Anesthesia with intraperitoneal propofol, medetomidine, and fentanyl in rats.
A safe and reliable method for anesthetizing rats has long been a leading concern of biomedical researchers. We recently found that the intraperitoneal administration of propofol combined with medetomidine and fentanyl is safe for mouse anesthesia. Here we studied whether the same combination could be used for general anesthesia in rats. We used male Wistar rats to test 10 combinations of propofol, medetomidine, and fentanyl administered intraperitoneally and reversed with intraperitoneal atipamezole 30 min after induction. The depth of anesthesia, induction time, loss of pedal withdrawal reflex, pulse rate, and respiratory rate were evaluated, along with the duration and quality of induction, surgical anesthesia, and recovery. The combination of propofol and medetomidine provided a predictable induction and sufficient hypnosis and muscle relaxation, but surgical anesthesia (loss of pedal withdrawal reflex) was difficult to achieve with this protocol. The addition of fentanyl increased analgesia, making it possible to achieve surgical anesthesia. In conclusion, combination of propofol (100 mg/kg), medetomidine (0.1 mg/kg), and fentanyl (0.1 mg/kg) is a safe and practical technique for intraperitoneal anesthesia in rats, providing a surgical window of 25 min and restraint for 30 min, with rapid recovery after administration of atipamezole.


Minireview: finding the sweet spot: peripheral versus central glucagon-like peptide 1 action in feeding and glucose homeostasis.
Glucagon-like peptide 1 (GLP-1) is both a gut-derived hormone and a neurotransmitter synthesized in the brain. Early reports suggested that GLP-1 acts in the periphery to promote insulin secretion and affect glucose homeostasis, whereas central GLP-1 reduces food intake and body weight. However, current research indicates that in fact, GLP-1 in each location plays a role in these functions. This review summarizes the evidence for involvement of peripheral and brain GLP-1 in food intake regulation and glucose homeostasis and proposes a model for the coordinated actions of GLP-1 at multiple sites.


Supplement use: is there any nutritional benefit?
To examine the role of dietary supplements in improving total nutrient intakes in adults. Dietitian-administered 24-hour recalls (of intake including supplements) were conducted in 1997 and 1998. Supplement users were categorized into groups based on the types of supplements used and nutrient intake was examined. Using a multistage, stratified random sampling, 1,530 Canadian adults aged 19 to 65 years were surveyed. Intakes from diet, supplements, and diet plus supplements were examined by age/gender stratification. Supplement users had dietary intakes, from food alone, similar to nonusers with mean intakes in some age/sex groups below the Recommended Daily Allowance (RDA)/Adequate Intake (AI) for iron, calcium, and folate. Multivitamin users had mean intakes (from diet plus supplement) of folate above the RDA and iron intakes also increased to RDA levels among women aged 19 to 50 years. Calcium supplement users had lower calcium and vitamin D intakes than nonusers from diet alone in some age/sex groups. Calcium tablets increased mean calcium intakes to AI levels among all age/sex groups. Many supplement users exceeded the new Upper Limits of safe intake; 47% in the case of niacin. Supplements are commonly used and can help some persons adhere to Dietary Reference Intake recommendations concerning intake of folate, calcium, vitamin D. and iron. We found multivitamin users to have higher total intakes of folic acid, iron, calcium, and vitamin D. Also, targeted use of calcium supplements effectively enhanced intakes. However, concurrent vitamin D supplementation is important and awareness of product composition with respect to Upper Limits is essential.


Ectopic tooth in the roof of the maxillary sinus.
Eruption of a tooth into a nonoral environs is rare. Ectopic eruption of the tooth into the nasal cavity and chin has been reported before. This is a report of an ectopic third molar tooth in the roof of the maxillary sinus, which has not, to our knowledge, been reported before.


Dynamic timber cell recognition using two-dimensional image measurement machine.
Image motion blur and defocus blur often occur when there is a relative motion between the imaging camera and the detected object. In this paper, we propose a robust timber cell recognition scheme using the low quality color timber cell images with the above-mentioned image blurs. First, a novel two-dimensional image measurement machine is devised, to obtain the object images sequentially by using a color camera. Second, the image-moment-based blur invariant features are calculated. Third, timber cell recognition is performed by using the computed Euclidean distance based on the moment invariants. We have experimentally proved that the effective use of image blur information improves the recognition accuracy of camera-captured timber cells. Moreover, the allowed maximum translation speed of the moving gallery is also discussed theoretically and experimentally. This scheme can identify the timber species by means of the cell recognition so as to judge the physical property and economic value of different timber species correctly.


Importance of VEGF for breast cancer angiogenesis in vivo: implications from intravital microscopy of combination treatments with an anti-VEGF neutralizing monoclonal antibody and doxorubicin.
In the present study, we evaluated the effects of a neutralizing anti-Vascular Endothelial Growth Factor (VEGF) mAb, A4.6.1(200 micrograms twice weekly, i.p.), on angiogenesis and growth of tumor spheroids of human breast cancer cell lines (MCF-7, ZR-75 and, SK-BR-3) in nude mice. Furthermore, we investigated if in the presence of effective VEGF blockade, a conventional chemotherapeutic drug (doxorubicin, (5 mg/kg, weekly) could be effective, and if so would there be an additive effect of the combination regimen. Tumor Spheroids were implanted in dorsal skinfold chambers in nude mice. Tumor cells were pre-labeled with a fluorescent vital dye (CMTMR), which allowed the estimation of growth of implanted tumor spheroids. FITC (fluorescein isothiocyanate)-Dextran was used to evaluate formation of neo-vasculature at the tumor site. In control animals all three cell-lines produced extensive neovasculature and there was significant tumor growth throughout the observation period. Treatment with the anti-VEGF mAb caused significant suppression of angiogenic activity for all cell lines, stressing the critical role VEGF plays in breast tumor angiogenesis. Doxorubicin alone reduced the growth rate of MCF-7 cells, but did not significantly affect angiogenesis. Doxorubicin in combination with A4.6.1 resulted in significant tumors regression. Histology indicated that some chambers lacked viable tumor cells at the end of the two week observation period, lending strong support that neutralization of VEGF in combination with conventional cytotoxic agents could be a new innovative treatment regimen for metastatic breast cancer.


Identification and Characterization of a Luteinizing Hormone Receptor (LHR) Homolog from the Chinese Mitten Crab Eriocheir sinensis.
Luteinizing hormone (LH), a pituitary gonadotropin, coupled with LH receptor (LHR) is essential for the regulation of the gonadal maturation in vertebrates. Although LH homolog has been detected by immunocytochemical analysis, and its possible role in ovarian maturation was revealed in decapod crustacean, so far there is no molecular evidence for the existence of LHR. In this study, we cloned a novel LHR homolog (named EsLHR) from the Chinese mitten crab Eriocheir sinensis. The complete sequence of the EsLHR cDNA was 2775bp, encoding a protein of 924 amino acids, sharing 71% amino acids identity with the ant Zootermopsis nevadensis LHR. EsLHR expression was found to be high in the ovary, while low in testis, gill, brain, and heart, and no expression in the thoracic ganglion, eye stalk, muscle, and hepatopancreas. Quantitative PCR revealed that the expression level of EsLHR mRNA was significantly higher in the ovaries in previtellogenic (Pvt), late vitellogenic (Lvt), and germinal vesicle breakdown (GVBD) stages than that in the vitellogenic (Mvt) and early vitellogenic (Evt) stages (P < 0.05), and, the highest and the lowest expression were in Lvt, and Evt, respectively. The strong signal was mainly localized in the ooplasm of Pvt oocyte as detected by in situ hybridization. The crab GnRH homolog can significantly induce the expression of EsLHR mRNA at 36 hours post injection in vivo (P < 0.01), suggesting that EsLHR may be involved in regulating ovarian development through GnRH signaling pathway in the mitten crab.


Output that counts: pedometers, sociability and the contested terrain of older adult fitness walking.
Based on five months of participant observation and interviews with members of a hospital-sponsored walking club, I explore the rejection of pedometer technology among older adult walkers. Health researchers praise pedometers as a useful tool for measuring walking activity, setting fitness goals, and charting progress towards goals. Older adult walkers, however, viewed pedometers and the monitoring they enable as anathema to walking group norms that stress sociability. I assess the differential construction of pedometers by fitness researchers, group leaders, and walkers themselves. While fitness researchers construct pedometer technology as a motivator for exercise adherence, walkers believed pedometers would create competition and hierarchy that might destroy group camaraderie. In contrast to biomedical models of health and wellness, which focus predominantly on exercise outputs like step counts, these findings suggest that sociability is an important component of health maintenance leisure activities for older adult walkers.


Determinants of fertility control in Korea.
The objective of this study is to examine the socioeconomic and intervening determinants of fertility control in Korea. The conceptual framework applied here is based on the synthesis framework of fertility control developed by Easterlin and Crimmins. The data came from the 1974 Korean National Family Survey, which was conducted as part of the World Fertility Survey. The study focuses on the relative importance of the socioeconomic factors and intervening variables in the determination of fertility control. The most interesting finding is that there are only small differentials in fertility control by socioeconomic factors. The analysis emphasizes the importance of examining the determinants of fertility control in terms of the intervening variables, which include the components of natural fertility, desired family size, and costs of fertility control. These intervening variables provide general support for the theoretical predictions. Moreover, most of the coefficients for these variables are statistically significant at the .05 level. The analysis also shows that motivation for fertility control is an important factor in determining use of fertility control.


Timing processes are correlated when tasks share a salient event.
Event timing is manifested when participants make discrete movements such as repeatedly tapping a key. Emergent timing is manifested when participants make continuous movements such as repeatedly drawing a circle. Here we pursued the possibility that providing salient perceptual events to mark the completion of time intervals could allow circle drawing and tapping to share a common timing process. Individual differences in timing performance were correlated in the tapping and circle drawing tasks when a salient auditory event marked the completion of a cycle. The results suggest that the distinction between event timing and emergent timing does not inhere solely in kinematics but inheres as well in the way task goals are represented.


Formation of light absorbing organo-nitrogen species from evaporation of droplets containing glyoxal and ammonium sulfate.
In the atmosphere, volatile organic compounds such as glyoxal can partition into aqueous droplets containing significant levels of inorganic salts. Upon droplet evaporation, both the organics and inorganic ions become highly concentrated, accelerating reactions between them. To demonstrate this process, we investigated the formation of organo-nitrogen and light absorbing materials in evaporating droplets containing glyoxal and different ammonium salts including (NH4)2SO4, NH4NO3, and NH4Cl. Our results demonstrate that evaporating glyoxal-(NH4)2SO4 droplets produce light absorbing species on a time scale of seconds, which is orders of magnitude faster than observed in bulk solutions. Using aerosol mass spectrometry, we show that particle-phase organics with high N:C ratios were formed when ammonium salts were used, and that the presence of sulfate ions promoted this chemistry. Since sulfate can also significantly enhance the Henry's law partitioning of glyoxal, our results highlight the atmospheric importance of such inorganic-organic interactions in aqueous phase aerosol chemistry.


Coping with change.
Although the NHS is continually changing, the qualifications and skills I have acquired will always be valuable. I have also learned that change provides an opportunity to develop new skills.


Intraperitoneal administration of nanoparticles containing tocopheryl succinate prevents peritoneal dissemination.
Intraperitoneal administration of anticancer nanoparticles is a rational strategy for preventing peritoneal dissemination of colon cancer due to the prolonged retention of nanoparticles in the abdominal cavity. However, instability of nanoparticles in body fluids causes inefficient retention, reducing its anticancer effects. We have previously developed anticancer nanoparticles containing tocopheryl succinate, which showed high in vivo stability and multifunctional anticancer effects. In the present study, we have demonstrated that peritoneal dissemination derived from colon cancer was prevented by intraperitoneal administration of tocopheryl succinate nanoparticles. The biodistribution of tocopheryl succinate nanoparticles was evaluated using inductively coupled plasma mass spectroscopy and imaging analysis in mice administered quantum dot encapsulated tocopheryl succinate nanoparticles. Intraperitoneal administration of tocopheryl succinate nanoparticles showed longer retention in the abdominal cavity than by its intravenous (i.v.) administration. Moreover, due to effective biodistribution, tumor growth was prevented by intraperitoneal administration of tocopheryl succinate nanoparticles. Furthermore, the anticancer effect was attributed to the inhibition of cancer cell proliferation and improvement of the intraperitoneal microenvironment, such as decrease in the levels of vascular endothelial growth factor A, interleukin 10, and M2-like phenotype of tumor-associated macrophages. Collectively, intraperitoneal administration of tocopheryl succinate nanoparticles is expected to have multifaceted antitumor effects against colon cancer with peritoneal dissemination.


Segmental Bile Duct-Targeted Liver Resection for Right-Sided Intrahepatic Stones.
Hepatectomy is a safe and effective treatment for intrahepatic stones (IHSs). However, the resection plane for right-sided stones distributed within 2 segments is obstacle because of atrophy-hypertrophy complex formation of the liver and difficult dissection of segmental pedicle within the Glissonean plate by conventional approach. Thus, we devised segmental bile duct-targeted liver resection (SBDLR) for IHS, which aimed at completely resection of diseased bile ducts. This study aimed to evaluate the outcomes of SBDLR for right-sided IHSs. From January 2009 to December 2013, 107 patients with IHS treated by SBDLR in our center were reviewed in a prospective database. Patients' intermediate and long-term outcomes after SBDLR were analyzed. A total of 40 (37.4%) patients with localized right-sided stone and 67 (62.7%) patients with bilateral stones underwent SBDLR alone and SBDLR combined with left-sided hepatectomy, respectively. There was no hospital mortality of this cohort of patients. The postoperative morbidity was 35.5%. The mean intraoperative blood loss was 414 mL (range: 100-2500). Twenty-one (19.6%) patients needed red blood cells transfusion. The intermediate stone clearance rate was 94.4%; the final clearance rate reached 100% after subsequent postoperative cholangioscopic lithotomy. Only 2.8% patients developed stone recurrence in a median follow-up period of 38.3 months. SBDLR is a safe and effective treatment for right-sided IHS distributed within 2 segments. It is especially suitable for a subgroup of patients with bilateral stones whose right-sided stones are within 2 segments and bilateral liver resection is needed.


Carotenoid changes of intact watermelons after storage.
Watermelon contains lycopene, a red carotenoid pigment that has strong antioxidant properties. The lycopene content of watermelon is substantial, contributing 8-20 mg per 180 g serving. There are no reports on carotenoid changes in whole watermelon during storage. Three types of watermelon, open-pollinated seeded, hybrid seeded, and seedless types, were stored at 5, 13, and 21 degrees C for 14 days and flesh color, composition, and carotenoid content were compared to those of fruit not stored. Watermelons stored at 21 degrees C had increased pH, chroma, and carotenoid content compared to fresh fruit. Compared to fresh fruit, watermelons stored at 21 degrees C gained 11-40% in lycopene and 50-139% in beta-carotene, whereas fruit held at 13 degrees C changed little in carotenoid content. These results indicate that carotenoid biosynthesis in watermelons can be affected by temperature and storage.


Ensuring accuracy and predictability with double-arch impressions.
The described double-arch impression technique provides an accurate and stable impression, accurate dies and the ability to make one or two crowns with minimal or no adjustments. Both scientific evidence and clinical observation attest to the adequacy of the double-arch impression concept, when it is accomplished in accordance with the requirements enumerated in this column.


Herpes simplex virus type 1 origins of DNA replication play no role in the regulation of flanking promoters.
Herpes simplex virus (HSV) exhibits altered gene regulation in neuronal compared to nonneuronal tissues. It has been hypothesized that initiation of DNA synthesis at the viral origins of replication (oriS and oriL) is a critical step in the upregulation of transcriptional activity of flanking divergent promoters, thereby increasing productive gene expression in neurons. Notably, oriS is flanked by the immediate-early (IE) ICP4 and ICP22/47 promoters, and oriL is flanked by the early (E) UL29 and UL30 promoters. To test this hypothesis further, a series of constructs were generated in which these promoters were placed upstream of luciferase genes. In addition, DNA replication origins were deleted in the context of these promoter constructs. All cassettes were recombined into the viral genome of HSV type 1 strain KOS at a site distal to its native origins. Recombinant reporter expression was monitored in vitro and in vivo to determine the role of viral origins of DNA replication in the regulation of their flanking promoters. Reporter gene expression was unaffected by the presence or absence of oriS or oriL, with the exception of a twofold increase in ICP22/47 promoter activity in the absence of oriS. DNA synthesis inhibitors resulted in a decrease of both IE- and E-promoter activity in primary cells but not continuous cell cultures. Reporter activity was readily assayed in vivo during acute infection and reactivation from latency and was also sensitive to DNA synthesis inhibitors. In all assays, reporter gene expression was unaffected by the presence or absence of either oriS or oriL. These data support the requirement of DNA synthesis for full viral gene expression in vivo but suggest that the origin elements play no role in the regulation of their flanking promoters.


Temporoparietal fascia: an anatomic and histologic reinvestigation with new potential clinical applications.
Temporoparietal fascia constitutes a very important structural unit from both an aesthetic and a reconstructive surgical point of view. A histologically supported anatomic study was conducted for the reappraisal of the anatomic relationships and clinical application potentials of the data obtained. Anatomy of the temporoparietal fascia was investigated on 20 sides from 10 cadavers. After dissections, necropsies were obtained to demonstrate histologic features of the temporoparietal fascia. The outer part of the temporoparietal fascia is continuous with the superficial musculoaponeurotic system (SMAS) in the inferior border and with orbicularis oculi and frontalis muscles in the anterior border. Therefore, plication of the temporoparietal fascia can increase tightness of the SMAS, orbicularis oculi, and frontalis muscle in rhytidectomy. The frontal branches of facial nerve were noted to course parallel to the frontal branch of the superficial temporal artery, lying deeper to the temporoparietal fascia within the innominate fascia. In the view of these findings, conventional subfascial dissection, which is performed to protect frontal branches of the facial nerve, is not reasonable during the temporal part of rhytidectomy. Careful subcutaneous dissection just under the hair follicles is more appropriate to avoid nerve injury and also provides excellent exposure of the temporoparietal fascia for plication in rhytidectomy with protection of the auriculotemporal nerve and the superficial temporal vessels. Furthermore, two layered structures of the temporoparietal fascia are very suitable to insert a framework into the temporoparietal fascia for ear reconstruction to eliminate some of the shortcomings of Brent's technique. A thin muscle layer was also noted within the outer part of the temporoparietal fascia below the temporal line; the term "temporoparietal myofascial flap" would, therefore, be more accurate than "temporoparietal fascial flap." Finally, the innominate fascia and the deep temporal fascia can be elevated with the two layers of the temporoparietal myofascial flap to obtain a well-vascularized, four-layered myofascial flap based on the superficial temporal vessels. This multilayered flap can be used to reconstruct all defects when fine, pliable, thin, multilayered flaps are required.


[Poisonings with psychotropic drug mixtures: analysis using the thin-layer chromatography method].
It is observed increase in number of remedy intoxications in Lithuania, especially important is intoxication with psychotropic drugs and their mixtures. The thin-layer chromatography (TLC) method was proposed for separation and identification of drugs in mixture aminazine: nitrazepam: barbamylum. The mixture of these drugs excreted from body fluids (blood and urine) was investigated by TLC. Most acceptable these mobile phases: 1. Diethyl ether: dioxane--40:60. Rf values for drugs: aminazine 0.23-0.25; barbamylum 0.85-0.9; nitrazepam 0.75-0.8. 2. Diethyl ether: NH3 (25%): benzenum--80:10:10. Rf values for drugs: aminazine 0.55-0.58; barbamylum 0.32-0.35; nitrazepam 0.17-0.2.


Anal sac adenocarcinoma in a Siamese cat.
A 12-year-old male neutered Siamese cat presented with a history of inappetance and lethargy and an enlarged left anal sac. The anal sac was surgically excised and histopathology confirmed the diagnosis of anal sac adenocarcinoma. Perianal tumours are rare in the cat and anal sac adenocarcinoma has not been previously reported. This is in contrast to the dog where anal sac adenocarcinoma is a well recognised albeit uncommon tumour.


Procalcitonin, neopterin and C-reactive protein in diagnostics of intrauterine infection and preterm delivery.
The purpose of this study was to find out whether Procalcitoni, Neopterin and C-reactive protein are sensitive and specific markers of intrauterine infection. We evaluated 155 patients from 26. to 41. week of pregnancy at the time of delivery. We measured serum concentrations of procalcitonin (PCT), neopterin and C-reactive protein (CRP) from mother's blood sample at the beginning of delivery and from umbilical cord blood after delivery. In first group occurred in higher percentage (27.41%) preterm delivery (26.-37. week of pregnancy), chorioamnionitis confirmed by histological examination (16.12%) and preterm premature rupture of membranes (24.19%). In this group occured perinatal infection of newborn in 61.29%. In the second group preterm delivery (6.31%) and perinatal infection of newborn (7.36%) occured in lower percentage. The results suggest that the simultaneous measurement of CRP, PCT and NPT in mother's blood sample before delivery and umbilical cord blood may provide an accurate early diagnosis of infection and then preterm delivery (Tab. 1, Fig. 3, Ref. 18). Full Text (Free, PDF) www.bmj.sk.


The Japan Lung Cancer Society-Japanese Society for Radiation Oncology consensus-based computed tomographic atlas for defining regional lymph node stations in radiotherapy for lung cancer.
The purpose of this study was to develop a consensus-based computed tomographic (CT) atlas that defines lymph node stations in radiotherapy for lung cancer based on the lymph node map of the International Association for the Study of Lung Cancer (IASLC). A project group in the Japanese Radiation Oncology Study Group (JROSG) initially prepared a draft of the atlas in which lymph node Stations 1-11 were illustrated on axial CT images. Subsequently, a joint committee of the Japan Lung Cancer Society (JLCS) and the Japanese Society for Radiation Oncology (JASTRO) was formulated to revise this draft. The committee consisted of four radiation oncologists, four thoracic surgeons and three thoracic radiologists. The draft prepared by the JROSG project group was intensively reviewed and discussed at four meetings of the committee over several months. Finally, we proposed definitions for the regional lymph node stations and the consensus-based CT atlas. This atlas was approved by the Board of Directors of JLCS and JASTRO. This resulted in the first official CT atlas for defining regional lymph node stations in radiotherapy for lung cancer authorized by the JLCS and JASTRO. In conclusion, the JLCS-JASTRO consensus-based CT atlas, which conforms to the IASLC lymph node map, was established.


Effect of pyrrolidone carboxylate (PCA) and pyridoxine on liver metabolism during chronic ethanol intake in rats.
Rats subjected to chronic ethanol intake for a period of 28 days showed significant elevation in blood ethanol levels, a marked decrease in hepatic reduced glutathione (GSH) content and a decrease in liver tryptophan pyrrolase (TPO) activity. A daily intraperitoneal injection of a combined solution of pyrrolidone carboxylate (PCA) and vitamin B6 (pyridoxine hydrochloride) (0.3 mmoles/kg) into ethanol-treated rats resulted in the blood ethanol levels becoming significantly reduced, while the hepatic GSH content and TPO activity were markedly elevated. Our results support the view that PCA and pyridoxine operate to restore the redox imbalance of the hepatocytes caused by chronic alcohol intake.


Correlation of Prolonged Corrected QT Interval With Ventricular Arrhythmias and In-Hospital Mortality Among ST-Elevation Myocardial Infarction Patients: A Mystique or Lucidity?
Background Ventricular arrhythmias (VAs) are a frequent cause of cardiovascular mortality, especially in developing countries. Prolongation of corrected QT (QTc) interval predisposes patients to life-threatening VAs. Our study aims to assess the correlation of prolonged QTc interval with VAs and in-hospital mortality among ST-elevation myocardial infarction (STEMI) patients. Methods This cross-sectional study analyzed the data from 40 patients with a confirmed diagnosis of STEMI and prolonged QTc interval. The patients were evaluated for several characteristics including their electrocardiography (ECG) findings. The frequency of in-hospital mortality and VAs developed after admission were recorded. Spearman correlation was used to assess the correlation of prolonged QTc interval with VAs and in-hospital mortality. Results Out of 40 cases, 30 patients were males and 10 were females with a mean age hovering at 52.95 ± 10.65 years. The mean QTc interval of our patients was 512.02 ± 49.74 milliseconds (ms). A total of 11 (27.5%) patients developed VAs while 14 (35%) of the patients succumbed to the disease complications. Spearman correlation showed a strong significant positive correlation of QTc interval with VAs (rho = 0.658, p < 0.001) and in-hospital mortality (rho = 0.314, p = 0.04). Conclusion Prolonged QTc interval is positively correlated with VAs and in-hospital mortality among STEMI patients. These patients should be regularly monitored and must be managed with caution as they have increased chances to develop VAs and in-hospital mortality. There is an utmost need for curation of guidelines that aid in risk stratification and appropriate management of such patients.


Dynamic Changes of Post-Translationally Modified Forms of CXCL10 and Soluble DPP4 in HCV Subjects Receiving Interferon-Free Therapy.
Serum levels of the interferon (IFN)-stimulated chemokine CXCL10 are increased during chronic HCV infection and associate with outcome of IFN-based therapy. Elevated levels of NH2-terminal truncated CXCL10 (3-77aa), produced by DPP4 cleavage, negatively associate with spontaneous clearance of acute HCV infection and sustained virological response (SVR) with IFN-based therapy for chronic infection. The association of different CXCL10 forms and DPP4 with outcome during IFN-free HCV therapy has not been examined. Using novel Simoa assays, plasma was analyzed from HCV genotype-1 (GT1) subjects who relapsed (n = 11) or achieved SVR (n = 10) after sofosbuvir and ribavirin (SOF/RBV) treatment, and from SOF/RBV relapsers who achieved SVR with a subsequent SOF/ledipasvir regimen (n = 9). While the NH2-truncated form of CXCL10 was elevated in HCV infection relative to healthy controls, pre-treatment plasma concentrations of CXCL10 forms failed to stratify subjects based on treatment outcome to IFN-free regimens. However, a trend (statistically non-significant) towards elevated higher levels of total and long CXCL10 was observed pre-treatment in subjects who relapsed. All forms of CXCL10 decreased rapidly following treatment initiation and were again elevated in subjects who experienced HCV relapse, indicating that CXCL10 production may be associated with active viral replication. While soluble DPP4 (sDPP4) and NH2-truncated CXCL10 concentrations were highly correlated, on-treatment sDPP4 levels and activity declined more slowly than CXCL10, suggesting differential regulation. These data suggest post-translationally modified forms of CXCL10 will not support the prediction of treatment outcome in HCV GT1 subjects treated with SOF/RBV.


Certain fatty acids and steroids protect Tetrahymena from cell division stress caused by shaking.
Cultures of Tetrahymena are routinely shaken to ensure proper access to oxygen. Recent work showed that growth of dilute cultures (inocula < 10(4) cells ml-1) of T. pyriformis was sensitive to shaking. Addition of oleic acid (9 microM) or linoleic acid (140 microM) before or at the onset of shaking gave considerable protection to the cells. A similar effect was seen with ergosterol (25 microM) and to some extent with cholesterol (100 microM). Octanoic acid (20 microM), palmitic acid (140 microM) and palmitoleic acid (100 microM) had no effect. Paraquat (230 microM), which induced peroxidation of unsaturated fatty acids, increased the effect of shaking-induced cell division stress. Such results may be due to changes in the membrane composition of Tetrahymena. It has not been possible to demonstrate differences in the 14C-oleic acid labelling of phospholipids of cells with and without shaking.


Extracellular matrix metalloproteinase inducer and matrix metalloproteinase-2 overexpression is associated with loss of hormone receptor expression and poor prognosis in endometrial cancer.
Extracellular matrix metalloproteinase inducer (CD147) and matrix metalloproteinase-2 (MMP-2) have been documented in various malignancies. CD147 is a member of the immunoglobulin superfamily, which promotes the production and release of MMPs in mesenchymal cells and tumor cells. MMP-2 has been extensively studied and is considered to be particularly important in cancer invasion and metastasis. However, studies investigating the expression and prognostic value of CD147 in endometrioid endometrial carcinoma (EEC) are limited. The present study analyzed the expression of CD147 and MMP-2 by immunohistochemistry in endometrial tissue samples from 107 patients with EEC and 30 patients with benign uterus myoma. The association between CD147 and MMP-2 expression and clinicopathological characteristics was evaluated. The results showed that the overexpression of MMP-2 was significantly associated with International Federation of Gynecology and Obstetrics stage (P=0.007), depth of invasion (P=0.037) and reduced expression of progesterone receptor (P=0.005). Kaplan-Meier analyses indicated that CD147 overexpression alone (P<0.05 for disease-specific survival) or in combination with MMP-2 (P<0.001 for disease-specific survival) was correlated with adverse prognosis in EEC patients. Multivariate analysis revealed that the combined overexpression of CD147 and MMP-2 was an independent prognostic factor for disease-specific survival (hazard ratio=5.141, P=0.001) in EEC patients. CD147 and MMP-2 overexpression was positively correlated with aggressive phenotypic features in EEC, however it was negatively correlated with hormone receptor expression. The combination of CD147 and MMP-2 overexpression in EEC further distinguished a subgroup of patients with poor prognosis. Thus, the results of present study indicate that the co-expression of CD147 and MMP-2 may be an independent prognostic factor in EEC patients.


Dimensional accuracy of acrylic resin maxillary denture base polymerized by a new injection pressing method.
The purpose of this study was to confirm the dimensional accuracy of a newly developed injection pressing method for resin polymerization by making use of the internal electric resistance of resin to determine the optimal timing for resin injection. A new injection pressing polymerization pot with a built-in system to measure the internal electric resistance of resin was used for resin polymerization. Fluid-type resin was injected into the mold of a maxillary complete denture base under nine different conditions: three different timings for resin injection according to the electric resistance of resin dough (early stage: 11 Mohms; intermediate stage: 16 Mohms; final stage: 21 Mohms) and three different motor powers for resin injection (2000 N, 4000 N, and 6000 N). In the best polymerization condition (injected during the early stage of resin dough under a motor power of 6000 N), the adaptation of the denture base showed a statistically significant improvement compared with the conventional pouring method.


A 1-year drug utilization evaluation of protamine in hospitalized patients to identify possible future roles of heparin and low molecular weight heparin reversal agents.
Despite widespread use of unfractionated heparin (UFH) and low molecular weight heparin (LMWH), protamine sulfate remains the only reversal agent for UFH that is approved by the Food and Drug Administration within the US. Availability of new reversal agents for approved anticoagulants and those in development may improve patient safety and care. Delparantag (PMX-60056) is a novel small molecule that shows ability to neutralize the anticoagulation effects of UFH and LMWH in animals and humans. This study examined the 1-year utilization of protamine within an acute care hospital in order to determine the need for a novel reversing agent like delparantag. All patients having documented protamine administration within a 1-year period were included. Pharmacy automated dispensing machines and computerized medication management systems were queried for all doses of protamine withdrawn, billed for, or dispensed. Scanned medical records were reviewed and protamine and anticoagulant information was abstracted. Primary procedural group categorizations for protamine patients were coronary artery bypass graft, cardiac valve surgeries, abdominal aortic aneurysm and other open abdominal surgeries, fistula placement, non-cardiac vascular, cardiac catheter and electrophysiology lab, and "other." Average doses of protamine administered were 439, 423, 126, 26, 46, 36, and 35 mg in these groups, respectively. Four major bleeds and one serious adverse event occurred over the year period. Protamine is used in a wide array of procedures. Evaluating protamine's current use may be beneficial in identifying roles for future UFH and LMWH reversal agent use.


Unbiased Identification of Angiogenin as an Endogenous Antimicrobial Protein With Activity Against Virulent Mycobacterium tuberculosis.
Tuberculosis is a highly prevalent infectious disease with more than 1.5 million fatalities each year. Antibiotic treatment is available, but intolerable side effects and an increasing rate of drug-resistant strains of Mycobacterium tuberculosis (Mtb) may hamper successful outcomes. Antimicrobial peptides (AMPs) offer an alternative strategy for treatment of infectious diseases in which conventional antibiotic treatment fails. Human serum is a rich resource for endogenous AMPs. Therefore, we screened a library generated from hemofiltrate for activity against Mtb. Taking this unbiased approach, we identified Angiogenin as the single compound in an active fraction. The antimicrobial activity of endogenous Angiogenin against extracellular Mtb could be reproduced by synthetic Angiogenin. Using computational analysis, we identified the hypothetical active site and optimized the lytic activity by amino acid exchanges. The resulting peptide-Angie1-limited the growth of extra- and intracellular Mtb and the fast-growing pathogens Escherichia coli, Pseudomonas aeruginosa, and Klebsiella pneumoniae. Toward our long-term goal of evaluating Angie1 for therapeutic efficacy in vivo, we demonstrate that the peptide can be efficiently delivered into human macrophages via liposomes and is not toxic for zebrafish embryos. Taken together, we define Angiogenin as a novel endogenous AMP and derive the small, bioactive fragment Angie1, which is ready to be tested for therapeutic activity in animal models of tuberculosis and infections with fast-growing bacterial pathogens.


[Changes of serum interleukin 2 and soluble interleukin 2 receptor and their clinical significance in multiple myeloma].
Serum interleukin 2 (IL-2) and soluble interleukin 2 receptor (sIL-2R) were serially determined in 44 patients with multiple myeloma (MM) by radioimmunoassay (RIA) and enzyme-linked immunosorbent assay (ELISA). Serum IL-2 and sIL-2R levels of 24 cases in stage I and II were not different from those in normal individuals. However, serum IL-2 level of 20 cases in stage III was significantly lower than that of normal individuals and of MM patients in stage I and II, while the serum sIL-2R level was significantly increased. The changes in serum IL-2 and sIL-2R level could reflect the severity of the disease.


Serous papillary adenocarcinoma and adult granulosa cell tumor in the same ovary. An unusual case.
Surface epithelial-stromal cell tumors are the most common neoplasms of the ovary but occurrence of a serous adenocarcinoma and an adult granulosa cell tumor in the same ovary is an unusual incident. In the present case report we describe this very uncommon occurrence in the ovary of a 50-year-old woman. The patient suffered abdominal distention and was referred to the state hospital where a 5x3 cm multilocular cystic lesion was observed on abdominal CT. Total abdominal hysterectomy with salpingo-oophorectomy and omentectomy was performed. Microscopy revealed an adult granulosa cell tumor and a serous papillary adenocarcinoma in the left ovary. Immunohistochemical staining with inhibin alpha and pancytokeratin confirmed the diagnosis.


[Nutrition of low birth weight infants].
The low birth weight infant's (LBW) nutrition needs special attention. Energy requirements are increased due to a high metabolic rate and a low thermogenesis. Increased protein requirements are, easy to be absorbed (from lacto-serum). Lipids, as important energetic source requires an appropriate content in essential fatty acids and medium chain triglycerides (TGM) which are easy absorbed in absence of lipase and deficit of bile salt secretion. The carbohydrates should be represented by lactose or equivalents like di-, oligo or polysaccharides. The addition of maltodextrin avoid an exaggerate supply and incomplete digestion of lactose. Sodium requirement are increased due to exaggerated loss consequence of renal immaturity. The rapid rate of growth impose the addition of Calcium, Phosphorus, Iron, Copper, and vitamins, especially Vitamin D, E and Folic acid. The appropriate nutrition of LBW must cover his special needs to maintain the homeostasis and rapid growth. Precise nutrient requirements are, however, difficult to establish.


Ventilatory care in myasthenia gravis crisis: assessing the baseline adverse event rate.
Myasthenic patients who require mechanical ventilation often develop pneumonia or atelectasis. Although there are differences in the prevalence of these complications among various institutions, there is no evidence that aggressive treatment shortens the course of the myasthenic crisis. We have quantified the severity of lung injury and aggressiveness of respiratory intervention in myasthenic patients admitted to the neuro-critical care unit. We retrospectively identified all mechanically ventilated myasthenic patients admitted in our unit between 1990 and 1998. Neuro-critical care unit of a tertiary care center in an urban area with a large, established, regional neuromuscular disease program. Eighteen myasthenia gravis patients with 24 episodes of respiratory failure requiring mechanical ventilation. A novel respiratory intervention index, comprising the use of suction, intermittent positive-pressure breathing or bronchodilator treatments, sighs, and chest physiotherapy represented the aggressiveness of the respiratory treatment. The respiratory intervention index was correlated with the lung injury score, used as a measure of lung involvement and other respiratory variables. MEASUREMENTS AND MAIN RESULTS Our patients had less atelectasis and pneumonia than previously published series (46% vs. 91%), leading to shorter mechanical support and neuro-critical care unit stay. The mean respiratory intervention index correlated with lung injury score and inversely with forced vital capacity. This study presents an estimate for both severity of pulmonary complications and intensity of respiratory therapy in the severe myasthenic patient with mechanical ventilatory compromise. Our results suggest that aggressive respiratory treatment should be used in myasthenic patients in crisis to diminish the risk for prolonged respiratory complications. These observations should be validated in a prospective study.


The comet assay, DNA damage, DNA repair and cytotoxicity: hedgehogs are not always dead.
DNA damage is commonly measured at the level of individual cells using the so-called comet assay (single-cell gel electrophoresis). As the frequency of DNA breaks increases, so does the fraction of the DNA extending towards the anode, forming the comet tail. Comets with almost all DNA in the tail are often referred to as 'hedgehog' comets and are widely assumed to represent apoptotic cells. We review the literature and present theoretical and empirical arguments against this interpretation. The level of DNA damage in these comets is far less than the massive fragmentation that occurs in apoptosis. 'Hedgehog' comets are formed after moderate exposure of cells to, for example, H2O2, but if the cells are incubated for a short period, 'hedgehogs' are no longer seen. We confirm that this is not because DNA has degraded further and been lost from the gel, but because the DNA is repaired. The comet assay may detect the earliest stages of apoptosis, but as it proceeds, comets disappear in a smear of unattached DNA. It is clear that 'hedgehogs' can correspond to one level on a continuum of genotoxic damage, are not diagnostic of apoptosis and should not be regarded as an indicator of cytotoxicity.


Methyltransferase-like 3 induces the development of cervical cancer by enhancing insulin-like growth factor 2 mRNA-binding proteins 3-mediated apoptotic chromatin condensation inducer 1 mRNA stability.
N6-methyladenosine (m6A) plays a critical role in the tumorigenesis of cervical cancer (CC). Here, we aimed to investigate the potential role of methyltransferase-like 3 (METTL3) in CC. Gene expression was determined via real-time quantitative polymerase chain reaction. Cellular functions were detected using colony formation, 5-ethynyl-2'-deoxyuridine (EdU), and Transwell assays. The interactions among METTL3, insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3), and apoptotic chromatin condensation inducer 1 (ACIN1) were confirmed using the MeRIP and RIP assays. An in vivo assay was performed to verify the role of METTL3 in CC development. METTL3 is overexpressed in CC, and therefore, its knockdown inhibits the proliferation and migration of CC cells. Silencing METTL3 inhibits tumor growth in vivo. Moreover, a positive association was observed between METTL3 and ACIN1. METTL3 interacts with IGF2BP3 to promote the mRNA stability of ACIN1, the overexpression of which induces the aggressiveness of CC cells. METTL3 promotes ACIN1 mRNA stability to accelerate CC progression, implying that METTL3 is a promising biomarker in CC.


A retrospective, observational cohort analysis of a nationwide database to compare heart failure prescriptions and related health care utilization before and after publication of updated treatment guidelines in the United States.
The current American College of Cardiology/American Heart Association (ACC/AHA) clinical guidelines for heart failure (HF), published September 20, 2005, provide a summary of the best evidence for treatment, but these recommendations are not always reflected in clinical practice. The aims of this study were to compare 6-month prescribing habits in the United States before and after the publication of updated clinical guidelines for the evaluation and management of HF and the impact of these prescribing habits on health care resource use. This retrospective, observational cohort analysis used the Humana nationwide health insurance administrative claims database that includes -3.5 million covered members from all 50 states and Puerto Rico who are enrolled in a health maintenance organization, a preferred provider organization, or a Medicare plan. The data included demographics (age, sex, type of insurance, and geographic location), medical information with up to 9 diagnostic codes per encounter, codes for procedures and medical equipment, laboratory tests, and pharmacy-dispensed medications. HF medication prescriptions and health care utilization were evaluated for 2 cohorts: those identified from claims before guideline publication (January 1, 2005-June 30, 2005) and those identified from claims after publication (October 1, 2006-March 31, 2007). Patients were eligible if they were aged ≥45 years, had 12 months of continuous enrollment (6 months before and 6 months after the index date, defined as the date of diagnosis or hospitalization for HF), and had ≥1 claim for HF. The primary outcome was the proportion of patients who received prescriptions for HF medications individually or in combination. Secondary outcomes were adherence to medication, all-cause and HF-specific hospitalizations, and emergency department and outpatient physician visits. The mean (SD) age in the before-publication cohort (n = 29,784) was 75 (11) years; in the after-publication cohort (n = 33,598), it was 74 (11) years (P < 0.001). Half of all patients in each cohort were female (50% [n = 14,796 and n = 16,803, respectively]); 9% (n = 2539) of the before-publication cohort and 7% (n = 2283) of the after-publication cohort were classified as having moderate to severe HF based on the baseline number of hospitalizations (P < 0.001). Fewer patients in the before-publication cohort received angiotensin-converting enzyme inhibitors (43% [12,811/29,784] vs 44% [14,776/33,598]; P = 0.01), β-blockers (37% [10,901/29,784] vs 41% [13,639/33,598]; P < 0.01), angiotensin receptor blockers (10% [3008/29,784] vs 13% [4378/33,598]; P < 0.01), or hydralazine (3% [865/29,784] vs 4% [1378/33,598]; P < 0.01). Among those with moderate to severe HF, there were no significant differences between groups in the use of combination therapy (ie, β-blockers with any combination of isosorbide dinitrate, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, or hydralazine; all combinations, P = NS between cohorts), except for less use of a β-blocker with either an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker among the before-publication cohort (23% [595/2539] vs38% [875/2283]; P = 0.005). Therewere significantly fewer all-cause and HF-related outpatient visits, all-cause and HF-related hospitalizations, and all-cause and HF-related emergency department visits in the after-publication cohort (all, P < 0.001); however, the absolute differences in the proportions of patients in each cohort who required such services were relatively small. Based on this analysis of real-world prescribing patterns, only small differences in prescribing practices were found before and after the 2005 publication of the ACC/AHA guidelines for HF treatment. Health care utilization was slightly, but significantly, reduced after publication of the guidelines.


Gut peptide signals in the control of food intake.
Extract: During and following a meal, ingested nutrients come into contact with multiple sites in the gastrointestinal tract that have the potential to alter peptide and neural signaling. Such signals can serve as feedback mediators influencing current or subsequent food intake. Ingested nutrients accumulate within the stomach, activating gastric mechanoreceptors and providing a signal of gastric fullness. Even during a meal, some ingested nutrients pass from the stomach and contact intestinal receptors. Such contact results in gastrointestinal peptide release and the activation of neural fibers producing reflex alterations in gastrointestinal motor and secretory activity and providing feedback information about the volume and nature of ingested nutrients that could alter the size of the current meal or affect subsequent eating. Recent work has characterized the ability of multiple gut peptides to affect eating and, consistent with their different patterns of release around meals, various roles for these peptides in overall eating control have been suggested. With the current rapid increase in rates of obesity, peripheral peptides with the ability to affect food intake provide attractive targets for antiobesity drug development.


Two-Dimensional Organic Single Crystals with Scale Regulated, Phase-Switchable, Polymorphism-Dependent, and Amplified Spontaneous Emission Properties.
The successful preparation of two-dimensional (2D) single crystals can promote the development of organic optoelectronic devices with excellent performance. A Schiff base compound salicylidene(4-dimethylamino)aniline with aggregation induced emission (AIE) property was employed as the building block to fabricate 2D thin single crystal plates with scales from around 50 μm to 1.5 cm. Yellow and red emissive polymorphs were concomitantly obtained during crystallization. The single-crystal-to-single-crystal (SC-to-SC) transformation from yellow polymorph to red one was demonstrated. Furthermore, both polymorphs exhibited amplified spontaneous emission (ASE) properties. Interestingly, the red polymorph displayed size-dependent ASE characteristics. The larger red polymorph showed near-infrared ASE with maximum at 706 nm, whereas the smaller one presented red ASE with maximum at 610 nm. These results suggest that the different scale single crystalline thin films with perfect optoelectronic properties may be fabricated by using the organic molecules with 2D assembly feature.


Load bearing and deformation characteristics of monofilament nylon 66 and their implications for ophthalmic surgery.
The load bearing and deformation characteristics of monofilament nylon 66 have been examined. This material has been shown to have increased strength and altered deformation properties compared to bulk nylon. These features are beneficial in its role as a corneal suture. However, the load bearing performance of monofilament nylon 66 has been shown to be influenced by the manner in which it is stressed, making the task of producing identical stitches difficult. Moreover, a period of rapid relaxation has been shown to occur immediately after installation which makes the time taken to install the suture a critical factor in its subsequent performance. These factors, which are essentially beyond the control of the ophthalmic surgeon, must surely play a significant role in the inconsistent post operative results seen.


Implementation of a Post-Surgical, Multimodal Analgesia Pain Management Order Set in Opioid-Naive Patients.
Perioperative pain management guidelines recommend using multimodal analgesia to improve pain control while reducing opioids administered. The primary objective of this study was to assess whether implementing multimodal analgesia on general surgery postoperative pain management order sets would reduce opioid quantities postoperatively. Opioid-naive patients undergoing nonemergent general surgery procedures were evaluated before and after order set revision. The primary outcome was the total quantity of inpatient opioids administered. The secondary outcomes were inpatient naloxone administration, patient-reported pain scores, and opioid quantities prescribed at discharge. The average daily opioid consumption was less each postoperative day (POD) after implementing the revised postsurgical multimodal analgesia pain management order set. On POD 1 and POD 2, average opioid consumption was 53.6 and 47.9 oral morphine equivalents (OME) before the multimodal analgesia order set, respectively, compared with 21.2 and 21.4 OME after, respectively (p < 0.01 and p < 0.01, respectively). Average daily opioid consumption through POD 3 was 60.6 OME before and 21.14 OME after the revision. Average daily pain scores were similar on POD 0, 1, and 2 before and after (3.2, 2.8, and 2.4 compared with 2.8, 3.1, and 2.7, respectively; p = 0.09, 0.33, and 0.12, respectively). On POD 3, pain scores were higher in the postorder set group (2.8 compared with 1.9; p < 0.01), but this was considered clinically insignificant. Average daily pain score through POD 3 was 2.6 before implementation compared with 2.8 after implementation. Neither group required naloxone administration. Using perioperative multimodal analgesia reduces opioid consumption without increasing pain scores.


Advantages of using the net-benefit approach for analysing uncertainty in economic evaluation studies.
No consensus has yet been reached on how to analyse uncertainty in economic evaluation studies where individual patient data are available for costs and health effects. This paper summarises the available results regarding the analysis of uncertainty on the cost-effectiveness plane and argues for using the net-benefit approach when analysing uncertainty in cost-effectiveness studies. The net-benefit approach avoids the interpretation and statistical problems related to the incremental cost effectiveness ratio and implies several advantages. First, traditional statistical methods can be used for confidence-interval estimation and hypothesis testing. Second, calculation of the optimal sample size and the power of the study are facilitated allowing the correlation between costs and effects to vary within and between patient groups. Third, the use of a Bayesian approach to cost-effectiveness analysis is facilitated. Fourth, a formal relation between cost-effectiveness acceptability curves and statistical inference is provided. Finally, the net-benefit approach gives the Fieller's limits of the confidence interval for the incremental cost-effectiveness ratio in the cost-effectiveness plane. Based on these advantages the net-benefit approach should strongly be considered when analysing uncertainty in cost-effectiveness analyses.


Therapeutic benefits of intravenous cardiosphere-derived cell therapy in rats with pulmonary hypertension.
Pulmonary arterial hypertension (PAH) is a progressive condition characterized by occlusive pulmonary arteriopathy, in which survival remains poor despite pharmacologic advances. The aim of this study was to evaluate the ability of cardiosphere-derived cells (CDCs), cardiac progenitor cells with potent anti-inflammatory and immunomodulatory properties, to attenuate hemodynamic and morphometric remodeling of the right ventricle (RV) and pulmonary arterioles in rats with established monocrotaline (MCT)-induced PAH. Animals were divided into 3 groups: 1) Control (CTL), 2) PAH in which CDCs were centrally infused (CDC) and 3) PAH in which saline was given (Sham). Significant increments in RV systolic pressure (RVSP) and RV hypertrophy were noted in Sham animals compared to CTL. In CDC rats at day 35, RSVP fell (- 38%; p< 0.001) and RV hypertrophy decreased (-26%; p< 0.01). TAPSE and cardiac output were preserved in all 3 groups at day 35. Pulmonary arteriolar wall thickness was greater in Sham rats compared to CTL, and reduced in CDC animals for vessels 20-50 μm (P<0.01; back to CTL levels) and 50-80μm (P<0.01) in diameter. The macrophage population was increased in Sham animals compared to CTL (P< 0.001), but markedly reduced in CDC rats. In conclusion, infusion of CDCs markedly attenuated several key pathophysiologic features of PAH. As adjunctive therapy to PAH-specific agents, CDCs have the potential to impact on the pathobiology of adverse pulmonary arteriolar remodeling, by acting on multiple mechanisms simultaneously.


Surgical treatment of pancreatic tumors in childhood and adolescence: uncommon neoplasms with favorable outcome.
Pancreatic tumors in children and adolescents are uncommon. The aim of the present paper was to analyze short- and long-term outcomes after surgical treatment of primary pancreatic neoplasms in children and adolescents at a single high-volume center for pancreatic diseases. Retrospective review of medical records and pathology reports of patients younger than 18 years who underwent surgery at Verona University Hospital from 1990 through 2010. The study population consisted of 20 patients. Abdominal pain and palpable mass were the most common presenting symptoms. No patient had a locally advanced, unresectable or metastatic disease. Complete resection (R0) was achieved in 19 patients. There was no postoperative mortality, but postoperative complications occurred in 5 cases (25%). Histological examination showed 12 solid pseudopapillary tumors, 5 neuroendocrine tumors, 2 cystadenomas and 1 epithelial malignant tumor. At a median follow-up of 49.5 months (range: 7-234), there was no tumor recurrence. Postoperative diabetes was diagnosed in 1 patient and 4 other patients developed pancreatic exocrine insufficiency. In the setting of a high-volume surgical center, radical resection of pancreatic tumors in children and adolescents is associated with acceptable postoperative morbidity and favorable long-term outcome.


Renin gene expression in the adrenal and kidney of patients with primary aldosteronism.
mRNA levels for renin in the adrenal gland and kidney were measured by ribonuclease protection assay (RPA). Renin mRNA was not detected by RPA in aldosteronoma and kidney tissues obtained from two patients with primary aldosteronism (PA). In these patients, the PRA values, plasma concentrations of active renin (ARC), and total renin (TRC = ARC + prorenin) were below the assay limit (less than 0.03 ng/L.s, 2.5 ng/L, and 10 ng/L, respectively). On the other hand, renin mRNA was recognized by RPA in aldosteronoma and kidney tissues obtained from two other patients with PA treated with 50 mg/day spironolactone for more than 2 months. Their TRC values were 49.8 and 16.6 ng/L, but their PRA and ARC were undetectable. Renin mRNA content was greater in normal adrenocortical tissue and in the normal kidneys obtained from three hypertensive patients with renal cell carcinoma. In these patients, the mean values of PRA, ARC, and TRC were 0.28 +/- 0.03 (mean +/- SD) ng/L.s, 18.4 +/- 7.8 ng/L, and 110 +/- 15 ng/L, respectively. This is the first report of the lack of renin gene expression in aldosteronoma and kidney tissues obtained from untreated patients with PA. Furthermore, treatment with spironolactone resulted in an increase in the levels of renin mRNA in the aldosteronoma and kidney tissues of patients with PA.


Quality of life after pulmonary embolism: validation of the PEmb-QoL Questionnaire.
Even though quality of life (QoL) has become a key component of medical care, there is no instrument available that specifically measures QoL after pulmonary embolism (PE). Recently, the Pulmonary Embolism Quality of Life (PEmb-QoL) Questionnaire has been developed to address this gap. To evaluate the validity of the PEmb-QoL questionnaire. We distributed the PEmb-QoL questionnaire and the Short Form-36 (SF-36) questionnaire twice among consecutive subjects with a history of objectively confirmed acute PE. Internal consistency reliability, test-retest reliability, convergent validity and criterion validity, and correlations between the PEmb-QoL and clinical patient characteristics were assessed using standard-scale construction techniques. Ninety participants completed the questionnaires twice. Internal consistency was adequate (Cronbach's alpha 0.62-0.94), as well as test-retest reliability (intra-class correlation coefficients: 0.78-0.94). Furthermore, correlation between the PEmb-QoL questionnaire and the SF-36 questionnaire supported convergent validity. Age, obesity, cardiopulmonary comorbidity, centrally located PE and a family history of venous thromboembolism were shown to be independent determinants of disease-specific QoL. The PEmb-QoL questionnaire is a reliable instrument to specifically assess QoL following PE, which is helpful in the identification of patients with decreased QoL following acute PE.


Palmar fascial complex anatomy and pathology in Dupuytren's disease.
Familiarity with the normal palmar fascial anatomy of the hand is necessary for understanding the convoluted pathologic changes that take place in Dupuytren's disease. This article includes a literature review and the findings of a study by the author of the fascial anatomy and pathology as related to Dupuytren's disease. Gross and microdissection of the palmar fascial structures were carried out with the aid of the operative microscope and an arthroscope, which allowed examination of the fine and undisturbed retinacular anatomy. The palmar fascial complex of the hand has five components: the radial aponeurosis, ulnar aponeurosis, central (palmar) aponeurosis, palmo-digital fascia, and digital fascia. The subtle constituents of each component are outlined and the transformation from normal to pathologic anatomy is clarified.


An Acceptance and Commitment Training (ACT) Framework for Teaching Cultural Humility: A Guide for Translating ACT from a Therapeutic Context into a Medical Education Curriculum.
The objective of this project was to train future physicians to work effectively and thoughtfully with diverse populations by teaching them to employ Acceptance and Commitment Training (ACT) skills to increase cultural humility, with the goal of improving attitudes, knowledge, and beliefs about working with diverse patients. We developed ACT for cultural humility online interactive modules as part of an elective course to teach Medical Spanish to 4th-year medical students. Pre- and post-pilot data pertaining to the cultural humility training modules on the Work-Related Acceptance and Action questionnaire, Multidimensional Cultural Humility Scale, knowledge, attitudes, and beliefs were analyzed using paired samples t-tests and Wilcoxon signed-rank tests. We also included descriptive data pertaining to overall satisfaction with the cultural humility modules and intent to apply the material learned to patient care. Our data showed a significant increase in the cultural humility of our participants as well as an increase in psychological flexibility, a higher favorability rating toward various ethnicities, improvements in attitude, and positive changes in beliefs and knowledge following completion of the modules. The modules were well received by the medical students, with high social validity ratings. The ACT for cultural humility curriculum has great potential to enhance medical education in diversity, equity, and inclusion by increasing both the understanding and the cultural humility of medical students and future professionals to work with diverse populations. The current paper provides a framework that can be used by other programs to shape the education of the future medical workforce to help promote culturally humble care.


Staphylococcus aureus rectal carriage and its association with infections in patients in a surgical intensive care unit and a liver transplant unit.
The role of rectal carriage of Staphylococcus aureus as a risk factor for nosocomial S. aureus infections in critically ill patients has not been fully discerned. Nasal and rectal swabs for S. aureus were obtained on admission and weekly thereafter until discharge or death from 204 consecutive patients admitted to the surgical intensive care unit and liver transplant unit Overall, 49.5% (101 of 204) of the patients never harbored S. aureus, 21.6% (44 of 204) were nasal carriers only, 3.4% (7 of 204) were rectal carriers only, and 25.5% (52 of 204) were both nasal and rectal carriers. Infections due to S. aureus developed in 15.7% (32 of 204) of the patients; these included 3% (3 of 101) of the non-carriers, 18.2% (8 of 44) of the nasal carriers only, 0% (0 of 7) of the rectal carriers only, and 40.4% (21 of 52) of the patients who were both nasal and rectal carriers (P - .001). Patients with both rectal and nasal carriage were significantly more likely to develop S. aureus infection than were those with nasal carriage only (odds ratio, 3.9; 95% confidence interval, 1.18 to 7.85; P= .025). By pulsed-field gel electrophoresis, the infecting rectal and nasal isolates were clonally identical in 82% (14 of 17) of the patients with S. aureus infections. Rectal carriage represents an underappreciated reservoir for S. aureus in patients in the intensive care unit and liver transplant recipients. Rectal plus nasal carriage may portend a greater risk for S. aureus infections in these patients than currently realized.


Nutritional evaluation of complementary porridge formulated from orange-fleshed sweet potato, amaranth grain, pumpkin seed, and soybean flours.
Supplementing breastmilk with poor energy and nutrient-dense complementary foodstuffs for young children and infants has resulted in malnutrition, poor growth, and retardation of infant development in many sub-Saharan African countries. Ensuring nutrient adequacy for infants because of their lower consumption requires energy and nutrient-dense food. In this context, the nutritional composition of porridge from complementary flour blends of locally available foodstuffs (orange-fleshed sweet potato, pumpkin seeds, amaranth grains, and soybeans) was carried out. Complementary flours formulated from flour blends of pumpkin seeds, extrusion cooked soybean, and orange-fleshed sweet potato, as well as germinated and extrusion cooked amaranth grains, resulted in varieties of complementary porridges (SAPO1-SAPO5). From these, proximate composition, mineral content (sodium, iron, magnesium, calcium, phosphorus, and zinc), vitamin contents (A and C), and nutrient density of the formulated complementary porridge were determined. Results showed that all the formulated complementary porridge were able to meet the stipulated standards of energy and nutrient (zinc, iron, vitamin A, and protein) densities. Flour blend ratio, germination process, and extrusion cooking significantly (p < .05) influenced the targeted nutrients of interest, as well as the nutrient and energy densities of the formulated complementary porridge. Specifically, the formulated complementary porridge with 40% amaranth grain, 25% orange-fleshed sweet potato, 20% soybean, and 15% pumpkin seed composite mixture had 76.92% compliance level with recommended standards, which assure adequate nutrient complementation to breastfeeding. The present study provides a valuable insight that complementary foods from locally obtainable foodstuffs are potential solutions for mitigating childhood malnutrition and adequate complementation to breastfeeding by proffering the needed energy and nutrient densities required for the immunity, well-being, growth, and development of young children and infants, without fortification.


[Results of a multidisciplinary program to quit smoking].
Therapies to quit smoking are based on counseling, psychological therapy (PT), nicotine replacement therapy, bupropion or varenidine. To report the results of a multidisciplinary program to quit smoking. Patients aged l8 years or more, motivated to quit smoking were admitted in a program based in counseling and PT, with or without pharmacological therapy. They were assessed by telephone during one year of follow up. Patients with unstable psychiatric diseases were excluded. Results were considered as "successful" when patients maintained abstinence during the year of follow up. A logistic regression analysis was done to identify factors associated with treatment success. Between 2005 and 2011, 198 patients aged 45 ± 11 years (56% males), who smoked 31.5 ± 20.6 packages/year, were treated. Of these, 155 (78%) were treated with varenidine, 26 (13%) with bupropion and 17 (9%>) did not receive pharmacological therapy. One hundred sixty eight patients completed the year of follow up. In 82 (49%>), treatment was successful and was negatively associated with a history of depression (odds ratio = 4 (95% confidence intervals 1.23-38.33). The main side effeets associated to varenidine and bupropion were nausea in 37 and 23%o, sleep disorders in 20 and 19%o and headache in 12 and 0%>, respectively. A multidisciplinary program to quit smoking achieved a 49%> of abstinence during a year of follow up.


Reversible detection of heparin and other polyanions by pulsed chronopotentiometric polymer membrane electrode.
The first fully reversible polymeric membrane-based sensor for the anticoagulant heparin and other polyanions using a pulsed chronopotentiometry (pulstrode) measurement mode is reported. Polymeric membranes containing a lipophilic inert salt of the form R(+)R(-) (where R(+) and R(-) are tridodecylmethylammonium (TDMA(+)) and dinonylnaphthalene sulfonate (DNNS(-)), respectively) are used to suppress unwanted spontaneous ion extractions under zero-current equilibrium conditions. An anodic galvanostatic current pulse applied across the membrane perturbs the equilibrium lipophilic ion distribution within the membrane phase in such a way that anions/polyanions are extracted into the membrane from the sample. The membrane is then subjected to an open-circuit zero current state for a short period, and finally a 0 V vs reference electrode potentiostatic pulse is applied to restore the membrane to its initial full equilibrium condition. Potentials are sampled as average values during the last 10% of the 0.5 s open circuit phase of the measurement cycle. Fully reversible and reproducible electromotive force (emf) responses are observed for heparin, pentosan polysulfate (PPS), chondroitin sulfate (CS), and oversulfated chondroitin sulfate (OSCS), with the magnitude of the potentiometric response proportional to charge density of the polyanions. The sensor provides an emf response related to heparin concentrations in the range of 1-20 U/mL. The responses to variations in heparin levels and toward other polyanions of the pulstrode configuration are analogous to the already established single-use, nonreversible potentiometric polyion sensors based on membranes doped only with the lipophilic anion exchanger TDMA(+).


Phase Composition Control in Microsphere-Supported Biomembrane Systems.
The popularization of studies in membrane protein lipid phase coexistence has prompted the development of new techniques to construct and study biomimetic systems with cholesterol-rich lipid microdomains. Here, microsphere-supported biomembranes with integrated α-helical peptides, referred to as proteolipobeads (PLBs), were used to model peptide/protein partitioning within DOPC/DPPC/cholesterol phase-separated membranes. Due to the appearance of compositional heterogeneity and impurities in the formation of model PLB assemblies, fluorescence-activated cell sorting (FACS) was used to characterize and sort PLB populations on the basis of disordered phase (Ld) content. In addition, spectral imaging was used to assess the partitioning of FITC-labeled α-helical peptide between fluorescently labeled Ld phase and unlabeled ordered phase (Lo) phase lipid microdomains. The apparent peptide partition coefficient, Kp,app, was measured to be 0.89 ± 0.06, indicating a slight preference of the peptide for the Lo phase. A biomimetic motif of the Lo phase concentration enhancement of the biotinyl-peptide ligand display in proteolipobeads was also observed. Finally, peptide mobility was measured by FRAP separately in each lipid phase, yielding diffusivities of 0.036 ± 0.005 and 0.014 ± 0.003 μm2/s in the Ld and Lo phases, respectively.


Highly uniform YBO3 hierarchical architectures: facile synthesis and tunable luminescence properties.
Highly uniform pancake-like YBO(3) hierarchical architectures have been successfully prepared by a designed two-step hydrothermal method. Yttrium precursor microprisms were first synthesized according to a simple hydrothermal route. Subsequently, nearly monodisperse multilayered YBO(3) products with a pancake-like shape were synthesized at the expense of the precursor during the hydrothermal process. The whole process was carried out under aqueous conditions without the use of any organic solvent, surfactant, or catalyst. The conversion process from the precursor to YBO(3) products has been investigated by time-dependent XRD experiments. Extending this method, other LnBO(3) (Ln=Ho, Er, Tm, Yb) samples with well-defined shape and dimensionality have also been obtained by a similar synthetic process. The luminescence colors of YBO(3) samples co-doped with Eu(3+) and Tb(3+) under ultraviolet or low-voltage electron beam excitation can be tuned from red, through yellow and green-yellow, to green by simply adjusting the relative doping concentrations of the activator ions. This merit of multicolor emissions in the visible region endows materials of this kind with potential application in the fields of light-display systems and optoelectronic devices.


[Clinical value of Echinococcus granulosus--specific immunoglobulin G antibody avidity in liver cystic echinococcosis].
Role of E. granulosus-specific IgG antibody avidity in evaluation of a natural history of the parasite cysts in the liver, duration of infection and immunogenic cysts activity was studied. Thirty-one patients with liver cysts suspected of echinococcosis were examined; E. granulosus infection was finally confirmed by a fine needle aspiration biopsy or surgery in 29 cases (93.5%) and two non-parasitic simple cysts in the liver were diagnosed. E. granulosus-specific IgG antibody was found in 21 patients (67.7%). High IgG avidity values were observed in 14 patients with liver cysts in a degeneration stage confirmed by imaging techniques. Low IgG avidity values were mostly detected in children with hypoechogenic echinococcal cysts being in a recent stage of infection. Determination of anti-E. granulosus immunoglobulin G antibody avidity is a very usefull diagnostic tool for a determination of parasitic cysts activity and their developmental age.


Superhard tungsten tetraboride films prepared by pulsed laser deposition method.
Attempts to synthesize and/or theoretically predict new superhard materials are the subject of an intense research activity. The trials to deposit them in the form of films have just began. WB(2) (77 wt % WB(2) and 23 wt % WB(4)) and WB(4) (65 wt % WB(4) and 35 wt % WB(2)) polycrystalline bulk samples were obtained in this work via electron beam synthesis technique and, subsequently, used as targets for films preparation by the pulsed laser deposition method. The targets were irradiated by a frequency-doubled Nd:glass laser with a pulse duration of 250 fs. The films grown on SiO(2) substrates at 600 °C were characterized by X-ray diffraction, scanning electron and atomic force microscopies, and Vickers microhardness technique. The deposited films are composed of WB(4). The intrinsic film hardness, calculated according to the "law-of-mixtures" model, lies in the superhardness region 42-50 GPa.


Prophylactic antibiotics in endoscopic sinus surgery: a short follow-up study.
The study was designed to assess the usefulness of postoperative antibiotics in patients undergoing endoscopic sinus surgery (ESS). The effects of antibiotics in the postoperative period of ESS patients were evaluated in a prospective, randomized, double-blind, placebo-controlled study. Fifty patients were treated with amoxicillin/clavulanate for 2 weeks after ESS, while the other half received placebo. Preoperatively, the symptom, endoscopic, and CT scores were recorded. In the postoperative period, symptom and endoscopic scores were recorded on the 5th, 12th, 21st, and 30th days. In estimating the length of the blood crust formation episode, a Kaplan-Meier plot was used. Seventy-five patients completed the study: forty in the antibiotic-treated group and thirty-five in the placebo group. On the 5th day, nasal obstruction and drainage were significantly better in the antibiotic-treated group. In addition, a statistically significant difference in the endoscopic scores was noted between the treatment and placebo groups on days 5 and 12. The use of an antibiotic (amoxicillin/clavulanate) in the postoperative period is able to improve the outcome in the early blood crust healing phase: nasal obstruction and drainage are reduced and the endoscopic score objectively showed a faster recovery.


PINK1/parkin-mediated mitophagy alleviates Staphylococcus aureus-induced NLRP3 inflammasome and NF-κB pathway activation in bovine mammary epithelial cells.
Staphylococcus aureus (S. aureus) is known to induce chronic and persistent bovine mammary infection, which affects milk quality and leads to premature culling. The ability of S. aureus to invade mammalian cells protects it from clearance by the immune system. Mitophagy is important in cell homeostasis, and can be utilized by pathogens for immune escape. However, mitophagy's role in S. aureus-associated bovine mastitis remains unclear. Here, S. aureus infection induced mitophagy and enhanced mitochondrial translocation of parkin in MAC-T cells. After mitophagy inhibition by Mdivi-1 treatment or PTEN-induced putative kinase 1 (PINK1) silencing in MAC-T cells infected with S. aureus, NOD-like receptor protein 3 (NLRP3) inflammasome activation and p65 and IκBα phosphorylation were increased. Meanwhile, PINK1 overexpression had the opposite effects. In addition, NLRP3 inflammasome overactivation and enhanced p65 and IκBα phosphorylation caused by PINK1 silencing were reversed by MitoTEMPO. Furthermore, PINK1/parkin-mediated mitophagy promoted S. aureus survival and contributed to persistent S. aureus infection. These findings provide new insights into S. aureus invasion in bovine mastitis.


The Effect of Sodium Total Substitution on the Quality Characteristics of Green Pickled Tomatoes (Solanum lycopersicum L.).
Green pickled tomatoes are a traditional fermented product in Romania. This study was focused on the effect of total substitution of NaCl with KCl and MgCl2 on physicochemical and microbiological quality; bioactive compounds; and microstructural, textural, and sensorial properties of fresh and pickled green tomatoes during 28 days of fermentation. By the means of physicochemical composition, the NaCl addition induced the most stable characteristics for the pickles compared to the other two types of salts. The content of total flavonoids in green pickled tomatoes with NaCl (34.72 ± 0.43 mg CE/g DW) was significantly lower compared with the control sample (63.80 ± 0.55 mg CE/g DW). The total number of lactic acid bacteria (LAB) at the final stage of fermentation varied between 4.11 and 4.63 log CFU for all variants. The textural analysis revealed that the NaCl has the lowest influence on the textural parameters. Finally, the overall acceptance of green pickled tomatoes containing KCl and MgCl2 was found to be proper to be consumed as a substitute for pickles with NaCl.


Multivariate meta-analysis of mixed outcomes: a Bayesian approach.
Multivariate random effects meta-analysis (MRMA) is an appropriate way for synthesizing data from studies reporting multiple correlated outcomes. In a Bayesian framework, it has great potential for integrating evidence from a variety of sources. In this paper, we propose a Bayesian model for MRMA of mixed outcomes, which extends previously developed bivariate models to the trivariate case and also allows for combination of multiple outcomes that are both continuous and binary. We have constructed informative prior distributions for the correlations by using external evidence. Prior distributions for the within-study correlations were constructed by employing external individual patent data and using a double bootstrap method to obtain the correlations between mixed outcomes. The between-study model of MRMA was parameterized in the form of a product of a series of univariate conditional normal distributions. This allowed us to place explicit prior distributions on the between-study correlations, which were constructed using external summary data. Traditionally, independent 'vague' prior distributions are placed on all parameters of the model. In contrast to this approach, we constructed prior distributions for the between-study model parameters in a way that takes into account the inter-relationship between them. This is a flexible method that can be extended to incorporate mixed outcomes other than continuous and binary and beyond the trivariate case. We have applied this model to a motivating example in rheumatoid arthritis with the aim of incorporating all available evidence in the synthesis and potentially reducing uncertainty around the estimate of interest.


Efficacy and adverse events of azacitidine in the treatment of hemodialysis patients with high-risk myelodysplastic syndrome.
We describe two hemodialysis patients with high-risk myelodysplastic syndrome (MDS) treated with azacitidine. A 65-year-old woman (case 1) received azacitidine at 75 mg/m(2) for 7 days, and a 52-year-old man (case 2) with liver cirrhosis received a 70% dose of azacitidine. Both cases developed grade 4 cytopenia, but they achieved transfusion independence after 3 and 2 courses, and the durations of remission were 10 and 11 months, respectively. Case 1 had the complication of febrile neutropenia (FN) twice during the 1(st) and 2(nd) courses, but continued to receive azacitidine treatment thereafter. Case 2 developed infectious peritonitis during the sixth course, and azacitidine treatment was thus discontinued. After a 4-month treatment interruption, he became transfusion-dependent, and re-induction of azacitidine was successful. Of note, the course of case 1 was complicated by erythema nodosum on admission, which then disappeared after one course of azacitidine treatment. The mean durations of hospitalization were 17.5 and 23 days per course of azacitidine treatment, respectively. Though there are few reports of azacitidine treatment for hemodialysis patients with high-risk MDS, we advocate administering azacitidine to such patients, while paying close attention to the dose intensity of azacitidine and taking prompt action to manage infectious complications.


Galvanic Vestibular Stimulation (GVS) effects on impaired interhemispheric connectivity in Parkinson's Disease.
Disrupted interhemispheric connectivity (IHC) is being increasingly recognized as a robust feature of a number of neurological diseases, including Parkinson's Disease (PD). We investigated whether or not Galvanic Vestibular Stimulation (GVS) - a proposed treatment for PD - affected IHC in 11 PD subjects (off medication). In order to avoid the confound of stimulation artifact disrupting the EEG, we investigated the immediate period (52 sec) after stimulation (72 sec) with noisy 1/f-type GVS stimuli. Partial Least Squares (PLS) regression was used to determine the subject-specific linear combination of EEG electrodes that maximized covariance between hemispheres and then computed coherence between the dominant PLS components. PD subjects had increased IHC <;~10 Hz and decreased IHC >13 Hz compared to 11 healthy, age-matched controls. After GVS in PD subjects, a significant increase in IHC was detected, especially above 30 Hz. We suggest that GVS may partially exert its beneficial effects in PD by "normalizing" impaired IHC.


Differentiation of human pluripotent stem cells to cells similar to cord-blood endothelial colony-forming cells.
The ability to differentiate human pluripotent stem cells into endothelial cells with properties of cord-blood endothelial colony-forming cells (CB-ECFCs) may enable the derivation of clinically relevant numbers of highly proliferative blood vessel-forming cells to restore endothelial function in patients with vascular disease. We describe a protocol to convert human induced pluripotent stem cells (hiPSCs) or embryonic stem cells (hESCs) into cells similar to CB-ECFCs at an efficiency of >10(8) ECFCs produced from each starting pluripotent stem cell. The CB-ECFC-like cells display a stable endothelial phenotype with high clonal proliferative potential and the capacity to form human vessels in mice and to repair the ischemic mouse retina and limb, and they lack teratoma formation potential. We identify Neuropilin-1 (NRP-1)-mediated activation of KDR signaling through VEGF165 as a critical mechanism for the emergence and maintenance of CB-ECFC-like cells.


Characterization of the late endosomal ESCRT machinery in Trypanosoma brucei.
The multivesicular body (MVB) is a specialized Rab7+ late endosome (LE) containing multiple intralumenal vesicles that function in targeting ubiquitinylated cell surface proteins to the lysosome for degradation. African trypanosomes lack a morphologically well-defined MVB, but contain orthologs of the ESCRT (Endosomal Sorting Complex Required for Transport) machinery that mediates MVB formation. We investigate the role of TbVps23, an early ESCRT component, and TbVps4, the terminal ESCRT ATPase, in lysosomal trafficking in bloodstream form trypanosomes. Both localize to the TbRab7+ LE and RNAi silencing of each rapidly blocks growth. TbVps4 silencing results in approximately threefold accumulation of TbVps23 at the LE, consistent with blocking terminal ESCRT disassembly. Trafficking of endocytic and biosynthetic cargo, but not default lysosomal reporters, is also negatively affected. Others reported that TbVps23 mediates ubiquitin-dependent lysosomal degradation of invariant surface glycoproteins (ISG65) (Leung et al., Traffic 2008;9:1698-1716). In contrast, we find that TbVps23 ablation does not affect ISG65 turnover, while TbVps4 silencing markedly enhances lysosomal degradation. We propose several models to accommodate these results, including that the ESCRT machinery actually retrieves ISG65 from the LE to earlier endocytic compartments, and in its absence ISG65 traffics more efficiently to the lysosome. Overall, these results confirm that the ESCRT machinery is essential in Trypanosoma brucei and plays important and novel role(s) in LE function in trypanosomes.


Addition of organometallic reagents to chiral N-methoxylactams: enantioselective syntheses of pyrrolidines and piperidines.
Enantioselective iridium-catalyzed allylic substitutions were used to prepare N-allyl hydroxamic acid derivatives that were suitable for ring-closing metathesis, giving N-methoxylactams. Reactions of these derivatives with Grignard or organolithium compounds gave hemiaminals, which could be reduced diastereoselectively via acyliminium intermediates to give cis-piperidines or cis-pyrrolidines with substituents in the 2,6- or 2,5-positions, respectively. In addition, compounds with a quaternary carbon center could be synthesized by corresponding reactions with potassium cyanide/AcOH. The procedures were applied in the syntheses of alkaloids (-)-209D and (+)-prosophylline.


A preliminary study of diltiazem in the prevention of coronary artery disease in heart-transplant recipients.
Accelerated coronary artery disease is a major cause of late morbidity and mortality among heart-transplant recipients. Because calcium-channel blockers can suppress diet-induced atherosclerosis in laboratory animals, we assessed the efficacy of diltiazem in preventing coronary artery disease in transplanted hearts. Consecutive eligible cardiac-transplant recipients were randomly assigned to receive diltiazem (n = 52) or no calcium-channel blocker (n = 54). Coronary angiograms obtained early after cardiac transplantation and annually thereafter were used for the visual assessment of the extent of coronary artery disease. The average diameters of identical coronary artery segments were measured on the angiograms obtained at base line and at the first and second follow-up examinations. In the 57 patients who had all three angiograms, the average coronary artery diameter (+/- SD) 0.27 decreased in the group that received no calcium-channel blocker from 2.41 +/- 0.27 mm at base line to 2.19 +/- 0.28 mm at one year, and to 2.22 +/- 0.26 mm at two years (P < 0.001 for both years). The average diameter in the diltiazem group changed little from the base-line value of 2.32 +/- 0.22 mm (2.32 +/- 0.27 mm at one year and 2.36 +/- 0.22 mm at two years). The average change in the diameter of the segment differed significantly between the two treatment groups (P < 0.001), and the estimated effect of treatment changed only negligibly after adjustment for other relevant clinical variables. New angiographic evidence of coronary artery disease developed in 14 patients not given calcium-channel blockers, as compared with 5 diltiazem-treated patients (P = 0.082). Coronary stenoses greater than 50 percent of the luminal diameter developed in seven patients not given calcium-channel blockers, as compared with two patients given diltiazem; death due to coronary artery disease or retransplantation occurred in five patients in the group that did not receive calcium-channel blockers and none of those who received diltiazem. Our preliminary results suggest that diltiazem can prevent the usual reduction in the diameter of the coronary artery in cardiac-transplant recipients, but further follow-up will be required to determine whether diltiazem can decrease the long-term incidence of symptomatic coronary artery disease.


Economic well-being following marital termination: a comparison of widowed and divorced women.
Several studies of divorced and widowed women show increased odds of becoming poor following the termination of marriage. Both cross-sectional and longitudinal data suggest that the end of marriage is correlated with higher poverty rates. Less is know, however, about factors that influence economic well-being over time, and whether these factors are similar for widows and divorced women. This analysis uses data from the National Longitudinal Surveys cohort of mature women (1967-1982) to examine the probability of becoming poor after widowhood or divorce among mid-life women, and factors that seem to influence economic well-being. Findings show that 40% of widows and over 1/4 of divorced women fall into poverty for at least some time during the 1st 5 years after leaving marriage. The type of marital transition experienced by the woman is not a significant factor in economic well-being, but both age and prior economic standing have positive estimated effects.


Directed evolution of bacterial polysialyltransferases.
Polysialyltransferases (polySTs) are glycosyltransferases that synthesize polymers of sialic acid found in vertebrates and some bacterial pathogens. Bacterial polySTs have utility in the modification of therapeutic proteins to improve serum half-life, and the potential for tissue engineering. PolySTs are membrane-associated proteins and as recombinant proteins suffer from inherently low solubility, low expression levels and poor thermal stability. To improve their physicochemical and biochemical properties, we applied a directed evolution approach using a FACS-based ultrahigh-throughput assay as a simple, robust and reliable screening method. We were able to enrich a large mutant library and, in combination with plate-based high-throughput secondary screening, we discovered mutants with increased enzymatic activity and improved stability compared to the wildtype enzyme. This work presents a powerful strategy for the screening of directed evolution libraries of bacterial polySTs to identify better catalysts for in vitro polysialylation of therapeutics.


Efficacy and safety of intravenous stronger neo-minophagen C and S-adenosyl-L-methionine in treatment of pregnant woman with chronic hepatitis B: a pilot study.
There have been no studies evaluating the efficacy and potential risks of stronger neo-minophagen C (SNMC) in pregnant women with chronic hepatitis B CHB. A total of 36 pregnant women with CHB, but without severe complications, were randomized to intravenously receive SNMC or S-adenosyl-L-methionine (SAM) daily for 4 weeks or until birth. Normalization of serum alanine transaminase (ALT) and aspartate transaminase (AST) levels and changes in ALT and AST levels from baseline were determined. All neonates were regularly examined for up to 1 year. Treatment with SNMC and SAM resulted in normalization of ALT levels at 4 weeks in 64.3% and 21.4% of patients, respectively (OR=6.60, 95% CI: 1.23-35.44, P=0.0540). SNMC and SAM significantly decreased ALT (from 558.28+/-390.24 to 47.07+/-24.94 IU/L, P<0.0001 and from 525.61+/-483.87 to 117.43+/-85.44 IU/L, P=0.0041, respectively) and AST (from 419.72+/-409.49 to 38.14+/-18.87 IU/L, P=0.0016, and from 510.78+/-621.58 to 79.93+/-63.25 IU/L, P=0.0152, respectively) at 4 weeks relative to baseline values. Hypokalemia was observed in 4 SNMC-treated patients and in 2 SAM-treated patients and hypernatremia in 3 SNMC-treated and in 3 SAM-treated patients. Hypertension was observed in 1 SNMC-treated patient. There was no significant difference in the volume of amniotic fluid or meconium between SNMC-treated and SAM-treated groups. All the neonates were physically normal at birth and at the 1-year follow-up examination. Both SNMC and SAM improve liver function, with SNMC appearing more effective, in pregnant women with chronic hepatitis B without impact on fetal development.


[Connection between cancer- and alcohol-related mortality in a rural practice of a South-Hungarian village].
The author, who is a sole general practitioner in a Hungarian village, has continuously followed mortality in his practice for a long period of time. He found connections between cancer- and alcohol-related mortality in the first observational period between 1987 and 1999. Among men, cancer mortality related to alcoholism reached 50% in men and 7.9% in women. The aim of the author was to obtain new data on the relation between cancer- and alcohol-related mortality during a 12-year period between 2000 and 2011, and compare them with findings in his earlier work. Data recorded in detailed death reports were analysed. For the main cause of death, long-term data from the medical history of patients were analysed thoroughly. Between 2000 and 2011 there were 326 cases of death (167 men and 159 women). Despite several changes in the structure of the cause of mortality (the frequency of alcohol-related deaths considerably decreased while the frequency of cancer-related deaths somewhat increased), the proportion of alcohol-related cancer mortality has increased to 60% in men and 9.1% in women. These data confirm earlier observation of the author showing that alcoholism is frequent in this Hungarian village and that it contributes to the high cancer mortality of the inhabitants, especially in men. Therefore, decreased alcohol consumption and alcohol-related harms would be an important step in cancer prevention.


[Longitudinal melanic nail bands (melanonychia): report of 22 cases].
Longitudinal melanonychia is a diagnostic and treatment problem for the surgeon. Fear of melanoma most frequently leads to total excision of nail bed, matrix and plate. Twenty two patients, aged from 7 to 77, were operated on from 89 to 98 in our department, using different techniques (total matrix biopsy, total excision of melanonichia with direct suture, Schernberg flap). Thumb and index are predominant locations (11 out of 16). No malignant lesions were found histologically. Aesthetic sequellae were frequent and directly linked to the width and location of the melanonychia. Limited matrix biopsy produce the best aesthetic result. Malignant lesions are rare and our series is short. Therefore an additional multicentric study is required. Our choice is to make a limited matrix biopsy in the first place with a minimal aesthetic prejudice. Histology determines the treatment choice: excision or follow up.