patients cited low response rates, high side-effect profiles, and the high cost of therapy as reasons for not referring the patient. There was significant improvement (58% vs 78%, p < 0.01) in the rate of patient referral during the 15-month study period but no substantial improvement in the other knowledge deficits. The knowledge base of the internal medicine residents about hepatitis C screening and management is suboptimal. New, more effective hepatitis C education programs for internal medicine residents should be initiated.


Requirement of HIV-1 Vif C-terminus for Vif-CBF-β interaction and assembly of CUL5-containing E3 ligase.
Human immunodeficiency virus type 1 (HIV-1) Vif hijacks an E3 ligase to suppress natural APOBEC3 restriction factors, and core binding factor β (CBF-β) is required for this process. Although an extensive region of Vif spanning most of its N-terminus is known to be critical for binding with CBF-β, involvement of the Vif C-terminus in the interaction with CBF-β has not been fully investigated. Here, through immunoprecipitation analysis of Vif C-terminal truncated mutants of various lengths, we identified that CBF-β binding requires not only certain amino acids (G126A, E134A, Y135A and G138A) in the HCCH region but also the HCCH motif itself, which also affects the Vif-mediated suppression of APOBEC3G/APOBEC3F (A3G/A3F). These mutants still maintained interactions with substrate A3G or A3F as well as other cellular factors ElonginB/C (ELOB/C), indicating that their structures were not functionally affected. Moreover, by determining that the BC box also is necessary for CBF-β interaction in vivo, we speculate that binding to ELOB/C induces conformational changes in Vif, facilitating its interaction with CBF-β and consequent interaction with CUL5. These results provide important information on the assembly of the Vif-CUL5-E3 ubiquitin ligase. Identification of the new binding interface with CBF-β at the C-terminus of HIV-1 Vif also provides novel targets for the development of HIV-1 inhibitors.


Numerical Analysis, Optimization, and Multi-Criteria Design of Vacuum Insulated Glass Composite Panels.
The subject of this study is Vacuum Insulated Glass (VIG) panels, which consist of two glass panes with an evacuated space and evenly distributed micro-support pillars between them. The deflection of panes towards the centre of the structure caused by atmospheric pressure is a mechanical problem that occurs in this type of structure. The aim of this study was to extend previous research on the optimal arrangement of support pillars in terms of eigenfrequencies and dynamics to include aesthetic aspects. Using Abaqus/CAE v2017 software, a large number of numerical models were created and subjected to a comprehensive multi-criteria analysis. Fractal analysis was employed to automatically assess the aesthetics of the proposed solutions. The study presents theoretical solutions that could be implemented in industrial production. The presented study shows that it is possible to effectively extend the criteria for optimizing the arrangement of pillars with new design criteria. Most studies focus on pillar placement, amount, or shape in terms of panes thermal or mechanical properties. Due to the increasing number of VIG panels applications in places exposed to external vibrations, other design criteria for VIG panels are also required and are provided by the following study.


Neonatal rotavirus vaccination with RIT 4237 bovine rotavirus vaccine: a preliminary report.
We vaccinated 244 newborn infants orally with RIT 4237 bovine rotavirus vaccine or placebo and followed them serologically and clinically for 16 months. Initially 39 of the 119 (33%) vaccine recipients compared with 1 of the 120 placebo recipients seroconverted by enzyme-linked immunosorbent assay-immunoglobulin M. After the first winter rotavirus season, at 7 months of age 55% of the vaccinated infants and 37% of the unvaccinated infants were rotavirus-seropositive by enzyme-linked immunosorbent assay-immunoglobulin G (P less than 0.01, chi square test). At 12 months of age, after a low rotavirus prevalence season, 34% of the vaccinated children and 23% of the unvaccinated children remained seropositive. There were 14 confirmed episodes of rotavirus gastroenteritis in the vaccine group and 10 episodes in the placebo group during the first 16 months. However, only 1 of the episodes in the vaccine group was severe, 4 were moderately severe and 9 were mild, whereas 7 episodes in the placebo group were severe and 3 were moderately severe (P less than 0.001 between groups, Fisher's exact test). There was no clear correlation between vaccine-induced clinical protection and initial serologic response (enzyme-linked immunosorbent assay-immunoglobulin M) to vaccination, but during follow-up severe rotavirus gastroenteritis was more likely to occur in children with no serum rotavirus immunoglobulin G antibody at the time of infection. We conclude at the present stage that neonatal rotavirus vaccination with RIT 4237 vaccine gives no protection against rotavirus infection but appears to modify the severity of gastroenteritis.


Down regulation of differentiated embryo-chondrocyte expressed gene 1 is related to the decrease of osteogenic capacity.
Differentiated embryo-chondrocyte expressed gene 1 (DEC1) is associated with chondrogenesis, neurogenesis, immune response, biological rhythm, lipogenesis, cell differentiation and carcinogenesis. However, there is little information about its contribution to osteoblast osteogenesis. In the present study, we report that DEC1 expression increases along with the degree of mineralization, which parallells with the increase of osteogenesis induction time in SaoS-2 cells. Dexamethasone (DEX) decreases the osteogenesis capacity such as alkaline phosphatase (ALP) activity and mineralization along with decreasing the DEC1 expression. On the contrary, 17β-estradiol (E2) increases the osteogenesis along with increasing the DEC1 expression. Moreover, the overexpression of DEC1 alone increases the ALP activity and mineralization synchronously, and it not only partially reverses the decrease of ALP activity induced by DEX, but almost abolishes the decrease of mineralized nodules induced by DEX. On the other hand, the DEC1 expression decreases in tibia bone marrow side of ovariectomy mice compared with that in sham-operated mice, and E2 treatment ameliorates the decrease of DEC1 expression induced by bilateral ovariectomy and prevents osteoporosis in ovariectomized mice . Taken together, downregulation of DEC1 expression is related to the decrease of osteogenic capacity. The findings provide a novel target for the therapy of osteoporosis.


Differential effects of estrogen treatment on canine seminal plasma components.
In castrate dogs, complete androgen-dependent restoration of seminal plasma content of fluid, electrolytes, and protein was induced by testosterone treatment alone. In contrast, a combination of androgen and estrogen treatment selectively reduced only the androgen induced stimulation of the electrolyte and fluid components without altering the total amount of protein secreted. Spontaneous cystic prostatic hyperplasia was found to be characterized by a similar decrease in total fluid and electrolyte content without a concomitant decrease in the total amount of protein in the seminal plasma. These results suggest that prostatic protein secretion may be a process distinct from electrolyte-fluid transport because either estradiol treatment or the development of spontaneous cystic prostatic hyperplasia dissociates these two processes.


Inhibition of lipolysis by ilexgenin A via AMPK activation contributes to the prevention of hepatic insulin resistance.
Adipose dysfunction links tightly to hepatic insulin resistance and gluconeogenesis. Ilexgenin A is reported with the ability to regulate lipid profile and protect the liver against high fat diet (HFD) -induced impairment. Here, we propose that ilexgenin A ameliorates hepatic insulin signaling and gluconeogenesis by regulating lipolysis in white adipose tissue (WAT). Pyruvate tolerance test and biochemical analysis coupled with the ex vivo siRNA knockdown and co-culture studies demonstrate that ilexgenin A suppresses inflammation-associated lipolysis in epididymal fat pad via 5'-AMP-activated protein kinase (AMPK) activation, thus inhibits diacylglycerol (DAG) accumulation and protein kinase C ε (PKCε) translocation in liver, leading to the improvement of insulin sensitivity and hepatic glucose production. These findings suggest that the relationship between adipose function and hepatic insulin action may be targeted by natural bioactive components for the potential treatment of hepatic insulin resistance related disorders.


F2-isoprostanes biomarkers of lipid peroxidation: their utility in evaluation of oxidative stress induced by toxic agents.
Isoprostanes are prostaglandin-like compounds that are produced by free radical mediated peroxidation of polyunsaturated fatty acids. There is a direct evidence showing that F2-isoprostanes can be utilized as a marker of lipid peroxidation due to the mechanism of their formation (nonenzymatic oxidation of arachidonic acid), chemical stability, sensitive and non-invasive methods of their estimation. An altered generation of F2-isoprostanes has been found in a variety of pathological syndromes associated with oxidative stress. Their quantification allows to elucidate the role of free radicals in oxidative injury. This paper reviews briefly the recent data on isoprostanes: biochemical mechanisms of their formation, methods of their measurement, and the possibilities of their utilization as a quantitative/qualitative marker of oxidative stress in vivo.


Viral Resistance Analyses From the Remdesivir Phase 3 Adaptive COVID-19 Treatment Trial-1 (ACTT-1).
Remdesivir is approved for treatment of coronavirus disease 2019 (COVID-19) in nonhospitalized and hospitalized adult and pediatric patients. Here we present severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) resistance analyses from the phase 3 ACTT-1 randomized placebo-controlled trial conducted in adult participants hospitalized with COVID-19. Swab samples were collected at baseline and longitudinally through day 29. SARS-CoV-2 genomes were sequenced using next-generation sequencing. Phenotypic analysis was conducted directly on participant virus isolates and/or using SARS-CoV-2 subgenomic replicons expressing mutations identified in the Nsp12 target gene. Among participants with both baseline and postbaseline sequencing data, emergent Nsp12 substitutions were observed in 12 of 31 (38.7%) and 12 of 30 (40.0%) participants in the remdesivir and placebo arms, respectively. No emergent Nsp12 substitutions in the remdesivir arm were observed in more than 1 participant. Phenotyping showed low to no change in susceptibility to remdesivir relative to wild-type Nsp12 reference for the substitutions tested: A16V (0.8-fold change in EC50), P323L + V792I (2.2-fold), C799F (2.5-fold), K59N (1.0-fold), and K59N + V792I (3.4-fold). The similar rate of emerging Nsp12 substitutions in the remdesivir and placebo arms and the minimal change in remdesivir susceptibility among tested substitutions support a high barrier to remdesivir resistance development in COVID-19 patients. Clinical Trials Registration. NCT04280705.


Finding sequence motifs in groups of functionally related proteins.
We have developed a method for rapidly finding patterns of conserved amino acid residues (motifs) in groups of functionally related proteins. All 3-amino acid patterns in a group of proteins of the type aa1 d1 aa2 d2 aa3, where d1 and d2 are distances that can be varied in a range up to 24 residues, are accumulated into an array. Segments of the proteins containing those patterns that occur most frequently are aligned on each other by a scoring method that obtains an average relatedness value for all the amino acids in each column of the aligned sequence block based on the Dayhoff relatedness odds matrix. The automated method successfully finds and displays nearly all of the sequence motifs that have been previously reported to occur in 33 reverse transcriptases, 18 DNA integrases, and 30 DNA methyltransferases.


Intraoperative cortical mapping has low sensitivity for the detection of motor function in proximity to a tumor in the primary motor area.
Six patients with brain tumors within or near the primary motor cortex underwent preoperative functional magnetic resonance imaging (fMRI) and intraoperative cortical mapping, and the accuracy of those techniques for localization of the primary motor cortex and motor function beside the tumor were determined by comparison against neuroanatomical correlates from pre-, intra- and postoperative neurological observations. The location of the primary motor cortex was detected by intraoperative cortical mapping in 5 of 6 cases and by fMRI in all 6 cases. Brain mapping provided equivocal information on the cortical representation of motor territories, and with the technique used in close proximity to the tumor, the motor territories were not detected in all but 1 case. In contrast, the areas controlling motor function in close proximity to the tumor were detected by fMRI in 4 of 6 cases. These data indicate that intraoperative cortical mapping has a low sensitivity for the detection of motor function in the area beside the tumor. Therefore, this technique may not be sufficient to prevent compromise of motor areas during tumor resection.


Clinical significance of M1 receptor antagonists.
The M1-selective antimuscarinic drugs pirenzepine and telenzepine moderately reduce gastric acid secretion without inhibiting smooth-muscle activity as much as nonselective antimuscarinics, e.g. atropine and 1-hyoscyamine. They hasten peptic ulcer healing and improve the symptoms of reflux oesophagitis. In combination with H2 receptor antagonists they abolish gastric acid secretion almost completely and can therefore be used in high-risk peptic conditions. Long-term trials have to show whether they can form a medical alternative to parietal cell vagotomy. The effect of M1-selective antimuscarinics on 'nonulcer dyspepsia' is equivocal, but they may possibly be useful in the treatment of spastic constipation.