Cluster of differentiation (CD) 9-positive mouse pituitary cells are adult stem/progenitor cells.
SOX2-positive cells are stem/progenitor cells that supply hormone-producing cells; they are found in the anterior lobe of the rodent pituitary gland. However, they are likely composed of several subpopulations. In rats, a SOX2-positive cell populations can be distinguished by the presence of S100β. We identified the novel markers cluster of differentiation (CD) CD9 and CD81, members of the tetraspanin superfamily, for the identification of S100β/SOX2-positive cells. Recently, CD9/CD81 double-knockout mice were generated. Although they grew normally until 3 weeks after birth, they exhibited atrophy of the pituitary gland. These findings suggested that CD9/CD81/S100β/SOX2-positive cells in the mouse pituitary are adult stem/progenitor cells. To substantiate this hypothesis, we examined CD9 and CD81 expression in the adult and developing anterior lobe. Immunohistochemistry showed that CD9/CD81-positive cells began appearing from postnatal day 0 and settled in the stem cell niches (marginal cell layer and parenchyma) of the adult anterior lobe while expressing S100β. We next isolated CD9 -positive cells from the adult anterior lobe, using the anti-CD9 antibody for cell characterisation. The cells in culture formed free-floating three-dimensional clusters (pituispheres); moreover, induction into all types of hormone-producing cells was successful. Furthermore, reduction of CD9 and CD81 mRNAs by siRNAs inhibited cell proliferation. These findings indicate that CD9/CD81/S100β/SOX2-positive cells may play a role as adult stem/progenitor cells in SOX2-positive subpopulations, thus supplying hormone-producing cells in the postnatal anterior lobe. Furthermore, CD9 and CD81 are implicated in cell proliferation. The current findings provide novel insights into adult pituitary stem/progenitor cells.


Kinetic mechanism of fully activated S6K1 protein kinase.
S6K1 is a member of the AGC subfamily of serine-threonine protein kinases, whereby catalytic activation requires dual phosphorylation of critical residues in the conserved T-loop (Thr-229) and hydrophobic motif (Thr-389). Previously, we described production of the fully activated catalytic kinase domain construct, His(6)-S6K1alphaII(DeltaAID)-T389E. Now, we report its kinetic mechanism for catalyzing phosphorylation of a model peptide substrate (Tide, RRRLSSLRA). First, two-substrate steady-state kinetics and product inhibition patterns indicated a Steady-State Ordered Bi Bi mechanism, whereby initial high affinity binding of ATP (K(d)(ATP)=5-6 microM) was followed by low affinity binding of Tide (K(d)(Tide)=180 microM), and values of K(m)(ATP)=5-6 microM and K(m)(Tide)=4-5 microM were expressed in the active ternary complex. Global curve-fitting analysis of ATP, Tide, and ADP titrations of pre-steady-state burst kinetics yielded microscopic rate constants for substrate binding, rapid chemical phosphorylation, and rate-limiting product release. Catalytic trapping experiments confirmed rate-limiting steps involving release of ADP. Pre-steady-state kinetic and catalytic trapping experiments showed osmotic pressure to increase the rate of ADP release; and direct binding experiments showed osmotic pressure to correspondingly weaken the affinity of the enzyme for both ADP and ATP, indicating a less hydrated conformational form of the free enzyme.


Patient-Derived Ex Vivo Cultures and Endpoint Assays with Surrogate Biomarkers in Functional Testing for Prediction of Therapeutic Response.
Prediction of therapeutic outcomes is important for cancer patients in order to reduce side effects and improve the efficacy of anti-cancer drugs. Currently, the most widely accepted method for predicting the efficacy of anti-cancer drugs is gene panel testing based on next-generation sequencing. However, gene panel testing has several limitations. For example, only 10% of cancer patients are estimated to have druggable mutations, even if whole-exome sequencing is applied. Additionally, even if optimal drugs are selected, a significant proportion of patients derive no benefit from the indicated drug treatment. Furthermore, most of the anti-cancer drugs selected by gene panel testing are molecularly targeted drugs, and the efficacies of cytotoxic drugs remain difficult to predict. Apart from gene panel testing, attempts to predict chemotherapeutic efficacy using ex vivo cultures from cancer patients have been increasing. Several groups have retrospectively demonstrated correlations between ex vivo drug sensitivity and clinical outcome. For ex vivo culture, surgically resected tumor tissue is the most abundant source. However, patients with recurrent or metastatic tumors do not usually undergo surgery, and chemotherapy may be the only option for those with inoperable tumors. Therefore, predictive methods using small amounts of cancer tissue from diagnostic materials such as endoscopic, fine-needle aspirates, needle cores and liquid biopsies are needed. To achieve this, various types of ex vivo culture and endpoint assays using effective surrogate biomarkers of drug sensitivity have recently been developed. Here, we review the variety of ex vivo cultures and endpoint assays currently available.


Enzyme-linked immunosorbent assay for HLA determination on fresh and dried lymphocytes.
HLA-A and -B antigens were detected on fresh and dried peripheral blood lymphocytes by an enzyme-linked immunosorbent assay. Intact cells fixed to plates with glutaraldehyde were used as antigen and anti-HLA alloantisera as a source of antibodies. Determination of HLA antigens by the ELISA technique was comparable with the complement-dependent cytotoxicity test. The relative stability of HLA antigens as shown in this report and the extensive polymorphism of the HLA system make the ELISA technique a promising tool for the analysis of HLA antigens on non-living cells including, for example, medicolegal investigation of blood stains.


Detection of experimentally induced root fractures on digital and conventional radiographs: an in vitro study.
This study compared the diagnostic accuracy of digital radiographic images with conventional radiographs for the detection of experimentally induced root fractures. Horizontal fractures were induced by a mechanical force to the root of 15 single rooted teeth. Vertical fractures were induced in 15 single rooted teeth and 15 molars, respectively, by disk cutting. The teeth were mounted in dried mandibles and were radiographed with the parallel technique using a CCD-based Planmeca imaging system and F-speed films. Seven observers recorded their findings and then 2 pairs of them examined the same images together. Az values expressed the diagnostic accuracy of the imaging systems and the degree of agreement was estimated using the Cohen's kappa statistic. The areas under the ROC curves (Az) in single rooted teeth were 0.61 for conventional radiography and 0.64 for digital radiography. Digital imaging system did not perform significantly better than conventional one (p > 0.01). Digital radiographs (Az: 0.72) provided higher detection accuracy in molars than conventional images (Az: 0.51) (p = 0.0102). The digital images scored higher kappa values with narrower range than conventional. Observers in pairs did not perform significantly better than individually. The results were not affected by the observers but were affected by the cases (p < 0.001). Digital images were equivalent to F-speed films for the detection of root fractures in single rooted teeth. The digital system performed significantly better than the conventional in detecting root fractures in molars.


Glutamate receptors in domestication and modern human evolution.
There has been a recent resurgence of interest in the hypothesis that anatomically modern humans and domesticated species have followed convergent evolutionary paths. Here, we review results from domestication and modern-human evolutionary studies in order to evaluate evidence for shared changes to neurotransmission across these species. We compare genomic and, where available, brain-expression differences across 488 neurotransmitter receptor genes in 14 domesticated species and modern humans relative to their wild and archaic counterparts. This analysis highlights prevalent changes to glutamate - most notably kainate and metabotropic - receptor genes. We review evidence for these genes' expression and their respective receptor functions in the central nervous system, as well as phenotypes commonly associated with alterations to them. This evidence suggests an important role for kainate and metabotropic receptors in regulating hypothalamic-pituitary-adrenal axis excitation, and we provide a mechanistic account of their actions in attenuating the stress response. We assess the explanatory potential of such actions in contributing to the emergence of the (self-)domesticated phenotype, in particular to reduced reactive aggression.


Bim dictates naive CD4 T cell lifespan and the development of age-associated functional defects.
With age, peripheral naive CD4 T cells become both longer lived and functionally impaired and they express reduced levels of Bim, a proapoptotic Bcl family member. In this study, we show that reduced Bim expression by naive CD4 T cells intrinsically mediates their longer lifespan in the periphery. Moreover, using mixed bone marrow chimeras reconstituted with Bim(+/+) and Bim(+/-) bone marrow cells, Bim(+/-) naive CD4 T cells exhibit accelerated development of age-associated dysfunctions, including reduced proliferation and IL-2 production and defective helper function for B cells, without any increase in their turnover. However, newly generated Bim(+/-) naive CD4 T cells in middle-aged mice are not defective, indicating an additional requirement for their persistence in the periphery. These age-associated immune defects develop independently of the "aged" host environment and without extensive division, distinguishing them from classic "senescence." We suggest that the reduction of Bim levels with age in naive CD4 T cell is the initiating step that leads to increased cellular lifespan and development of age-associated functional defects.


The role of CAP3 in CD95 signaling: new insights into the mechanism of procaspase-8 activation.
Formation of the CD95 (APO-1/Fas) death inducing signaling complex (DISC) plays a central role in CD95 signaling. Previously, CD95 DISC composition was analyzed by two-dimensional gel electrophoresis and four major cytotoxicity-associated proteins (CAP1-4) were found. CAP1 and CAP2 were defined to be unmodified and phosphorylated FADD, respectively. CAP4 was identified as procaspase-8a. CAP3, however, has remained elusive. In this study, we demonstrate that CAP3 is an intermediate of procaspase-8 processing. CAP3 is generated within seconds of DISC formation and subsequently processed to the prodomain of procaspase-8a that is known as p26 (CAP5). These findings lead to new insights into the mechanism of procaspase-8 processing and apoptosis initiation.


Kinetics of hemopoietic recovery after peripheral blood stem cell transplantation: impact of stem cell purification and G-CSF.
We investigated the role of stem cell purification and G-CSF (early vs. delayed vs. no G-CSF) administration on hemopoietic recovery and supportive care requirements after stem cell transplantation. Thirty-two patients submitted to autologous CD34(+) peripheral blood stem cell transplantation (PBSCT) were studied, and data were compared to patients undergoing unfractionated peripheral blood stem cell transplantation (uPBSCT) matched for age, disease, and conditioning regimen. Except for PMN, hemopoietic recovery was significantly slower and supportive care requirements were significantly higher after CD34(+) PBSCT. Median time to PMN >0.5 x 10(9)/l was 13 days (range 9-27) and 13 d (range 9-23); reticulocytes (Ret) >1% was 14.5 d (range 12-34) and 12 d (range 10-27); high-fluorescence reticulocytes (HFR) >5% was 12 d (range 9-26) and 9 d (range 7-11); platelets >50 x 10(9)/l and >100 x 10(9)/l was 20 d (range 10-240), 12 d (range 9-60) and 33 d (range 15-720), 15 d (range 11-210). When the analysis was performed on subgroups of patients (early/delayed/no G-CSF), early G-CSF significantly promoted PMN recovery (>0.5 x 10(9)/l and >1.0 x 10(9)/l) compared to no G-CSF, without affecting RBCs or platelet recovery. Delayed G-CSF did not improve PMN recovery compared to patients not receiving G-CSF, did not result in a significant reduction of drug requirements, and had a negative impact on erythroid and platelet recovery. In conclusion, these preliminary data suggest that G-CSF is useful if given early after CD34(+) PBSCT. CD34(+) PBSCT may overall require a significant increase of resource utilization that should be outweighed by proven clinical benefit.


Intermittent access to sweet high-fat liquid induces increased palatability and motivation to consume in a rat model of binge consumption.
Binge eating disorders are characterized by discrete episodes of rapid and excessive food consumption. In rats, giving intermittent access to sweet fat food mimics this aspect of binge eating. These models typically employ solid food; however, the total amount consumed depends on motivation, palatability and satiety, which are difficult to dissociate with solid food. In contrast, lick microstructure analysis can be used to dissociate these parameters when the ingestant is a liquid. Therefore, we developed a binge model using a liquid emulsion composed of corn oil, heavy cream and sugar. We show that rats given intermittent access to this high-fat emulsion develop binge-like behavior comparable to that previously observed with solid high-fat food. One feature of this behavior was a gradual escalation in consumption across 2.5 weeks of intermittent access, which was not apparent in rats given lower-fat liquid on the same access schedule. Lick microstructure analysis suggests that this escalation was due at least in part to increases in both motivation to consume and palatability-driven consumption.


Trefoil factor 3 related to gastrointestinal failure in pediatric critical illness.
To determine the relationship between the serum concentration of trefoil factor 3 (TFF3) and gastrointestinal failure (GIF) in pediatric critical illness in order to provide knowledge for disease management. We enrolled 137 cases and divided them into three groups, including a control group (group A), critical illness without GIF (group B), and critical illness with GIF (group C). The serum TFF3 concentration was determined by ELISA and compared among the groups. Serum TFF3 concentrations measured before the occurrence of GIF in group C were significantly higher than in groups A and B (P<0.01). Under the conditions of GIF in group C, serum TFF3 concentration was significantly related to the gastrointestinal tract function score (r=-0.712). Cox's proportional hazards model analysis showed that the serum TFF3 concentrations at the time of occurrence of GIF, and 48hours later, could be used as prognostic factors in critically ill pediatric patients with GIF (r=1.443 and 1.872, respectively). TFF3 may play an important role in predicting GIF in pediatric critical illness and has a protective function in the mucosal repair process.


Female Infertility Caused by Mutations in the Oocyte-Specific Translational Repressor PATL2.
Infertility is a relatively common disorder of the reproductive system and remains unexplained in many cases. In vitro fertilization techniques have uncovered previously unrecognized infertility phenotypes, including oocyte maturation arrest, the molecular etiology of which remains largely unknown. We report two families affected by female-limited infertility caused by oocyte maturation failure. Positional mapping and whole-exome sequencing revealed two homozygous, likely deleterious variants in PATL2, each of which fully segregates with the phenotype within the respective family. PATL2 encodes a highly conserved oocyte-specific mRNP repressor of translation. Previous data have shown the strict requirement for PATL2 in oocyte-maturation in model organisms. Data gathered from the families in this study suggest that the role of PATL2 is conserved in humans and expand our knowledge of the factors that are necessary for female meiosis.


Assessment of the relationship between measures of disease severity, quality of life, and willingness to pay in asthma.
The primary objective was to evaluate the relationship between willingness-to-pay (WTP), quality-of-life (QOL), and disease-severity measures in patients with asthma. The hypothesis studied was that patients with asthma with more severe disease are willing to pay more for a hypothetical cure of asthma than those with less severe disease. DESIGN SETTING/PATIENTS AND PARTICIPANTS: One hundred patients with asthma were recruited from community pharmacies in Kentucky for 30-minute face-to-face interviews. Spirometry assessed objective disease severity in terms of pulmonary function, while a multiple choice question measured subjective disease severity. The Medical Outcomes Study 36-item Short Form (SF-36) health survey and Asthma Technology of Patient Experience (Asthma TyPE) measured quality of life. WTP was obtained via a dichotomous choice contingent valuation question. In this exploratory evaluation, WTP was significantly related to both objective disease severity (p = 0.02) and subjectively assessed disease severity (p = 0.01). For objective disease severity the mean monthly WTP was dollars US90 for mild asthma, dollars US131 for moderate asthma and dollars US331 for severe asthma and for subjective disease severity the mean monthly WTP was dollars US48 for mild asthma, dollars US166 for moderate asthma and dollars US241 for severe asthma. The results suggest that the WTP for a cure from asthma is related to both objective and subjective disease severity. These findings contribute to the case for construct validity of the dichotomous choice contingent valuation method in the healthcare sector.


Features of ribosome-peptidyl-tRNA interactions essential for tryptophan induction of tna operon expression.
Certain nascent peptide sequences, when within the ribosomal exit tunnel, can inhibit translation termination and/or peptide elongation. The 24 residue leader peptidyl-tRNA of the tna operon of E. coli, TnaC-tRNA(Pro), in the presence of excess tryptophan, resists cleavage at the tnaC stop codon. TnaC residue Trp12 is crucial for this inhibition. The approximate location of Trp12 in the exit tunnel was determined by crosslinking Lys11 of TnaC-tRNA(Pro) to nucleotide A750 of 23S rRNA. Methylation of nucleotide A788 of 23S rRNA was reduced by the presence of Trp12 in TnaC-tRNA(Pro), implying A788 displacement. Inserting an adenylate at position 751, or introducing the change U2609C in 23S rRNA or the change K90H or K90W in ribosomal protein L22, virtually eliminated tryptophan induction. These modified and mutated regions are mostly located near the putative site occupied by Trp12 of TnaC-tRNA(Pro). These findings identify features of the ribosomal exit tunnel essential for tna operon induction.


Intramural ectopic pregnancy: treatment using uterine artery embolization.
Herein is described the case of a 28-year-old woman in whom uterine artery embolization (UAE) was performed to treat intramural ectopic pregnancy. The intramural ectopic pregnancy was diagnosed at magnetic resonance imaging, which showed a gestational sac surrounded completely by myometrium. The UAE procedure was uncomplicated, with satisfactory results. Intramural ectopic pregnancy may be treated using UAE, which aids in maintaining fertility.


Tolosa-Hunt syndrome.
Ten cases of painful ophthalmoplegia are reported. In all cases pain marked the onset of the disease; the condition was mostly unilateral. Recurrence and dramatic response to steroid therapy were more constant features than angiographic findings which may be completely normal. CAT permitted us to eliminate a tumor of the cavernous sinus in 7 cases, but in one case, which was operated, an aggravation followed surgery. Despite complete investigations of all patients, some questions remain unanswered. Is it an inflammatory or an allergic inflammatory process? (And the presence of antinuclear factor in an only case does not permit it to respond.) Why is the process confined to the superior orbital fissure? Mathew and Chandy tried to find a similarity between this syndrome and Bell's palsy although the 2 syndromes have not been shown to coexist. Is the Tolosa-Hunt syndrome comparable to the pseudotumor of the orbit? Although the dura mater is inserted on the border of the sphenoidal cleft, some patients may altern the 2 syndromes.


Fluorescence polarization study of tertiary structure of DNA within bacteriophage lambda.
The fluorescence polarization of acridine orange-stained, oriented lambda phages was measured. The parameters of DNA packing within the phage head cos2 theta and cos4 theta were calculated (theta, angle between the direction of a small segment of DNA and the phage axis). It is shown that simple models of lambda phage DNA tertiary structure are not consistent with calculated values. A new model is proposed.


Castleman's disease arising from the accessory spleen: ultrasonography, computed tomography, and magnetic resonance imaging findings.
Castleman's disease is a rare lymphoproliferative disorder of unknown etiology. To our knowledge, Castleman's disease arising from the accessory spleen has not been reported in the literature. We report the case of localized Castleman's disease arising from the accessory spleen in a 34-year-old woman and discuss the characteristic findings of ultrasonography (US), computed tomography (CT), and magnetic resonance (MR) imaging.


Cardiac reoperation by Carpentier bicaval femoral venous cannula: GATA experience.
Division of the sternum is primarily a blind procedure in reoperation and carries an increased risk of injury for major cardiac structures in the presence of adhesions between the posterior table and the heart. Two hundred patients were randomly divided into two groups. Cardiopulmonary bypass was established through the femoral artery and vein in group 1 (n = 100) patients before sternal reentry. Carpentier dual-stage femoral venous return cannula was used in all group 1 patients. Cardiopulmonary bypass was performed after sternal reentry in group 2 (n = 100) patients. Six severe cardiac injuries developed in group 2. Cardiopulmonary bypass time was 93 +/- 9 minutes in group 1 and 71 +/- 11 minutes in group 2 (p = 0.011), and the operation time was 155 +/- 23 minutes in group 1 and 185 +/- 32 minutes in group 2 (p = 0.024). Inotropic therapy was required in 52 patients in group 1 and 76 patients in group 2 (p = 0.032). Average chest drainage was 450 +/- 135 mL in group 1 and 850 +/- 250 mL in group 2 (p < 0.001). Average fresh whole blood transfusion was 3.3 +/- 1.2 U in group 1 and 5.8 +/- 0.9 U in group 2 (p = 0.033). Average intensive care unit stay was 2.2 +/- 1.3 days in group 1 and 4.5 +/- 2.3 days in group 2 (p = 0.025). Average hospital stay was 7.3 +/- 2.4 days in group 1 and 9.1 +/- 3.1 days for group 2 (p = 0.011). Cardiopulmonary bypass by bicaval Carpentier femoral venous cannula before resternotomy not only allows adequate cardiopulmonary bypass flow but also significantly reduces the risk of cardiac injury and catastrophic hemorrhage and allows safe reopening. Although this procedure increases cardiopulmonary bypass time, the operation time, bleeding, and blood transfusion requirement are significantly reduced.


Revision hip arthroscopic surgery: outcome at three years.
This study describes the medium-term results of revision hip arthroscopy. Patients with persistent hip pain and a positive impingement sign were considered for revision surgery after the exclusion of other causes of groin pain. Seventy-four consecutive patients were prospectively assessed using the modified Harris hip score for a period of 3 years after surgery. Of the 74 patients, 11 had inadequate follow-up data; thus, a total of 63 patients were qualified for the study. The mean age at index surgery was 37 years, comprising 27 males and 36 females. Revision surgery was performed at a mean of 3 years from index surgery. Chondral lesion associated with labral re-injury was the most common finding at revision arthroscopy. In contrast to other authors, however, only 31 % of our patients underwent revision for persistent femoroacetabular impingement. The mean pre-operative mHHS for all 63 patients was 54 (SD 14.5). The mean post-operative mHHS was 53 (SD 14.9) at 6 weeks, 62 (SD 17.5) at 6 months, 63 (SD 16.5) at 1 year, 64 (SD 16.5) at 2 years and 59 (SD 16.5) at 3 years (p = n.s., 0.02, 0.045, 0.039 and n.s., respectively). Revision arthroscopy results in improvement in outcome in the first 3 years after revision surgery with a success rate of 63.4 % at 1 year, falling to 55.6 % by 3 years.


Australian dermatologists' perspective on skin of colour: Results of a national survey.
This study documents the perspectives of Australian dermatologists on the adequacy of teaching and training in skin of colour (SOC), and their confidence in diagnosing and treating common medical, surgical and cosmetic issues in SOC and to gauge their desire for further training in this area. Surveys were distributed to Australasian Dermatologists during their annual scientific meeting in Melbourne, Australia in 2014. Completed surveys from dermatologists nationwide were collected and evaluated. Altogether 270 surveys were distributed. In total, 140 surveys were completed and returned. Four surveys were excluded as they were completed by dermatologists who were not practicing in Australia. Thus, 136 surveys were deemed appropriate for analysis. While 75% of participants were confident in managing common medical issues in SOC 85% were not confident in managing common cosmetic issues in SOC and 75% were not confident performing procedures on SOC. Over 80% stated they would have liked more teaching in SOC during their training and over 50% of those surveyed believe they had enough time to undertake further training in this area. We propose here the first analysis of issues relating to SOC dermatology among Australian dermatologists in the context of the changing patient demographic in the country. The findings of this survey clearly demonstrate there is a need and desire for more training in medical, cosmetic and procedural aspects of SOC dermatology and that most of the Australian dermatologists surveyed have the desire and time to undertake such training.


Transforming waste disposals into building materials to investigate energy savings and carbon emission mitigation potential.
This work aims to enhance the energy cost-saving potential of conventional mud-brick by including natural waste materials as insulators. The solid waste materials considered for mud bricks are rice husk, sawdust, coir pith, and fly ash. This work investigates the structural and thermoeconomic performance of four types of insulated mud bricks and three roofs of ferrocement, clay, and ceramic materials. The thermal properties of walls and roofs were measured as per ASTM D 5334 standards. The utilization of solid waste in mud bricks enhanced the structural properties and air-conditioning cost-saving potential of the mud bricks. The results also showed the mitigation of greenhouse gas emissions with the usage of insulated bricks for buildings. The rice husk mud-brick wall showed better results of higher time lag, lower decrement factor, higher air-conditioning cost-savings, acceptable payback periods, and higher annual carbon mitigation values of 11.11 h, 0.24, 1.74 $/m2, 1.17 years, and 33.35 kg/kWh, respectively, among all the studied multilayer walls. Among the roofs, clay tile roof showed a lower decrement factor (0.989), higher time lag (0.73 h), higher air-conditioning cost-savings (2.58 $/m2), lower payback periods (0.61 years), and higher annual carbon mitigation (21.73 kg/kWh). The results are in designing eco-friendly and energy-efficient envelopes for buildings.


Dose response of thyrotropin-releasing hormone on pulmonary maturation in corticosteroid-treated preterm rabbits.
The dose-response effect of thyrotropin-releasing hormone in enhancing pulmonary maturation was investigated with six dosing regimens. Pregnant does received thyrotropin-releasing hormone (5, 10, or 50 micrograms/kg every 12 hours for four doses or one dose of 20 micrograms/kg) in conjunction with betamethasone beginning on day 25 of gestation, with betamethasone alone or saline solution used as comparison treatment groups. Half of the newborn rabbits received supplemental surfactant therapy after delivery on day 27, and all were ventilated on a ventilator plethysmography system for 30 minutes. There were no differences among the four thyrotropin-releasing hormone doses in surfactant pool sizes, compliances, or proteins leak into or out of the air spaces. The groups that received multiple doses of thyrotropin-releasing hormone had significantly higher perinatal loss rates than the single-dose group. The lungs of the group treated with thyrotropin-releasing hormone plus steroid and the rabbits treated only with steroid were more compliant than the controls without surfactant therapy, and showed significant improvements in protein leak. The addition of thyrotropin-releasing hormone to betamethasone improved several of the protein leak measurements compared with use of betamethasone alone. These results question the necessity of multiple doses of thyrotropin-releasing hormone to induce pulmonary maturation, especially when the higher perinatal mortality and the theoretical long-term effects of fetal hyperthyroidism on thyroid axis function are considered.


Polymorphisms and expression analysis of SOX-6 in relation to porcine growth, carcass, and meat quality traits.
The aim of the study was to investigate single nucleotide polymorphisms (SNPs) and expression of SOX-6 to support its candidacy for growth, carcass, and meat quality traits in pigs. The first SNP, rs81358375, was associated with pH 45 min post mortem in loin (pH1L), the thickness of backfat and side fat, and carcass length in Pietrain (Pi) population, and related with backfat thickness and daily gain in Duroc × Pietrain F2 (DuPi) population. The other SNP, rs321666676, was associated with meat colour in Pi population. In DuPi population, the protein, not mRNA, level of SOX-6 in high pH1L pigs was significantly less abundant compared with low pH1L pigs, where microRNAs targeting SOX-6 were also differently regulated. This paper shows that SOX-6 could be a potential candidate gene for porcine growth, carcass, and meat quality traits based on genetic association and gene expression.


Characteristics and Outcomes of Renal Transplant Recipients with Hemolytic Uremic Syndrome in the United States.
Hemolytic uremic syndrome (HUS) accounts for <1% of renal transplants in the US. There are limited data on the characteristics and outcomes of HUS in pediatric and adult kidney transplant recipients in the US. This study included all renal transplant recipients identified with HUS (N=1,233) as a cause of end-stage renal disease between 1987 and 2013 using the UNOS/OPTN database. The cohort was divided into two age groups: pediatric (N=447) and adult (N=786). Main outcomes were acute rejection rate at one-year, allograft and patient survival, and recurrence of HUS post-transplant. Both age groups were then compared with a propensity score (1:2 ratio) matched control group with an alternative primary kidney disease (non-HUS cohort: pediatric [N= 829] and adult [N=1,547]). In pediatric cohort, when compared to the PS matched controls, acute rejection, death censored allograft and patient survival was similar in the HUS group. However, in the adult cohort, the graft and patient survivals were significantly worse in the HUS group. HUS was associated with allograft loss (HR=1.40, 95%CI 1.14-1.71) in adult recipients. Patients with HUS recurrence had significantly lower allograft and patient survival rates compared to the non-recurrent group in both age groups. Acute rejection was one of the major predictor of HUS recurrence in adults (OR=2.64, 95%CI 1.25-5.60). Calcineurin inhibitors (CNI) were not associated HUS recurrence in both age groups. Pediatric HUS-patients, unlike adult recipients, have similar outcomes compared to the PS matched controls. Recurrence of HUS is associated with poor allograft and patient survival in pediatric and adult patients. Use of CNIs seem to be safe as a part of maintenance immunosuppression post-transplantation. A comprehensive national registry is urgently needed.


The safety and efficacy between remimazolam and propofol in intravenous anesthesia of endoscopy operation: a systematic review and meta-analysis.
Propofol is the most widely used intravenous anesthetic in endoscopic surgery, but is associated with several adverse reactions. Public research has shown that remimazolam, a safe general anesthetic, is increasingly being used as a substitute for propofol in clinical operations. Our meta-analysis aimed to analyze whether the adverse reaction rate of remimazolam in endoscopic surgery is acceptable and whether the surgical success rate is not lower than that of propofol. This meta-analysis examined the adverse events and efficacy of remimazolam vs. propofol during endoscopic surgery. MEDLINE, Embase, ClinicalTrials.gov, and Google Scholar were comprehensively searched. Seven studies comparing remimazolam and propofol were included in our meta-analysis. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and Cochrane manual were used to assess the quality of the results published in all included studies to ensure that our meta-analysis results are reliable and worthwhile. Compared to propofol, the use of remimazolam reduced postoperative injection pain [relative risk (RR)=0.06, 95% confidence interval (CI): 0.03-0.12, P <0.00001], postoperative hypotension (RR=0.45, 95% CI: 0.28-0.73, P =0.001), and postoperative respiratory depression (RR=0.20, 95% CI: 0.08-0.47, P =0.0002); however, it also slightly reduced the success rate of the operation [risk difference (RD)=-0.02, 95% CI: -0.04 to -0.01, P =0.0007]. There were no significant differences in the occurrence of bradycardia symptoms after the operation (RD=-0.01, 95% CI: -0.03 to 0.01, P =0.35), recovery time after the operation [standardized mean difference (SMD)=0.68, 95% CI: -0.43 to 1.80, P =0.23] or discharge time (SMD=0.17, 95% CI: -0.58 to 0.23, P =0.41). We also performed a subgroup analysis of each corresponding outcome. Our analysis showed that remimazolam may be a safer shock option than propofol for endoscopic surgery. However, further research is required to determine their utility.


Serum bioactive and immunoreactive follicle-stimulating hormone in oligozoospermic and azoospermic men: application of a modified granulosa cell bioassay.
Serum follicle-stimulating hormone (FSH) levels measured by radioimmunoassay (RIA) usually correlate well with the rate of spermatogenesis. However, in certain cases this correlation does not exist. The purpose of this study was to establish a reliable bioassay of FSH for the andrological clinic. Follicle-stimulating hormone was measured by both standard RIA and bioassay in 98 men subgrouped into normospermic, oligospermic, and azoospermic. Bioactivity of FSH was determined using in vitro cultures of granulosa cells utilizing progesterone measurements for assessing FSH activity. Results of FSH levels obtained by both methods correlated well (r = 0.55, P less than 0.01) within themselves, and both correlated negatively and significantly with sperm concentration. The ratio between bioactivity and immunoreactivity of FSH did not correlate with sperm density. Thus, the decrease in sperm concentration and other sperm variables resulting from a germinal epithelial dysfunction was not mediated or associated with low biological activity of FSH. The application of this method can be of clinical value in cases where a discrepancy is found between serum RIA-FSH levels and sperm quality.


The usefulness of a checklist approach-based confirmation scheme in identifying unreliable COVID-19-related health information: a case study in Japan.
Consumers are increasingly able to easily access health information online about food products. However, consumers have difficulty identifying reliable health information from diverse sources along with information about the coronavirus disease (COVID-19) pandemic because the inundation of information (both true and false) overwhelm consumers. We investigated the usefulness of a checklist confirmation scheme for identifying unreliable COVID-19-related health information. Data were collected from June 30-July 1, 2021. First, we measured 700 participants' baseline health literacy levels by having them read unreliable health information about the efficacy of green tea intake in preventing COVID-19 based on the results of animal experimentation. Second, participants read an explanation with a five-step flowchart of how to identify reliable health information. Thereafter, we remeasured participants' health literacy levels. To identify the factors hindering the effect of the confirmation scheme, a logistic regression analysis was performed to calculate odds ratios (ORs) and 95% confidence intervals (CIs). Overall, 77.9% (293/376) of those with low health literacy levels at baseline still had low literacy after the intervention. The factor that hindered the confirmation scheme's usefulness was benefit perceptions of food ingredients (OR: 0.493; 95% CI: 0.252-0.966). Consumers with higher benefit perceptions of a target product faced more difficulties using the confirmation scheme effectively. Therefore, the most effective strategies involve filtering information at the organizational level rather than the individual level, which should help consumers correctly identify misinformation concerning food and health and promote accurate decision-making.


An overview of current knowledge concerning the inventory and sources of plutonium in the China Seas.
This study reviews the current understanding of the inventory and sources of plutonium (Pu) in the marine environment adjacent to China. The 239+240Pu inventory in the China Seas was found to have large spatial variations. The quantity in sediments decreases away from the shore, generally tracing the sedimentation rate distribution. High 239+240Pu inventories indicated that Pu in the water column was easily scavenged since Pu has a high particle affinity. Indeed, substantially higher 240Pu/239Pu atom ratios were observed in the sediment and seawater of the China Seas than are found in global fallout. We thus clarified that Pu sources in the China Seas were from both global fallout and the Pacific Proving Grounds (PPG) in the Pacific Marshall Islands. Plutonium from the latter source is transported into the China Seas through the North Equatorial Current (NEC) and Kuroshio. Using a two end-member mixing model, we revealed that the contribution of Pu from the PPG accounts for over 40% of the Pu in the East China Sea (ECS) and South China Sea (SCS), and less than 20% of the Pu in the Yellow Sea (YS). The distributions and isotopic composition of Pu in the China Seas indicate strong scavenging of Pu in the ECS and high Pu accumulation in the SCS. This information on the inventory and isotopic composition of Pu helps to establish a background for the future study of Pu in the China Seas.


Planning study for available dose of hypoxic tumor volume using fluorine-18-labeled fluoromisonidazole positron emission tomography for treatment of the head and neck cancer.
To investigate the feasibility of fluorine-18-labeled fluoromisonidazole positron emission tomography/computed tomography ((18)F-FMISO PET/CT)-guided intensity-modulated radiotherapy (IMRT) in dose escalation to attack the hypoxic volume of a tumor mass without increasing the normal tissue dose in head and neck cancer patients. Eight consecutive head and neck cancer patients underwent (18)F-FMISO PET/CT simulation. Hypoxic tumor volume (HTV) was defined using a tumor-to-cerebellum ratio (T/C) of 1.3 as the threshold for (18)F-FMISO PET/CT. Dose-escalation plans for treating HTVs using (18)F-FMISO PET/CT-guided IMRT were performed for these patients. The standard plan was 72Gy to the gross tumor volume (GTV) administered as 30 daily fractions of 2.4Gy. In biologically optimized IMRT plans, the daily dose to the HTV ranged from 2.6 to 3.6Gy. Dose-volume histograms (DVHs) were generated as part of each plan, and the results of planning were analyzed. Dose-escalation IMRT plans, delivering 30 daily doses of 2.6Gy (total of 78Gy) to the HTVs without increases in normal tissue doses, were feasible for six patients. Further acceptable dose escalation on HTV depended primarily on the primary tumor site and the extent of disease. It was possible to dose escalate the HTV radiation to 78Gy in six of eight head and neck cancer patients using (18)F-FMISO PET/CT-guided IMRT.


Current Concepts in Nodal Peripheral T-Cell Lymphomas.
This review summarizes the current understanding of mature T-cell neoplasms predominantly involving lymph nodes, including ALK-positive and ALK-negative anaplastic large cell lymphomas, nodal T-follicular helper cell lymphoma, Epstein-Barr virus-positive nodal T/NK-cell lymphoma, and peripheral T-cell lymphoma (PTCL), not otherwise specified. These PTCLs are clinically, pathologically, and genetically heterogeneous, and the diagnosis is made by a combination of clinical information, morphology, immunophenotype, viral positivity, and genetic abnormalities. This review summarizes the pathologic features of common nodal PTCLs, highlighting updates in the fifth edition of the World Health Organization classification and the 2022 International Consensus Classification.


Patterned Interference Radiation Force for Transcranial Neuromodulation.
Compared with the conventional method of transcranial focused ultrasound stimulation using a single transducer or a focused beam, the compression and tensile forces are generated from the high-pressure gradient of a standing wave that can generate increased stimulation. We experimentally verified a neuromodulation system using patterned interference radiation force (PIRF) and propose a method for obtaining the magnitude of the radiation force, which is considered the main factor influencing ultrasound neuromodulation. The radiation forces generated using a single focused transducer and a standing wave created via two focused transducers were compared using simulations. Radiation force was calculated based on the relationship between the acoustic pressure, radiation force and time-averaged second-order pressure obtained using an acoustic streaming simulation. The presence of the radiation force was verified by measuring the time-averaged second-order pressure generated due to the radiation force, by using a glass tube.


Activation timecourse of ventral visual stream object-recognition areas: high density electrical mapping of perceptual closure processes.
Object recognition is achieved even in circumstances when only partial information is available to the observer. Perceptual closure processes are essential in enabling such recognitions to occur. We presented successively less fragmented images while recording high-density event-related potentials (ERPs), which permitted us to monitor brain activity during the perceptual closure processes leading up to object recognition. We reveal a bilateral ERP component (N(cl)) that tracks these processes (onsets approximately 230 msec, maximal at approximately 290 msec). Scalp-current density mapping of the N(cl) revealed bilateral occipito-temporal scalp foci, which are consistent with generators in the human ventral visual stream, and specifically the lateral-occipital or LO complex as defined by hemodynamic studies of object recognition.


Effects of Aerobic Exercise Training on the Growth, Swimming Performance, Antipredation Ability and Immune Parameters of Juvenile Rock Carp (Procypris rabaudi).
Many studies have found that aerobic exercise training at a moderate water velocity can improve the growth, swimming performance and survival rate of fish. To investigate the effects of aerobic exercise training on the growth, swimming performance, antipredation ability and immune parameters of rock carp, juveniles were placed in training channels with different water velocities (i.e., 3 cm s-1, 1 (body length s-1) bl s-1, 2 bl s-1 and 4 bl s-1) for 6 weeks. Then, the specific growth rate, critical swimming speed (Ucrit) and its metabolism, constant acceleration speed (Ucat), survival rate under predation, spleen index, lysozyme (LZM) activity and immunoglobulin (IgM) level were measured. Training showed no significant effect on the length-specific growth rate, weight-specific growth rate, Ucrit, maximum metabolic rate (MMR), metabolic scope (MS), Ucat or spleen index. The resting metabolic rates (RMRs) of the 2 bl s-1 and 4 bl s-1 training groups were significantly higher than those of the control group and 1 bl s-1 training group. The survival rate of the 1 bl s-1 training group in the presence of predators was significantly higher than that of the control group but significantly lower than those of the 2 bl s-1 and 4 bl s-1 training groups. The LZM activity of the 4 bl s-1 training group was significantly higher than that of the control group. The IgM level of the 2 bl s-1 training group was significantly higher than that of the control group. These data indicate that aerobic exercise training does not improve the growth and swimming performance of juvenile rock carp but can improve their antipredation ability and immunologic function.


[Extrarenal changes in the isotopic nephrogram of surgical patients with abdominal pathology and the potentials for an erroneous interpretation].
Eighty-three patients with surgical abdominal pathology were included in the study. On the isotopic nephrogram they all had bilateral symmetric and analogous pathologic changes with varying degree of severity. The most common cause of renal function changes in patients with abdominal pathology was the reduced intravascular volume or vascular capacity changes, registered on the isotopic nephrogram with characteristic symmetrical pathologic curves. The sharp renal perfusion decrease, leading to decrease of glomerular filtration and diminution of diuresis explains the bilateral changes in the isotopic nephrogram which most frequently resemble obturation. The curves returned to normal 1 to 2 weeks after the physiologic state of the patients was stabilized, indicating extrarenal origin of the registered changes in the isotopic nephrogram. The latter should carefully be interpreted, in view of the possible influence of it of extrarenal factors.


Acute posterior multifocal placoid pigment epitheliopathy and late-onset meningo-encephalitis.
A steroid-sensitive meningo-encephalopathy developed in a healthy young woman 5 1/2 years after the occurrence of acute posterior multifocal placoid pigment epitheliopathy (APMPPE). The association of APMPPE with systemic and neurologic inflammatory disorders has been well documented, but to the knowledge of the authors, this is the first report of an APMPPE patient in which there was delayed onset of the meningo-encephalopathy. The association with dermal vasculitis, nephropathy, meningo-encephalitis, cerebral vasculitis, and thyroiditis suggests that APMPPE may be one manifestation of a diffuse systemic inflammatory condition.


Use of a Non-cross-linked Xenograft (Xenform) in Surgical Treatment of Peyronie's Disease.
To evaluate the effectiveness in Peyronie's disease surgical treatment using Xenform, a non-cross-linked graft derived from dermal bovine tissue, to close the defect obtained after plaque incision, without penile prosthesis implant. A further objective is to evaluate the satisfaction of patients. We treated with plaque incision 28 patients with a stable penile curvature ≥60° hindering penetration and with erectile function conserved. International Index of Erectile Function-15 and a not-validated questionnaire constituted of 7 questions about their satisfaction were administered after 1 year of follow-up. Furthermore, specific questions were relative about penile straightening, penile postoperative length, glandular sensitivity, and feeling palpability. Graft is resulted compatible with albugineal features, like thickness, consistency, and elasticity; it is waterproof, allowing the visualization of complete correction of the curvature after the suture. No severe complications were observed except 1 hematoma requiring surgical revision. Sixteen patients were seen after at least 1 year of follow-up. Curvature improvement was obtained in all cases, with the complete straightening in 75%; we did not observe any retraction of the graft and any recurrence on the curvature. Significant reduced glans sensibility and erectile dysfunction were the more frequent postoperative complications, resulting in 43.8% and 25%, respectively. All patients are satisfied with the straightening. Only 2 patients are dissatisfied about the overall result. Plaque incision corporoplasty with Xenform graft is an effective and safe surgical treatment. Xenform is a secure and a reliable albugineal substitute, comparable to other heterologous graft. We have not observed any retraction. Patient's satisfaction is linked to the treatment result and to sexual life.


Diazo probe-based chemical isotope labeling assisted liquid chromatography-tandem mass spectrometry analysis for sensitive determination of amino acids in biofluids.
Amino acids are important biomolecules and contribute to essential biological processes. Liquid chromatography tandem mass spectrometry (LC-MS) now is a powerful tool for the analysis of amino acid metabolites; however, the structural similarity and polarity of amino acids can lead to the poor chromatographic retention and low detection sensitivities. In this study, we used a pair of light and heavy isotopomers of diazo probes, d0/d5-2-(diazomethyl)-N-methyl-N-phenyl-benzamide (2-DMBA/d5 -2-DMBA) to label amino acids. The paired MS probes of 2-DMBA and d5 -2-DMBA carry diazo groups that can efficiently and specifically react with the carboxyl group on free amino acid metabolites under mild conditions. Benefiting from the transfer of the 2-DMBA/d5 -2-DMBA to carboxyl group on amino acids, the ionization efficiencies of amino acids presented great enhancement during LC-MS analysis. The results suggested that the detection sensitivities of 17 amino acids increased by 9-133-fold upon 2-DMBA labeling, and the obtained limits of detection (LODs) of amino acids on-column ranged from 0.011 fmol-0.057 fmol. With the application of the developed method, we successfully achieved the sensitive and accurate detection of the 17 amino acids in microliter level of serum sample. Moreover, the contents of most amino acids were different in the serum from normal and B16F10-tumour mice, demonstrating that endogenous amino acids may play important roles in the regulation of tumors development. This developed method of chemical labeling of amino acids with diazo probes assisted LC-MS analysis provides a potentially valuable tool to investigate the relationships between amino acids metabolism and diseases.


Order in phospholipid Langmuir-Blodgett layers and the effect of the electrical potential of the substrate.
The ordering in dipalmitoylphosphatidylcholine (DPPC) Langmuir-Blodgett monolayers and bilayers on a semiconducting indium tin oxide (ITO) surface has been investigated at the equilibrium potential of the interface and at various externally applied potentials. Second- and fourth-rank order parameters of a diphenylhexatriene (DPH) containing phospholipid probe were derived from total internal reflection fluorescence measurements, and orientation distributions were calculated using the maximum-entropy method. Generally, bimodal orientation distributions were obtained, suggesting that only part of the probes is aligned with the DPPC molecules. The effect of applied potentials is small for DPPC layers on unmodified (hydrophilic) ITO; with decreasing potential the ordering changes slightly to more random distributions, possibly because of the onset of hydrogen evolution at the substrate surface. For monolayers on hydrophobized ITO, where the phospholipids are initially with their tails directed toward the surface, the changes are more significant. At the highest positive potential applied, the derived order parameters indicate that nearly all probes are flat on the surface. This can be understood as a result of enhanced competition between headgroups and tails for access to the surface as it becomes more polarized. On unmodified ITO the electrochemistry of Fe(CN)6(3-/4-) and Ru(bipyridyl)3(2+/3+) is hardly hindered by the presence of DPPC monolayers or bilayers. On hydrophobized ITO a DPPC monolayer enhances the redox reactions.


HSF1 and Its Role in Huntington's Disease Pathology.
Heat shock factor 1 (HSF1) is the master transcriptional regulator of the heat shock response (HSR) in mammalian cells and is a critical element in maintaining protein homeostasis. HSF1 functions at the center of many physiological processes like embryogenesis, metabolism, immune response, aging, cancer, and neurodegeneration. However, the mechanisms that allow HSF1 to control these different biological and pathophysiological processes are not fully understood. This review focuses on Huntington's disease (HD), a neurodegenerative disease characterized by severe protein aggregation of the huntingtin (HTT) protein. The aggregation of HTT, in turn, leads to a halt in the function of HSF1. Understanding the pathways that regulate HSF1 in different contexts like HD may hold the key to understanding the pathomechanisms underlying other proteinopathies. We provide the most current information on HSF1 structure, function, and regulation, emphasizing HD, and discussing its potential as a biological target for therapy. We performed PubMed search to find established and recent reports in HSF1, heat shock proteins (Hsp), HD, Hsp inhibitors, HSF1 activators, and HSF1 in aging, inflammation, cancer, brain development, mitochondria, synaptic plasticity, polyglutamine (polyQ) diseases, and HD. Research and review articles that described the mechanisms of action of HSF1 were selected based on terms used in PubMed search. HSF1 plays a crucial role in the progression of HD and other protein-misfolding related neurodegenerative diseases. Different animal models of HD, as well as postmortem brains of patients with HD, reveal a connection between the levels of HSF1 and HSF1 dysfunction to mutant HTT (mHTT)-induced toxicity and protein aggregation, dysregulation of the ubiquitin-proteasome system (UPS), oxidative stress, mitochondrial dysfunction, and disruption of the structural and functional integrity of synaptic connections, which eventually leads to neuronal loss. These features are shared with other neurodegenerative diseases (NDs). Currently, several inhibitors against negative regulators of HSF1, as well as HSF1 activators, are developed and hold promise to prevent neurodegeneration in HD and other NDs. Understanding the role of HSF1 during protein aggregation and neurodegeneration in HD may help to develop therapeutic strategies that could be effective across different NDs.


Intensive virtual reality-based training for upper limb motor function in chronic stroke: a feasibility study using a single case experimental design and fMRI.
To evaluate feasibility and neurophysiological changes after virtual reality (VR)-based training of upper limb (UL) movements. Single-case A-B-A-design with two male stroke patients (P1:67 y and 50 y, 3.5 and 3 y after onset) with UL motor impairments, 45-min therapy sessions 5×/week over 4 weeks. Patients facing screen, used bimanual data gloves to control virtual arms. Three applications trained bimanual reaching, grasping, hand opening. Assessments during 2-week baseline, weekly during intervention, at 3-month follow-up (FU): Goal Attainment Scale (GAS), Chedoke Arm and Hand Activity Inventory (CAHAI), Chedoke-McMaster Stroke Assessment (CMSA), Extended Barthel Index (EBI), Motor Activity Log (MAL). Functional magnetic resonance imaging scans (FMRI) before, immediately after treatment and at FU. P1 executed 5478 grasps (paretic arm). Improvements in CAHAI (+4) were maintained at FU. GAS changed to +1 post-test and +2 at FU. P2 executed 9835 grasps (paretic arm). CAHAI improvements (+13) were maintained at FU. GAS scores changed to -1 post-test and +1 at FU. MAL scores changed from 3.7 at pre-test to 5.5 post-test and 3.3 at FU. The VR-based intervention was feasible, safe, and intense. Adjustable application settings maintained training challenge and patient motivation. ADL-relevant UL functional improvements persisted at FU and were related to changed cortical activation patterns. Implications for Rehabilitation YouGrabber trains uni- and bimanual upper motor function. Its application is feasible, safe, and intense. The control of the virtual arms can be done in three main ways: (a) normal (b) virtual mirror therapy, or (c) virtual following. The mirroring feature provides an illusion of affected limb movements during the period when the affected upper limb (UL) is resting. The YouGrabber training led to ADL-relevant UL functional improvements that were still assessable 12 weeks after intervention finalization and were related to changed cortical activation patterns.


Negative Bystander Behavior in Bullying Dynamics: Assessing the Impact of Social Capital Deprivation and Anti-social Capital.
Bystanders witness bullying, but are not directly involved as a bully or victim; however, they often engage in negative bystander behavior. This study examines how social capital deprivation and anti-social capital are associated with the likelihood of engaging in negative bystander behavior in a sample (N = 5752) of racially/ethnically diverse rural youth. Data were collected using an online, youth self-report; the current study uses cross sectional data. Following multiple imputation, a binary logistic regression with robust standard errors was run. Results partially supported the hypothesis and indicated that social capital deprivation in the form of peer pressure and verbal victimization and anti-social capital in the form of delinquent friends, bullying perpetration, verbal perpetration, and physical perpetration were significantly associated with an increased likelihood of engaging in negative bystander behavior. Findings highlight the importance of establishing sources of positive social support for disenfranchised youth.


Intensive fattening of beef cattle by stall feeding on the Lilongwe Plain, Malawi. II. Utilisation of crop residues, crop by-products and leucaena.
Experiments were conducted over three dry seasons to investigate the value for fattening beef cattle, of crop residues (maize stover, groundnut haulm) and madeya (maize bran) with varying levels of dried leucaena leaf or cottonseed cake. The inclusion of groundnut haulm in the roughage increased animal performance when madeya was restricted. Increasing the protein content of the madeya supplement but restricting the quantity of madeya fed did not influence liveweight gain although the efficiency of concentrate conversion was enhanced. Restricting the amount of maize stover and feeding madeya to appetite had no significant effect on liveweight gain, but the inclusion of leucaena up to a level of 12 per cent crude protein improved animal performance. There were no differences between cottonseed cake or leucaena when fed with madeya at the same levels of crude protein.


Two new C21 steroidal glycosides isolated from Cynanchum komarovii.
The present study was designed to further investigate the C21 steroidal glycosides in Cynanchum plants. Two new steroidal glycosides based on a 13, 14:14, 15-disecopregnane-type aglycone, komaroside P (1) and komaroside Q (2), together with three known compounds (3-5) were isolated from the whole herbs of Cynanchum komarovii. The aglycones of compounds 1 and 2 were two new disecopregnane. Their structures were elucidated on the basis of 1D, 2D NMR spectroscopic data and acid hydrolysis. All the compounds (1-5) showed potent inhibitory activities against human leukemia cell lines (HL-60) with IC50 values ranging from 16.6 to 26.3 μmol·L-1, compared to the positive control 5-fluorouracil (6.4 μmol·L-1).


Ethionine in the analysis of the possible separate roles of methionine and choline deficiencies in carcinogenesis.
The importance of ethionine, the ethyl analogue of methionine, as a metabolic probe to study the possible roles of methionine and choline in liver carcinogenesis has been briefly reviewed. Ethionine-induced liver carcinogenesis is similar in many aspects, including initiation, promotion, and progression, to carcinogenesis with other agents. However, the special role of methionine in preventing virtually all metabolic and pathologic effects of ethionine, including liver cancer, places ethionine in a special position. On the basis of these observations and our current knowledge about choline deficiency in the genesis of liver cancer, we proposed that choline and methionine play separate but overlapping roles in the initiation and promotion of liver carcinogenesis.


Standardized Care Pathways as a Means to Improve Patient Safety.
The literature overwhelmingly supports standardized, evidence-based care to improve patient safety in the surgical setting, including checklists and enhanced recovery programs. Although local culture, patient complexity, and hospital setting can represent barriers to implanting standardized practices, they can be overcome with thoughtful strategies.


Prevention of thromboembolic disease by external pneumatic compression in patients undergoing total hip arthroplasty.
A prospective study was undertaken in order to test the efficacy of intermittent calf compression for prevention of thromboembolism in patients undergoing total hip arthroplasty. The patients were studied pre- and postoperatively by routine Doppler ultrasound examinations in addition to clinical assessment. Statistically significant evidence substantiates the view that intermittent calf compression decreased the incidence of thr thromboembolic problem.


Sonography: an underutilized diagnostic tool in the assessment of metastatic groin nodes.
To assess the diagnostic value of gray-scale sonography in differentiating benign reactive nodes from metastatic nodes in the groin. Twenty-seven patients with carcinoma of the penis, 3 patients with cutaneous melanoma, and 2 patients with squamous cell carcinoma of the lower extremity with inguinal lymphadenopathy were studied. A total of 122 nodes in the groin were examined sonographically using a 7.5-MHz probe. Sonographic features studied included lymph node size, longitudinal/transverse diameter (L/T) ratio, presence or absence of echogenic hilum, and appearance of the cortex. Pathologic confirmation was obtained via lymph node biopsy in 14 patients and groin dissection in 18 patients. Sonographic features were correlated with final pathology. Forty-four of 122 nodes were metastatic and 78 were benign. L/T <2 had a sensitivity of 81% in the diagnosis of metastasis. Absent hilum had a sensitivity of only 68% but a specificity of 95%. An eccentric cortex was also highly specific for malignancy (96%). Presence of any sonographic feature suggestive of metastasis has a high sensitivity (95%) and negative predictive value (96%). The combination of L/T ratio <2 and absent hilum had the highest specificity (97%) combined with a high positive predictive value (93%). Sonography is useful in the evaluation of groin nodes for metastatic disease. It can help select a suspicious lymph node for cytologic/histologic confirmation.


The Distinct Effects of Estrogen and Hydrostatic Pressure on Mesenchymal Stem Cells Differentiation: Involvement of Estrogen Receptor Signaling.
This study aimed to investigate the differential and synergistic effects of mechanical stimulation and estrogen on the proliferation and osteogenic or chondrogenic differentiation potential of bone marrow mesenchymal stem cells (BMSCs) and the roles of estrogen receptor (ER) in them. BMSCs were isolated and cultured using the whole bone marrow adherence method, and flow cytometry was used to identify the surface marker molecules of BMSCs. Cells were pre-treated with 1 nM 17β-estradiol or 1 nM of the estrogen receptor antagonist tamoxifen. Then, the cells were stimulated with hydrostatic pressure. Assessment included flow cytometry analysis of the cell cycle; immunofluorescent staining for F-actin; protein quantification for MAPK protein; and mRNA analysis for Col I, OCN, OPN and BSP after osteogenic induction and Sox-9, Aggrecan and Col-II after chondrogenic induction. Hydrostatic pressure (90 kPa/1 h) and 1 nM 17β-estradiol enhanced the cellular proliferation ability and the cytoskeleton activity but without synergistic biological effects. Estrogen activated ERKs and JNKs simultaneously and promoted the osteogenic differentiation, whereas the pressure just caused JNK-1/2 activation and promoted the chondrogenic differentiation of BMSCs. Estrogen had antagonism effect on chondrogenic promotion of hydrostatic pressure. Mechanobiological effects of hydrostatic pressure are closely associated with ERα activity. MAPK molecules and F-actin were likely to be important mediator molecules in the ER-mediated mechanotransduction of BMSCs.


Evolutionary perspective of drug eluting stents: from thick polymer to polymer free approach.
Introduction of Bare Metal Stents (BMS) was itself a revolutionary step in the history of the medical industry; however, Drug Eluting Stents (DES) maintained its superiority over BMS in every aspect from restenosis rate to late lumen loss. The reason behind the magnanimous position of the DES in the stent market is the degree of improvement with which it evolves. New and better stents come into the market every year, surpassing their predecessors by many folds. This review paper discusses the journey of DES with supporting clinical trials in detail. In the first generation, there were stainless-steel stents with thicker coatings. Although they had superior results compared to BMS, there was still room for improvement. Afterward came the second-generation stents, which had superior metal platforms with thinner struts and thin coatings. The drugs were also changed from Paclitaxel and Sirolimus to Zotrolimus and Everolimus. These stents performed best; however, there was an issue of permanent coating, which remained intact over the stent surface after complete drug elution and started to cause issues in longer-term studies. Hence, an improved version of DES was introduced to these permanent coatings called the third generation of drug eluting stents, which initially utilized biodegradable polymer and ultimately moved towards polymer free drug coatings. This generation has introduced a unique amalgam of technologies to achieve its polymer free coatings; however, researchers have numerous prospects of growth in this field. This review paper highlights the major coups of stent technology evolution from BMS to DES, from thick polymeric coatings to thin coatings and from durable polymers to polymer free DES. In conclusion, though the medical industry promptly accepted BMS as the best treatment option for cardiovascular diseases; however, DES has provided even better results than BMS. In DES, the first and second generation has ruled the technology for many years and are still on the shelves. Still, the issues aroused due to durable polymer shifted the attention towards biodegradable drug eluting stents, the third generation growing rapidly. But the scientific community has not restricted themselves and is investigating bioresorbable stents that completely eliminate the polymer intervention in drug eluting stent technology.


DNA single-strand breaks and cytotoxicity induced by sodium chromate(VI) in hydrogen peroxide-resistant cell lines.
Hydrogen peroxide-resistant Chinese hamster ovary (CHOR) cells were developed by exposing parental (CHO(P)) cells to sequential increases in H2O2 concentration. Cytotoxicity as well as DNA single-strand breaks induced by Na2CrO4 were then compared in CHOR and CHO(P) cell lines. Using the colony-forming assay, it was found that the cytotoxicity caused by Na2CrO4 did not differ in the parent and resistant cells. However, alkaline elution studies showed that the production of DNA single-strand breaks in CHOR cells treated with Na2CrO4 was reduced by about 50% as compared with that in CHO(P) cells. Similarly, electron spin resonance (ESR) studies revealed that the level of chromium(V) in CHOR cells during treatment with Na2CrO4 was about 50% that in CHO(P) cells. CHOR cells were also found to be cross-resistant to the cytotoxicity and DNA breaks caused by other toxic metals such as CdCl2 and HgCl2. Catalase activity in resistant cells was 2-fold and the cellular content of glutathione was 3-fold that in parental cells. However, no obvious differences were seen in superoxide dismutase and glutathione reductase activity, although the contents of ascorbic acid or alpha-tocopherol were slightly decreased in CHOR cells, suggesting that the resistance in CHOR cells may be associated with the increase in both catalase activity and glutathione contents in cells. These results indicate that chromate-induced DNA breaks appear to be mediated by a different mechanism than that for the cytotoxicity of this metal, and also suggest that the formation of active oxygen species and/or chromium(V) during reduction of chromium(VI) inside cells might be associated with the induction of the DNA strand breaks caused by the metal.


Gamma-induced interconnected networks in microporous activated carbons from palm petiole under NaNO3 oxidizing environment towards high-performance electric double layer capacitors (EDLCs).
Activated carbons (ACs) were developed from palm petiole via a new eco-friendly method composed of highly diluted H2SO4 hydrothermal carbonization and low-concentration KOH-activating pyrolysis followed by gamma-induced surface modification under NaNO3 oxidizing environment. The prepared graphitic carbons were subsequently used as an active material for supercapacitor electrodes. The physiochemical properties of the ACs were characterized using field emission scanning electron microscope-energy dispersive X-ray spectroscopy, N2 adsorption/desorption isotherms with Brunauer-Emmett-Teller surface area analysis, Fourier transform infrared spectroscopy, X-ray diffraction and Raman spectroscopy. The electrochemical performance of the fabricated electrodes was investigated by cyclic voltammetry, galvanostatic charge-discharge and electrochemical impedance spectroscopy. Even treated with extremely low H2SO4 concentration and small KOH:hydrochar ratio, the maximum SBET of 1365 m2 g-1 for an AC was obtained after gamma irradiation. This was attributed to radiation-induced interconnected network formation generating micropores within the material structure. The supercapacitor electrodes exhibited electric double-layer capacitance giving the highest specific capacitance of 309 F g-1 as well as excellent cycle stability within 10,000 cycles. The promising results strongly ensure high possibility of the eco-friendly method application in supercapacitor material production.


Enhancement of hydroperoxide-dependent lipid peroxidation in rat liver microsomes by ascorbic acid.
Simultaneous addition of ascorbic acid and organic hydroperoxides to rat liver microsomes resulted in enhanced lipid peroxidation (approximately threefold) relative to incubation of organic hydroperoxides with microsomes alone. No lipid peroxidation was evident in incubations of ascorbate alone with microsomes. The stimulatory effect of ascorbate on linoleic acid hydroperoxide (LAHP)-dependent peroxidation was evident at all times whereas stimulation of cumene hydroperoxide (CHP)-dependent peroxidation occurred after a lag phase of up to 20 min. EDTA did not inhibit CHP-dependent lipid peroxidation but completely abolished ascorbate enhancement of lipid peroxidation. Likewise, EDTA did not significantly inhibit peroxidation by LAHP but dramatically reduced ascorbate enhancement of lipid peroxidation. The results reveal a synergistic prooxidant effect of ascorbic acid on hydroperoxide-dependent lipid peroxidation. The inhibitory effect of EDTA on enhanced peroxidation suggests a possible role for endogenous metals mobilized by hydroperoxide-dependent oxidations of microsomal components.


Independent component-cross correlation-sequential epoch (ICS) analysis of high field fMRI time series: direct visualization of dual representation of the primary motor cortex in human.
A new technique for functional magnetic resonance imaging (fMRI) time series analysis is presented. The technique referred to here as independent component-cross correlation-sequential epoch (ICS) analysis is a hybrid technique of two standard methodologies of biological signal analysis, namely, data driven methods, represented by independent component analysis, and hypothesis driven methods, represented by a general linear model. The technique successfully identified four functionally discrete areas within the primary sensorimotor cortex (SMI) in normal human subjects based on blood oxygenation level dependent (BOLD) contrast functional magnetic resonance imaging (fMRI) time series performed on a high field (3.0 T) system. Each of the four areas identified corresponded to the four physiological subdivisions of SMI, recognized in primates to be essential for voluntary hand motion, namely, 4 anterior (MI-4a) and 4 posterior (MI-4p) of the primary motor cortex, and 3a and the 'classical' (Brodmann areas 1, 2, and 3b) primary sensory cortex, respectively. ICS analysis appears to be a highly reliable and versatile technique for fMRI time series analysis.


The involvement of Rho-associated kinases in agonist-dependent contractions of human maternal and placental arteries at term gestation.
The purpose of this study was to assess the involvement of rho kinase (ROK) in agonist-dependent contraction of omental, myometrial, and placental arteries of pregnant women at term. Wire myography was used to assess if contractions of intact or alpha-toxin-permeabilized arteries obtained from women at elective cesarean section were influenced by the ROK inhibitor Y-27632. Western blotting indicated the presence of ROKalpha in each of the 3 tissue types. In intact human omental, myometrial, or placental arteries, Y-27632 dose-dependently reduced constrictions to the thromboxane-mimetic U46619. In permeabilized vessels, U46619 induced substantial Ca(2+)-sensitization of contraction that was inhibited by Y27632. The phosphatase inhibitor calyculin A induced a Ca(2+)sensitization of contraction similar to that of U46619 in permeabilized omental arteries that was unaffected by Y-27632, suggesting that ROK may signal via myosin phosphatase in these vessels. These results are the first report of the involvement of ROK in the receptor-coupled constriction of intact and permeabilized arteries from pregnant women.


HMGB1: a potential target for treatment of benign prostatic hyperplasia.
Previous studies have demonstrated an increased incidence of benign prostatic hyperplasia (BPH) in men with prostatitis. In addition to androgens and age, recent studies also pointed to an important role for inflammation in causing and promoting the progression of BPH. Inflammatory infiltrates are frequently observed in prostate tissue specimens, and the degree of inflammation has been correlated with prostate volume and weight. Furthermore, a pro-inflammatory microenvironment is closely related to BPH stromal hyperproliferation and tissue remodeling, although its role in BPH remains unclear. Accumulating evidence indicates that HMGB1 acts as a potent proinflammatory cytokine that contributes to the pathogenesis of many inflammatory and infectious disorders. Experimental studies also reported that HMGB1 promotes cell chemotaxis and proliferation. These observations led us to propose that HMGB1 contributes to the progress of BPH, and that targeting the HMGB1 signaling pathway might be a new strategy to treat prostatic enlargement.


Development and therapeutic potential of allosteric retinoic acid receptor-related orphan receptor γt (RORγt) inverse agonists for autoimmune diseases.
The transcription factor retinoic acid receptor-related orphan receptor γt (RORγt) is an attractive drug target for some autoimmune diseases owing to its roles in the differentiation of human T helper 17 (Th17) cells which produce pro-inflammatory cytokine interleukin (IL)-17. RORγt agonists and inverse agonists are classically targeted to the hydrophobic and highly conserved orthosteric binding pocket of RORγt ligand binding domain (LBD). Although successful, this approach also brings some challenges, including off-target effects due to lack of selectivity over other nuclear receptors (NRs). Allosteric regulation of RORγt by synthetic small molecules has recently emerged as novel research interests for its interesting modes of action (MOA), satisfying bioactivity profile and improved selectivity. In this review, we delineated the discovery and identification of the allosteric pocket of RORγt. Subsequently, we focused on examples of small molecules that allosterically inhibit RORγt, with a central attention on structural-activity-relationship (SAR) information, biological activity, pharmacokinetic (PK) property, and the ligand binding mode of these compounds. We also discussed the potential role of RORγt allosteric inverse agonists as small molecule therapeutics for autoimmune diseases.


Role and treatment of mitochondrial DNA-related mitochondrial dysfunction in sporadic neurodegenerative diseases.
Several sporadic neurodegenerative diseases display phenomena that directly or indirectly relate to mitochondrial function. Data suggesting altered mitochondrial function in these diseases could arise from mitochondrial DNA (mtDNA) are reviewed. Approaches for manipulating mitochondrial function and minimizing the downstream consequences of mitochondrial dysfunction are discussed.


Scattered Seed and the Harvest: The Best Things That I've Grown I Never Planted.
A physician struggling to grow in her career finds an apt analogy in being a fledgling gardener and learns to trust that God's hand has been planting the seeds all along.


Tuning the structure of cerium-based metal-organic frameworks for efficient removal of arsenic species: The role of organic ligands.
The ability of organic ligands to change the structure of metal-organic frameworks (MOFs) in nature and influence their adsorption efficiency for arsenic species is enormous. The current work was designed to investigate the adsorption performance of cerium-based MOFs with tunable structures through the use of organic ligands (Ce-MOF-66 and Ce-MOF-808) towards arsenic species from water. The structural features of Ce-MOF-66 and Ce-MOF-808 with varying crystallinity, morphology, particle size, and surface area are considerably altered by organic ligands tuning, resulting in clearly distinct arsenate (As (V)) and arsenite (As (III)) adsorption capabilities. The experimental results showed that the Langmuir adsorption capacities of As (V) by Ce-MOF-66 and Ce-MOF-808 reached 355.67 and 217.80 mg/g, respectively, while for As (III) were 5.52 and 402.10 mg/g for Ce-MOF-66 and Ce-MOF-808, respectively. Except for the impact of PO43- on As (V), co-existing ions had no significant influence on adsorption, illustrating the high selectivity. Furthermore, to understand the structure and adsorption mechanism, two adsorbents were characterized by powder X-ray diffraction, scanning electron microscopy, thermogravimetric analysis, specific surface area, Fourier transform infrared and X-ray photoelectron spectroscopy, in which identified that unsaturated sites and ligand exchange were the main adsorption mechanisms of As (V) and As (III). Overall, this research presents a novel approach for developing high-performance Ce-derived MOFs adsorbents to capture arsenic species.


Shotgun Lipidomics Discovered Diurnal Regulation of Lipid Metabolism Linked to Insulin Sensitivity in Nondiabetic Men.
Meal timing affects metabolic homeostasis and body weight, but how composition and timing of meals affect plasma lipidomics in humans is not well studied. We used high throughput shotgun plasma lipidomics to investigate effects of timing of carbohydrate and fat intake on lipid metabolism and its relation to glycemic control. 29 nondiabetic men consumed (1) a high-carb test meal (MTT-HC) at 09.00 and a high-fat meal (MTT-HF) at 15.40; or (2) MTT-HF at 09.00 and MTT-HC at 15.40. Blood was sampled before and 180 minutes after completion of each MTT. Subcutaneous adipose tissue (SAT) was collected after overnight fast and both MTTs. Prior to each investigation day, participants consumed a 4-week isocaloric diet of the same composition: (1) high-carb meals until 13.30 and high-fat meals between 16.30 and 22:00 or (2) the inverse order. 12 hour daily lipid patterns showed a complex regulation by both the time of day (67.8%) and meal composition (55.4%). A third of lipids showed a diurnal variation in postprandial responses to the same meal with mostly higher responses in the morning than in the afternoon. Triacylglycerols containing shorter and more saturated fatty acids were enriched in the morning. SAT transcripts involved in fatty acid synthesis and desaturation showed no diurnal variation. Diurnal changes of 7 lipid classes were negatively associated with insulin sensitivity, but not with glucose and insulin response or insulin secretion. This study identified postprandial plasma lipid profiles as being strongly affected by meal timing and associated with insulin sensitivity.


Inherited cylindromas: lessons from a rare tumour.
Cylindroma is a rare skin tumour that is inherited in several skin-tumour syndromes caused by germline mutations in the tumour suppressor gene, CYLD. In this Review, we provide insight into the clinical features of patients who develop multiple cylindromas and other related tumours. The CYLD protein is also dysfunctional in various sporadic cancers and we discuss how such dysfunction relates to the role of CYLD in regulating key cellular pathways. Clinical management of patients with germline CYLD mutations is challenging and we discuss genetic counselling and surgical interventions. Finally, we discuss how the study of these rare syndromes might provide insights into understanding more common diseases.


Natural and Chernobyl-caused radioactivity in mushrooms, mosses and soil-samples of defined biotops in SW Bavaria.
Different mushrooms, mosses and corresponding soil samples have been collected mainly from two sites in the alpine region of southwestern Bavaria. At the end of the growthseason, September 1986, gamma spectroscopic analysis showed that the moss-, mould, and needle-layer contained considerably more 134Cs and 137Cs activity per unit fresh weight than eight different species of mushroom. These two isotopes were carried into the biotop mainly as a consequence of the Chernobyl accident. 131J could not be found any more in the samples ca. 5-6 months after the catastrophe. The activity of the cesium isotopes decreased with increasing soil depth. In the mushrooms the activity was relatively high in Xerocomus badius and surprisingly low in Boletus edulis; samples of the latter and of Cantharellus cibarius collected in September 1985 (before the accident) and kept deep frozen contained almost identical amounts of 137Cs as those collected from August to October 1986. Mushrooms contained considerably more of the natural isotope 40K than the needlelayers and the soil samples in the neighbourhood. In all mushrooms except Xerocomus badius the activity of 40K was generally higher than the 137Cs activity. The results indicate that except Xerocomus badius the analyzed mushrooms do not actively take up Cs from the soil, in contrast to K.


Pretransplant hyperthermia promotes permanent survival of murine thyroid allografts.
Hyperthermic treatment of skin has been shown to abolish stimulation of allogeneic lymphocytes in a mixed skin-lymphocyte reaction. These experiments test the hypothesis that hyperthermic pretreatment of endocrine tissue can promote its permanent survival in allogeneic recipients. Murine thyroid tissues were treated at 37, 43, or 45 degrees C for 0.5-4.0 hr and transplanted to the left renal capsule of recipient mice. Graft survival was determined after 100 days by the ratio of counts between the left and right kidneys 24 hr after administration of 0.5 microCi 125I. Balb/c recipients of C57BL/6 thyroids treated at 43 degrees C for 2 or 4 hr had viable grafts in 4/7 (P = 0.032) and 4/5 (P = 0.015) cases, respectively, compared to controls (0/10). C57BL/6 recipients of Balb/c thyroid treated at 43 degrees C for 4 hr had viable grafts in 6/10 cases (P = 0.009) compared to control (0/10). Treatment at 45 degrees C was lethal, evidenced by failure of all isografts. Pretransplant treatment at 43 degrees C promotes permanent thyroid allograft survival without immunosuppression.


Planning and intraoperative visualization of liver catheterizations: new CTA protocol and 2D-3D registration method.
Two-dimensional and three-dimensional (2D-3D) registration for angiographic liver interventions is an unsolved problem mainly because of two reasons. First, a suitable protocol for computed tomography angiography (CTA) to contrast liver arteries is not used in clinical practice. Second, in spite of a valuable body of research results in the neuroradiology community, an adequate registration algorithm that addresses the difficult task of 2D-3D alignment of abdominal vessel structures has not been developed yet. We address the first issue by introducing an angiographic computed tomography (CT) scanning phase. The scan visualizes arteries similar to the vasculature captured with an intraoperative C-arm acquiring digitally subtracted angiograms. Furthermore, we propose a registration algorithm using the new CT phase that aligns arterial structures in two steps: 1) Initialization of one corresponding feature using diameter information and 2) optimization on three rotational and one translational parameters to register vessel structures that are represented as centerline graphs. We form a space of good features by iteratively creating new graphs from projected centerline images and by restricting the correspondence search only on branching points (the vertices) of the vessel tree. We show convergence and robustness of the proposed algorithm on synthetic data, as well as head phantom and four consistent patient data sets. We compare our results with those of a recently proposed method. Moreover, we evaluate different visualization techniques and show that a transfer of planning information to intraoperative data is a benefit for interventional workflow. Introducing a new CTA protocol and a two-step 2D-3D registration algorithm, the proposed method creates a strong link between radiologists and interventionalists by bringing preoperative patient and planning information to interventional workflow.


Hybrid kappa\lambda antibody is a new serological marker to diagnose autoimmune pancreatitis and differentiate it from pancreatic cancer.
The only generally accepted serological marker currently used for the diagnosis of autoimmune pancreatitis (AIP) is IgG4. Our aim was mainly to determine whether hybrid κ\λ antibody can help to diagnose AIP and to differentiate it from pancreatic cancer. We established an enzyme-linked immunosorbent assay (ELISA) system to measure the levels of hybrid κ\λ antibodies in human sera. Sera were obtained from 338 patients, including 61 with AIP, 74 with pancreatic cancer, 50 with acute pancreatitis, 40 with ordinary chronic pancreatitis, 15 with miscellaneous pancreatic diseases, and 98 with normal pancreas. Our study showed levels of hybrid κ\λ antibodies in the AIP group were significantly higher than in the non-AIP group (P < 0.001). The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for the diagnosis of AIP were 80.3%, 91%, 66.2% and 95.5% respectively. Furthermore, the combined measurement of serum hybrid κ\λ antibody and IgG4 tended to increase the sensitivity although the difference was not statistically significant (90.2% vs. 78.7%, P = 0.08), compared to measurement of IgG4 alone. Our findings suggest that hybrid κ\λ antibody could be a new serological marker to diagnose AIP and differentiate it from pancreatic cancer.


Measurement of cerebral oxidative metabolism with near-infrared spectroscopy: a validation study.
Predicting the onset of secondary energy failure after a hypoxic-ischemic insult in newborns is critical for providing effective treatment. Measuring reductions in the cerebral metabolic rate of oxygen (CMRO(2)) may be one method for early detection, as hypoxia-ischemia is believed to impair oxidative metabolism. We have developed a near-infrared spectroscopy (NIRS) technique based on the Fick Principle for measuring CMRO(2). This technique combines cerebral blood flow (CBF) measurements obtained using the tracer indocyanine green with measurements of the cerebral deoxy-hemoglobin (Hb) concentration. In this study, NIRS measurements of CMRO(2) were compared with CMRO(2) determined from the product of CBF and the cerebral arteriovenous difference in oxygen measured from blood samples. The blood samples were collected from a peripheral artery and the sagittal sinus. Eight piglets were subjected to five cerebral metabolic states created by varying the plane of anesthesia. No significant difference was found between CMRO(2) measurements obtained with the two techniques at any anesthetic level (P>0.5). Furthermore, there was a strong correlation when concomitant CMRO(2) values from the two techniques were compared (R(2)=0.88, P<0.001). This work showed that CMRO(2) can be determined accurately by combining NIRS measurements of CBF and Hb. Since NIRS is safe and measurements can be obtained at the bedside, it is believed that this technique could assist in the early diagnosis of cerebral energy dysfunction after hypoxia-ischemia.


DFT studies on the palladium-catalyzed dearomatization reaction between naphthalene allyl chloride and allyltributylstannane.
The Pd-catalyzed dearomatization of naphthalene allyl chloride with allyltributylstannane has been investigated using density functional theory (DFT) calculations at the B3LYP level. The calculations indicate that the (ŋ(1)-allyl)(ŋ(3)-allyl)Pd(PH3) complex is responsible for the formation of ortho-dearomatized product. Moreover it is easy to produce the ortho-dearomatized product when reductive elimination starts from (ŋ(3)-allylnaphthalene)(ŋ(1)-allyl)Pd complex 7, while it is easy to form the para-dearomatized product when reductive elimination starts from (ŋ(3)-allylnaphthalene)(ŋ(1)-allyl)Pd complex 9. The Stille coupling products can't be produced due to high reaction energy barrier. Graphical Abstract Two mechanisms of dearomatization are investigated by DFT, and (ŋ(1)-allyl)(ŋ(3)-allyl)Pd(PH3) complexes are the main intermediates for ortho-dearomatized product.


Mea2/Golga3 gene is disrupted in a line of transgenic mice with a reciprocal translocation between Chromosomes 5 and 19 and is responsible for a defective spermatogenesis in homozygotes.
A line of transgenic mouse T604 transmitted a transgene to progeny together with a set of chromosomes with a reciprocal translocation. The transgene was integrated at a single site in the translocated chromosomes, as revealed by fluorescence in situ hybridization. The transgenic hemizygous males, also heterozygous for the translocation of chromosomes, showed apparently normal spermatogenesis, while the males homozygous for the transgene as well as for the translocated chromosomes showed a defect in spermatogenesis. Considering that the genetic rearrangement by either insertion of the transgene or the chromosome translocation in the T604 mouse line might have caused a recessive mutation in a gene indispensable for spermatogenesis, we have mapped the transgene integration site and the translocation breakpoints in mouse chromosomes. Linkage analysis with SSLP markers showed that the loci for the transgene and the translocation breakpoints were closely located to D5Mit24 on Chromosome (Chr) 5, and to a region between D19Mit19 and D19Jpk2 on Chr 19. Mea2 gene, mapped only 2 cM from D5Mit24 and known to show male-specific enhanced expression in the testis, was analyzed as a candidate for the gene disrupted in T604 transgenic mice. Southern blot analysis revealed that Mea2 gene was indeed disrupted in T604 mice, and Northern blot analysis of the testis RNA showed that the expression of Mea2 was annihilated in the testis of T604 transgenic homozygotes.


Gitelman syndrome: novel mutation and long-term follow-up.
We report a case of Gitelman syndrome presenting with fatigue, paresthesias, weakness of limbs and neck muscles since 2.5 years of age. Investigations showed hypokalemia and hypomagnesemia with urinary magnesium wasting. Genetic analysis revealed the presence of a novel homozygous mutation in the SLC12A3 gene (c.2879_2883+9ins14bp, p.Val 960 Glu fsx12). Management with potassium and magnesium supplements and spironolactone resulted in a significant improvement in symptoms. Over a follow-up of 11 years, the patient showed satisfactory growth and physical development.


Conformational studies on wheat embryo 5S RNA using nuclease S1 as a probe.
Ribosomal 5S 32 P-labelled RNA was isolated from imbibing wheat embryos and digested with nuclease S1, a single-strand specific nuclease. The products of enzymic digestion were separated by polyacrylamide gel electrophoresis and identified by fingerprint analysis of their RNase T1 digestion products. The results indicate that the most sensitive portion of the molecule, and hence, the region containing the least helical structure, is close to the 5'-terminus. Similarly, the most resistant portion of the molecule is close to, but does not include, the 3'-terminus. These findings are discussed in relation to proposed models for the secondary structure of 5S RNA.


Dynamic characteristics of soil aggregate stability and related carbon and nitrogen pools at different developmental stages of plantations in northern China.
The carbon and nitrogen reserves of forest soil play a key role in combating global climate change. Afforestation is considered an effective measure for increasing carbon and nitrogen reserves in terrestrial forest ecosystems. However, the mechanisms governing how different developmental stages of plantations affect soil carbon and nitrogen stability and storage remain unclear. In this study, we selected three developmental stages of the Larix principis-rupprechtii plantations: medium mature forest (30 yr), near mature forest (40 yr) and mature forest (50 yr). We studied the distribution and stability of soil aggregates at distinct developmental stages, the distribution of carbon and nitrogen pools related to aggregates, and their relationship to environmental factors. We found that with increasing forest age, the soil sand particles became finer. In each developmental stage, the proportion of aggregates >0.25 mm reached more than 85%. The concentrations of carbon and nitrogen in the soil aggregates were lower in the near mature forest (40 a) than in the medium mature forest (30 a), but reached a maximum in the mature forest (50 a). There were significant positive correlations between soil carbon and nitrogen concentrations and soil relative water content (RWC), forest age, and stand density. Soil texture strongly affected the distribution of aggregates. TOC/TN was mainly influenced by aggregate distribution, which was most vulnerable to environmental factors. Environmental factors have a significant negative impact on soil texture, and the path coefficient was -0.812. Environmental factors indirectly affected the concentrations of soil carbon and nitrogen by influencing the distribution and stability of soil aggregates. Therefore, different developmental stages of plantations strongly affected forest carbon and nitrogen pools by changing the soil structure and environmental factors. This study provides a basis for understanding the mechanisms of forest soil carbon and nitrogen storage.


Preparation of Low-Resistance and Residue-free ITO Films for Large-scale 3D Displays.
The large-sized naked-eye three-dimensional (3D) display is a critical device in the real-time topographic survey for deep-sea scientific research. As a core component, the low-impedance transparent conductive indium tin oxide (ITO) thin-film electrode lacks a reliable industrial preparation method. In the 3D display, the grating element with a low-resistance ITO film electrode should have a good binocular parallax to drive the display favorably. However, an increase in the ITO film temperature during deposition may induce its crystallization, and its etching residue may cause a short circuit between the ITO electrodes and abnormal display operation. In this work, we propose a simple and straightforward technique to produce amorphous thin ITO films by controlling the water vapor flow rate during the deposition process. The obtained ITO amorphous thick film (300 nm) can be etched without leaving residues on the display surface, ensuring vivid display performance of the 3D display. A field test employing the 3D display, consisting of a 3D parallax barrier and a two-dimensional (2D) display, does not exhibit a short-circuit phenomenon caused by residues encountered in previous devices. This work makes the 3D display applicable for the real-time topographic survey on the basis of both satisfying the nonetching residue and the decrease of the resistance value.