Serologic cross-reactions among rabbit secretory IgA molecules: evidence for multiple subclasses of secretory IgA-f molecules.
Serologic cross-reactions among allotypes of rabbit secretory IgA (sIgA) of the f-subclass were examined by quantitative radiobinding assays with various allo-anti-alpha chain reagents. Numerous cross-reactions were observed which demonstrated the complexity of the C alpha f allotypes. One of the reagents used in these studies reacted not only with all sIgA molecules of the immunogen C alpha f allotype but also with all sIgA molecules of the other C alpha f allotypes. Aliquots of the antiserum were each adsorbed with IgA molecules of these C alpha f allotypes and then used in radiobinding studies with sIgA-f molecules of the various C alpha f allotypes. The adsorbed reagents reacted with some but not all sIgA-f molecules, thus indicating that the C alpha f allotypes each comprise more than one serologically distinguishable subset. Results from these radiobinding experiments were used to develop a model in which each of the five IgA-f allotypes comprises at least two serologically distinguishable subsets. Each of these subsets expresses a unique pattern of C alpha determinants. These C alpha determinants appear to be protein in nature rather than carbohydrate as periodate oxidation of the sIgA-f glycoproteins does not affect the reactions of the molecules with the cross-reactive alloreagents. IgA molecules of the serologically distinguishable subsets presumably differ in amino acid sequence in the constant region and, thus, would be products of distinct C alpha genes. Therefore, it is probable that the cross-reactions of these molecules, which were previously thought to comprise a single subclass, sIgA-f, may reflect the presence of more than one subclass of sIgA-f molecules, i.e., a third subclass of rabbit sIgA.


Contralateral renal hyperplasia and increased renal function after relief of chronic unilateral ureteral obstruction.
Following relief of 1, 2 or 3 weeks of unilateral ureteral obstruction, contralateral compensatory renal growth and increased renal function were measured 3 and 6 months later. Compensatory growth occurred predominantly by hyperplasia, demonstrated by a significant increase in DNA content and a decrease in the RNA:DNA ratio (p less than 0.04). This is in contrast to compensatory growth following nephrectomy or unrelieved unilateral ureteral obstruction, which occurred primarily by hypertrophy with no significant change in DNA content but a significant increase in RNA content and the RNA:DNA ratio (p less than 0.04). Contralateral renal function in animals with relieved unilateral ureteral obstruction was greater than in controls with 2 normal kidneys (p less than 0.05). The contralateral increase in renal function was greater than that in animals subjected to ipsilateral nephrectomy or unrelieved ureteral obstruction, but this did not reach statistical significance. Thus, when growth occurred by hyperplasia, there was a trend to greater increases in renal function than when growth occurred by hypertrophy. Contralateral compensatory renal hyperplasia and increased renal function occurred in conjunction with a decrease in renal mass and function of the ipsilateral post-obstructed kidney. These experiments suggest that the post-obstructed, poorly functioning kidney stimulates contralateral hyperplastic growth and increased renal function. This hyperplastic response is different from the hypertrophic response following nephrectomy or unrelieved unilateral ureteral obstruction, implicating the post-obstructed kidney as the stimulus of the hyperplastic response.


Ultrasonic anatomical study of the lesser omental sac: a pictorial essay.
The peritoneal and visceral limits of the lesser omental sac have been studied by ultrasound in ten patients with gross ascites. Ascitic fluid provides necessary contrast and ultrasound examination gives valuable anatomic information. A few pathologic examples are also studied.


[Prophylaxis of cytomegalovirus infection in intestinal transplantation].
Intestinal transplant recipients are at high risk of cytomegalovirus (CMV) disease due to the specific characteristics of the graft and the intense cellular immunosuppression caused by immunosuppressive induction therapy in this type of transplantation. The most frequent form of CMV disease is graft enteritis. Diagnosis of this entity is not always straightforward given that antigenemia for CMV is frequently low grade or negative and the pathological findings can be confused with those of rejection. Diagnosis is aided by immunohistochemistry or molecular biological detection in biopsies of the colon. Current recommendations for the preventive management of CMV disease are based on sporadic experiences and expert opinion, given the lack of specifically-designed, high-quality studies in this type of transplant recipient. In general, universal prophylaxis against CMV is preferred in these patients, initially with intravenous ganciclovir and subsequently with oral valganciclovir for a minimum of 6 months, although this prophylaxis can be prolonged for up to 1 year depending on the type of immunosuppressive therapy used. Several groups also use CMV-specific immunoglobulin.


[ESC guidelines 2015 for ventricular arrhythmias and prevention of sudden cardiac death. What is new?].
The new European Society of Cardiology (ESC) guidelines for the management of patients with ventricular arrhythmia and the prevention of sudden cardiac death, recently published at the annual ESC meeting in London, contain an extensive update of the recommendations for the diagnostics, drug therapy, interventional and device therapy of ventricular arrhythmia. The new recommendations for implantable cardioverter defibrillator (ICD) treatment for primary and secondary prophylaxis of sudden cardiac death can be seen as a focused update of the previously published guidelines. Pre-existing recommendations for catheter ablation of ventricular arrhythmias have been partly extensively expanded with respect to the results of recent clinical trials. The guideline committee also adapted their recommendations regarding the hereditary arrhythmia syndromes to the 2013 consensus report of the American Heart Association (AHA), the European Heart Rhythm Association (EHRA) and the Asia Pacific Heart Rhythm Society (APHRS).


Chromatographic behavior of six lanthanides on a centrifugal mixer-settler extractor cascade.
This work furthers the development of counter-current chromatography as an industrial separation process method. It was demonstrated that the industrial counter-current chromatography methods, in particular, for the separation groups of rare earth metals, can be implemented in a modified cascade of centrifugal mixer-settler extractors. The retention behavior of rare earth elements (samarium, europium, gadolinium, terbium, dysprosium and yttrium) on the pilot chromatographic unit consisting of 70 serially connected centrifugal mixer-settler extractors was experimentally studied under isocratic elution conditions using the mixture of 30 vol.% CyanexⓇ572 + 10 vol.% tributylphosphate in a hydrocarbon diluent as the stationary phase and aqueous nitric acid as the mobile phase. Theoretical analysis of experimental studies showed an acceptable agreement between the assumptions of the theory and experimental results.


"Glial bundles" in the spinal cord late after paralytic anterior poliomyelitis.
"Glial bundles" in the proximal portion of the anterior spinal roots, identical to those in Werdnig-Hoffmann disease, were observed in 3 patients many years after attacks of acute paralytic anterior poliomyelitis. These structures should therefore be considered a nonspecific astrocytic reaction secondary to the destruction of motor neurons and their axons rather than a malformation specific for Werdnig-Hoffman disease.


Homocysteine-induced enhancement of spontaneous contractions of myometrium isolated from pregnant women.
Although many associations have been demonstrated between hyperhomocysteinemia and pregnancy complications, such as spontaneous abortion, preterm labor, preeclampsia and low birthweight, it is still not clear whether hyperhomocysteinemia is the cause or the consequence of these pregnancy complications. The aim of this study was to investigate the effects of homocysteine on the spontaneous contractility of isolated pregnant human myometrium. Myometrium samples obtained from women undergoing elective caesarean section were suspended in a jacketed organ bath containing Krebs' solution at 37 degrees C (pH 7.4), continuously gassed with 95% O2 and 5% CO2. After manifestation of spontaneous contractions under 2 g of resting tension, homocysteine was applied to the organ bath, and amplitude and frequency of contractions were evaluated at 20-min intervals. Statistical analysis of amplitude and frequency of the contractions was performed using the Kruskal-Wallis analysis of variance test. Application of 0.1 mm homocysteine had no significant effect on either frequency (4.63 +/- 0.42 vs. 4.01 +/- 0.53 for the control period; p > 0.05) or amplitude (3.20 +/- 0.07 g vs. 3.15 +/- 0.07 g; p > 0.05) of spontaneous contractions, while 1 and 2 mm homocysteine significantly increased the frequency (8.54 +/- 0.62 vs. 3.9 +/- 0.44, p < 0.02, and 12.32 +/- 0.72 vs. 3.96 +/- 0.51, p < 0.001, respectively) of spontaneous contractions but caused only a modest change in amplitude (2.92 +/- 0.04 g vs. 2.87 +/- 0.05 g, p > 0.05, and 3.02 +/- 0.06 g vs. 2.93 +/- 0.05 g, p > 0.05, respectively). Results from this study indicate for the first time that homocysteine causes enhancement of spontaneous contractions of myometrium derived from pregnant women.


Sequence specificity of DNA cleavage by bisnetropsin-linked hydroxamic acid-metal complexes: highly specific cleavage by ferrous complexes.
Bisnetropsin-linked hydroxamic acids (BNHA) were shown to cleave DNA stands at a single residue with a preferred binding orientation in the presence of ferrous ion. In contrast, the corresponding cerium (III) complexes cleaved DNA with low sequence specificity.


Ultrastructural study of rabbit lung tissue subsequent to capsaicin treatment over several days.
The neurogenic basis of nonspecific airway hyperresponsiveness (NAH) is poorly understood. Under experimental conditions isocyanates can elicit bronchial hyperresponsiveness in animals. The purpose of our study was to determine whether reactions of neurosecretory granules in nonmedullated C fibers might play a role in NAH. Our experiments were based on the fact that capsaicin treatment causes depletion of neurosecretory granules in vicinity of C fibers. We gave rabbits repeated subcutaneous injections of capsaicin. The animals were then treated with toluene diisocyanate (TDI), inducing airway hyperresponsiveness upon acetylcholine (ACH) inhalation. In capsaicin-treated animals the neurosecretory granules were not evident ultrastructurally and airway hyperresponsiveness did not occur in response to TDI treatment. Controls that were not treated with capsaicin displayed both neurosecretory granules ultrastructurally as well as airway hyperresponsiveness to ACH. We conclude that in the rabbit, NAH is related to the presence of neurosecretory granules adjacent to nonmedullated C fibers.


The design, development, and in vivo performance of intestinal anastomosis ring fabricated by magnesium‑zinc‑strontium alloy.
In the current work, an intestinal anastomosis ring made of magnesium‑zinc‑strontium (Mg-Zn-Sr) alloy was developed and fabricated in order to take advantages of the appropriate biocompatibility and degradability of Mg-based alloys. As-fabricated anastomosis rings were implanted into the intestinal tracts of Bama miniature pigs to evaluate their biological performance in vivo. At the injury site, the formation of edema and granulation tissue was observed for 2 weeks after surgery. Till week 4, the edema transformed to firm scar tissue, which reached the healing standard of intestinal tissue. The levels of biochemical indicators such as blood routine, liver and kidney functions as well as electrolytes were all under normal conditions, indicating that the implantation of Mg alloy did not have remarkable influence on the blood system as well as liver and kidney functions. Pathological results revealed that no obvious abnormality was found in heart, liver, spleen, lung, kidney and brain tissues. The Mg ions were found to be excreted from the body through urine. The intestinal anastomosis ring could be discharged through excretion around 2 weeks after surgery, of which the surface was corroded and covered by a layer of Ca- and P-containing minerals. According to histological images, a mild inflammatory response was noticed on week 2. At this stage, dilated and congested capillaries were found in the muscular layer. Moreover, the mucosal layer and villi at the injury site were disordered. Till week 4, the muscular and mucosal layer were similar to their healthy counterparts even though the villi were slightly shorter than normal ones. Together, the results indicate that Mg-Zn-Sr alloy is a promising candidate for the fabrication of biodegradable intestinal anastomosis ring.


Pharmacotherapy for the treatment of obesity.
The recognition of the complex counter-regulatory hormonal, metabolic and neurochemical mechanisms that promote weight regain following weight loss and the conceptualisation of obesity as a chronic disease requiring long-term management has led to increasing focus on the role of adjunctive therapies for obesity, particularly pharmacotherapy. Currently available pharmacotherapy achieves a weight loss intermediate between that commonly attained by lifestyle intervention and bariatric surgery, however its accessibility, compared to bariatric surgery increases its appeal. Despite the poor history of obesity pharmacotherapy, novel agents that are in development appear to have several advantages over predecessors. They are generally more selective in their mechanism of action, thereby potentially minimising adverse sequelae and improving the risk-benefit ratio of pharmacotherapy. Another approach has been to use combined pharmacotherapy to better counteract the multiple counter-regulatory neuroendocrine mechanisms which promote weight regain, as well as allowing lower constituent doses of the combined monotherapy agents, which improves the safety and tolerability of these agents that are usually required long-term for chronic weight maintenance. This review will provide an overview of past, present and future pharmacotherapy for obesity. The efficacy and safety profile of currently available pharmacotherapy will be discussed in the setting of stringent regulatory review processes now in place given the fraught history of pharmacological interventions for obesity. Potential novel therapies that seek to better target the multiple complex counter-regulatory mechanisms promoting weight regain while improving the efficacy/safety profile, will also be examined.


Removal of benzene, MTBE and toluene from contaminated waters using biochar-based liquid activated carbon.
Fuel components such as benzene, toluene, and methyl tertiary-butyl ether (MTBE) are frequently detected pollutants in groundwater resources. Ex-situ remediation technologies by activated carbon have been used for treatment for many years. However, due to high cost of these technology, more attention has been given to the in-situ remediation methods of contaminated groundwaters using liquid carbon adsorbents. Literature search showed limited studies on using adsorbents in liquid form for the removal of such contaminants. Therefore, this lab-scale study investigates the capacity of using raw biochar-based liquid activated carbon and iron-modified biochar-based liquid activated carbon to remove these pollutants. The adsorption efficiency of the synthesized liquid activated carbon and iron-modified liquid activated carbon mixed with sand, limestone, and 1:1 mixture of sand/limestone, was tested using batch suspension experiments. Adsorption by granular activated carbon was also investigated for comparison with liquid activated carbon. Results of the study revealed that mixing of liquid activated carbon or LAC-Fe on subsurface materials had not improved the removal efficiency of MTBE. At the same time, it showed a slight improvement in the adsorption efficiency of benzene and toluene. In all cases, the removal by GAC was higher with around 80% and 90% for MTBE and BT, respectively. Results also showed that benzene and toluene were better removed by liquid activated carbon and iron-modified liquid activated carbon (∼ 40%) than MTBE (∼ 20%). It is also found that water chemistry (i.e., salinity and pH) had insignificant effects on the removal efficiency of pollutants under the study conditions. It can be concluded that more research is needed to improve the capacity of biochar-based liquid-activated carbon in removing MTBE, benzene and toluene compounds that will lead to improve the utilization of liquid activated carbon for the in-situ remediation of contaminated groundwaters.


Evidence-based indications for elbow arthroscopy.
The purpose was to review the literature on the outcomes of elbow arthroscopy and to make evidence-based recommendations for or against elbow arthroscopy for the treatment of various conditions. Our hypothesis was that the evidence would support the use of elbow arthroscopy in the management of common elbow conditions. A literature search was performed by use of the PubMed database in October 2010. All therapeutic studies investigating the results of treatment with elbow arthroscopy were analyzed for outcomes and complications. The literature specific to common elbow arthroscopy indications was summarized and was assigned a grade of recommendation based on the available evidence. There is fair-quality evidence for elbow arthroscopy in the treatment of rheumatoid arthritis of the elbow and lateral epicondylitis (grade B recommendation). There is poor-quality evidence for, rather than against, the arthroscopic treatment of degenerative arthritis, osteochondritis dissecans, radial head resection, loose bodies, post-traumatic arthrofibrosis, posteromedial impingement, excision of a plica, and fractures of the capitellum, coronoid process, and radial head (grade C(f) recommendation). There is insufficient evidence to give a recommendation for or against the arthroscopic treatment of posterolateral rotatory instability and septic arthritis (grade I recommendation). The available evidence supports the use of elbow arthroscopy in the management of the majority of conditions where it is currently used. The quality of the evidence, however, is generally fair to poor. Level IV, systematic review of Level II-IV studies.


Plant physiology: spreading a drought warning.
Communication between the root and the shoot forms a central part of the coordinated response of plants to drought. Recent evidence suggests that a K+ channel expressed in the stelar tissue of the root may have a major role in this process.


Access to pyrrolidine imino sugars via tin(II)-mediated aldol reactions of bislactim ethers: synthesis of 2,5-dideoxy-2,5-imino-D-glucitol.
2,5-Dideoxy-2,5-imino-D-glucitol (DGDP) has been synthesized via the tin(II)-mediated anti-selective aldol reaction of bislactim ether 5 and a 3-O-silylated 2,4-ethylidene-D-erythrose derivative 6. In accordance with density functional theory calculations (at the B3LYP/cc-pVDZ-PP level), pericyclic transition structures with a boat-like conformation and a stabilizing hydrogen bond can account for the unexpected stereoselectivity.


p63 expression in sclerosing mucoepidermoid carcinomas with eosinophilia arising in the thyroid.
Primary sclerosing mucoepidermoid carcinomas with eosinophilia (SMECE) of the thyroid gland are rare tumors that can present diagnostic difficulties to the pathologist due to the unusual histologic features. Furthermore, the etiology of these tumors has been debated in the literature, with some authors believing that the tumors arise from remnants of the ultimobranchial body (UBB, solid cell nests) and others proposing that they arise from follicular epithelial cells. Because SMECE often occur in glands with chronic lymphocytic thyroiditis and UBB hyperplasia, and do not stain like follicular or parafollicular cells, it is likely that the tumors do arise from UBB/solid cell nests. In this study, we provide additional evidence for this relationship, by demonstrating that SMECE stain strongly positive for p63, which is a new marker for UBB/solid cell nests.


Biotin recycling impairment in phenylketonuric children with seborrheic dermatitis.
To investigate the effect of a therapeutic diet on serum biotin levels and to explain the seborrheic dermatitis in phenylketonuric (PKU) patients on a "loose" diet. Forty-seven patients were divided into two groups: group A (n=21) demonstrated good compliance to a special diet and group B (n=26) were on a "loose" diet. Most of the patients in group B (20/26), who suffered from mild seborrheic dermatitis, were requested to return to phenylalanine (Phe)-restricted diet for at least 15 days. Seventy-nine healthy children of comparable age were used as controls. Biotin serum levels and plasma biotinidase activity were measured in patients as well as controls. In addition, biotinidase activity was evaluated in vitro after incubation with various concentrations of Phe. Biotin levels in group A patients (636+/-118 ng/L) were statistically significantly elevated (P < 0.01) compared with those of group B patients before (412+/-184 ng/L) and after (501+/-160 ng/L) 15 days on a Phe-restricted diet, as well as with those of controls (337+/-290 ng/L). Furthermore, biotinidase activities were decreased in group B patients (4.2+/-1.68 nmol/min/L) compared with those of group A patients (6.4+/-0.7 nmol/min/L) and controls (6.10+/-0.8 nmol/min/L). Additionally, biotinidase activities in the patients of group B were restored to normal (5.78+/-0.81 nmol/min/L), with a simultaneous remission of their skin lesions, after 15 days on a Phe-restricted diet. Moreover, the in vitro findings showed a 51% inhibition of biotinidase activity when incubated with Phe (20 mg/dL). It is suggested that the high biotin levels in group A patients reflect the intake of water-soluble biotin of vegetable origin. In contrast, the low biotinidase activity in group B patients may be attributed to their high Phe plasma levels, which acts as an enzyme inhibitor, as shown by the in vivo and in vitro results. Consequently, the observed seborrheic dermatitis in PKU children (group B) is associated with an impairment of biotin recycling.


Target-directed microRNA degradation regulates developmental microRNA expression and embryonic growth in mammals.
MicroRNAs (miRNAs) are post-transcriptional regulators of gene expression that play critical roles in development and disease. Target-directed miRNA degradation (TDMD), a pathway in which miRNAs that bind to specialized targets with extensive complementarity are rapidly decayed, has emerged as a potent mechanism of controlling miRNA levels. Nevertheless, the biological role and scope of miRNA regulation by TDMD in mammals remains poorly understood. To address these questions, we generated mice with constitutive or conditional deletion of Zswim8, which encodes an essential TDMD factor. Loss of Zswim8 resulted in developmental defects in the heart and lungs, growth restriction, and perinatal lethality. Small RNA sequencing of embryonic tissues revealed widespread miRNA regulation by TDMD and greatly expanded the known catalog of miRNAs regulated by this pathway. These experiments also uncovered novel features of TDMD-regulated miRNAs, including their enrichment in cotranscribed clusters and examples in which TDMD underlies "arm switching," a phenomenon wherein the dominant strand of a miRNA precursor changes in different tissues or conditions. Importantly, deletion of two miRNAs, miR-322 and miR-503, rescued growth of Zswim8-null embryos, directly implicating the TDMD pathway as a regulator of mammalian body size. These data illuminate the broad landscape and developmental role of TDMD in mammals.


Structural variations and growth potential of Yersinia enterocolitica under different culture conditions.
The growth potential and the polypeptide composition of Yersinia enterocolitica serotype 0:3 isolated from patients with uncomplicated diarrhoea, reactive arthritis or septicemia were evaluated under different culture conditions. The expression of polypeptides varied with presence of the virulence-associated 40-48 Mdal plasmid, growth medium, growth temperature and gas composition of the culture (air, carbon dioxide, oxygen). Also the initial growth medium at 26 degrees C, before temperature shift to 37 degrees C, influenced the subsequent growth potential and expression of polypeptides. The plasmid encoded at least 7 polypeptides. This plasmid also inhibited the multiplication of bacteria under defined culture conditions. The dominating plasmid-encoded polypeptides were optimally expressed in air or oxygen-supplemented growth medium. The majority of the chromosomally encoded polypeptides were expressed independently of presence of the plasmid, whereas the expression of at least 8 were repressed by the plasmid. Five chromosomally encoded polypeptides were expressed only in carbon dioxide and five only in oxygen environment. These results indicate that Y. enterocolitica may express different molecules in different environments in vivo. This may be of importance for host-parasite relationship and immune response.


A bowl-shaped fullerene encapsulates a water into the cage.
The sequential carbon-carbon bond cleaving reactions of the diketone derivative of C60 with o-phenylenediamine give a novel bowl-shaped fullerene bearing a 20-membered ring orifice. The product reversibly encapsulates a water molecule into the fullerene cage for the first time.


Postoperative de novo epilepsy after resection of brain arteriovenous malformations: A national database study of 536 patients.
We aimed to assess the incidence and risk factors for de novo epilepsy after arteriovenous malformation (AVM) resection and compare them with a nonresection cohort after propensity score matching, utilizing a national database. Utilizing the TriNetX Research Network, we queried cases from January 1, 2004 to March 1, 2022. We included patients of all ages who underwent supratentorial AVM resection, presenting without seizures on or before surgery and without being on antiseizure medications at least 1 day before surgery. The primary outcome was seizures manifesting at least 6 weeks after surgery. Patient characteristics and outcomes were compared between the cohorts with and without postoperative epilepsy. Further cohorts were created to compare cohorts with and without embolization or rupture. After propensity score matching, we compared an additional cohort of patients with an AVM diagnosis who did not undergo resection. Of the 536 patients (mean age = 38.9 ± 19.6, 52% females) presenting without seizure who underwent AVM resection, 99 (18.5%) developed de novo epilepsy, with a 1-year cumulative incidence of 13.8%. Patients with epilepsy had higher rates of intracerebral hemorrhage, and intracerebral hemorrhage was less common in the embolization cohort. Patients in the ruptured cohort were older and more often males. After propensity score matching with 18 588 patients with AVM diagnosis but no resection, each group consisted of 529 patients, and de novo epilepsy at 1 year was significantly higher in the AVM resection cohort compared to the nonresection cohort (11.5% vs. 3.4%, p < .001). This analysis of 536 patients provides evidence that de novo epilepsy after brain AVM resection occurs at a 1-year cumulative incidence of 13.8%, with a total of 19.4% developing de novo epilepsy. Intracerebral hemorrhage was inconsistently associated with postoperative de novo epilepsy. De novo epilepsy was significantly less frequent after AVM diagnosis without resection.


Thoracoplasty in thoracic adolescent idiopathic scoliosis.
Retrospective study. To evaluate the effect and outcome of thoracoplasty in conjunction with pedicle screw instrumentation in the treatment of thoracic adolescent idiopathic scoliosis (AIS). Some spine surgeons recently think more correction of hump deformity using pedicle screws without thoracoplasty. Although thoracoplasty has been conventional treatment of rib hump, there are few papers about the results of pedicle screw instrumentation and concomitant thoracoplasty. Eighty-seven patients with thoracic AIS (mean age, 14.4 years) treated by pedicle screw instrumentation were retrospectively analyzed after a minimum follow-up of 2 years. Patients were divided into 3 groups; N-T group (no thoracoplasty with iliac bone graft, n = 37), T+N-DVR [thoracoplasty without direct vertebral rotation (DVR), n = 20] and T+DVR group (thoracoplasty with DVR, n = 30). In the T (T+N-DVR and T+DVR) group, 4 to 8 ribs were resected and used for bone graft. Patients were evaluated for deformity correction, balance, pulmonary function, height and angle of rib hump, clinical outcomes (SRS-30), and complications. In the N-T group, the thoracic curve was corrected from 53 degrees to 16 degrees (69% correction), in the T+N-DVR group from 55 degrees to 18 degrees (69%) and in the T+DVR group from 54 degrees to 10 degrees (81%). There was no difference in postoperative spinal balance and pulmonary function among the 3 groups. The correction rates of hump height and angle were 35% and 38% in the N-T group, respectively, 57% and 58% in the T+N-DVR, and 70% and 72% in the T+DVR. The T group showed significantly better correction of rib hump and self-image score in the SRS-30 questionnaire than the N-T group. There were 8 iliac donor site problems in the N-T group and 3 hemothorax in the T group, which had no adverse effect in the final result. Thoracoplasty showed significantly better rib hump correction, satisfactory clinical outcomes without pulmonary function compromise, or iliac bone graft site morbidity in the treatment of thoracic AIS with pedicle screw instrumentation.


A systematic review of the evidence on symptom management of cancer-related anorexia and cachexia.
To evaluate and synthesize the evidence regarding cancer-related anorexia and cachexia symptom management and make recommendations for future directions. Cochrane Library, MEDLINE, CANCERLIT, CINAHL, Dissertation Abstracts, EBM Reviews--Best Evidence, EMBASE, and the Computer Retrieval of Information on Scientific Projects. Current overviews, clinical trials, systematic research reviews, and meta-analyses. All studies focused on increasing food intake. Nonpharmacologic clinical trials increased caloric and protein intake but resulted in no improvement in nutritional status, weight, tumor response, survival, or quality of life. Weight, appetite, and well-being were improved with megestrol acetate, but nutritional status was not improved. Some exercise studies demonstrated improvements in nutrition-related outcomes, but these were not primary research outcomes. Symptom management of anorexia and cachexia should focus on decreasing energy expenditure or minimizing factors creating a negative energy balance, as well as improving food intake. Increased measurement sensitivity also is needed. Improved nutritional assessment skills are needed with an emphasis on anticipated problems and current status.


Predictive values of beta-trace protein (prostaglandin D synthase) by use of laser-nephelometry assay for the identification of cerebrospinal fluid.
beta-Trace protein (beta-TP) is an immunological marker for the detection of cerebrospinal fluid traces. The aim of the study was to evaluate the predictive values of a new research assay for beta-TP. A total of 154 specimens from patients with otorrhea or rhinorrhea were investigated for cerebrospinal fluid (CSF) by use of a laser-nephelometric assay for beta-TP. Samples were obtained between January 1994 and November 2000. A sample was reported to be positive for CSF when the beta-TP concentration was more than 6 mg/L. Case evaluations were performed retrospectively and tabulated for indication, clinical course, additional investigations, surgical procedure, and follow-up. beta-TP was detected in 16 specimens; 138 samples were negative for beta-TP with a value less than 3 mg/L. One sample was suggestive of CSF traces at 4.6 mg/L. In correlation with the clinical course, the intraoperative findings, intraoperative visualization with sodium fluorescein, high-resolution computed tomography of the paranasal sinuses or the petrous bone, computed tomographic cisternography, magnetic resonance imaging, and radionuclide cisternography, there was no false-positive result. On four occasions, false-negative results occurred, with an overall accuracy of 0.974. The beta-TP test had a negative predictive value of 0.971 and a positive predictive value of 1. Analysis of betas-TP via the nephelometric assay is a valuable and reliable test in cranial base surgery for the identification of CSF.


The role of body size in predator recognition by untrained birds.
It is supposed that body size serves as an important cue in the recognition of relevant stimuli in nature. As predators of varying body size pose differing levels of threat, their potential prey should be able to discriminate between them. We tested the reaction of great tits (Parus major) to the dummies of their common predator (the European sparrowhawk-Accipiter nisus) in natural and reduced body sizes under laboratory conditions. All of the tested dummies possessed local raptor-specific features (hooked beak, claws with talons, and conspicuous eyes), but differed in global species-specific features: body size (large - the size of a sparrowhawk, small - the size of a great tit) and colouration (sparrowhawk, great tit, robin, and pigeon). The sparrowhawk-coloured dummies evoked fear regardless of their size while both great tit- and pigeon-coloured dummies evoked no fear reaction. The body size was used as the cue only for the discrimination of the robin-coloured dummies. The differences in reactions to the dummies with robin colouration (species unimportant to the great tits) could be explained as that the tits are able to recognize these birds in nature, but not so undoubtedly as the predator or the conspecific.


Electrophysiologic characteristics of a dilated atrium in patients with paroxysmal atrial fibrillation and atrial flutter.
This study investigated the difference of atrial electrophysiologic characteristics between a normal and dilated atrium and compared them among patients with paroxysmal atrial fibrillation and flutter. Twenty-seven patients with paroxysmal atrial fibrillation and 28 patients with paroxysmal atrial flutter were divided into four subgroups, according to the presence of a normal atrium or bilateral atrial enlargement. Thirty patients without atrial arrhythmia (20 patients with normal atrium and 10 patients with bilateral atrial enlargement) were included in control group. The atrial refractoriness in patients with a dilated atrium was longer than those with normal atrial size. In patients with paroxysmal atrial fibrillation and patients of control group, the P-wave duration and interatrial conduction velocity with or without atrial enlargement were similar. However, in patients with paroxysmal atrial flutter, P-APCS (86 +/- 10 ms vs. 73 +/- 9 ms, p < 0.05) and P-ADCS (109 +/- 9 ms vs. 95 +/- 9 ms, p < 0.05) in patients with a dilated atrium were longer than in patients with a normal atrium. The patients with paroxysmal atrial fibrillation or atrial flutter all demonstrated longer P-wave duration and interatrial conduction time than control group. Among the groups with a normal atrium or a dilated atrium, atrial refractoriness in patients with paroxysmal atrial flutter was shorter than that in control group. Moreover, in the patients with a normal atrium, the potential minimal wavelength in control group (6.6 +/- 1.7) was longer than that of paroxysmal atrial fibrillation (5.3 +/- 1.1), or atrial flutter (5.0 +/- 1.2). These findings suggest that atrial electrophysiologic characteristics of a dilated atrium were different from those of normal atrium, and these changes were different between paroxysmal atrial fibrillation and flutter. Multiple factors are considered to be related to the genesis of atrial tachyarrhythmias.


Overage labor, value perceptions, and happiness in urban older adults' lives: Empirical evidence from China.
Over the past four decades, China has seen a rapid increase in the level of urbanization, along with an increasing number of older adults. How to promote active aging in the midst of rapid urbanization has become a new challenge for the Chinese government and all sectors of society. This study attempts to verify the relationship between overage labor and happiness in life, and further explore the possible mediating role of multidimensional value perceptions. Based on 5010 valid samples from the 2011, 2013, 2015, and 2018 China Health and Aging Tracking Survey datasets (CHARLS), the study explored and tested the differences in happiness in life between older adults with overage labor and retired older adults. In addition, this study further examined the mediating role of multidimensional value perceptions using a mediation model. (1) Urban older adults with overage labor had significantly higher levels of happiness in life compared to urban retired older adults. (2) The higher level of life happiness of urban older adults with overage labor depends on their perceptions of different values; (3) Specifically, the realization of value perceptions in personal, family and social dimensions through labor contributes to the life happiness of urban older adults with overage labor. There is a significant difference between urban old adults with overage labor and urban retired old adults in terms of happiness in life. At the same time, the study confirmed that all three aspects of value perceptions, such as personal, family and social, are the mediating mechanisms between overage labor and urban old adults in terms of happiness in life.


Supporting implementation science and health equity in cancer prevention and control through research networks.
The Cancer Prevention and Control Research Network (CPCRN) is a national network of academic, public health, and community organizational partners across multiple geographic sites who collaborate to reduce the cancer burden in diverse communities. Given key recommendations that suggest the need for cross-disciplinary collaboration in cancer prevention and control, we sought to explore the historical and contemporary evolution of health equity and disparities research as an area of focus within the CPCRN over time. We conducted 22 in-depth interviews with former and current leaders, co-investigators, and other members of the network. Several key themes emerged from data that were analyzed and interpreted using a constructivist, reflexive, thematic analysis approach. Nearly all participants reported a strong focus on studying health disparities since the inception of the CPCRN, which offered the network a distinct advantage in recent years for incorporating an intentional focus on health equity. Recent law enforcement injustices and the inequities observed during the COVID-19 pandemic have further invigorated network activities around health equity, such as development of a health equity-focused workgroup toolkit, among other cross-center activities. Several participants noted that, in terms of deep, meaningful, and impactful health equity-oriented research, there are still great strides for the network to make, while also acknowledging CPCRN as well-aligned with the national dialogue led by federal agency partners around health equity. Finally, several future directions were mentioned by the participants, including a focus on supporting a diverse workforce and engaging organizational partners and community members in equity-focused research. Findings from these interviews provide direction for the network in advancing the science in cancer prevention and control, with a strengthened focus on health equity.


Synergistic embryotoxicity of combination pyrimethamine and folic acid in rats.
The increased embryotoxicity of pyrimethamine (PYM) with concomitant oral dosing of folic acid (FA) was examined in rats. The preventive effects of folinic acid (FNA) on PYM embryotoxicity were also examined. Six groups were constructed: PYM I (PYM 1.2 mg/kg/day), FA (FA 50 mg/kg/day), PYM I+FA (1.2 and 50 mg/kg/day, respectively), PYM II (2.7 mg/kg/day), PYM II+FNA (2.7 and 12 mg/kg/day, respectively), and a vehicle control group. The agents were administered for 11 days from day 7 throughout 17 of gestation. PYM and FA were administered by gavage and FNA was administered intraperitoneally. Visceral and skeletal malformations were observed in the fetuses of both PYM I+FA and PYM II groups; these included dilatation of the lateral ventricle and fused ribs. No malformed fetuses were observed in the fetuses of the other four groups. External malformations were observed only in the fetuses of PYM II groups; these included cleft palate, cleft lips, and brachygnathia, among others. These results show that the concomitant gavage dosing of FA augments PYM embryotoxicity. The preventive effects of FNA were also confirmed.


Mycorrhizal detection of native and non-native truffles in a historic arboretum and the discovery of a new North American species, Tuber arnoldianum sp. nov.
During a study comparing the ectomycorrhizal root communities in a native forest with those at the Arnold Arboretum in Massachusetts (USA), the European species Tuber borchii was detected on the roots of a native red oak in the arboretum over two successive years. Since T. borchii is an economically important edible truffle native to Europe, we conducted a search of other roots in the arboretum to determine the extent of colonization. We also wanted to determine whether other non-native Tuber species had been inadvertently introduced into this 140-year-old Arboretum because many trees were imported into the site with intact soil and roots prior to the 1921 USDA ban on these horticultural practices in the USA. While T. borchii was not found on other trees, seven other native and exotic Tuber species were detected. Among the North American Tuber species detected from ectomycorrhizae, we also collected ascomata of a previously unknown species described here as Tuber arnoldianum. This new species was found colonizing both native and non-native tree roots. Other ectomycorrhizal taxa that were detected included basidiomycetes in the genera Amanita, Russula, Tomentella, and ascomycetes belonging to Pachyphlodes, Helvella, Genea, and Trichophaea. We clarify the phylogenetic relationships of each of the Tuber species detected in this study, and we discuss their distribution on both native and non-native host trees.


Structure and function analysis of the essential 3'X domain of hepatitis C virus.
The 3'X domain of hepatitis C virus has been reported to control viral replication and translation by modulating the exposure of a nucleotide segment involved in a distal base-pairing interaction with an upstream 5BSL3.2 domain. To study the mechanism of this molecular switch, we have analyzed the structure of 3'X mutants that favor one of the two previously proposed conformations comprising either two or three stem-loops. Only the two-stem conformation was found to be stable and to allow the establishment of the distal contact with 5BSL3.2, and also the formation of 3'X domain homodimers by means of a universally conserved palindromic sequence. Nucleotide changes disturbing the two-stem conformation resulted in poorer replication and translation levels, explaining the high degree of conservation detected for this sequence. The switch function attributed to the 3'X domain does not occur as a result of a transition between two- and three-stem conformations, but likely through the sequestration of the 5BSL3.2-binding sequence by formation of 3'X homodimers.


Effects of changes in diet energy density and milking frequency and a single injection of cabergoline at dry-off on feeding behavior and rumination time in dairy cows.
Dry-off is a typical management practice, but research on the effects of dry-off on feeding behavior in high-yielding cows is limited. The present study investigated the effects of 2 diet energy densities: lactation diet (normal energy density, NORM) versus a lactation diet diluted with 30% straw (reduced energy density, REDU), both offered ad libitum, and 2 daily milking frequencies (2× vs. 1×) during the 7 d before dry-off day (d 0), and the effects of an injection of either a dopamine agonist [cabergoline (CAB); Velactis, Ceva Santé Animale; labeled for use only with abrupt dry-off; i.e., no reduction in feeding level or milking frequency before the last milking] or saline (SAL) following the last milking on d 0 (2 × 2 × 2 factorial arrangement), on automatically monitored feeding behavior and rumination time in 119 clinically healthy, loose-housed, pregnant, lactating Holstein cows during the week before and after d 0. From d 0, all cows were fed the same dry-cow diet ad libitum. Data were analyzed in R using mixed-effects models. Over the days before d 0, REDU cows spent 30% more time feeding at a 50% lower feeding rate, visited both assigned and unassigned feed bins more frequently, and spent more time ruminating than NORM cows. No clear behavioral effects of reduced milking frequency were found. Within 24 h following injection, CAB cows spent approximately 40% less time feeding at a lower feeding rate, visited their feed bin 28% less often, and spent 40% less time ruminating than SAL cows, irrespective of treatment before dry-off. The current study demonstrates that reducing diet energy density for 1 wk before dry-off led to clear behavioral changes in high-yielding cows. Administering CAB after the last milking induced decreased feeding behavior lasting approximately 24 h, indicating collateral effects other than reduced prolactin secretion.


Backbone resonances assignment of 19 kDa CD1 domain of human mitotic checkpoint serine/threonine-protein kinase, Bub1.
Bub1 is an evolutionarily conserved mitotic checkpoint control protein that is present in diverse organisms including yeast and humans. Bub1 is a serine/threonine protein kinase and is required for recruitment of Mad1, Mad2, Bub3, and CENP-E to kinetochores (Sharp-Baker and Chen in J Cell Biol 153:1239-1250, 2001). The evolutionarily conserved amino acid region in the N-terminus has been called as the CD1 domain. To clarify the action mechanism of Bub1 in controlling check point signals, we initiated an NMR structure determination of the Bub1 CD1 domain. Here, we report the sequence-specific backbone resonance assignments of CD1 domain of human Bub1 (hBub1CD1).


Nanometallic glasses: size reduction brings ductility, surface state drives its extent.
We report tensile experiments on Ni80P20 metallic glass samples fabricated via a templated electroplating process and via focused ion beam milling, which differed only in their surface energy states: Ga-ion-irradiated and as-electroplated. Molecular dynamics simulations on similar Ni80Al20 systems corroborate the experimental results, which suggest that the transition from brittle to ductile behavior is driven by sample size, while the extent of ductility is driven by surface state.


Binding varicella zoster virus: an underestimated facet of insulin-degrading enzyme´s implication for Alzheimer´s disease pathology?
We shortly discuss a possible contribution of insulin-degrading enzyme to Alzheimer´s disease pathology by binding varicella zoster virus glycoprotein E, which increases the infectivity and cell-cell spread of the virus.


Pyrene degradation by yeasts and filamentous fungi.
The saprotrophic soil fungi Fusarium solani (Mart.) Sacc., Cylindrocarpon didymum (Hartig) Wollenw, Penicillium variabile Sopp. and the yeasts Rhodotorula glutinis (Fresenius) Harrison and Rhodotorula minuta (Saito) Harrison were cultured in mineral medium with pyrene. The remaining pyrene concentrations were periodically determined during 20 incubation days, using HPLC. To assess the metabolism of pyrene degradation we added 0.1 microCi of [4,5,9,10] 14C-pyrene to each fungi culture and measured the radioactivity in the volatile organic substances, extractable, aqueous phase, biomass and 14CO2 fractions. The assays demonstrated that F. solani and R. glutinis metabolized pyrene as a sole source of carbon. Differences in their activities at the beginning of the cultures disappeared by the end of the experiment, when 32 and 37% of the original pyrene concentration was detected, for the soil fungi and yeasts, respectively. Among the filamentous fungi, F. solani was highly active and oxidized pyrene; moreover, small but significant degradation rates were observed in C. didymum and P. variahile cultures. An increase in the 14CO2 evolution was observed at the 17th day with cosubstrate. R. glutinis and R. minuta cultures showed similar ability to biotransform pyrene, and that 35% of the initial concentration was consumed at the end of the assay. The same results were obtained in the experiments with or without glucose as cosubstrate.


Direct in vivo assessment of human stem cell graft-host neural circuits.
Despite the potential of stem cell-derived neural transplants for treating intractable neurological diseases, the global effects of a transplant's electrical activity on host circuitry have never been measured directly, preventing the systematic optimization of such therapies. Here, we overcome this problem by combining optogenetics, stem cell biology, and neuroimaging to directly map stem cell-driven neural circuit formation in vivo. We engineered human induced pluripotent stem cells (iPSCs) to express channelrhodopsin-2 and transplanted resulting neurons to striatum of rats. To non-invasively visualize the function of newly formed circuits, we performed high-field functional magnetic resonance imaging (fMRI) during selective stimulation of transplanted cells. fMRI successfully detected local and remote neural activity, enabling the global graft-host neural circuit function to be assessed. These results demonstrate the potential of a novel neuroimaging-based platform that can be used to identify how a graft's electrical activity influences the brain network in vivo.


Expression, purification, and characterization of human malonyl-CoA decarboxylase.
The recombinant human malonyl-CoA decarboxylase (hMCD) was overexpressed in Escherichia coli with and without the first 39 N-terminal amino acids via a cleavable MBP-fusion construct. Proteolytic digestion using genenase I to remove the MBP-fusion tag was optimized for both the full length and truncated hMCD. The apo-hMCD enzymes were solubilized and purified to homogeneity. Steady-state kinetic characterization showed similar kinetic parameters for the MBP-fused and apo-hMCD enzymes with an apparent Km value of approximately 330-520 microM and a turnover rate kcat of 13-28s(-1). For the apo-hMCD enzymes, the N-terminal truncated hMCD was well tolerated over a broad pH range (pH 4-10); whereas the full-length hMCD appeared to be stable only at pH >/= 8.5. Our results showed that the N-terminal region of hMCD has no effect on the catalytic activity of the enzyme but plays a role in the folding process and conformation stability of hMCD.


Synchronization of the circadian clock by time-restricted feeding with progressive increasing calorie intake. Resemblances and differences regarding a sustained hypocaloric restriction.
Circadian rhythms are the product of the interaction of molecular clocks and environmental signals, such as light-dark cycles and eating-fasting cycles. Several studies have demonstrated that the circadian rhythm of peripheral clocks, and behavioural and metabolic mediators are re-synchronized in rodents fed under metabolic challenges, such as hyper- or hypocaloric diets and subjected to time-restricted feeding protocols. Despite the metabolic challenge, these approaches improve the metabolic status, raising the enquiry whether removing progressively the hypocaloric challenge in a time-restricted feeding protocol leads to metabolic benefits by the synchronizing effect. To address this issue, we compared the effects of two time-restricted feeding protocols, one involved hypocaloric intake during the entire protocol (HCT) and the other implied a progressive intake accomplishing a normocaloric intake at the end of the protocol (NCT) on several behavioural, metabolic, and molecular rhythmic parameters. We observed that the food anticipatory activity (FAA) was driven and maintained in both HCT and NCT. Resynchronization of hepatic molecular clock, free fatty acids (FFAs), and FGF21 was elicited closely by HCT and NCT. We further observed that the fasting cycles involved in both protocols promoted ketone body production, preferentially beta-hydroxybutyrate in HCT, whereas acetoacetate was favoured in NCT before access to food. These findings demonstrate that time-restricted feeding does not require a sustained calorie restriction for promoting and maintaining the synchronization of the metabolic and behavioural circadian clock, and suggest that metabolic modulators, such as FFAs and FGF21, could contribute to FAA expression.


[Novel mutation of the GPIIIa gene in the Russian population, Leu40Arg, linked to the Leu33Pro].
Glycoprotein IIb/IIIa complex, a platelet surface fibrinogen receptor, plays a key role in producing primary hemostasis. At present, only a single mutation in the GPIIla gene, Leu33Pro, and a single mutation in the GPIIb gene, lle843Ser, has been described. The mutations are known to enhance signaling functions of the receptor and are associated with the development of arterial thromboses. In the present study, we describe a novel GPIIIa mutation, which is T to G nucleotide substitution in position 1585, resulting in the replacement of Leu for Arg in position 40 of the amino acid sequence of the protein.


Partial resistance to peroxisome proliferator-activated receptor-alpha agonists in ZDF rats is associated with defective hepatic mitochondrial metabolism.
Fluxes through mitochondrial pathways are defective in insulin-resistant skeletal muscle, but it is unclear whether similar mitochondrial defects play a role in the liver during insulin resistance and/or diabetes. The purpose of this study is to determine whether abnormal mitochondrial metabolism plays a role in the dysregulation of both hepatic fat and glucose metabolism during diabetes. Mitochondrial fluxes were measured using (2)H/(13)C tracers and nuclear magnetic resonance spectroscopy in ZDF rats during early and advanced diabetes. To determine whether defects in hepatic fat oxidation can be corrected by peroxisome proliferator-activated receptor (PPAR-)-alpha activation, rats were treated with WY14,643 for 3 weeks before tracer administration. Hepatic mitochondrial fat oxidation in the diabetic liver was impaired twofold secondary to decreased ketogenesis, but tricarboxylic acid (TCA) cycle activity and pyruvate carboxylase flux were normal in newly diabetic rats and elevated in older rats. Treatment of diabetic rats with a PPAR-alpha agonist induced hepatic fat oxidation via ketogenesis and hepatic TCA cycle activity but failed to lower fasting glycemia or endogenous glucose production. In fact, PPAR-alpha agonism overstimulated mitochondrial TCA cycle flux and induced pyruvate carboxylase flux and gluconeogenesis in lean rats. The impairment of certain mitochondrial fluxes, but preservation or induction of others, suggests a complex defect in mitochondrial metabolism in the diabetic liver. These data indicate an important codependence between hepatic fat oxidation and gluconeogenesis in the normal and diabetic state and potentially explain the sometimes equivocal effect of PPAR-alpha agonists on glycemia.


The miR-126-5p and miR-212-3p in the extracellular vesicles activate monocytes in the early stage of radiation-induced vascular inflammation implicated in atherosclerosis.
People exposed to radiation in cancer therapy and nuclear accidents are at increased risk of cardiovascular outcomes in long-term survivors. Extracellular vesicles (EVs) are involved in radiation-induced endothelial dysfunction, but their role in the early stage of vascular inflammation after radiation exposure remains to be fully understood. Herein, we demonstrate that endothelial cell-derived EVs containing miRNAs initiate monocyte activation in radiation-induced vascular inflammation. In vitro co-culture and in vivo experimental data showed that endothelial EVs can be sensitively increased by radiation exposure in a dose-dependent manner, and stimulate monocytes releasing monocytic EVs and adhesion to endothelial cells together with an increase in the expression of genes encoding specific ligands for cell-cell interaction. Small RNA sequencing and transfection using mimics and inhibitors explained that miR-126-5p and miR-212-3p enriched in endothelial EVs initiate vascular inflammation by monocyte activation after radiation exposure. Moreover, miR-126-5p could be detected in the circulating endothelial EVs of radiation-induced atherosclerosis model mice, which was found to be tightly correlated with the atherogenic index of plasma. In summary, our study showed that miR-126-5p and miR-212-3p present in the endothelial EVs mediate the inflammatory signals to activate monocytes in radiation-induced vascular injury. A better understanding of the circulating endothelial EVs content can promote their use as diagnostic and prognostic biomarkers for atherosclerosis after radiation exposure.


Total urine oestriol by a modification of a commercial plasma oestriol kit.
An adaptation of a radioimmunoassay for plasma oestriol for assaying urine oestriol is presented. The method has been shown to be precise, reliable, and directly comparable with the manual spectrophotometric technique for urine oestriol.


Reversible and irreversible changes of the stria vascularis. An evaluation of the effects of ethacrynic acid separately and in combination with atoxyl.
The morphological changes in the cochlea following administration of ethacrynic acid occur initially in the stria vascularis of the basal coils as an increased intracellular vesiculation of the marginal cells followed by inter- and intracellular oedema in the intermediate cell layer. The combined administration of ethacrynic acid and atoxyl (individual doses) can cause irreversible damage to the cochlear hair cells and the stria vascularis, while the administration of each of them separately in the same low dose did not cause hair cell degeneration or persistent morphological changes of the stria vascularis. An increased penetration of atoxyl into the cochlea is likely to occur due to the ethacrynic acid-induced changes in the permeability of the endolymphatic partition so that the earlier known penetration of atoxyl into the cochlea is increased.


Wright central plication of lateral rectus versus standard medial rectus recession in adult divergence insufficiency esotropia.
Wright central plication is a minimally invasive tightening procedure described for the first time by Wright and colleagues in 2012. We compare outcomes of lateral rectus central plication (LRCP) to medial rectus recession (MRR) in the treatment of adult divergence insufficiency esotropia (ADIE). A retrospective chart review of 30 consecutive patients with ADIE, who underwent either LRCP or MRR between 2010 and 2015 was performed. age ≥45 years, LRCP or MRR surgery fixed suture technique, esotropia (ET) at least 10Δ greater at distance than at near, subjective diplopia at distance, fusion at near fixation, follow-up of at least 6 months. Primary outcome was postoperative single binocular vision. Secondary outcome was postoperative deviation of <5Δ. A total of 28 patients (15 females) met inclusion criteria: 15 had LRCP and 13 MRR. Primary outcome of no diplopia was not significantly different between LRCP and MRR group having a success rate of 93.3% versus 92.3%, respectively (P ≤ 0.01). Secondary outcome of a deviation of ≤5Δ at distance was better in the LRCP group than the MRR group (15/15 vs 11/13 [P ≥ 0.01]). One patient in LRCP group had an early overcorrection corrected by in-office suture lysis. Both procedures had excellent primary outcomes eliminating diplopia in over 90% of cases. The LRCP group had statistically better postoperative alignment of <5Δ. The Wright LRCP has the advantage of being minimally invasive, semi-reversible, vessel sparing, and can be done with topical anesthesia.


Synthesis of zigzag-chain and cyclic-octanuclear calcium complexes and hexanuclear bulky aryl-phosphate sodium complexes with ortho-amide groups: structural transformation involving a network of inter- and intramolecular hydrogen bonds.
Three new polynuclear Ca(II)- and Na(I) phosphate complexes with two strategically oriented bulky amide groups, 2,6-(PhCONH)(2)C(6)H(3)OPO(3)H(2), were synthesized, including one with a zigzag-chain, [Ca(II)[O(3)POC(6)H(3)-2,6-(NHCOPh)(2)](H(2)O)(4)(EtOH)](n), a cyclic-octanuclear form, [Ca(II)(8)[O(3)POC(6)H(3)-2,6-(NHCOPh)(2)](8)(O=CHNMe(2))(8)(H(2)O)(12)], and a hexanuclear complex, (NHEt(3))[Na(3)[O(3)POC(6)H(3)-2,6-(NHCOPh)(2)](2)(H(2)O)(MeOH)(7)]. X-ray crystallography revealed that all have an unsymmetric ligand position due to the bulky amide groups. A dynamic transformation of the Ca(II) zigzag-chain structure to the cyclic-octanuclear complex was induced by changing coordination of DMF molecules, which caused a reorganization of the intermolecular/intramolecular hydrogen bond network.


A novel dual-function molecularly imprinted polymer on CdTe/ZnS quantum dots for highly selective and sensitive determination of ractopamine.
A novel dual-function material was synthesized by anchoring a molecularly imprinted polymer (MIP) layer on CdTe/ZnS quantum dots (QDs) using a sol-gel with surface imprinting. The material exhibited highly selective and sensitive determination of ractopamine (RAC) through spectrofluorometry and solid-phase extraction (SPE) coupled with high performance liquid chromatography (HPLC). A series of adsorption experiments revealed that the material showed high selectivity, good adsorption capacity and a fast mass transfer rate. Fluorescence from the MIP-coated QDs was more strongly quenched by RAC than that of the non-imprinted polymer, which indicated that the MIP-coated QDs acted as a fluorescence sensing material could recognize RAC. In addition, the MIP-coated QDs as a sorbent was also shown to be promising for SPE coupled with HPLC for the determination of trace RAC in feeding stuffs and pork samples. Under optimal conditions, the spectrofluorometry and SPE-HPLC methods using the MIP-coated QDs had linear ranges of 5.00×10(-10)-3.55×10(-7) and 1.50×10(-10)-8.90×10(-8) mol L(-1), respectively, with limits of detection of 1.47×10(-10) and 8.30×10(-11) mol L(-1), the relative standard deviations for six repeat experiments of RAC (2.90×10(-9) mol L(-1)) were below 2.83% and 7.11%.


Characteristics and metal leachability of incinerated sewage sludge ash and air pollution control residues from Hong Kong evaluated by different methods.
The improper disposal of incinerated sewage sludge ash (ISSA) and air pollution control residues (APCR) from sewage sludge incinerators has become an environmental concern. The physicochemical, morphological and mineralogical characteristics of ISSA and APCR from Hong Kong, and the leachability and risk of heavy metals, are presented in this paper. The results showed that a low hydraulic and pozzolanic potential was associated with the ISSA and APCR due to the presence of low contents of SiO2, Al2O3 and CaO and high contents of P, S and Cl (especially for APCR). Although high concentrations of Zn and Cu (especially for ISSA) followed by Ni, Pb and As, Se were detected, a low leaching rate of these metals (especially at neutral and alkaline pH) rendered them classifiable as non-hazardous according to the U.S. EPA and Chinese national regulatory limits. The leached metals concentrations from ISSA and APCR were mainly pH dependent, and metals solubilization occurred mainly at low pH. Different leaching tests should be adopted based on the simulated different environmental conditions and exposure scenarios for assessing the leachability as contrasting results could be obtained due to the differences in complexing abilities and final pH of the leaching solutions.


Cerebral arteriovenous malformations (C. AVM) and associated arterial aneurysms (AA). Analysis of 101 C. AVM cases, with 37 AA in 23 patients.
We report a series of 101 patients with cerebral arteriovenous malformations (CAVM), in which 23 cases presented with one or several arterial aneurysm(s) (AA). Each AA could be classified into distal intra-lesional, proximal or remote. Patients with CAVM + AA tend to be older and more frequently present with epilepsy, haemorrhage events and neurological deficits. Of these 23 patients, 16 had their AVM treated partially or totally by embolization. In our series, the endovascular treatment of the arteriovenous shunt with a proximal AA on the same vessel has resulted in at least a regression, and sometimes a disappearance of the arterial ectasia. Although partial treatment of the AVM does no erase the risk of haemorrhage from the malformation itself, it may diminish the chance of developing a flow-related AA or any other expression of the high-flow angiopathy.


Potentiating action of MKC-242, a selective 5-HT1A receptor agonist, on the photic entrainment of the circadian activity rhythm in hamsters.
Serotonergic projections from the midbrain raphe nuclei to the suprachiasmatic nuclei (SCN) are known to regulate the photic entrainment of circadian clocks. However, it is not known which 5-hydroxytryptamine (5-HT) receptor subtypes are involved in the circadian regulation. In order to verify the role of 5-HT1A receptors, we examined the effects of 5-¿3-[((2S)-1,4-benzodioxan-2-ylmethyl)amino]-propoxy¿-1,3-b enzodioxole HCl (MKC-242), a selective 5-HT1A receptor agonist, on photic entrainment of wheel-running circadian rhythms of hamsters. MKC-242 (3 mg kg(-1), i.p.) significantly accelerated the re-entrainment of wheel-running rhythms to a new 8 h delayed or advanced light-dark cycle. MKC-242 (3 mg kg(-1), i.p.) also potentiated the phase advance of the wheel-running rhythm produced by low (5 lux) or high (60 lux) intensity light pulses. In contrast, 8-hydroxydipropylaminotetralin (8-OH-DPAT)(5 mg kg(-1), i.p.), a well known 5-HT1A/5-HT7 receptor agonist, only suppressed low intensity (5 lux) light-induced phase advances. The potentiating actions of MKC-242 on light pulse-induced phase advances were observed even when injected 20 or 60 min after the light exposure. The potentiating action of MKC-242 was antagonized by WAY100635, a selective 5-HT1A receptor blocker, but not by ritanserin, a 5-HT2/5-HT7 receptor blocker, indicating that MKC-242 is activating 5-HT1A receptors. Light pulse-induced c-fos expression in the SCN and the intergeniculate leaflet (IGL) were unaffected by MKC-242 (3 mg kg(-1), i.p.). HPLC analysis demonstrated that MKC-242 (3 mg kg(-1), i.p.) decreased the 5-HIAA content in the SCN. The present results suggest that presynaptic 5-HT1A receptor activation may be involved in the potentiation of photic entrainment by MKC-242 in hamsters.


Purine agonists prevent trophic changes caused by sympathetic denervation.
Surgical denervation of the lateral saphenous vein of the dog causes marked extraneuronal changes, both of a morphological and functional type. In an attempt to investigate the factor(s) responsible for the trophic effects exerted by the sympathetic innervation on the dog saphenous vein we studied the effects of noradrenaline, adenosine, inosine and N-ethylcarboxamidoadenosine (NECA) on vascular tissue after sympathetic denervation. The saphenous vein was denervated using either surgical or chemical (6-hydroxydopamine, 6-OHDA) methods. Noradrenaline (0.1 microgram/kg per h), adenosine (10 micrograms/kg per h), inosine (10 micrograms/kg per h) or NECA (0.1 microgram/kg per h) were delivered continuously for 5 days through Alzet minipumps connected to the vein. 6-OHDA-induced denervation resulted in morphological changes similar to those described for surgical denervation. Smooth muscle cells and fibroblasts showed ultrastructural signs of increased synthetic activity and their size was significantly increased. In confirmation of earlier studies, constant i.v. infusions of noradrenaline did not prevent the morphological changes induced by denervation. Adenosine prevented the morphological changes induced by chemical or surgical denervation. Similarly to adenosine, infused NECA prevented the structural consequences of denervation. In contrast, inosine did not prevent the changes caused by surgical denervation. The results are compatible with an involvement of purines in the trophic effects of sympathetic innervation. Moreover, the effects of adenosine do not appear to be mediated by inosine.


Development of enzyme-linked immunosorbent assays for the detection of deacetoxycephalosporin C and isopenicillin N synthase activity.
Although there are a number of existing assays for monitoring the activity of both isopenicillin N synthase (IPNS) and deacetoxycephalosporin C synthase (DAOCS), none have demonstrated the qualities required for screening a mutant library. Hence, enzyme-linked immunosorbent assays (ELISAs) for IPNS and DAOCS were developed based on the detection of the catalytic turnover products isopenicillin N and cephalexin/phenylacetyl-7-aminodeacetoxycephalosporanic acid (G-7-ADCA), respectively. These assays are relatively fast compared to existing assays, such as the hole-plate bioassay, and are amenable with high-throughput screening. Both the IPNS and DAOCS-ELISAs were optimised for use with crude protein extracts rather than purified protein, thereby eliminating any additional time required for purification. The ELISA developed for the detection of cephalexin had an IC50 value of 154+/-9 ng mL(-1) and LOD of 7.2+/-2.2 ng mL(-1) under conditions required for the assay. Good recoveries and correlation was observed for spiked samples when the concentration of crude protein was kept below 1 mg mL(-1). The DAOCS-ELISA was found to have increased sensitivity compared to the hole-plate bioassay (10.3 microg mL(-1)). The IPNS-ELISA did not significantly increase the sensitivity (approximately 5 microg mL(-1)) compared to that of the hole-plate bioassay (16 microg mL(-1)) for isopenicillin N. The minimum amount of crude protein extract required for producing detectable amounts of product for both assays was below 0.5% of the maximum amount of protein that the assay could contain without any effect on the ELISA. This suggests that when screening a mutant library, mutants producing low amounts of the product could still be detected using these assays.


Immunohistochemical localization of S100A1 and S100A6 in postnatally developing salivary glands of rats.
S100 proteins are calcium-binding proteins of the EF-hand superfamily and are involved in the regulation of a number of cellular processes. The present study deals with the immunohistochemical expression of S100A1 and S10100A6 in the rat submandibular and sublingual glands during postnatal development from day 0 to 12 weeks. Expression of S100A1 was particularly concentrated in pillar and transition cells in the granular convoluted tubule (GCT) and in striated duct cells of the submandibular gland age 4 weeks to maturity. None or only weak staining for S100A1 was observed in the duct segment at 0-5 days. On the contrary, immunostaining of S100A6 was present in proacinar cells in undifferentiated submandibular gland at age 3 days to 2 weeks. S100A6 immunoreactivity in rat submandibular gland coexisted with chromogranin reactivity. It is possible that S100A6 regulates secretion of chromogranin in proacinar cells. Secretion of growth factors and biologically active peptides in the GCT are regulated by calcium signals, and S100A1 may be involved in the secretory mechanism of granular cells. S100A1 and S100A6 are potentially of great importance in secretory functions of granular cells and proacinar cells, as well as in rat salivary glands.


Alteration in lymphocyte population and humoral immune response in type 2 diabetic Goto-Kakizaki rats.
Proinflammatory cytokine production by a skewed T cell compartment has been shown to be elevated in patients with type 2 diabetes (T2D). However, it is unknown whether humoral immune response controlled by lymphocytes is altered in T2D. Lymphocyte populations and immunoglobulin production were investigated in Goto-Kakizaki (G-K) rat, which is a genetic experimental model for T2D, and Wistar rat as a control. Each lymphocyte population was analyzed using flow cytometry. Immunoglobulin in plasma was measured before and after immunization with ovalbumin. The immunoglobulin subclasses and ovalbumin-specific immunoglobulins were measured by enzyme-immunoassay. Effects of improvement in hyperglycemia of G-K rats by chronic diet restriction on lymphocyte populations were also investigated. T/B lymphocyte ratios in blood and spleen from the G-K rats were significantly higher than those from the Wistar rats. The difference in the T/B cell ratio in blood of the G-K and Wistar rats was not affected by the diet restriction and the immunization. The ability of immunoglobulin production in G-K rats was comparable to that in Wistar rats, while the levels of natural IgM and ovalbumin-specific IgG2a were higher in plasma from the G-K rats than in plasma from the Wistar rats. Since helper T cell type 2 (Th2) is known to regulate the class switch to IgG2a in rats, the results of this study suggest that G-K rats are characterized as immunologically Th2 dominant, resulting in increases in natural IgM and T/B cell ratio.


Adiponectin levels in patients with colorectal cancer and adenoma: a meta-analysis.
Inconsistent results with regard to adiponectin levels in patients with colorectal cancer (CRC) and adenoma have been reported. To evaluate adiponectin levels in patients with CRC and adenoma, a meta-analysis on studies which compared adiponectin levels in patients with CRC or adenoma with healthy controls was carried out. A literature search was performed through Pubmed, EMBASE, and Science Citation Index Expanded database. Pooled-weighted mean differences and 95% confidence intervals (95%CI) were calculated by using random-effects models. Heterogeneity between studies was assessed using the Cochran's Q and I statistics. A total of 13 studies were identified, which included 2632 cases of CRC or adenoma and 2753 healthy controls. Adiponectin levels were significantly lower in patients with CRC or adenoma compared with healthy controls, with significant heterogeneity [weighted mean differences of -1.51 (95% CI: -2.42 to -0.59; Pheterogeneity<0.001) for CRC and -1.29 (95% CI: -2.01to -0.58; Pheterogeneity<0.001) for colorectal adenoma, respectively]. On stratified analysis of CRC, significant difference in adiponectin levels between patients with CRC and healthy controls was reported only in case-control studies or small sample size studies (n<100), but not in nested case-control studies or large sample size studies (n≥100). In addition, metaregression analysis indicated that study design and sample size partly contributed to the significant heterogeneity (P=0.022 for study design and P=0.018 for sample size, respectively). For colorectal adenoma studies, stratified analysis indicated that sample size was one of the heterogeneous factors. Sensitivity analysis showed that there were no changes in the direction of effect when any one study was excluded. No publication bias was detected. Adiponectin levels are lower in patients with CRC or colorectal adenoma compared with those in healthy controls. Future studies are warranted to clarify the association of adiponectin levels and carcinogenesis of the colorectum.


Identification of a 7-basepair deletion in the adenine phosphoribosyltransferase gene as a cause of 2,8-dihydroxyadenine urolithiasis.
We describe a family of Turkish origin with adenine phosphoribosyltransferase (APRT) deficiency and renal stone disease. The proband had 2,8-dihydroxyadenine urolithiasis but an older sister, who was also deficient in enzyme activity, is so far asymptomatic. The proband was homozygous for a 7-bp deletion in exon 3 of the APRT gene. One allele from each of the parents also contained this deletion. The patient and her father were homozygous for an intragenic TaqI RFLP (1.25-kb fragment) whereas the mother was heterozygous (1.25- and 1.91-kb fragments), indicating that the mutation was present on the allele carrying the 1.25 kb TaqI fragment. The deletion alters the reading frame downstream of codon 93 and would be expected to abolish enzyme activity.


Do children with left ventricular noncompaction and a noncompaction-to-compaction ratio < 2 have a better prognosis?
Ultrasonography is commonly used to diagnose left ventricular noncompaction (LVNC). A ratio of noncompacted to compacted myocardium (NC/C ratio) > >2 is often used to diagnose LVNC. However, a large proportion of patients with noncompact myocardium have NC/C < 2, and the prognosis of these patients have not been studied. We included children diagnosed with LVNC between 0 and 15 years of age from January 2007 to December 2018. LVNC was diagnosed based on Stöllberger standard when over three trabeculae were found to be associated with the interventricular recesses. A maximal end systolic ratio of noncompacted to compacted layers was NC/C ratio. Outcomes for LVNC subjects with NC/C < 2 and NC/C > 2 were compared using Kaplan-Meier methods. There were 124 newly diagnosed LVNC cases, classified as isolated (i-LVNC, n = 47) or non-isolated (ni-LVNC, n = 77) LVNC and NC/C > 2 (n = 43) or < 2 (n = 81). The median (interquartile range) follow-up duration was 12 (3-30) months for all patients and 16 (6-36) months for survivors. Sixteen patients with i-LVNC died during follow-up. Patients with i-LVNC and NC/C > 2 had worse survival than those with NC/C < 2 (p = 0.022). In conclusion, during a 12-month follow-up, patients with i-LVNC with NC/C < 2 had a benign prognosis and better outcomes than those with NC/C > 2, suggesting that the former could have a more active and routine lifestyle.


Usefulness of ECG to differentiate apical hypertrophic cardiomyopathy from non-ST elevation acute coronary syndrome.
Apical hypertrophic cardiomyopathy (ApHCM) is a phenotypic variant of nonobstructive HCM. ApHCM is characterized by left ventricular hypertrophy involve the distal apex. The electrocardiographic character of ApHCM can mimic non-ST elevation acute coronary syndrome (NSTEACS), triggering a series of studies and treatments that may be unnecessary. This study aimed to clarify the electrocardiogram (ECG) differences between the two diseases. Initial ECG recordings of 41 patients with ApHCM and 72 patients with NSTEACS were analyzed retrospectively. We analyzed the voltage of negative T (neg T) and R wave, the change of ST-segment as well as the number of leads with neg T wave in the 12-lead ECGs. Across the 12-lead ECGs, the magnitude of R wave significantly differed between ApHCM and NSTEACS in 10 leads excluding leads aVR and V1. ApHCM was associated with a greater maximal amplitude of R wave in lead V5 (3.13 ± 1.08 vs. 1.38 ± 0.73 mV, P < 0.001). The magnitude of T wave significantly differed between ApHCM and NSTEACS in 10 leads excluding leads II and V1. ApHCM was associated with a greater maximal amplitude of neg T wave in lead V4 (0.85 ± 0.69 vs. 0.35 ± 0.23 mV, P < 0.001). The frequency of giant neg T (1mv or more) wave was higher in ApHCM (36.5% vs. 0%, P < 0.001). The magnitude of ST-segment deviation significantly differed between ApHCM and NSTEACS in 10 leads excluding leads aVF and V2. ApHCM was associated with a greater maximal amplitude of ST-segment depression in lead V5 (0.19 ± 0.07 vs. 0.03 ± 0.06 mV, P < 0.001). The number of leads with neg T wave also differed between ApHCM and NSTEACS (6.75 ± 1.42 vs. 6.08 ± 1.51, P = 0.046). The sum of R wave in lead V5, neg T wave in lead V6 and ST-segment depression in lead V4 > 2.585 mV identified ApHCM with 90.2% sensibility and 87.5% specificity, representing the highest diagnostic accuracy. Compared with NSTEACS patients, ApHCM patients presented higher R and neg T wave voltage as well as a greater ST-segment depression in the 12-lead ECG. The ECG characteristics can help to differentiate ApHCM from NSTEACS in clinical setting.


Higher-order nucleoprotein complexes in transcription: analogies with site-specific recombination.
Regulation of transcription involves the assembly of multiprotein complexes at enhancers and promoters. Interactions between adjacent and non-adjacent DNA-binding proteins can augment the specificity and stability of multi-component nucleoprotein complexes. Recently, several proteins have been identified that can function as 'architectural' elements in the assembly of higher-order nucleoprotein structures reminiscent of those involved in site-specific recombination in prokaryotes.


P-glycoprotein, lung resistance-related protein and multidrug resistance-associated protein in de novo adult acute lymphoblastic leukaemia.
P-glycoprotein (P-gp), lung resistance-related protein (LRP) and multidrug resistance-associated protein (MRP) expression, and blast cell intracellular daunorubicin accumulation (IDA) were evaluated in 95 previously untreated cases of adult acute lymphoblastic leukaemia (ALL) using flow cytometry. Forty-five out of 95 (47%) patients were P-gp positive (+), 12/66 (18%) were LRP+ and 11/66 (17%) were MRP+. Eighteen out of 66 (28%) patients showed a simultaneous multidrug resistance (MDR)-related protein expression higher than controls for more than one protein, while 24/66 (36%) cases did not overexpress any protein. Twenty-one out of 24 (87%) cases overexpressing at least one MDR-related protein had a defect in accumulating daunorubicin into their blast cells, while only 4/24 (16%) cases who did not overexpress any protein had similar features. The complete remission rates were similar in MDR-positive and -negative (-) patients but relapses within 6 months were more frequent in P-gp+ cases, and therefore the disease-free survival duration was shorter in P-gp+ than in P-gp- patients (P = 0.01). The number of MRP+ and/or LRP+ cases was too small to be able to draw any conclusion on their role in affecting or predicting therapy outcome. In conclusion, P-gp overexpression associated with a defect in daunorubicin accumulation is a frequent feature in adult ALL at onset and seems to be related to poorer therapy outcome and, consequently, a shorter disease-free survival. LRP and MRP overexpression seems to be a rare event and no conclusion can be drawn on its prognostic role.


Coffin-Lowry syndrome in a girl with 46,XX,t(X;11)(p22;p15)dn: Identification of RPS6KA3 disruption by whole genome sequencing.
We report a Japanese girl with Coffin-Lowry syndrome phenotype such as hypertelorism, hypodontia, and tapering fingers and 46,XX,t(X;11)(p22;p15)dn. Whole genome sequencing revealed RPS6KA3 disruption by the translocation, and X-inactivation analysis indicated preferential inactivation of the normal X chromosome. The results explain the development of an X-linked disease in this girl.


Stereoselective method to quantify bupropion and its three major metabolites, hydroxybupropion, erythro-dihydrobupropion, and threo-dihydrobupropion using HPLC-MS/MS.
Bupropion metabolites formed via oxidation and reduction exhibit pharmacological activity, but little is known regarding their stereoselective disposition. A novel stereoselective liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed to separate and quantify enantiomers of bupropion, 4-hydroxybupropion, and erythro- and threo-dihydrobupropion. Liquid-liquid extraction was implemented to extract all analytes from 50 μL human plasma. Acetaminophen (APAP) was used as an internal standard. The analytes were separated on a Lux 3 μ Cellulose-3 250×4.6 mm column by methanol: acetonitrile: ammonium bicarbonate: ammonium hydroxide gradient elution and monitored using an ABSciex 5500 QTRAP triple-quadrupole mass spectrometer equipped with electrospray ionization probe in positive mode. Extraction efficiency for all analytes was ≥70%. The stability at a single non-extracted concentration for over 48 h at ambient temperature resulted in less than 9.8% variability for all analytes. The limit of quantification (LOQ) for enantiomers of bupropion and 4-hydroxybupropion was 0.3 ng/mL, while the LOQ for enantiomers of erythro- and threo-hydrobupropion was 0.15 ng/mL. The intra-day precision and accuracy estimates for enantiomers of bupropion and its metabolites ranged from 3.4% to 15.4% and from 80.6% to 97.8%, respectively, while the inter-day precision and accuracy ranged from 6.1% to 19.9% and from 88.5% to 99.9%, respectively. The current method was successfully implemented to determine the stereoselective pharmacokinetics of bupropion and its metabolites in 3 healthy volunteers administered a single 100mg oral dose of racemic bupropion. This novel, accurate, and precise HPLC-MS/MS method should enhance further research into bupropion stereoselective metabolism and drug interactions.


Gene expression changes of inflammatory mediators in posterior laryngitis due to laryngopharyngeal reflux and evolution with PPI treatment: a preliminary study.
Standard of care in laryngopharyngeal reflux (LPR) is acid suppression therapy. Its treatment efficacy and mechanism of action are not well documented. No objective study investigating the molecular patterns of inflammation in LPR or in response to proton pump inhibitor (PPI) treatment has been accomplished. We hypothesized that gene expression levels of mediators of inflammation -- interleukin 6 (IL6), interleukin 8 (IL8), interleukin 1a (IL1a), interleukin 1b (IL1b), transforming growth factor beta 1 (TGFbeta1), vascular endothelial growth factor (VEGF), fibroblast growth factor-2 (FGF2), and tumor necrosis factor alpha (TNFalpha) -- in posterior larynx tissue would be increased in those with diagnosed LPR and would be then reduced with PPI treatment. Prospective uncontrolled trial. Biopsies from the posterior larynx were taken from 25 participants with LPR before and after a 10-week period with rabeprazole (40 mg). RNA isolation and real-time PCR was used to measure gene expression levels. No significant differences were measured for any of the cytokines, either for the entire participant group (n = 25) or for the subset of participants who did not have a previous history of PPI usage (n = 15). In those participants who had a history of PPI usage (n = 10), a significant increase in gene expression levels post medication was measured for TGFbeta1 (P = .0396), VEGF (P = .0216), IL8 (P = .0297), after adjusting for compliance, subjective improvement, and reflux severity. Our findings are provocative and speak to the unresolved understanding of the pathophysiology of LPR, its diagnosis, and its differences from gastroesophageal reflux disease.


Atypical Carney's triad with coincidental clear cell renal carcinoma in an 84-year old patient-a finding at autopsy.
Carney's triad is a syndrome of unknown etiology, representing a combination of gastrointestinal stromal tumors, bronchial chondromas and vagal, adrenal or paraadrenal paragangliomas. Two of the Carney's triad components-the paragangliomas and the gastrointestinal stromal tumors-are potentially lethal. Since its first description in 1977, 79 cases have been reported so far. We report an 84-year-old male patient, who died of a hypertensive cerebral hemorrhage. Well-differentiated clear cell carcinoma of the right kidney, chondroma of the right bronchus and multiple jejunal stromal tumors were detected at autopsy. To our knowledge, this is the first report of a coincidental clear cell renal carcinoma in a patient with an atypical Carney's triad.


Metabolic polygenic risk scores effect on antipsychotic-induced metabolic dysregulation: A longitudinal study in a first episode psychosis cohort.
Metabolic syndrome is a health-threatening condition suffered by approximately one third of schizophrenia patients and largely attributed to antipsychotic medication. Previous evidence reports a common genetic background of psychotic and metabolic disorders. In this study, we aimed to assess the role of polygenic risk scores (PRSs) on the progression of the metabolic profile in a first-episode psychosis (FEP) cohort. Of the 231 FEP individuals included in the study, 192-220 participants were included in basal analysis and 118-179 in longitudinal 6-month models. Eleven psychopathologic and metabolic PRSs were constructed. Basal and longitudinal PRSs association with metabolic measurements was assessed by statistical analyses. No major association of psychopathological PRSs with the metabolic progression was found. However, high risk individuals for depression and cholesterol-related PRSs reported a higher increase of cholesterol levels during the follow-up (FDR ≤ 0.023 for all analyses). Their effect was comparable to other well-established pharmacological and environmental risk factors (explaining at least 1.2% of total variance). Our findings provide new evidence of the effects of metabolic genetic risk on the development of metabolic dysregulation. The future establishment of genetic profiling tools in clinical procedures could enable practitioners to better personalize antipsychotic treatment selection and dosage.


Recreational benefits of urban forests: explaining visitors' willingness to pay in the context of the theory of planned behavior.
The extension of contingent valuation models with an attitude-behavior based framework has been proposed in order to improve the descriptive and predictive ability of the models. This study examines the potential of the theory of planned behavior to explain willingness to pay (WTP) in a contingent valuation survey of the recreational benefits of the Zurich city forests. Two aspects of WTP responses, protest votes and bid levels, were analyzed separately. In both steps, models with and without the psychological predictors proposed by the theory of planned behavior were compared. Whereas the inclusion of the psychological predictors significantly improved explanations of protest votes, their ability to improve the performance of the model explaining bid levels was limited. The results indicate that the interpretation of bid levels as behavioral intention may not be appropriate and that the potential of the theory of planned behavior to improve contingent valuation models depends on which aspect of WTP responses is examined.


pIL6-TRAIL-engineered umbilical cord mesenchymal/stromal stem cells are highly cytotoxic for myeloma cells both in vitro and in vivo.
Mesenchymal/stromal stem cells (MSCs) are favorably regarded in anti-cancer cytotherapies for their spontaneous chemotaxis toward inflammatory and tumor environments associated with an intrinsic cytotoxicity against tumor cells. Placenta-derived or TRAIL-engineered adipose MSCs have been shown to exert anti-tumor activity in both in-vitro and in-vivo models of multiple myeloma (MM) while TRAIL-transduced umbilical cord (UC)-MSCs appear efficient inducers of apoptosis in a few solid tumors. However, apoptosis is not selective for cancer cells since specific TRAIL receptors are also expressed by a number of normal cells. To overcome this drawback, we propose to transduce UC-MSCs with a bicistronic vector including the TRAIL sequence under the control of IL-6 promoter (pIL6) whose transcriptional activation is promoted by the MM milieu. UC-MSCs were transduced with a bicistronic retroviral vector (pMIGR1) encoding for green fluorescent protein (GFP) and modified to include the pIL6 sequence upstream of the full-length human TRAIL cDNA. TRAIL expression after stimulation with U-266 cell conditioned medium, or IL-1α/IL-1β, was evaluated by flow cytometry, confocal microscopy, real-time PCR, western blot analysis, and ELISA. Apoptosis in MM cells was assayed by Annexin V staining and by caspase-8 activation. The cytotoxic effect of pIL6-TRAIL + -GFP + -UC-MSCs on MM growth was evaluated in SCID mice by bioluminescence and ex vivo by caspase-3 activation and X-ray imaging. Statistical analyses were performed by Student's t test, ANOVA, and logrank test for survival curves. pIL6-TRAIL + -GFP + -UC-MSCs significantly expressed TRAIL after stimulation by either conditioned medium or by IL-1α/IL-1β, and induced apoptosis in U-266 cells. Moreover, when systemically injected in SCID mice intratibially xenografted with U-266, those cells underwent within MM tibia lesions and significantly reduced the tumor burden by specific induction of apoptosis in MM cells as revealed by caspase-3 activation. Our tumor microenvironment-sensitive model of anti-MM cytotherapy is regulated by the axis pIL6/IL-1α/IL-1β and appears suitable for further preclinical investigation not only in myeloma bone disease in which UC-MSCs would even participate to bone healing as described, but also in other osteotropic tumors whose milieu is enriched of cytokines triggering the pIL6.


Optimising multistage dairy cattle breeding schemes including genomic selection using decorrelated or optimum selection indices.
The prediction of the outcomes from multistage breeding schemes is especially important for the introduction of genomic selection in dairy cattle. Decorrelated selection indices can be used for the optimisation of such breeding schemes. However, they decrease the accuracy of estimated breeding values and, therefore, the genetic gain to an unforeseeable extent and have not been applied to breeding schemes with different generation intervals and selection intensities in each selection path. A grid search was applied in order to identify optimum breeding plans to maximise the genetic gain per year in a multistage, multipath dairy cattle breeding program. In this program, different values of the accuracy of estimated genomic breeding values and of their costs per individual were applied, whereby the total breeding costs were restricted. Both decorrelated indices and optimum selection indices were used together with fast multidimensional integration algorithms to produce results. In comparison to optimum indices, the genetic gain with decorrelated indices was up to 40% less and the proportion of individuals undergoing genomic selection was different. Additionally, the interaction between selection paths was counter-intuitive and difficult to interpret. Independent of using decorrelated or optimum selection indices, genomic selection replaced traditional progeny testing when maximising the genetic gain per year, as long as the accuracy of estimated genomic breeding values was ≥ 0.45. Overall breeding costs were mainly generated in the path "dam-sire". Selecting males was still the main source of genetic gain per year. Decorrelated selection indices should not be used because of misleading results and the availability of accurate and fast algorithms for exact multidimensional integration. Genomic selection is the method of choice when maximising the genetic gain per year but genotyping females may not allow for a reduction in overall breeding costs. Furthermore, the economic justification of genotyping females remains questionable.


The reaction order of the dissociation reaction of the B820 subunit of Rhodospirillum rubrum light-harvesting I complex.
We have studied the equilibrium between the dissociated B777 form (absorbing at 777 nm) of the light-harvesting complex of Rhodospirillum rubrum and the oligomeric B820 form. Analysis of the reaction order for the B820 dissociation reaction to form B777 shows that this reaction depends on the concentration of octylglucoside detergent (n-octyl-beta-D-glucopyranoside (betaOG)) present in the sample. At low betaOG concentrations (less than 1.2%) this reaction requires two components, presumably one alpha-B777 and one beta-B777, implying that the B820 subunit is a dimer. At higher betaOG concentrations this reaction requires four components, implying that B820 is a tetramer. These results partly explain the discrepancies in the literature about the stoichiometry of B820 and open an original way for studying protein-detergent interactions.


Case study: caries in young children.
This article describes the aetiology and specific diagnoses of two different children that presented to the dental surgery with a form of dental caries. The management of both cases is being discussed as well as the differences in the prevention of early childhood caries.


Segmental copy number loss in the region of Semaphorin 4D gene in patients with acetabular dysplasia.
Acetabular dysplasia (AD) appears to be a multi-factorial disease, which may involve both genetic and environmental factors and whose pathogenesis remains obscure. The present study aims to identify a genetic variation that might confer risk of AD. We performed whole-genome screening of a copy number variation (CNV) using a deCODE-Illumina CNV beadchip with 20 female AD patients and 131 control subjects. Subsequently, Agilent's region-targeted high-density oligonucleotide tiling microarray was used to analyze 64 female AD patients and 32 female control subjects. By sequential analyses, we found a copy number loss in 18 of 64 AD patients, but none in the 32 controls. The loss occurred within a 472 kb region on 9q22.2, which harbors the gene for Semaphorin 4D (Sema4D; 18/64 vs. 0/32, p = 4.81 × 10(-4) , OR = 25.86). We suggest that a copy number loss of the Sema4D gene region may play a role in the etiology of AD.