Differential expressions of PD-1, PD-L1 and PD-L2 between primary and metastatic sites in renal cell carcinoma.
In clinical practice, the detection of biomarkers is mostly based on primary tumors for its convenience in acquisition. However, immune checkpoints may express differently between primary and metastatic tumor. Therefore, we aimed to compare the differential expressions of PD-1, PD-L1 and PD-L2 between the primary and metastatic sites of renal cell carcinoma (RCC). Patients diagnosed with RCC by resection or fine needle aspiration of metastasis were included. Immunohistochemistry (IHC) was applied to detect PD-1, PD-L1 and PD-L2 expressions. SPSS 22.0 was applied to conduct Chi-square, consistency tests and Cox's proportional hazards regression models. GraphPad Prism 6 was used to plot survival curves and R software was used to calculate Predictive accuracy (PA). In the whole cohort (N = 163), IHC results suggested a higher detection rate of PD-L1 in the metastasis than that of the primary site (χ2 = 4.66, p = 0.03), with a low consistent rate of 32.5%. Among different metastatic tumors, PD-1 was highly expressed in the lung/lymph node (65.3%) and poorly expressed in the brain (10.5%) and visceral metastases (12.5%). PD-L1 was highly expressed in lung/lymph node (37.5%) and the bone metastases (12.2%) on the contrary. In terms of survival analysis, patients with PD-1 expression either in the primary or metastasis had a shorter overall survival (OS) (HR: 1.59, 95% CI 1.08-2.36, p = 0.02). Also, PD-L1 expression in the primary was associated with a shorter OS (HR 2.55, 95% CI 1.06-6.15, p = 0.04). In the multivariate analysis, the predictive accuracy of the whole model for PFS was increased from 0.683 to 0.699 after adding PD-1. PD-1, PD-L1 and PD-L2 were differentially expressed between primary and metastatic tumors. Histopathological examination of these immune check points in metastatic lesions of mRCC should be noticed, and its accurate diagnosis may be one of the effective ways to realize the individualized treatment.


Female preferences for male traits and territory characteristics in the cichlid fish Tropheus moorii.
Female mate preferences for male traits and resource characteristics affect trait evolution and diversification. Here, we test the effects of male body traits and territory characteristics on within-population female preferences and on population-assortative mating in the cichlid Tropheus moorii. Within-population preferences of females were independent of male body size, coloration and territory size but were strongly dependent on territory quality and co-varied with male courtship activity. Courtship activity of individual males was contingent on the quality of their assigned territory, and therefore, courtship may not only indicate intrinsic male quality. On the basis of these results we suggest that female preferences for high-quality territories reinforce the outcome of malemale competition and ensure male mating success. Mating preferences of females for males of their own color variant (ascertained in a previous experiment) were not overturned when males of another color variant were presented in a superior territory, indicating that within- and between-population mate preferences of females depend on different cues.


Residual Tumor Patterns of Breast Cancer on MRI after Neo-Adjuvant Chemotherapy: Impact on Clinicopathologic Factors and Prognosis.
(1) Background: Residual breast cancer after neoadjuvant chemotherapy (NAC) could have a variable image pattern on a follow-up breast magnetic resonance image (MRI). In this study, we compared the clinical outcome of breast cancer patients with different residual tumor patterns (RTP) on a breast MRI after NAC. (2) Methods: A total of 91 patients with breast cancer who received NAC and subsequent curative surgery were selected. All included patient had residual breast cancer after NAC and showed a partial response on a breast MRI. Pre- and post-treatment were reviewed by an experienced radiologist to evaluate different RTP, and classified into two groups: concentric and scattered patterns. The clinicopathologic parameters and survival outcomes [recurrence-free survival (RFS) and distant metastasis-free survival (DMFS)] were analyzed according to different RTP. (3) Results: Patients with a scattered pattern had a larger extent of pre-treated non-mass enhancement and more frequently received total mastectomy. With a median follow-up period of 37 months, RTP were not significantly associated with RFS or DMFS. (4) Conclusions: In the patients with residual breast cancer after NAC, RTP on an MRI had no effect on the patients' clinical outcome. The curative resection of the tumor bed and securing the negative resection margins appear to be important in the treatment of patients with residual breast cancer after NAC.


Acute Spinal Cord Injury: A Systematic Review Investigating miRNA Families Involved.
Acute traumatic spinal cord injury (SCI) involves primary and secondary injury mechanisms. The primary mechanism is related to the initial traumatic damage caused by the damaging impact and this damage is irreversible. Secondary mechanisms, which begin as early as a few minutes after the initial trauma, include processes such as spinal cord ischemia, cellular excitotoxicity, ionic dysregulation, and free radical-mediated peroxidation. SCI is featured by different forms of injury, investigating the pathology and degree of clinical diagnosis and treatment strategies, the animal models that have allowed us to better understand this entity and, finally, the role of new diagnostic and prognostic tools such as miRNA could improve our ability to manage this pathological entity. Autopsy could benefit from improvements in miRNA research: the specificity and sensitivity of miRNAs could help physicians in determining the cause of death, besides the time of death.


Comparison of chemical-induced temporomandibular osteoarthritis rat models (monosodium iodoacetate versus collagenase type II) for the study of prolonged drug delivery systems.
To compare two agents that can induce a rat model of temporomandibular joint osteoarthritis (TMJOA) by chemical induction: monosodium iodoacetate (MIA) and collagenase type 2 (Col-2). We wished to ascertain the best agent for assessing drug-delivery systems (DDSs). Male Wistar rats underwent intra-articular injection with MIA or Col-2. They were manipulated for 30 days. The head withdrawal threshold (HWT), immunohistological assessment, and positron emission tomography (PET) were used to evaluate the relevance of our models. For both the MIA and Col-2 groups, pain persisted for 30 days after injection. Change in the HWT showed that Col-2 elicited a strong action initially that decreased progressively. MIA had a constant action upon pain behavior. Histology of TMJ tissue from both groups showed progressive degradation of TMJ components. MIA and Col-2 induced orofacial pain by their local chemical action on TMJs. However, based on a prolonged and greater sustained effect on the pain threshold, persistent histological changes, and imaging results, MIA appeared to be more suitable for creation of a rat model of TMJOA for the study of DDSs.


Quantification of meCCNU-induced dG-dC crosslinks in oligonucleotide duplexes by liquid chromatography/electrospray ionization tandem mass spectrometry.
Chloroethynitrosoureas (CENUs) are important alkylating agents widely used in the treatment of cancers. Decomposition of CENUs generates active electrophilic ions that damage DNA, including the formation of dG-dC crosslinks which represents the most important cytotoxic mechanism of CENUs. In this work, a high-performance liquid chromatography/electrospray ionization tandem mass spectrometry (HPLC/ESI-MS/MS) method was employed to analyze the dG-dC crosslinks induced by 1-(2-chloroethyl)-3-(4-methylcyclohexyl)-1-nitrosourea (meCCNU, Semustine). The direct quantitation of dG-dC crosslinks in oligonucleotide duplexes was achieved by the selected reaction monitoring (SRM) mode using synthesized (15) N(3) -labeled dG-dC as an internal standard. Methods of enzymatic digestion and HPLC separation were developed for obtaining separation and reproducibility of the dG-dC peak in chromatograms. The limit-of-detection (LOD) was determined to be 0.08 nM and the limit-of-quantification (LOQ) was determined to be 0.16 nM. The linearity of the calibration curve was 0.9997 over the range of 0.08 to 32 nM. The precision and accuracy of the method ranged from 1.1 to 6.6% and 96 to 109%, respectively. The recovery of the dG-dC crosslink in the enzymatic hydrolysates from the oligonucleotide duplex was determined to be from 91 to 106%. The results of the validation study indicate that the method is suitable for quantifying dG-dC crosslinks in DNA. Consequently, this method was used to determine meCCNU-induced dG-dC crosslinks in four duplexes with different GC contents. The results showed that the crosslinking fraction (CF) increased as the GC content in the duplex increased, and a relatively low CF was observed in the early period of the reaction.


[Colony-forming ability of bone marrow hematopoietic cells in mice with transplanted leukemia during administration of carminomycin].
Effects of carminomycin on the colony-forming ability of bone marrow haemopoietic stem cells (CFUs) were compared in normal mice with steady state and actively regenerating bone marrow, and in P-388 and La leukemia-bearing mice. CFUs assays were performed 24 h after treatment of donor mice with the increasing doses of the drug. Leukemia-bearing mice received carminomycin on the 5th day after transplantation. The dose-effect curves were exponential for CFUS normal mice with both the steady state and active proliferation state of bone marrow. The maximal effect was found 24 h after injection of 0.7 mg/kg of carminomycin (ED50 for CFUS) being more pronounced in regenerating bone marrow. The dose-effect curves for leukemias were also exponential. In the case of La leukemia the killing of CFUs by carminomycin was the highest as compared with P-388 leukemia.


Setting a benchmark for the Test of Essential Academic Skills (TEAS) V: striving for first-semester success in nursing school.
Every nursing school strives to admit students who will be successful in completing their program and passing the NCLEX(®). Many schools use standardized testing, such as the Test of Essential Academic Skills (TEAS) V, as part of their admission criteria. This study was conducted to set an institutional benchmark of the TEAS V composite score, as recommended by the test developers. Having a benchmark would help the authors' school of nursing to identify students who were more likely to be successful during the first semester of their nursing studies. Using past students' composite TEAS V scores and ATI RN Fundamentals of Nursing 2010 Assessment results, a benchmark was identified.


The Relationship Between Public Service Motivation and Affective Commitment in the Public Sector Change: A Moderated Mediation Model.
How can public organizations promote change recipients' affective commitment to public sector change? Based on socially desirable responding theory, this study explores the theoretical mechanism and boundary effect of the relationship between public service motivation and affective commitment to change. By conducting a survey of 465 front-line public employees in an eastern Chinese city undergoing public sector change, this study found that voice behavior partially mediates the relationship between public service motivation and affective commitment to change. Superficial harmony also negatively moderates the relationship between public service motivation and affective commitment to change through the mediation of voice behavior. This study mainly contributes to our understanding of the theoretical mechanism and the conditional effect of change recipients' affective commitment during public sector change.


Young men exempted from compulsory military or civil service in Finland--a group of men in need of psychosocial support?
The aim of this study was to find out whether young men exempted from compulsory military or civil service constitute a group of young men in need of psychosocial support from the social and health services. The study involved a total of 356 men exempted from military or civil service and 440 young men conscripted into service. The research data were collected using questionnaires and register data. Men exempted from military or civil service differed from conscripts in terms of psychosocial well-being. Compared with conscripts, they had already been in a more disadvantaged position with regard to their childhood living conditions. As young adults, they had met with a greater number of mental and social problems than conscripts: alcohol-related problems, unemployment, financial problems, homelessness, lack of social support and psychological distress. Young men exempted from service typically suffered from an accumulation of problems. Diverse problems were common particularly among men who had interrupted their service. There was a moderate correlation between current and childhood adversities. Men exempted from military or civil service comprise a group with a wide range of psychosocial problems and are a target group for supportive interventions. Special attention should be paid to the prevention of problems and promotion of well-being of men who interrupt their service. The accumulation of problems poses a challenge for the development of such interventions.


Metabolic Alterations Induced by Kudingcha Lead to Cancer Cell Apoptosis and Metastasis Inhibition.
Kudingcha is implicated in alleviating metabolic disorders in traditional Chinese medicine. However, the role of Kudingcha, one of the Ligustrum robustum species, in metabolic regulations and its antitumor activity in triple-negative breast cancer (TNBC) remains to be determined. Two breast cancer cell lines and immunocompetent and immunodeficient mice were used to evaluate the therapeutic effects of Kudingcha treatment. The production of reactive oxygen species (ROS) and glucose uptake were examined by flow cytometry. Metabolic shift was examined by metabonomics and western blot analysis. In this study, we found that aqueous extract of Kudingcha dose dependently inhibited cell growth and induced apoptosis in vitro and in vivo. Moreover, Kudingcha supplementation significantly reduced cancer metastasis. Kudingcha significantly inhibited glycolysis and glutamine metabolism. In addition, we demonstrated that the antitumor effects of Kudingcha were dependent on ROS production, which was increased by β-oxidation and oxidative phosphorylation. These findings provide a novel potential benefit of Kudingcha from targeting the cancer metabolism.


Long-term use of dienogest for the treatment of primary and secondary dysmenorrhea.
To investigate the safety and efficacy of dienogest (DNG), a progestational 19-norsteroid, administered for 52 weeks in patients with primary and secondary dysmenorrhea. A total of 147 patients with dysmenorrhea received 1 mg of DNG orally each day for 52 weeks. The dose could be increased to 2 mg/day at or after Week 12 according to the investigator's determination. The primary safety endpoint was evaluation of adverse events, and the secondary safety endpoint was evaluation of adverse drug reactions. The number of days and severity of genital bleeding were assessed according to records in the patients' diary. Lower abdominal pain and/or low back pain because of dysmenorrhea were assessed according to the dysmenorrhea score. The most frequent adverse drug reaction was irregular uterine bleeding (94.6%). Most subjects completed the 52-week administration. Genital bleeding was more likely to occur in subjects with secondary dysmenorrhea than in those with primary dysmenorrhea, and in subjects with "uterine myoma or adenomyosis" than in those with "endometriosis alone." In any of the categorizations, there tended to be fewer days with genital bleeding as the treatment period increased in length, and most of the genital bleeding cases were mild. The change from baseline in the dysmenorrhea score (mean ± standard deviation [SD]) was -3.7 ± 1.6 at Week 24 of treatment and -4.0 ± 1.3 at Week 52. This study showed favorable tolerability of the long-term use of DNG to patients with dysmenorrhea and a sustainable pain relief effect.


Mechanisms of Arg-Pro-Pro-Gly-Phe inhibition of thrombin.
Investigations determined the mechanism(s) by which Arg-Pro-Pro-Gly-Phe (RPPGF) inhibits thrombin-induced platelet activation. High concentrations of RPPGF inhibit thrombin-induced coagulant activity. RPPGF binds to the active site of thrombin by forming a parallel beta-strand with Ser214-Gly216 and interacts with His57, Asp189, and Ser195 of the catalytic triad. RPPGF competitively inhibits alpha-thrombin from hydrolyzing Sar-Pro-Arg-paranitroanilide with a Ki = 1.75 +/- 0.03 mM. Other mechanisms were sought to explain why RPPGF inhibits thrombin activation of platelets at concentrations below that which inhibits its active site. Soluble RPPGF blocks biotinylated NATLDPRSFLLR of the thrombin cleavage site on protease-activated receptor (PAR)1 from binding to the peptide RPPGC (IC50 = 20 microM). The soluble recombinant extracellular domain of PAR1 (rPAR1EC) blocks biotinylated RPPGF binding to rPAR1EC (IC50 = 50 microM) bound to microtiter plates, but rPAR1EC deletion mutants missing the sequence LDPR or PRSF do not. RPPGF and related forms prevent the thrombin-like enzyme thrombocytin from proteolyzing rPAR1EC at concentrations that do not block thrombocytin's active site. These studies indicate that RPPGF is a bifunctional inhibitor of thrombin: it binds to PAR1 to prevent thrombin cleavage at Arg41 and interacts with the active site of alpha-thrombin.


The sociocultural theory in the development of anorexia nervosa.
The relationship between anorexia nervosa (AN) and sociocultural factors is examined. Anorexia nervosa was first described in the West and was reported as particularly rare or absent in Eastern cultures. However, the frequency of its presentation has increased worldwide over the past two decades, probably as a consequence of changes in cultural norms and concepts of feminine beauty and an increasing inflow of Western values into other countries. Sociocultural factors are important in the development of AN in psychologically vulnerable young females, although other factors may also be implicated.


Haemolysis in athletes due to hereditary spherocytosis.
Three athletes, one cross-country skier and two middle distance runners, experiencing poor response to intensified training and decline in performance during prolonged periods of frequent competitions, associated with a tendency to develop anaemia, were found to have spherocytosis, and increased osmotic fragility of the red blood cells. All had family members with the same blood abnormality, but without symptoms. The observations suggest that the frequency of hereditary spherocytosis is higher than indicated by overtly affected cases and that mild cases are easily overlooked. Hereditary spherocytosis should be looked for in athletes with a tendency to decline in blood haemoglobin concentration during periods of intensive training and competition.


Photon versus carbon ion irradiation: immunomodulatory effects exerted on murine tumor cell lines.
While for photon radiation hypofractionation has been reported to induce enhanced immunomodulatory effects, little is known about the immunomodulatory potential of carbon ion radiotherapy (CIRT). We thus compared the radio-immunogenic effects of photon and carbon ion irradiation on two murine cancer cell lines of different tumor entities. We first calculated the biological equivalent doses of carbon ions corresponding to photon doses of 1, 3, 5, and 10 Gy of the murine breast cancer cell line EO771 and the OVA-expressing pancreatic cancer cell line PDA30364/OVA by clonogenic survival assays. We compared the potential of photon and carbon ion radiation to induce cell cycle arrest, altered surface expression of immunomodulatory molecules and changes in the susceptibility of cancer cells to cytotoxic T cell (CTL) mediated killing. Irradiation induced a dose-dependent G2/M arrest in both cell lines irrespective from the irradiation source applied. Likewise, surface expression of the immunomodulatory molecules PD-L1, CD73, H2-Db and H2-Kb was increased in a dose-dependent manner. Both radiation modalities enhanced the susceptibility of tumor cells to CTL lysis, which was more pronounced in EO771/Luci/OVA cells than in PDA30364/OVA cells. Overall, compared to photon radiation, the effects of carbon ion radiation appeared to be enhanced at higher dose range for EO771 cells and extenuated at lower dose range for PDA30364/OVA cells. Our data show for the first time that equivalent doses of carbon ion and photon irradiation exert similar immunomodulating effects on the cell lines of both tumor entities, highlighted by an enhanced susceptibility to CTL mediated cytolysis in vitro.


Macular Findings in Carriers of Ocular Albinism With a Novel GPR143 Mutation.
This case series details macular findings in three female siblings who were found to be carriers of a previously unreported splice mutation in GPR143 (X-linked ocular albinism [OA1]). Presumed lyonization is responsible for both the subtle and varied findings in OA1 carriers, even among siblings, and especially in patients with darker skin pigmentation. In this series, we used green-light autofluorescence to reveal subtle subfoveal involvement and used optical coherence tomography angiography to uncover previously unreported narrowing of the foveal avascular zone, consistent with foveal hypoplasia. [Ophthalmic Surg Lasers Imaging Retina 2022;53:460-463.].


fMRI in an oddball task: effects of target-to-target interval.
The amplitude of the P3 event-related potential (ERP) elicited by task-relevant target ("oddball") stimuli has been shown to vary in proportion to the length of time between targets. Here we use functional magnetic resonance imaging (fMRI) to identify neural systems modulated by target interval in a large sample of healthy adults (n=100) during performance of an auditory oddball task that included both target and novel stimuli. A positive relationship was found between target interval and hemodynamic activity in the anterior cingulate and in bilateral lateral prefrontal cortex, temporal-parietal junction, postcentral gryi, thalamus, and cerebellum. This modulation likely represents updating of the working memory template for the target stimuli. There was no such effect of novel interval, suggesting that neuronal modulation may only occur for task-relevant stimuli, possibly in the service of strategic resource allocation processes.


Regiospecific synthesis of neuroprotective 1,4-benzoxazine derivatives through a tandem oxidation-Diels-Alder reaction.
The tandem oxidation-inverse electron demand Diels-Alder reaction of o-aminophenol derivatives and enamines has been accomplished at room temperature using a stoichiometric amount of manganese dioxide as the oxidant to furnish highly substituted 1,4-benzoxazine cycloadducts with complete regiochemical control. Because of its efficiency in introducing diverse elements in both cycloaddition partners, this one-pot process should allow the assembly of libraries of biologically relevant 1,4-benzoxazine derivatives. In this respect, the 3,3-diphenyl-substituted-1,4-benzoxazine derivative 3n was found to be a potent neuroprotective agent in an animal model of excitotoxic lesions in newborn mice.


Conformational features of the full-length HIV and SIV Nef proteins determined by mass spectrometry.
The Nef protein from human or simian immunodeficiency virus enhances viral replication, downregulates immune cell receptors, and activates multiple host cell signaling pathways. Conformational information about full-length Nef has been difficult to obtain as the full-length protein is not readily amenable to NMR or X-ray crystallography due to aggregation at high concentrations. As an alternative, full-length HIV and SIV Nef were probed with hydrogen exchange mass spectrometry, a method compatible with the low concentration requirements of Nef. The results showed that HIV Nef contains a solvent-protected core, as previously demonstrated with both NMR and X-ray crystallography. SIV Nef, for which there is no structural information, had a similar protected core, although it was more flexible and dynamic than its HIV counterpart. Many of the regions outside the core in both SIV and HIV Nef were highly solvent exposed. However, limited protection from exchange was observed in both N- and C-terminal regions, suggesting the presence of structured elements. Protection from exchange was also observed in a large loop emanating from the core that was deleted for NMR and X-ray analysis. These data show that while the majority of Nef was highly solvent exposed, regions outside the core may have structural attributes which may contribute to Nef functions known to map to these regions.


Nicorandil and leukocyte activation.
Nicorandil, a hybrid compound of an ATP-sensitive potassium (KATP ) channel opener and a nitric oxide donor, has been reported to preserve microvascular integrity in patients with reperfused myocardial infarction. The aim of the current study was to test the hypothesis that nicorandil suppresses activation of polymorphonuclear leukocytes (PMNLs), resulting in reduction of PMNL migration into tissue upon ischemia/reperfusion. Nicorandil, along with the mitochondrial KATP channel opener diazoxide and the nitric oxide donors nitroglycerin and isosorbide dinitrate, suppressed pseudopod projection in human PMNLs treated with 10(-9)-formyl-methionyl-leucyl-phenylalanine (FMLP) and subjected to shear stress (5 dyn/cm(2)) with a cone-and-plate shear device. Suppression by nicorandil and diazoxide was reversed by KATP channel blockers, 5 hydroxydecanoate and glibenclamide. FMLP-induced increase of [Ca2+] in PMNLs was suppressed by nicorandil and diazoxide, and 5 hydroxy-decanoate and glibenclamide reversed this suppression. Results of reverse transcription polymerase chain reaction with rat PMNL mRNA indicated the presence of mRNAs of Kir6.2 and Kir6.1 but not mRNAs of sulfonylurea receptor 1 or 2. Isosorbide dinitrate, diazoxide, and nicorandil reduced leukocyte migration and microvascular obstruction in reperfused ischemic tissue of rat mesenteric microcirculation. In conclusion, nicorandil attenuates ischemia/reperfusion-induced PMNL activation via donation of nitric oxide and K channel-related cascade.


Damage-induced neuronal endopeptidase (DINE/ECEL) expression is regulated by leukemia inhibitory factor and deprivation of nerve growth factor in rat sensory ganglia after nerve injury.
Damage-induced neuronal endopeptidase (DINE) is a novel metallopeptidase and is expressed in response to various neuronal injuries. The expression regulation of DINE mRNA in the dorsal root ganglia (DRGs) after sciatic nerve injury is examined. A substantial increase of DINE mRNA expression was observed in relatively small-sized DRG neurons after nerve injury. The expression was observed in isolectin B4-negative and partly TrkA-positive neurons, and the expression profile was fairly similar to that of the neuropeptide galanin. More than 80% of DINE mRNA-positive neurons simultaneously demonstrated galanin immunoreactivity after nerve injury. In cultured DRG, DINE mRNA expression was enhanced by leukemia inhibitory factor (LIF) but not by other growth factors and cytokines. LIF treatment to rat sciatic nerve induced DINE mRNA expression in DRG without nerve injury, and, conversely, the intranerve injection of anti-gp130 antibody after sciatic nerve injury significantly inhibited the upregulation of DINE mRNA in DRG. Furthermore, nerve growth factor (NGF) deprivation, which can induce galanin expression, also enhanced DINE mRNA expression in vitro and in vivo. Both LIF application and NGF deprivation additively enhanced DINE expression in vitro. These results suggest that DINE gene expression is regulated separately by both LIF and NGF deprivation, and this regulation pattern is similar to that of galanin gene expression. Because both DINE and galanin have a neuroprotective function, their simultaneous induction may provide more successful protection for injured sensory neurons.


Sequential depletion of human serum for the search of osteoarthritis biomarkers.
The field of biomarker discovery, development and application has been the subject of intense interest and activity, especially with the recent emergence of new technologies, such as proteomics-based approaches. In proteomics, search for biomarkers in biological fluids such as human serum is a challenging issue, mainly due to the high dynamic range of proteins present in these types of samples. Methods for reducing the content of most highly abundant proteins have been developed, including immunodepletion or protein equalization. In this work, we report for the first time the combination of a chemical sequential depletion method based in two protein precipitations with acetonitrile and DTT, with a subsequent two-dimensional difference in-gel electrophoresis (2D-DIGE) analysis for the search of osteoarthritis (OA) biomarkers in human serum. The depletion method proposed is non-expensive, of easy implementation and allows fast sample throughput. Following this workflow, we have compared sample pools of human serum obtained from 20 OA patients and 20 healthy controls. The DIGE study led to the identification of 16 protein forms (corresponding to 14 different proteins) that were significantly (p < 0.05) altered in OA when compared to controls (8 increased and 7 decreased). Immunoblot analyses confirmed for the first time the increase of an isoform of Haptoglobin beta chain (HPT) in sera from OA patients. Altogether, these data demonstrate the utility of the proposed chemical sequential depletion for the analysis of sera in protein biomarker discovery approaches, exhibit the usefulness of quantitative 2D gel-based strategies for the characterization of disease-specific patterns of protein modifications, and also provide a list of OA biomarker candidates for validation.


Noninferiority tests based on concordance correlation coefficient for assessment of the agreement for gene expression data from microarray experiments.
Microarray is one of the breakthrough technologies in the twenty-first century. Despite of its great potential, transition and realization of microarray technology into the clinically useful commercial products have not been as rapid as the technology could promise. One of the primary reasons is lack of agreement and poor reproducibility of the intensity measurements on gene expression obtained from microarray experiments. Current practices often use the testing the hypothesis of zero Pearson correlation coefficient to assess the agreement of gene expression levels between the technical replicates from microarray experiments. However, Pearson correlation coefficient is to evaluate linear association between two variables and fail to take into account changes in accuracy and precision. Hence, it is not appropriate for evaluation of agreement of gene expression levels between technical replicates. Therefore, we propose to use the concordance correlation coefficient to assess agreement of gene expression levels between technical replicates. We also apply the Generalized Pivotal Quantities to obtain the exact confidence interval for concordance coefficient. In addition, based on the concept of noninferiority test, a one-sided (1 - alpha) lower confidence limit for concordance correlation coefficient is employed to test the hypothesis that the agreement of expression levels of the same genes between two technical replicates exceeds some minimal requirement of agreement. We conducted a simulation study, under various combinations of mean differences, variability, and sample size, to empirically compare the performance of different methods for assessment of agreement in terms of coverage probability, expected length, size, and power. Numerical data from published papers illustrate the application of the proposed methods.


Emergency room management of hypertensive urgencies and emergencies.
Hypertensive crisis affects upward of 500,000 Americans each year. Although the incidence of hypertensive crisis is low, affecting fewer than 1% of hypertensive adults, more than 50 million adult Americans suffer from hypertension. Presentation of a patient with severe hypertension to the emergency room demands immediate evaluation, prompt recognition of a hypertensive emergency or urgency, and the prompt institution of appropriate therapeutic measures to prevent progression of target-organ damage and to avoid a catastrophic event. Hypertensive emergencies are severe elevations in blood pressure that are complicated by evidence of progressive target-organ dysfunction such as coronary ischemia, disordered cerebral function, a cerebrovascular event, pulmonary edema, or renal failure. Although therapy with parenteral antihypertensive agents may be initiated in the emergency department, these patients warrant prompt admission to an intensive care unit where continuous monitoring of blood pressure can be assured during therapy.


Microtubules in the spermatids of the domestic fowl.
Spermiogenesis in chicken has been examined in order to see whether the radical changes observed in cell shape can be related to the presence of cytoplasmic microtubules. A highly ordered array of tubules has been found which surrounds the nucleus as it elongates from a sphere to a slender cylinder. The structure of the array has been determined by following the tubules through 12-14 adjacent serial sections, and it is a left-handed double helix. Faint cross-bridges connect consecutive turns of the two helices. After the change in nuclear shape is complete, the helical system of microtubules disappears and is replaced by a set of almost straight tubules which run parallel to the long axis of the nucleus. These tubules remain while the spermatid nucleus condenses isotropically to its final size. We suggest that the helix is the agent which effects nuclear elongation and that the subsequent system of paraxial tubules determines the curvature of the final sperm head. Evidence for these suggestions is found in the form of spermatids which have failed to develop properly. In an appendix we consider the kinematics of single and multiple helix systems and discuss the revelance of these models to the morphogenesis of chicken spermatids.


Comparison of Metals and Tetracycline as Selective Agents for Development of Tetracycline Resistant Bacterial Communities in Agricultural Soil.
Environmental selection of antibiotic resistance may be caused by either antibiotic residues or coselecting agents. Using a strictly controlled experimental design, we compared the ability of metals (Cu or Zn) and tetracycline to (co)select for tetracycline resistance in bacterial communities. Soil microcosms were established by amending agricultural soil with known levels of Cu, Zn, or tetracycline known to represent commonly used metals and antibiotics for pig farming. Soil bacterial growth dynamics and bacterial community-level tetracycline resistance were determined using the [3H]leucine incorporation technique, whereas soil Cu, Zn, and tetracycline exposure were quantified by a panel of whole-cell bacterial bioreporters. Tetracycline resistance increased significantly in soils containing environmentally relevant levels of Cu (≥365 mg kg-1) and Zn (≥264 mg kg-1) but not in soil spiked with unrealistically high levels of tetracycline (up to 100 mg kg-1). These observations were consistent with bioreporter data showing that metals remained bioavailable, whereas tetracycline was only transiently bioavailable. Community-level tetracycline resistance was correlated to the initial toxicant-induced inhibition of bacterial growth. In conclusion, our study demonstrates that toxic metals in some cases may exert a stronger selection pressure for environmental selection of resistance to an antibiotic than the specific antibiotic itself.


Persistence of the cholera epidemic in the Tillabery district (Niger): epidemiological analysis of determining factors.
To analyze the determinants of the persistence of the cholera epidemic in Tillabery to obtain a durable solution. Case-control study conducted in three health centers in June 2013 in Tillabery. Cholera cases were confirmed by laboratory testing or epidemiologically linked with a confirmed index case. Controls were individuals with no history of diarrhea, of the same sex, from the same village and with an age difference that did not exceed five years. A logistic regression model was used to analyze the appearance of cholera according to the determining factors. The analysis showed significant association between the occurrence of cholera and variables related to behavior. The adjusted OR confirm higher risks of cholera for persons in households with more than five inhabitants (crude OR = 1.55 95 % CI (1.06 to 2.28) and adjusted OR 95 % CI 2.68 (1.79 to 4.56)), or in contact with a person with diarrhea (crude OR = 1.86 95% CI (1.26 to 2.75) and adjusted OR = 1.61 95% CI (1.5 to 2.68)), and who report not washing their hands after defecation (crude OR = 3.44 95% CI (2.20 to 5.41) and adjusted OR = 2.76 95% CI (1.73 to 3.79)). This study concludes that the Tillabery cholera victims are primarily those with hazardous hygienic practices. Niger must define operational recommendations to limit the continuance of cholera in certain river areas, particularly in the Tillabery.


Studies on adenosine triphosphate transphosphorylases. Amino acid sequence of rabbit muscle ATP-AMP transphosphorylase.
The total amino acid sequence of rabbit muscle adenylate kinase has been determined, and the single polypeptide chain of 194 amino acid residues starts with N-acetylmethionine and ends with leucyllysine at its carboxyl terminus, in agreement with the earlier data on its amino acid composition [Mahowald, T. A., Noltmann, E. A., & Kuby, S. A. (1962) J. Biol. Chem. 237, 1138-1145] and its carboxyl-terminus sequence [Olson, O. E., & Kuby, S. A. (1964) J. Biol. Chem. 239, 460-467]. Elucidation of the primary structure was based on tryptic and chymotryptic cleavages of the performic acid oxidized protein, cyanogen bromide cleavages of the 14C-labeled S-carboxymethylated protein at its five methionine sites (followed by maleylation of peptide fragments), and tryptic cleavages at its 12 arginine sites of the maleylated 14C-labeled S-carboxymethylated protein. Calf muscle myokinase, whose sequence has also been established, differs primarily from the rabbit muscle myokinase's sequence in the following: His-30 is replaced by Gln-30; Lys-56 is replaced by Met-56; Ala-84 and Asp 85 are replaced by Val-84 and Asn-85. A comparison of the four muscle-type adenylate kinases, whose covalent structures have now been determined, viz., rabbit, calf, porcine, and human [for the latter two sequences see Heil, A., Müller, G., Noda, L., Pinder, T., Schirmer, H., Schirmer, I., & Von Zabern, I. (1974) Eur. J. Biochem. 43, 131-144, and Von Zabern, I., Wittmann-Liebold, B., Untucht-Grau, R., Schirmer, R. H., & Pai, E. F. (1976) Eur. J. Biochem. 68, 281-290], demonstrates an extraordinary degree of homology.(ABSTRACT TRUNCATED AT 250 WORDS)


Transcriptional Regulation of RIP2 Gene by NFIB Is Associated with Cellular Immune and Inflammatory Response to APEC Infection.
Avian pathogenic E. coli (APEC) can cause localized or systemic infection, resulting in large economic losses per year, and impact health of humans. Previous studies showed that RIP2 (receptor interacting serine/threonine kinase 2) and its signaling pathway played an important role in immune response against APEC infection. In this study, chicken HD11 cells were used as an in vitro model to investigate the function of chicken RIP2 and the transcription factor binding to the RIP2 core promoter region via gene overexpression, RNA interference, RT-qPCR, Western blotting, dual luciferase reporter assay, CHIP-PCR, CCK-8, and flow cytometry assay following APEC stimulation. Results showed that APEC stimulation promoted RIP2 expression and cells apoptosis, and inhibited cells viability. Knockdown of RIP2 significantly improved cell viability and suppressed the apoptosis of APEC-stimulated cells. Transcription factor NFIB (Nuclear factor I B) and GATA1 (globin transcription factor 1) binding site was identified in the core promoter region of RIP2 from -2300 bp to -1839 bp. However, only NFIB was confirmed to be bound to the core promoter of RIP2. Overexpression of NFIB exacerbated cell injuries with significant reduction in cell viability and increased cell apoptosis and inflammatory cytokines levels, whereas opposite results were observed in NFIB inhibition treatment group. Moreover, RIP2 was up-regulated by NFIB overexpression, and RIP2 silence mitigated the effect of NFIB overexpression in cell apoptosis, inflammation, and activation of NFκB signaling pathways. This study demonstrated that NFIB overexpression accelerated APEC-induced apoptosis and inflammation via up-regulation of RIP2 mediated downstream pathways in chicken HD11 cells.


Clinical characteristics of depressed youths in child psychiatry.
To describe the clinical characteristics of depressed children and adolescents according to age groups and sex. A retrospective chart review study was conducted on 75 youths aged 6-17 years referred for depressive disorders to child psychiatry in 2002-2003. Descriptive statistics and tests of association were completed to compare boys aged 6-11 years, boys aged 12-17 years and girls aged 12-17 years. One out of two youths has repeated a school year. About 60% of depressed boys aged 6-11 years are referred to child psychiatry services for behavioral difficulties and 71% of boys in this age group have a depressive disorder comorbid with disruptive behavior disorder. Adolescent boys and girls are more likely to present internalized symptoms than children. However, suicidal ideation is as widespread in children (71%) as in adolescent population, both boys (72%) and girls (85%). Parent-child relational problems are observed in the majority of the sample with a higher prevalence among adolescent girls. : It is as important to assess depressive symptoms and suicidal ideation among young boys with behavioral difficulties as in adolescent boys and girls. Family functioning is important to consider in evaluating and treating youth.


[How to manage the rebound effect at denosumab discontinuation and avoid multiple vertebral fractures?]
Denosumab discontinuation is associated with a severe rebound effect combining elevation of bone remodeling markers for two years and loss of the gained bone density. In the absence of a potent bisphosphonate prescription at denosumab discontinuation, multiple vertebral fractures are frequent. The median number of vertebral fractures is 5, within 7 to 20 months (median 11) after the last denosumab injection. A potent bisphosphonate prescribed at denosumab discontinuation may reduce this risk. This strategy requires close monitoring of bone remodeling markers and adjustment of treatment if bone remodeling is not controlled.


Role of Rock Saturation Condition on Rock-Mud Interaction: Sandstone Geomechanics Study.
The rock saturation condition affects the rock elastic and strength characteristics due to the role of fluid-rock interaction. However, the role of this parameter has not been studied well for mud-rock exposure during drilling operations. Hence, this study targets to assess the role of different rock saturation conditions on the rock geomechanics changes during the rock exposure for the drilling fluids. During the drilling operation, the mud filtrate invades the drilled formation pore system and replaces the saturating fluid and consequent alterations occur for the rock elastic moduli and failure properties. The current study employed Berea Buff sandstone rock type with different saturation conditions (brine-saturated, dry, and oil-saturated) to interact with drilling mud (water-based) through the filtration test to mimic the downhole rock-mud exposure under pressure, temperature, and time conditions. Extensive laboratory analysis was accomplished that covered the scratching test to get the strength of rock samples, acoustic data determination, elastic moduli evaluation, and scanning electron microscopy to assess the internal alterations of the rock pore system. The obtained results showed that the oil-saturated sample showed the least filtration characteristics for the rock-mud exposure and the best condition to maintain the rock strength from deterioration compared to the dry and brine-saturated samples. The rock strength showed a weakening behavior for the brine-saturated and dry samples by 5 and 18% respectively, while the oil-saturated sample showed only a 2% strength reduction after the mud exposure. Poisson's ratio showed a 21% increase for the brine-saturated sample and the dry sample showed a small increase from 0.2 to 0.22, while the oil-saturated sample maintains a stable Poisson's ratio at 0.24. Young's modulus showed an increase for the dry and brine-saturated rock samples by 10 and 7%, respectively, while a 25% reduction for the oil-saturated. The spectrometry analysis results showed the internal changes in the rock samples' pore system for the brine-saturated and dry samples, while the oil-saturated sample showed no internal changes that maintain the rock structure and strength after the mud exposure.


Bis[μ-N'-(5-bromo-3-meth-oxy-2-oxido-benzyl-idene)-2-hydroxybenzohydra-zidato]bis[(N,N-dimethyl-formamide)-copper(II)].
The title compound, [Cu(2)(C(15)H(11)BrN(2)O(4))(2)(C(3)H(7)NO)(2)], is derived from the reaction of N'-(5-bromo-2-hy-droxy-3-meth-oxy-benzyl-idene)-2-hy-droxy-benzohydrazide and copper nitrate in a dimethyl-formamide solution in the presence of sodium hydroxide. The compound can be regarded as a binuclear centrosymmetric complex. In the crystal, the Cu(II) atom is fivefold surrounded and adopts a distorted square-pyramidal coordination environment. An intra-molecular O-H⋯N hydrogen bond stabilizes the mol-ecular conformation.


Review of maxillary expansion appliance activation methods: engineering and clinical perspectives.
Objective. Review the reported activation methods of maxillary expansion devices for midpalatal suture separation from an engineering perspective and suggest areas of improvement. Materials and Methods. A literature search of Scopus and PubMed was used to determine current expansion methods. A U.S. and Canadian patent database search was also conducted using patent classification and keywords. Any paper presenting a new method of expansion was included. Results. Expansion methods in use, or patented, can be classified as either a screw- or spring-type, magnetic, or shape memory alloy expansion appliance. Conclusions. Each activation method presented unique advantages and disadvantages from both clinical and engineering perspectives. Areas for improvement still remain and are identified in the paper.


Diversity in in-group bias: structural factors, situational features, and social functions.
Four experiments addressed the different forms and functions of in-group bias in different contexts. The authors proposed 2 functions: an identity-expressive function and an instrumental function (or promotion of positive social change). The authors manipulated status differentials, the stability of these differences, and the communication context (intra- vs. intergroup) and measured in-group bias and both functions. As predicted, identity expression via in-group bias on symbolic measures was most important for stable, high-status groups. By contrast, material in-group bias for instrumental motives was most prevalent in unstable, low-status groups but only when communicating with in-group members. This latter effect illustrates the strategic adaptation of group behavior to audience (i.e., displaying in-group bias may provoke the out-group and be counterproductive in instrumental terms). Stable, low-status groups displayed more extreme forms of in-group bias for instrumental reasons regardless of communication context (i.e., they had nothing to lose). Results are discussed in terms of a contextual-functional approach to in-group bias.


Gingival crevice neutrophil function in periodontosis.
This study examined gingival crevicular polymorphonuclear leucocyte function in periodontosis patients. Cells were examined for viability, function and ultrastructure. Eighty percent or more of the cells in each sample were viable as assessed by the fluorescein diacetate technique, but the test organism, Candida guillermondiae, was not phagocytosed. Gingival crevicular fluid contained many lysing neutrophils and nonphagocytosed organisms. Recognizable polymorphs contained Gram-negative and Gram-positive organisms. On the basis of this and previous studies it is concluded that gingival crevice neutrophils from periodontosis sites show reduced phagocytic function compared with cells from normal or periodontitis-affected gingival crevices. It is possible that the behavior of neutrophils from gingival crevices may be irrelevant. Original changes by that stage may have obscured their capabilities.


Atherosclerosis in intracranial, extracranial, and coronary arteries with aortic plaques in patients with ischemic stroke of undetermined etiology.
We investigated the association of cerebral and coronary artery atherosclerosis with the presence, burden and type of atherosclerotic plaques of the aorta (AP) in patients with ischemic stroke of undetermined etiology. 48 consecutive patients (32 males, mean age 68 ± 11 years) with acute ischemic stroke of unknown etiology after thorough stroke workup were investigated using ECG-gated CT-Angiography (CTA) for the detection of embolic AP. Intima media thickness (IMT), presence of carotid plaques and stenosis ≥ 50% and intracranial stenosis were assessed as parameters of cerebral atherosclerosis, the Agatston score (AS) and coronary artery stenosis ≥ 50% (CAS) in CTA as parameters of coronary atherosclerosis. Plaque burden was classified as mild or severe and plaque types were classified according to their morphology in calcified, non-calcified or mixed. APs were found in 36 patients (75%). AP presence was associated with higher IMT values (p = 0.029), intracranial stenosis (p = 0.047), CAS (p = 0.033) and AS (p = 0.026). Twenty-three of 31 (74.2%) patients with both carotid atherosclerosis and AP revealed plaque calcification (p = 0.041). Ten of 14 (71.4%) patients with AP and intracranial stenosis had calcified plaques (p = 0.030). AP in more than one aortic segment was found in patients with bilateral carotid stenosis ≥ 50% (p = 0.038), intracranial stenosis (p = 0.042), high IMT (p = 0.040) and higher AS (p = 0.019). Aortic atherosclerotic plaques are common in patients with ischemic stroke of undetermined etiology and in particular those with carotid, intracranial and coronary atherosclerosis or high IMT values. In these patients, CTA of aorta should be seriously considered.


Preferential binding of a novel polyhistidine peptide dendrimer ligand on quantum dots probed by capillary electrophoresis.
Fluorescence detection coupled to capillary electrophoresis (CE-FL) effectively separates molecules in solution and at the same time allows monitoring of the fluorescence spectrum of each individual species. The integration of separation and fluorescence detection results in a powerful method superior to the ensemble in-cuvette fluorescence measurement, in probing the binding interaction between ligands and quantum dots (QDs) in complex solutions. Förster resonance energy transfer (FRET) between fluorescent ligands and QDs could be readily detected by CE-FL, which together with the migration times of the fluorescent peaks provides an indication of the binding interaction between ligands and QDs. In the present study, the binding interaction between a multivalent ligand, polyhistidine peptide denderimer (PHPD), and CdSe-ZnS QDs was probed by CE-FL using the monovalent hexahistidine peptide as a control. Cy5 labeled PHPD assembles on glutathione capped QDs, showing a higher FRET signal than that of the assembly between Cy5 labeled hexahistidine peptide and QDs. Capillary electrophoresis further revealed that PHPD outcompetes other QD binding small molecules, peptides, and proteins in cell lysate. Our study demonstrates the power of CE-FL in analyzing the binding interaction between ligands and QDs in a complex binding solution. It also shows that clustering surface binding motifs yields multivalent ligands that can preferentially assemble with nanoparticles.


Investigation of protein adsorption performance of Ni2+-attached diatomite particles embedded in composite monolithic cryogels.
As a low-cost natural adsorbent, diatomite (DA) (2 μm) has several advantages including high surface area, chemical reactivity, hydrophilicity and lack of toxicity. In this study, the protein adsorption performance of supermacroporous composite cryogels embedded with Ni(2+)-attached DA particles (Ni(2+)-ADAPs) was investigated. Supermacroporous poly(2-hydroxyethyl methacrylate) (PHEMA)-based monolithic composite cryogel column embedded with Ni(2+)-ADAPs was prepared by radical cryo-copolymerization of 2-hydroxyethyl methacrylate (HEMA) with N,N'-methylene-bis-acrylamide (MBAAm) as cross-linker directly in a plastic syringe for affinity purification of human serum albumin (HSA) both from aqueous solutions and human serum. The chemical composition and surface area of DA was determined by XRF and BET method, respectively. The characterization of composite cryogel was investigated by SEM. The effect of pH, and embedded Ni(2+)-ADAPs amount, initial HSA concentration, temperature and flow rate on adsorption were studied. The maximum amount of HSA adsorption from aqueous solution at pH 8.0 phosphate buffer was very high (485.15 mg/g DA). It was observed that HSA could be repeatedly adsorbed and desorbed to the embedded Ni(2+)-ADAPs in poly(2-hydroxyethyl methacrylate) composite cryogel without significant loss of adsorption capacity. The efficiency of albumin adsorption from human serum before and after albumin adsorption was also investigated with SDS-PAGE analyses.


Global correlation analysis between redundant probe sets using a large collection of Arabidopsis ath1 expression profiling data.
Oligo-based expression microarrays from Affymetrix typically contain thousands of redundant probe sets that match different regions of the same gene. We used linear regression and correlation to survey redundant probe set behavior across nearly 500 quality-screened experiments from the Arabidopsis ATH1 array manufactured by Affymetrix. We found that expression values from redundant probe set pairs were often poorly correlated. Pre-filtering expression results using MAS5.0 "present-absent" calls increased the overall percentage of well-correlated probe sets. However, poor correlation was still observed for a substantial number of probe set pairs. Visual inspection of non-correlated probe sets' target genes suggests that some may be inappropriately merged gene models and represent independently expressed, but neighboring loci. Others may reflect differential regulation of alternative 3-prime end processing. Results are on-line at http://www.transvar.org/exp_cor/analysis.


The medical-irradiation characteristics for neutron capture therapy at the Heavy Water Neutron Irradiation Facility of Kyoto University Research Reactor.
At the Heavy Water Neutron Irradiation Facility of the Kyoto University Research Reactor, the mix irradiation of thermal and epi-thermal neutrons, and the solo irradiation of epi-thermal neutrons are available additionally to the thermal neutron irradiation, and then the neutron capture therapy (NCT) at this facility became more flexible, after the update in 1996. The estimation of the depth dose distributions in NCT clinical irradiation, were performed for the standard irradiation modes of thermal, mixed and epi-thermal neutrons, from the both sides of experiment and calculation. On the assumption that the 10B concentration in tumor part was 40 ppm and the ratio of tumor to normal tissue was 3.5, the advantage depth were estimated to 5.4, 6.0, and 8.0, for the respective standard irradiation modes. It was confirmed that the various irradiation conditions can be selected according to the target-volume conditions, such as size, depth, etc. Besides, in the viewpoint of the radiation shielding for patient, it was confirmed that the whole-body exposure is effectively reduced by the new clinical collimators, compared with the old one.


Application of Immunohistochemistry in Cytology.
Immunohistochemistry (IHC), also referred to as immunocytochemistry in cytology literature, has revolutionized the practice of cytopathology. Because of the complexity of cytology preparation and limited diagnostic material, performing IHC remains a challenge. Formalin-fixed paraffin-embedded (FFPE) cell block (CB) is the optimal choice for IHC. In this review, the approaches for improving CB preparation will be discussed. When CB material is not available, various cytology specimens can also be used for IHC. With the utilization of Antigen Retrieval (AR) technique, these nonformalin-fixed cytology specimens can achieve successful IHC staining, comparable with the results from FFPE tissue sections. In the last part of this review, we will discuss the use of positive controls and the important role of AR in standardization of IHC in cytology.


Dependence of lysozyme-catalysed solubilization of Proteus mirabilis peptidoglycan on the extent of O-acetylation.
The degree of peptidoglycan O-acetylation in 14 strains of Proteus mirabilis has been accurately determined by a procedure which employs the quantitation of mild-base-released acetic acid by HPLC, and the estimation of peptidoglycan concentration by cation-exchange amino acid analysis. The beta-D-N,6-O-diacetylmuramyl content of all isolated and purified peptidoglycans was ranged 20-52.8%, relative to the total muramic acid concentration. Each of the O-acetylated peptidoglycans was found to be resistant to solubilization by both human and hen egg-white lysozymes and for hen egg-white lysozyme, the extent of this resistance was dependent upon the degree of O-acetylation. The steady-state parameters, Km and V, for the hen-egg-white-lysozyme-catalysed solubilization of various peptidoglycan preparations were determined at pH 6.61 and 25 degrees C. Values of Km for the different peptidoglycan samples were found to increase with increasing O-acetylation, whereas with V no such relationship appeared to exist. An increase in the overall change in the standard Gibbs free energy of activation [delta(delta G#)], a consequence of increasing O-acetylation, was observed, and is shown to result from the weaker affinity of the enzyme for the modified substrates.


Obesity and nutrition behaviours in Western and Palestinian outpatients with severe mental illness.
While people with severe mental illness have been found to be more overweight and obese in Western nations, it is unknown to what extent this occurs in Middle Eastern nations and which eating behaviours contribute to obesity in Middle Eastern nations. A total of 665 responses were obtained from patients with serious mental illness attending out-patient clinics in Western developed countries (Germany, UK and Australia; n = 518) and Palestine (n = 147). Patients were evaluated by ICD-10 clinical diagnosis, anthropometric measurements and completed a self-report measure of frequencies of consuming different food items and reasons for eating. Nutritional habits were compared against a Western normative group. More participants from Palestine were overweight or obese (62%) compared to Western countries (47%). In the Western sample, obese patients reported consuming more low-fat products (OR 2.54, 95% CI 1.02-6.33) but also greater eating due to negative emotions (OR 1.84, 95% CI 1.31-2.60) than patients with a healthy body-mass index. In contrast, obese patients from Palestine reported increased consumption of unhealthy snacks (OR 3.73 95% CI 1.16-12.00). Patients with mental illness have poorer nutritional habits than the general population, particularly in Western nations. Separate interventions to improve nutritional habits and reduce obesity are warranted between Western nations and Palestine.


Prognostic classification of mild cognitive impairment and Alzheimer's disease: MRI independent component analysis.
Identifying predictors of mild cognitive impairment (MCI) and Alzheimer's disease (AD) can lead to more accurate diagnosis and facilitate clinical trial participation. We identified 320 participants (93 cognitively normal or CN, 162 MCI, 65 AD) with baseline magnetic resonance imaging (MRI) data, cerebrospinal fluid biomarkers, and cognition data in the Alzheimer's Disease Neuroimaging Initiative database. We used independent component analysis (ICA) on structural MR images to derive 30 matter covariance patterns (ICs) across all participants. These ICs were used in iterative and stepwise discriminant classifier analyses to predict diagnostic classification at 24 months for CN vs. MCI, CN vs. AD, MCI vs. AD, and stable MCI (MCI-S) vs. MCI progression to AD (MCI-P). Models were cross-validated with a "leave-10-out" procedure. For CN vs. MCI, 84.7% accuracy was achieved based on cognitive performance measures, ICs, p-tau(181p), and ApoE ε4 status. For CN vs. AD, 94.8% accuracy was achieved based on cognitive performance measures, ICs, and p-tau(181p). For MCI vs. AD and MCI-S vs. MCI-P, models achieved 83.1% and 80.3% accuracy, respectively, based on cognitive performance measures, ICs, and p-tau(181p). ICA-derived MRI biomarkers achieve excellent diagnostic accuracy for MCI conversion, which is little improved by CSF biomarkers and ApoE ε4 status.


[The use of mechanical suturing in colorectal anastomoses].
In 16 patients affected by cancer of the mild or lower 3 of the rectum, has been performed a colorectal anastomosis by EEA Stapler, with abdomino-transanal approach. In the postoperative period no case of anastomotic bleeding or stenosis has been observed. 3 patients (18%) presented minor anastomotic dehiscence detected by radiologic examination, without clinical symptomatology. The EEA Stapler anastomosis seem sure almost as the traditional hand sutures, and allow the execution of anterior resection instead of abdominal perineal amputation of rectum.


Protective Role of Vanillic Acid against Diethylnitrosamine- and 1,2-Dimethylhydrazine-Induced Hepatocarcinogenesis in Rats.
This study aimed to evaluate the cancer chemopreventive activity of vanillic acid (VA) in diethylnitrosamine- and 1,2-dimethylhydrazine-induced liver and colon carcinogenesis in rats. VA did not induce the formation of hepatic glutathione S-transferase placental form (GST-P) positive foci and colonic aberrant crypt foci, demonstrating no carcinogenic activity. VA (75 mg kg-1 body weight) could significantly reduce the number and areas of hepatic GST-P positive foci when administered before carcinogen injections, but no such effect was seen when it was administered after carcinogen injection. No protection was seen in the colon when VA was treated before or after carcinogen injection. Immunohistochemical studies demonstrated the decreased expression of proliferating cell nuclear antigen and the induction of apoptosis. Mechanistic studies showed that VA significantly induced the expression of GSTA-5 and Nrf-2 genes, which are associated with the detoxification system. Likewise, the antiproliferative effect was noticed by the reduction of Cyclin D1 expression. The apoptotic activity may be due to the upregulation of Caspase-3 and Bad levels and downregulation of the Bcl-2 level. These data suggest that VA exhibited significant protection against diethylnitrosamine- and 1,2-dimethylhydrazine-induced hepatocarcinogenesis, which might be related to the induction of the detoxifying enzyme, the reduction of proliferation and the induction of apoptosis.


Baccharis trimera Infusion Reduces Macrophages Activation and High-Fat Diet-Induced Metabolic Disorders in Mice.
The aim of this study is to evaluate the efficacy of Baccharis trimera infusion on high-fat diet-induced metabolic disorders in mice and macrophages activation. This study evaluated obesity, insulin resistance, dyslipidemia and hepatic steatosis induced by a high-fat diet in Swiss mice. Cellular parameters in macrophages, such as cell viability (MTT), the production and release of nitric oxide (NO) and hydrogen peroxide (H2O2), cell spreading, cell adhesion and phagocytosis were determined. Our results showed that treatment with B. trimera prevented the mentioned conditions, except for the production of hydrogen peroxide. B. trimera prevented the development of obesity and associated comorbidities, as well as activation of macrophages. In conclusion, B. trimera is able to prevent obesity and metabolic disorders and macrophages activation, minimizing inflammation and validating the popular use of this plant tea.


Antibodies to HIV-1 nef(p27): prevalence, significance, and relationship to seroconversion.
A sensitive and specific enzyme-linked immunoassay for antibodies to the human immunodeficiency virus type 1 (HIV-1) nef gene product, p27, has been developed using recombinant Escherichia coli-derived protein from the LAV-1-Bru sequence. Of 92 HIV-1 infected hemophiliacs, 72 (78%) produced anti-nef antibodies in this assay; the early appearance of anti-nef prior to full seroconversion was a rare event in this population, occurring in only one subject (approximately 1%). Anti-nef antibodies were not detected in any of 500 sera from 98 repeatedly HIV seronegative subjects who had been exposed to sexually transmitted modes of HIV infection (45 subjects) or through blood products (53 subjects). There was no significant association of titer or anti-nef antibody with protection from disease in HIV infection (p = 0.1). Although the nef protein is relatively immunogenic in natural infection, this study cannot confirm the previously reported high prevalence of anti-nef antibodies prior to seroconversion, nor the finding of anti-nef antibodies in HIV seronegative but exposed subjects.


Biology and pathology of the placenta in relation to antiphospholipid antibody-associated pregnancy failure.
The placenta is a complex organ composed of maternal and foetal components whose anatomy and function is often greatly simplified in order to explain a range of presumed placenta-related pregnancy complications. Since one of the major roles of the placenta is its materno-foetal transfer function, abnormalities at the materno-foetal interface may be responsible for a range of pregnancy complications manifesting from the first through third trimesters according to the severity of the pathological process in each case. This article reviews some aspects of abnormal early placental development and its consequences, with particular regard to recurrent pregnancy failure and obstetric complications in association with primary antiphospholipid antibody syndrome.


Autoantibodies to N-terminally truncated GAD improve clinical phenotyping of individuals with adult-onset diabetes: Action LADA 12.
Adult-onset type 1 diabetes, in which the 65 kDa isoform of GAD (GAD65) is a major autoantigen, has a broad clinical phenotype encompassing variable need for insulin therapy. This study aimed to evaluate whether autoantibodies against N-terminally truncated GAD65 more closely defined a type 1 diabetes phenotype associated with insulin therapy. Of 1114 participants with adult-onset diabetes from the Action LADA (latent autoimmune diabetes in adults) study with sufficient sera, we selected those designated type 1 (n = 511) or type 2 diabetes (n = 603) and retested the samples in radiobinding assays for human full-length GAD65 autoantibodies (f-GADA) and N-terminally truncated (amino acids 96-585) GAD65 autoantibodies (t-GADA). Individuals' clinical phenotypes were analysed according to antibody binding patterns. Overall, 478 individuals were f-GADA-positive, 431 were t-GADA-positive and 628 were negative in both assays. Risk of insulin treatment was augmented in t-GADA-positive individuals (OR 4.69 [95% CI 3.57, 6.17]) compared with f-GADA-positive individuals (OR 3.86 [95% CI 2.95, 5.06]), irrespective of diabetes duration. Of 55 individuals who were f-GADA-positive but t-GADA-negative, i.e. with antibody binding restricted to the N-terminus of GAD65, the phenotype was similar to type 2 diabetes with low risk of progression to insulin treatment. Compared with these individuals with N-terminal GAD65-restricted GADA, t-GADA-positive individuals were younger at diagnosis (p = 0.005), leaner (p < 0.0001) and more often had multiple diabetes-associated autoantibodies (28.3% vs 7.3%; p = 0.0005). In individuals with adult-onset diabetes, presence of N-terminally truncated GAD65 autoantibodies is associated with the clinical phenotype of autoimmune type 1 diabetes and predicts insulin therapy.


The effect of pitch type on ground reaction forces in the baseball swing.
Coaches have identified the batter's weight shift as a critical component for promoting proper timing and balance in a baseball swing. Analysing the weight shift through maximum horizontal (Fx) and vertical (Fz) ground reaction forces (GRFs) of professional batters (N = 29; height = 185 +/- 6 cm; mass = 92 +/- 9 kg), the purpose of this study was to compare GRFs among swings against fastballs and changeups. General linear models were used to compare three conditions of interest: successful results against fastballs, successful results against changeups, and unsuccessful results against changeups. Batters had a similar loading mechanism and initial weight transfer from back foot to front foot regardless of pitch type, but peak front foot GRFx and GRFz occurred with significantly different magnitudes and at significantly different times, depending on the pitch type and hit result. Peak front foot GRFs were greater for successful swings against fastballs compared to both successful and unsuccessful swings against changeups. Peak front foot GRFs of unsuccessful swings against changeups occurred, on average, 15-20 ms earlier than successful swings against changeups and 30-35 ms earlier than successful swings against fastballs, quantifying how a changeup can disrupt the coordination of a hitter's weight shift.


Implementation and Postoperative Management of Continuous Adductor Canal Catheters for Total Knee Arthroplasty to Reduce Surgical Backlog Related to the COVID-19 Pandemic: An Acute Pain Service Nursing Perspective and Educational Resource.
In response to the surgical backlog created by the COVID-19 pandemic and to spare valuable hospital resources, we developed and implemented a continuous adductor canal catheter (CACC) program for total knee arthroplasty (TKA) patients. CACC's offer superior analgesia, decrease opioid use, and increase patient satisfaction while simultaneously promoting a decreased length of hospital stay and even same day discharges. The implementation of analgesia protocols using continuous peripheral nerve catheters and isometric pumps has been described for other surgical procedures and populations; however, the role of the Acute Pain Service Nurse (APS RN) in the implementation of such a program has not been described. An best practice initiative for TKA patients receiving CACC was developed and implemented for patients recovering both in the hospital and at home. We describe the development and implementation of a CACC program for TKA patients in response to the surgical backlog created by the COVID-19 pandemic from the perspective of the APS RN. We provide a detailed narrative description of our postoperative assessment and experience, and offer practical insights for the postoperative care of these patients. We share the educational resources and assessment tools we developed to ensure consistent, safe, and effective clinical management of CACC patients in the hospital and at home. CACCs via elastomeric pumps have been shown to offer significant advances to pain control following TKA, decrease opioid use, enable earlier discharge, and improve patient satisfaction, all of which we observed unequivocally in our patients. In our experience, implementation of a daily telephone follow up by an APS RN for discharged TKA patients with a CACC was crucial for patient safety, patient satisfaction, and reducing emergency phone calls and emergency room visits. We anticipate this description will provide an invaluable educational resource for other Acute Pain Service programs as similar outpatient peripheral nerve catheter programs are developed in response to the pandemic.


Characterization of the gene BmEm4, a homologue of Drosophila E(spl)m4, from the silkworm, Bombyx mori.
The Drosophila E(spl)m4 gene contains some highly conserved motifs (such as the Brd box, GY box, K box, and CAAC motif) in its 3' untranslated region (3' UTR). It was shown to be a microRNA target gene in Drosophila and to play an important role in the regulation of neurogenesis. We identified a homologue of the E(spl)m4 gene from Bombyx mori called BmEm4 and examined the expression patterns of BmEm4 mRNA and protein. There was a lack of correlation in the expression of the mRNA and protein between the different developmental stages, which raises the possibility of posttranscriptional regulation of the BmEm4 mRNA. Consistent with this idea is the finding that the 3' UTR contains two putative binding sites for microRNAs. Moreover, given that the expression is the highest in the larval head, as confirmed by immunohistochemistry, we propose that BmEm4 may also be involved in the regulation of neurogenesis. Immunostaining indicated that BmEm4 is located primarily in the cytoplasm.


Activation of mTOR signaling in medullary and aggressive papillary thyroid carcinomas.
Because mammalian target of rapamycin (mTOR) may be involved in thyroid carcinogenesis, we investigated the expression and activation patterns of mTOR signaling proteins in thyroid carcinoma cells and tumors and their association with tumor histology and aggressiveness. Tissue specimens from 50 patients with thyroid cancer were analyzed for eIF4E, a critical downstream target of the mTOR pathway, using immunohistochemistry. In addition, fresh-frozen samples from patients, and primary tumor cell cultures were analyzed for expression and activation of mTOR signaling proteins by Western blot. Moreover, pharmacologic studies with rapamycin were performed. High expression of eIF4E was observed in medullary thyroid carcinomas (MTC) and in aggressive variants of papillary thyroid carcinomas (PTC) as compared with conventional PTC and follicular thyroid carcinomas (P < .0001). The level of eIF4E expression also correlated with tumor stage (P = .002). Using Western blot analysis, p-rpS6, p-4EBP1, 4EBP1, and eIF4E were detected at higher levels in aggressive PTC and MTC cells. Treatment of MTC cells with increasing concentrations of rapamycin resulted in significant cell death and in decreased cell growth associated with deactivation of the mTOR pathway. mTOR signaling, which controls protein synthesis through regulation of translation initiation, is activated in aggressive PTC and MTC and represents a promising target for investigational therapies in these patients.


Effects of phosphoric acid and glutaraldehyde-HEMA on dentin collagen.
The purpose of this study was to evaluate the effects of phosphoric acid (PA) and a proprietary glutaraldehyde-HEMA aqueous solution (Gluma Desensitizer; GD) on dentin collagen. Specimens of demineralized bovine dentin collagen were treated with either 37% or 50% PA for 1 or 5 min. An additional set of specimens was treated with 37% PA for 1 min followed by GD for 1 min. All specimens were washed with distilled water, lyophilized. reduced with standardized NaB3H4, hydrolyzed with 6 M HCl and subjected to amino acid and cross-link analyses. The results demonstrated that the treatment of demineralized dentin with PA under the conditions tested did not significantly alter the collagen cross-links. The GD-treated samples showed reduction of free lysine (Lys) and hydroxylysine (Hyl) residues, as well as a decrease in the levels of collagen reducible cross-links. In addition, unidentified reducible compounds were detected by high-performance liquid chromatography (HPLC) analysis. These compounds may be derived from cross-links formed between GD-derived aldehyde and Lys/Hyl of collagen. The findings indicate that PA treatment does not significantly affect dentin collagen amino acid and cross-link composition, and that GD treatment affects dentin collagen amino acid and cross-link composition.


Cervical interlaminar epidural steroid injection for unilateral cervical radiculopathy: comparison of midline and paramedian approaches for efficacy.
The objective of this study was to compare the clinical outcomes of the cervical interlaminar epidural steroid injection (CIESI) for unilateral radiculopathy by the midline or paramedian approaches and to determine the prognostic factors of CIESI. We retrospectively analyzed 182 patients who underwent CIESI from January 2009 to December 2012. Inclusion criteria were no previous spinal steroid injection, presence of a cross-sectional image, and presence of follow-up records. Exclusion criteria were patients with bilateral cervical radiculopathy and/or dominant cervical axial pain, combined peripheral neuropathy, and previous cervical spine surgery. Short-term clinical outcomes were evaluated at the first follow-up after CIESI. We compared the clinical outcomes between the midline and paramedian approaches. Possible prognostic factors for the outcome, such as age, gender, duration of radiculopathy, and cause of radiculopathy were also analyzed. Cervical interlaminar epidural steroid injections were effective in 124 of 182 patients (68.1%) at the first follow-up. There was no significant difference in the clinical outcomes of CIESI, between midline (69.6%) and paramedian (63.7%) approaches (p = 0.723). Cause of radiculopathy was the only significant factor affecting the efficacy of CIESI. Patients with disc herniation had significantly better results than patients with neural foraminal stenosis (82.9% vs. 56.0%) (p < 0.001). There is no significant difference in treatment efficacy between the midline and paramedian approaches in CIESI, for unilateral radiculopathy. The cause of the radiculopathy is significantly associated with the treatment efficacy; patients with disc herniation experience better pain relief than those with neural foraminal stenosis.


Patient-Centered Insights and Biases Regarding Cardiologists Via Online Review Platform Analysis.
Background Online cardiologist reviews, such as those on the Yelp website, are a frequently used method for patients to find a cardiologist. It remains unknown how bias may influence such reviews. Our objectives for this study were to (1) determine which cardiologist- or practice-related factors influence the overall rating of cardiologists and patient satisfaction and (2) discover any associations between sex and race with the overall rating of cardiologists or with cardiologist- or practice-related factors. Methods and Results Cardiologist Yelp reviews from practices in the United States from 2007 to 2020 were analyzed. A total of 563 reviews were coded for positive and negative themes. Binary logistic regression was used to determine whether certain factors increased the likelihood of high ratings. Chi-squared tests were used to determine associations between sex and race with certain factors and overall cardiologist ratings. Cardiologists were more likely to receive higher ratings when reviewers noted the characteristics of competency/knowledge base and thoroughness, positive interactions with staff, and when the cardiologist's name was mentioned in the review. Negative interactions with staff were associated with lower ratings. Female cardiologists received lower ratings and more negative mentions of cardiologist-patient communication than expected. White and Black cardiologists received lower ratings than expected compared with other racial groups. Conclusions Patient-perceived cardiologist competency, thoroughness, and positive staff interactions were associated with positive reviews in online assessments. Sex and racial differences were also found. Further research must be done to confirm these findings and to understand the association of online reviews with clinical care and patient outcomes.


Role of strain differences on host resistance and the transcriptional response of macrophages to infection with Yersinia enterocolitica.
The outcome of a host-pathogen encounter is determined by virulence factors of the pathogen and defense factors of the host. We characterized the impact of host factors [resistant (C57BL/6) or susceptible (BALB/c) genetic background and exposure to interferon (IFN)-gamma] on transcriptional responses of bone marrow-derived macrophages (BMDM) to infection with Yersinia enterocolitica. IFN-gamma treatment more profoundly altered the transcriptome of BMDM than did bacterial infection or genetic background. In BALB/c BMDM, 1,161 genes were differentially expressed in response to Yersinia infection with or without IFN-gamma prestimulation. Fourteen genes (1.2%) could only be induced by BALB/c BMDM in response to Yersinia infection after IFN-gamma pretreatment. These genes inhibit apoptosis, activate NF-kappaB and Erk signaling, are chemotactic to neutrophils, and are involved in cytoskeletal reorganization, hence possibly in phagocytosis. Ten of these genes possess a common module of binding sites for Hox, Pou, and Creb transcription factors in 2 kb of upstream genomic sequence, suggesting a possible novel role of these transcription factors in regulation of immune responses. Fifty-two of one thousand fifty differentially expressed genes (4.9%) were induced more strongly by C57BL/6 BMDM in response to Yersinia infection than BALB/c BMDM. These genes activate NK cells, have antibacterial properties, or are involved in sensing chemokines and lipopolysaccharide (LPS). These data show that host resistance factors modulate a surprisingly small, but identifiable and functionally significant, portion of the macrophage transcriptome in response to Yersinia infection.


Left Ventricular Global Longitudinal Strain (GLS) Is a Superior Predictor of All-Cause and Cardiovascular Mortality When Compared to Ejection Fraction in Advanced Chronic Kidney Disease.
Echocardiographic global longitudinal strain (GLS) is increasingly recognised as a more effective technique than conventional ejection fraction (EF) in detecting subtle changes in left ventricular (LV) function. This study investigated the prognostic value of GLS over EF in patients with advanced Chronic Kidney Disease (CKD). The study included 183 patients (57% male, 63% on dialysis) with CKD stage 4, 5 and 5Dialysis (D). 112 (61%) of patients died in a follow up of 7.8 ± 4.4 years and 41% of deaths were due to cardiovascular (CV) disease. GLS was calculated using 2-dimensional speckle tracking and EF was measured using Simpson's biplane method. Cox proportional hazard models were used to assess the association of measures of LV function and all- cause and CV mortality. The mean GLS at baseline was -13.6 ± 4.3% and EF was 45 ± 11%. GLS was a significant predictor of all-cause [Hazard Ratio (HR) 1.09 95%; Confidence Interval (CI) 1.02-1.16; p = 0.01] and CV mortality (HR 1.16 95%; CI 1.04-1.30; p = 0.008) following adjustment for relevant clinical variables including LV mass index (LVMI) and EF. GLS also had greater predictive power for both all- cause and CV mortality compared to EF. Impaired GLS (>-16%) was associated with a 5.6-fold increased unadjusted risk of CV mortality in patients with preserved EF. In this cohort of patients with advanced CKD, GLS is a more sensitive predictor of overall and CV mortality compared to EF. Studies of larger populations in CKD are required to confirm that GLS provides additive prognostic value in patients with preserved EF.


Conflicts of interest in oncology expanded access studies.
Expanded access is a treatment use of investigational drugs, biologicals or medical devices outside of clinical trials. The purpose of our study was to assess self-reported conflicts of interest (COIs) in oncology expanded access studies. One hundred fifty-eight oncology expanded access studies published from 2013 through 2020 were included. The pharmaceutical industry funded either completely or in part 94 studies (59.49%). The authors disclosed mostly financial COIs, while the number of the reported nonfinancial conflicts was relatively small (3528 and 57 COIs, respectively). The number of articles in which at least one author had a financial COI was 118 (74.68%). The most common financial COI types included advisory board membership/consulting (1471 COIs; 41.7%), followed by honoraria (570 COIs; 16.16%) and research funding (441 COIs; 12.5%). Logistic regression was performed to identify predictors of disclosing financial COIs and positive study's conclusions. On univariate analysis, financial COIs were more likely to occur in studies with at least one center located in the United States (odds ratio [OR], 5.62; 95% confidence interval [CI], 1.57-35.98; P = .02). We also found that positive conclusions about the studied treatments were less likely in studies without industry funding (OR, 0.26; CI, 0.08-0.77; P = .01). Most of the research on COIs in oncology performed to date focused on other types of studies, especially clinical trials. To our knowledge, our study is the first to evaluate COIs in oncology expanded access studies.


Individual, culture-specific alterations in the human endothelial glutathione system: relationships to oxidant toxicity.
In this communication we report on the effects of serial passage of human umbilical vein endothelial cells on the levels of GSH and activities of selenium-dependent GSH peroxidase (SeGSHpx) and GSSG reductase (GSSGred) in confluent monolayers of human umbilical vein endothelial cells derived from 4 individual donors. The mean levels of GSH in confluent monolayers of individual human umbilical vein endothelial cells batches fell from an average of 35 nmol/mg protein to 16 nmol/mg protein from primary culture to the third passage, with little interindividual variation noted. Simultaneously, the mean activities of SeGSHpx and GSSGred remained unaltered during serial culture, again with little interindividual variation noted. However, serial passage of the cells from different individuals did not affect the sensitivity of the cells to sublethal injury induced by H2O2 (10 or 100 microM), as judged by the stimulated release of (3H)-deoxyglucose. When these GSH-dependent parameters were assayed during the coarse of the growth of an individual passage of cells, GSH levels declined following trypsinisation, but the activities of SeGSHpx and GSSGred remained essentially unaltered, when the data were standardised to cell number. On the other hand, standardisation of these data to cell protein revealed decreases in all three parameters following trypsinisation, indicating the introduction of artefacts into the data and the unsuitability of this standardisation procedure. For the first four hours following plating, all of the GSH-dependent parameters remained essentially unaltered, but began increasing thereafter.(ABSTRACT TRUNCATED AT 250 WORDS)


The resilient brain: psychological resilience mediates the effect of amplitude of low-frequency fluctuations in orbitofrontal cortex on subjective well-being in young healthy adults.
Psychological resilience reflects the capacity to bounce back from stress, which plays an important role in health and well-being. However, less is known about the neural substrate for psychological resilience and the underlying mechanism for how psychological resilience enhances subjective well-being in the healthy brain. To investigate these issues, we employed fractional amplitude of low-frequency fluctuations (fALFF) measured with resting-state fMRI in 100 young healthy adults. The correlation analysis found that higher psychological resilience was related to lower fALFF in the left orbitofrontal cortex (OFC), which is involved in reward-related processing and emotion regulation. Furthermore, the mediation analysis indicated that psychological resilience acted as a full mediator of the association between the fALFF in left OFC and subjective well-being indicators (i.e. life satisfaction and hedonic balance). Importantly, these results remained significant after controlling for the effect of gray matter volume and regional homogeneity in the region. Overall, the present study provides the further evidence for functional neural substrates of psychological resilience and reveals a potential mechanism that psychological resilience mediates the effect of spontaneous brain activity on subjective well-being.


CT scan assessment of the pathway of the true lateral approach for transforaminal endoscopic lumbar discectomy: is It possible?
We performed a prospective study to examine the influence of the patient's position on the location of the abdominal organs, to investigate the possibility of a true lateral approach for transforaminal endoscopic lumbar discectomy. Pre-operative abdominal CT scans were taken in 20 patients who underwent endoscopic lumbar discectomy. Axial images in parallel planes of each intervertebral disc from L1 to L5 were achieved in both supine and prone positions. The most horizontal approach angles possible to avoid injury to the abdominal organs were measured. The results demonstrated that the safe approach angles were significantly less (i.e., more horizontal) in the prone than in the supine position. Obstacles to a more lateral approach were mainly the liver, the spleen and the kidneys at L1/2 (39 of 40, 97.5%) and L2/3 (28 of 40, 70.0%), and the intestines at L3/4 (33 of 40, 82.5%) and L4/5 (30 of 30, 100%). A true lateral approach from each side was possible for 30 of the 40 discs at L3/4 (75%) and 23 of the 30 discs at L4/5 (76.7%). We concluded that a more horizontal approach for transforaminal endoscopic lumbar discectomy is possible in the prone position but not in the supine. Prone abdominal CT is more helpful in determining the trajectory of the endoscope. While a true lateral approach is feasible in many patients, our study shows it is not universally applicable.


[Pulmonary mucormycosis in a patient with diabetes mellitus: favorable evolution under medical treatment].
Pulmonary mucormycosis is a relatively uncommon but an important opportunistic fungal infection in immunocompromised patients. It may be acquired by inhalation of spores into the lungs. The pathogenic hallmark of mucormycosis is vascular invasion resulting in thrombosis and tissue infarction/necrosis. The diagnosis can be difficult since presentation does not differ from other forms of pneumonia. Risk factors include neutropenia, haematologic malignancies, uncontrolled diabetes mellitus, skin burns and deferoxamine therapy in dialysis patients. Early recognition, control of underlying diseases and medical-surgical aggressive management are warranted to better outcomes. Pulmonary mucormycosis has a high mortality and medical treatment strategy alone has been associated in several studies to greater mortality. We describe a case of pulmonary mucormicosis with favorable evolution only under medical treatment. We reviewed the bibliography.


FEN1 knockdown improves trastuzumab sensitivity in human epidermal growth factor 2-positive breast cancer cells.
Trastuzumab has been widely applied as a treatment for human epidermal growth factor 2 (HER2)-overexpressing breast cancer. However, the therapeutic efficacy of trastuzumab is limited. Flap endonuclease 1 (FEN1) is a multifunctional endonuclease that has a crucial role in DNA recombination and repair. Inhibition of FEN1 is associated with the reversal of anticancer drug resistance. However, it is unclear whether FEN1 is involved in trastuzumab resistance. In the present study, it was demonstrated that trastuzumab increases the expression of FEN1, and FEN1 knockdown significantly enhanced the sensitivity of BT474 cells to trastuzumab (P<0.05). It was also revealed that trastuzumab induced HER receptor activation, increased binding with FEN1 and estrogen receptor α (ERα), and upregulated ERα-target gene transcription (P<0.05). Upon silencing of FEN1 expression with siRNA, activation of HER receptor and FEN1 binding to ERα were decreased, and trastuzumab-induced ERα target gene upregulation was partially ameliorated (P<0.05). These results suggest that FEN1 may mediate trastuzumab resistance via inducing HER receptor activation and enhancing ERα-target gene transcription. The findings of the present study indicate a novel role of FEN1 in trastuzumab resistance, suggesting that targeting FEN1 may enhance the efficiency of trastuzumab as a treatment for HER2-positive breast cancer.


Confusing criminal and civil law: when may a hospital refuse to release a dead body?
A United Kingdom bereavement advice group has expressed concern that hospitals in Britain may be acting "illegally" in refusing to release dead bodies to relatives unless they provide evidence that funeral arrangements have been made. In some cases, hospitals may have refused to release a body to anyone other than an undertaker. The charity argues that this behaviour constitutes the common law offence of preventing the lawful burial of a body. This article considers the confusion that may occur between this offence and interference with the right to possession of a body for lawful burial. The conclusion is that it is extremely unlikely a hospital or its employees would fall foul of the criminal law in refusing to release a dead body and may be liable in the civil courts if they release a body to someone who does not have the duty and consequent right to possession of the body for lawful burial.


[A new thyrotoxicosis index (bases for calculation and applications)].
A new thyrotoxicosis index (pointer) is calculated according to frequency of signs and symptoms in a well documented population of 189 thyrotoxicosis and pseudo thyrotoxicosis cross matined patients. Applied to a computerized population of 3 596 thyroid complained patients, this index provides four groups. Index greater than or equal to 8,5 : thyrotoxicosis is quite sure (92.5%), 8,5 less than or equal to index less than or equal to 5 : 3 of 5 patients are thyrotoxicosic 5 less than index less than - 1:1 of 5 patients is thyrotoxicosic (rough thyrotoxicosis), index less than or equal to - 1 : thyrotoxicosis can be refuded (98%).


The Importance of Protecting the Structure and Viability of Adipose Tissue for Fat Grafting.
Fat grafting is widely used for soft-tissue augmentation; however, the related clinical outcome remains variable and technique-dependent. The mechanisms underlying fat graft survival are not fully understood, particularly regarding the contributions of different cell types, such as functional adipocytes. This study evaluated the importance of adipose tissue structure and viability in fat grafting and, to some extent, revealed the effect of adipocytes in fat grafting. Human lipoaspirate was harvested using suction-assisted liposuction and processed using three separate methods: cotton-pad filtration, soft centrifugation (400 g for 1 minute), and Coleman centrifugation (1200 g for 3 minutes). Then all samples were subjected to second cotton-pad concentration. Adipose tissue structure and viability, the numbers of adipose-derived stem cells, and their proliferation and multilineage differentiation abilities were compared in vitro. The volume retention rate and fat graft quality were evaluated in vivo. Cell structure destruction and viability decline were more evident in the Coleman centrifugation group compared to the cotton-pad filtration group and the soft centrifugation group. However, no intergroup differences were observed in the numbers, proliferation, or multilineage differentiation abilities of adipose-derived stem cells. After transplantation, the volume retention rates were similar in the three groups. However, greater structural and functional damage was associated with poorer graft quality, including decreased levels of graft viability, vessel density, and vascular endothelial growth factor secretion and increased levels of vacuoles, necrotic areas, fibrosis, and inflammation. Protecting adipose tissue structure and viability is crucial for improving fat grafting outcomes. The protection of the structure and viability of adipose tissue should be ensured throughout the whole process of fat grafting to reduce complications and improve graft quality.


Analysis of the Escherichia coli Tol-Pal and TonB systems by periplasmic production of Tol, TonB, colicin, or phage capsid soluble domains.
The aim of this review is to describe an in vivo assay of the interactions taking place in the Tol-Pal or TonB-ExbB-ExbD envelope complexes in the periplasm of Escherichia coli and between them and colicins or g3p protein of filamentous bacteriophages. Domains of colicins or periplasmic soluble domains of Tol or TonB proteins can be artificially addressed to the periplasm of bacteria by fusing them to a signal sequence from an exported protein. These domains interact specifically in the periplasm with the Tol or TonB complexes and disturb their function, which can be directly detected by the appearance of specific tol or tonB phenotypes. This technique can be used to detect new interactions, to characterize them biochemically and to map them or to induce tol or tonB phenotypes to study the functions of these two complexes.