Letrozole cotreatment with progestin-primed ovarian stimulation in women with polycystic ovary syndrome undergoing IVF treatment.
Background: Progestin is an alternative to gonadotropin-releasing hormone (GnRH) analogues in the follicular phase to suppress the premature luteinizing hormone (LH) surge in women with polycystic ovary syndrome (PCOS). However, progestin-primed ovarian stimulation (PPOS) is always accompanied by increased pituitary suppression and gonadotropin consumption. Previous studies suggested that letrozole appeared to have the potential to reduce the total gonadotropin dose required for ovarian stimulation. A retrospective cohort study was performed to evaluate the efficacy of PPOS with or without letrozole in infertile women with PCOS. Methods: This retrospective cohort study included 448 women with PCOS who underwent controlled ovarian stimulation (COS) with human menopausal gonadotropin (hMG) and medroxyprogesterone acetate (MPA) (n = 224) or hMG and MPA cotreatment with LE (n = 224) from January 2018 to March 2021 after propensity-score matching. The primary outcome measure was the hMG dose. The secondary outcomes were the durations of ovarian stimulation, the implantation rate, the number of oocytes retrieved and viable embryos, oocyte maturity and fertilization rates, the percentage of women with profound pituitary suppression (luteinizing hormone [LH] <1.0 IU/L on the trigger day). Results: The hMG doses (1949.89 ± 725.03 IU vs 2017.41 ± 653.32 IU, p > 0.05) and durations of ovarian stimulation (9.03 ± 1.79 days vs 9.21 ± 2.18 days, p > 0.05) were similar between the two groups. The implantation rate was significantly higher in the study group (MPA + hMG + LE) than in the control group (MPA + hMG) (42.22 vs 34.69%, p < 0.05). The numbers of oocytes and embryos retrieved were similar between the two groups. Interestingly, letrozole cotreatment was associated with decreased oocyte maturity and fertilization rates in comparison with standard PPOS protocols even though mature and fertilized oocyte yields were comparable. Compared with those in the control group, the LH values on the trigger day were significantly higher in the study group, together with significantly reduced pituitary suppression. Conclusion: Letrozole combined with PPOS cannot reduce hMG consumption in PCOS patients undergoing IVF treatment and shows no beneficial effect on cycle characteristics of COS. However, letrozole supplementation manifests as a superior implantation rate to that of the standard PPOS protocol in women with PCOS.


Psallusthomashenryi sp. n. and Psalluslucanicus from Turkey (Hemiptera, Heteroptera, Miridae).
Psallus (Psallus) thomashenryisp. n. (Hemiptera: Heteroptera: Miridae: Phylinae: Phylini: Phylina) is described from southern Anatolia, Turkey. Illustrations of the dorsal habitus and male genitalia are provided. Its habitus is similar to other uniformly orange species of the subgenus Psallus Fieber, 1858, particularly P.asthenicus Seidenstücker, 1966 from which it can be easily distinguished by the combination of extremely small size (2.3 mm in both sexes) and different morphology of the vesica. Psallus (Psallus) lucanicus Wagner, 1968 is recorded for the first time from Turkey. Psallus (Psallus) aurora (Mulsant & Rey, 1852) is removed from the list of Turkish fauna based on a reevaluation of the voucher specimen. An updated checklist of the species of Psallus known to occur in Turkey is provided. The relevance of Anatolia and the Syro-anatolian-transcaucasian region in the Palearctic distribution of Psallus is discussed. The westernmost record of another mirid, Plagiognathusmarivanensis Linnavuori, 2010, is provided.


[Relationship between folic acid supplements during peri-conceptional period and the adverse pregnancy outcomes: a cohort study].
To examine the association between folic acid supplements during peri-conception and the related adverse birth outcome. Pregnant women who received first prenatal care at 4 municipal-level medical institutions in Maanshan, from Oct. 2008 to Oct. 2010 were selected as the target population. All participants were asked to complete a self-administered questionnaire which including data on demographic characteristics, interval, complications and frequency of taking folic acid etc., during pregnancy. The follow-up-records after delivery would include factors as: fetal weight, height, circumference of head, chest circumference of the neonates. Finally, 4448 valid questionnaires were gathered, including 190 premature, 147 small for gestational age and 104 low birth weight babies. Descriptive statistics and logistic regression models were used for data analysis. Data showed that the weight, height and head circumference of the fetal at birth among pregnant women who had taken supplementary standard folic acid during peri-conception period or only during the first trimester, were all better than those pregnant women who had not taken the standard folic acid supplements. After adjustment for potential confounders as gestational weeks, maternal age, mather's education level, results from the logistic regression showed that intake of standard folic acid supplements appeared a protective factor for those babies who were smaller than the gestational age (RR = 0.45, 95%CI: 0.24 - 0.86), at premature delivery (RR = 0.52, 95%CI: 0.32 - 0.87) or with low birth weight (RR = 0.39, 95%CI: 0.19 - 0.80). However, data from this study showed that provision of folic acid supplements to the pre-pregnant or at first trimester alone did not make obvious impact on those babies as prematured, small for gestational age and at low birth weight. Standardized provision of folic acid supplements during peri-conceptional period could improve the outcomes of birth.


Using Proteomic Approaches to Unravel the Response of Ctenocephalides felis felis to Blood Feeding and Infection With Bartonella henselae.
Among the Ctenocephalides felis felis-borne pathogens, Bartonella henselae, the main aetiological agent of cat scratch disease (CSD), is of increasing comparative biomedical importance. Despite the importance of B. henselae as an emergent pathogen, prevention of the diseases caused by this agent in cats, dogs and humans mostly relies on the use of ectoparasiticides. A vaccine targeting both flea fitness and pathogen competence is an attractive choice requiring the identification of flea proteins/metabolites with a dual effect. Even though recent developments in vector and pathogen -omics have advanced the understanding of the genetic factors and molecular pathways involved at the tick-pathogen interface, leading to discovery of candidate protective antigens, only a few studies have focused on the interaction between fleas and flea-borne pathogens. Taking into account the period of time needed for B. henselae replication in flea digestive tract, the present study investigated flea-differentially abundant proteins (FDAP) in unfed fleas, fleas fed on uninfected cats, and fleas fed on B. henselae-infected cats at 24 hours and 9 days after the beginning of blood feeding. Proteomics approaches were designed and implemented to interrogate differentially expressed proteins, so as to gain a better understanding of proteomic changes associated with the initial B. henselae transmission period (24 hour timepoint) and a subsequent time point 9 days after blood ingestion and flea infection. As a result, serine proteases, ribosomal proteins, proteasome subunit α-type, juvenile hormone epoxide hydrolase 1, vitellogenin C, allantoinase, phosphoenolpyruvate carboxykinase, succinic semialdehyde dehydrogenase, glycinamide ribotide transformylase, secreted salivary acid phosphatase had high abundance in response of C. felis blood feeding and/or infection by B. henselae. In contrast, high abundance of serpin-1, arginine kinase, ribosomal proteins, peritrophin-like protein, and FS-H/FSI antigen family member 3 was strongly associated with unfed cat fleas. Findings from this study provide insights into proteomic response of cat fleas to B. henselae infected and uninfected blood meal, as well as C. felis response to invading B. henselae over an infection time course, thus helping understand the complex interactions between cat fleas and B. henselae at protein levels.


The heparin-binding growth factor midkine: the biological activities and candidate receptors.
The heparin-binding growth factor midkine (MK) comprises a family with pleiotrophin/heparin-binding growth-associated molecule. The biological phenomena in which MK is involved can be categorized into five areas: (i) cancer, (ii) inflammation/immunity, (iii) blood pressure, (iv) development and (v) tissue protection. The phenotypes are clear in vivo, but the mechanisms by which MK exerts these actions are not fully understood. Candidate receptors for MK include anaplastic lymphoma kinase, protein tyrosine phosphatase ζ, Notch2, LDL receptor-related protein 1, integrins and proteoglycans. Some physical associations between these candidate receptors are also known. Because of the striking in vivo phenotypes after manipulation of MK, MK could be an important molecular target for the treatment of various diseases. To this end, it will be important to pursue studies to fully understand the mechanisms of MK action.


Effects of caffeine on locomotor activity of horses: determination of the no-effect threshold.
Caffeine is the legal stimulant consumed most extensively by the human world population and may be found eventually in the urine and/or blood of race horses. The fact that caffeine is in foods led us to determine the highest no-effect dose (HNED) of caffeine on the spontaneous locomotor activity of horses and then to quantify this substance in urine until it disappeared. We built two behavioural stalls equipped with juxtaposed photoelectric sensors that emit infrared beams that divide the stall into nine sectors in a 'tic-tac-toe' fashion. Each time a beam was interrupted by a leg of the horse, a pulse was generated; the pulses were counted at 5-min intervals and stored by a microcomputer. Environmental effects were minimized by installing exhaust fans producing white noise that obscured outside sounds. One-way observation windows prevented the animals from seeing outside. The sensors were turned on 45 min before drug administration (saline control or caffeine). The animals were observed for up to 8 h after i.v. administration of 2.0, 2.5, 3.0 or 5.0 mg caffeine kg(-1). The HNED of caffeine for stimulation of the spontaneous locomotor activity of horses was 2.0 mg kg(-1). The quantification of caffeine in urine and plasma samples was done by gradient HPLC with UV detection. The no-effect threshold should not be greater than 2.0 microg caffeine ml(-1) plasma or 5.0 microg caffeine ml(-1) urine.


Serum levels of S-100B after recreational scuba diving.
Recreational scuba diving is a sport of increasing popularity. Previous studies indicating subtle brain injury in asymptomatic divers imply a cumulative effect of minor neural insults in association with diving for professional and/or recreational purposes, over the long-term. This is the first study to investigate putative neural tissue burden during recreational scuba diving by measuring circulating levels of S-100B, a sensitive biomarker of brain injury. 5 male divers performed 3 consecutive dives under conservative recreational diving settings (maximum depth 15 m, duration of dive 56 min, ascend rate 1.15 m/min) with an interval of 12 h between each session. Although a small increase in serum S-100B levels after each dive was apparent, this increase did not quite reach statistical significance (p=0.057). Moreover, no abnormal S-100B values were recorded (mean baseline: 0.06 μg/L, mean post-dive: 0.086 μg/L) and no effect of the 3 consecutive dives on changes in S-100B levels was detected. These results suggest that under the experimental conditions tested, diving does not seem to have a discernible and/or cumulative impact on central nervous system integrity. The extent to which variable diving settings and practices as well as individual susceptibility factors underlie putative neural tissue burden in asymptomatic divers, remains to be established.


Operative stabilization of skeletal chest injuries secondary to cardiopulmonary resuscitation in a cardiac surgical patient.
Chest injury, including sternal and rib fractures, is the most common complication of cardiopulmonary resuscitation (CPR) that usually heals spontaneously. However, a small subset of patients has fractures that need mechanical treatment. We present a case of flail chest with sternum and left anterior rib fractures secondary to CPR in a cardiac surgical patient, which was mechanically ventilated due to respiratory complications. Open reduction and operative fixation with titanium osteosynthesis plates and locking screws in sternum and ribs was performed by a thoracic surgeon assisted by an orthopaedic surgeon. Anterior plating achieved chest stability and facilitated weaning from mechanical ventilation. The patient had an uneventful postoperative course, painfree, and experienced no sternal instability or infection throughout a six-month follow-up period. Sternal instability after cardiac surgery occurs infrequently but can be challenging to manage. Titanium plate fixation is an effective method to stabilize complicated flail chest, with clinical utility in a cardiothoracic practice.


Bone morphogenetic protein-mediating receptor-associated Smads as well as common Smad are expressed in human articular chondrocytes but not up-regulated or down-regulated in osteoarthritic cartilage.
Bone morphogenetic proteins (BMPs) are supposed to be important for cartilage matrix anabolism. In this study, we investigated whether the intracellular mediators of BMP activity, Smads 1, 4, 5, and 8, are expressed in normal human articular chondrocytes in vivo and in vitro and whether alterations in expression and distribution pattern are found in osteoarthritic cartilage or in vitro after stimulation with interleukin (IL)-1, because down-regulation of these mediators could be responsible for the decrease of anabolic activity in osteoarthritic cartilage. RNA was isolated from normal and osteoarthritic human knee cartilage and analyzed by (quantitative) polymerase chain reaction (PCR) technology. Articular chondrocytes were cultured in alginate beads and short-term high-density monolayer cultures with and without stimulation by IL-1. In addition, immunolocalization of the receptor-associated Smads (R-Smads) was performed on sections of normal and diseased articular cartilage. Reverse-transcription (RT)-PCR analysis showed a moderate expression of all Smads investigated in normal, early degenerative, and late stage osteoarthritic cartilage. Immunolocalization detected the R-Smads in most chondrocytes on the protein level in all specimen groups investigated. In vitro, the Smads were also expressed and partly up-regulated by Il-1beta in alginate bead culture. Of note, for Smad 1, two truncated splice variants were expressed by articular chondrocytes missing exon 4 as well as exons 3 and 4. Our study showed that BMP-receptor Smads 1, 5, and 8 as well as common Smad (C-Smad) 4 are expressed and present in human normal and osteoarthritic articular chondrocytes corroborating the importance of BMPs and BMP signaling for articular cartilage. This study is the first to describe splicing variants for Smad 1. Smads 1, 4, and 5 are up-regulated in vitro by Il-1beta, suggesting a linkage of the Il-1 and BMP-signaling pathways within the chondrocytes. None of the Smads were grossly up- or down-regulated in osteoarthritic chondrocytes, suggesting that differences in overall expression levels of the investigated Smad proteins are not relevant for metabolic activity of articular chondrocytes in vivo.


Socioeconomic conditions as determining factors in the prevalence of systemic and ocular toxoplasmosis in Northeastern Brazil.
To determine the prevalence of systemic and ocular toxoplasmosis among 1024 students in the city of Natal, Northeastern Brazil, and correlate it with demographic, socioeconomic and epidemiological risk factors. The study population was randomly selected, asked to fill out a questionnaire, provide a blood sample for IgG and IgM (MEIA) serology and a hemogram, and undergo an eye examination. The seroprevalence for IgG was 46% (95% CI = 42.9-49.2%) and that for IgM was 1.4% (95% CI = 0.8-2.4%). The prevalence of ocular lesions was 1.15% (95% CI = 0.6-2.0%). In the univariate analyses, confirmed by multivariate analysis, the socioeconomic conditions were determinants in the prevalence of systemic and ocular toxoplasmosis (mother's schooling = literacy/OR = 2.9 and p < 0.001). The prevalence of systemic toxoplasmosis, although high, was lower than that found in studies performed in the South and Southeast of Brazil, and the incidence of ocular lesions was totally different, being lower by a factor varying from 5 to 17. Although important epidemiological variables, such as owning a cat, drinking unfiltered water or having had contact with lakes or rivers, were found to be correlated with toxoplasmosis in the preliminary analysis, they lost their influence when included in the logistic model. However, further studies must be undertaken to identify the reasons for these findings, including the determination of the strains of Toxoplasma gondii encountered in different regions of the country and the sources of the water utilized by these populations.


Biotreatment of Petrochemical Wastewater: A Case Study from Northern Tunisia.
A full-scale study has been conducted to assess the bioaugmentation efficiency of trickling filter process to treat petrochemical wastewater from a lubricant industry recycling waste oils. During 45 weeks, the organic loading rate (OLR) in the trickling filter was increased stepwise from 0.9 to 4 kg of chemical oxygen demand (COD)/(m3·day) at the end of the upgrading period as the flow rate (FR) reached the value of 30 m3/day. The removal, obtained in terms of percentage, for COD ranged from 60 to 84.5 and greater than 98 for total n-alkane (TNA), while those of total kjeldahl nitrogen (TKN) and total phosphor (TP) were about 32 and 55, respectively. The analytical profile index (API) of trickling biofilm has confirmed that 5 strains are closely related to Acinobacter junii, Stenotrophomonas maltophilia, Vibrio vulnificus, Vibrio metschnikovi, Pseudomona slulzeri and Trichosporon spp2.


Case Report: Splenic Infarction in Infectious Mononucleosis due to Epstein-Barr Virus Infection.
Epstein-Barr virus (EBV) is the most common cause of infectious mononucleosis (IM) and IM is a clinical syndrome typically characterized by fever, pharyngitis, and cervical lymph node enlargement. We describe the case of a 19-year-old man with IM complicated by splenic infarction. The patient visited our hospital because of upper abdominal pain without a fever and sore throat. Abdominal computed tomography revealed a low-density area in the spleen, which indicated splenic infarction. The next day, he developed a fever. After diminishing abdominal pain and fever, he developed pharyngitis accompanied by fever. Acute EBV infection was confirmed by serological tests. The patient was successfully managed with no specific therapy. Splenic infarction is a rare complication of IM and this case showed that splenic infarction can precede a fever and pharyngitis.


Differential regulation of telencephalic pallial-subpallial boundary patterning by Pax6 and Gsh2.
In the embryonic telencephalon, the pallial-subpallial boundary (PSB) separates the dorsal Pax6+ pallium from the ventral Gsh2+ subpallium. Previous studies have revealed that this region is a source of cells that will populate both the olfactory bulb and basal telencephalic limbic system. However, the level of progenitor cell heterogeneity and developmental genetic regulation of this progenitor region remains to be fully elucidated. In this study we carried out a comprehensive analysis of gene expression patterns at the PSB, in addition to an examination of the combinatorial function of Pax6 and Gsh2 in the specification of the PSB. First, we reveal that the PSB is comprised of a complex mix of molecularly distinct progenitor pools. In addition, by analysis of single Sey, Gsh2, and Sey/Gsh2 double mutant mice, we demonstrate that both Pax6 and Gsh2 are directly required for major aspects of PSB progenitor specification. Our analysis also reveals that the establishment of the epidermal growth factor receptor positive lateral cortical stream migratory route to the basal telencephalon is Pax6 dependent. Thus, in addition to their well-characterized cross-repressive roles in dorsal/ventral patterning our analyses reveal important novel functions of Gsh2 and Pax6 in the regulation of PSB progenitor pool specification and patterning.


[Infection with equine herpesvirus and its manifestation in the central nervous system of the horse].
Infections with EHV1 can lead to manifestation at the CNS of horses followed by encephalomyelitis and "equine stroke". Horse experiments could confirm the clinical picture and gave links to the potential pathogenesis of the disease. We also have been in the position to isolate and characterize an EHV4 virus out of the brain of a horse with CNS disorders. The two viruses carry different biological properties which obviously dominate the pathogenesis. These properties as well as experimental and field cases are described and different diagnostic tests are discussed.


Transactivating-transduction protein-polyethylene glycol modified liposomes traverse the blood-spinal cord and blood-brain barriers.
Naive liposomes can cross the blood-brain barrier and blood-spinal cord barrier in small amounts. Liposomes modified by a transactivating-transduction protein can deliver antibiotics for the treatment of acute bacterial infection-induced brain inflammation. Liposomes conjugated with polyethylene glycol have the capability of long-term circulation. In this study we prepared transactivating-transduction protein-polyethylene glycol-modified liposomes labeled with fluorescein isothiocyanate. Thus, liposomes were characterized by transmembrane, long-term circulation and fluorescence tracing. Uptake, cytotoxicity, and the ability of traversing blood-spinal cord and blood-brain barriers were observed following coculture with human breast adenocarcinoma cells (MCF-7). Results demonstrated that the liposomes had good biocompatibility, and low cytotoxicity when cocultured with human breast adenocarcinoma cells. Liposomes could traverse cell membranes and entered the central nervous system and neurocytes through the blood-spinal cord and blood-brain barriers of rats via the systemic circulation. These results verified that fluorescein isothiocyanate-modified transactivating-transduction protein-polyethylene glycol liposomes have the ability to traverse the blood-spinal cord and blood-brain barriers.


Purification and Properties of the Plasma Membrane H-Translocating Adenosine Triphosphatase of Phaseolus mungo L. Roots.
The plasma membrane ATPase of mung bean (Phaseolus mungo L.) roots has been solubilized with a two-step procedure using the anionic detergent, deoxycholate (DOC) and the zwitterionic detergent, zwittergent 3-14 as follows: (a) loosely bound membrane proteins are removed by treatment with 0.1% DOC; (b) The ATPase is solubilized with 0.1% zwittergent in the presence of 1% DOC; (c) the solubilized material is further purified by centrifugation through a glycerol gradient (45-70%). Typically, about 10% of the ATPase activity is recovered, and the specific activity increases about 11-fold. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis shows that the peak fraction from the glycerol gradient contains three major polypeptides of M(r) = 105,000, 67,000, and 57,000 daltons. The properties of the purified ATPase are essentially the same as those of membrane-bound ATPase, with respect to pH optimum, substrate specificity, inhibitor sensitivity, and ion stimulation.


Arterial retention of apolipoprotein B(48)- and B(100)-containing lipoproteins in atherogenesis.
The "response to retention" hypothesis of atherosclerosis suggests that the arterial deposition of cholesterol is directly proportional to the concentration of circulating plasma lipoproteins. However, there is increasing evidence to support the concept that specific lipoproteins may be preferentially retained within the arterial wall, possibly as a result of greater affinity for cell surface and extracellular matrices. Recently, key studies have provided insight into mechanisms involved in the interaction of apolipoprotein B (apoB)-containing lipoproteins with extracellular matrices. In addition, novel methods and innovative experimental design has enabled us to differentiate between the delivery, retention and efflux of apoB(48)- and apoB(100)-containing lipoproteins. Other studies have demonstrated a relationship between extracellular matrix proteoglycan expression and the development of atherosclerosis. Discussion in the present review also extends to the mechanisms that are involved in the relative intimal retention of apoB(48)- and apoB(100)-containing lipoproteins in order to explain the atherogenicity of these macromolecules. The perspective of this review is to highlight recent advances in the area of arterial lipoprotein retention and the physiological significance these processes may have in the aetiology of cardiovascular disease. Importantly, an understanding of the mechanisms responsible for the retention of apoB(48)/B(100)-containing lipoproteins will enable new strategies to be developed for the future management of cardiovascular disease.


Electronic energy transfer through non-adiabatic vibrational-electronic resonance. I. Theory for a dimer.
Non-adiabatic vibrational-electronic resonance in the excited electronic states of natural photosynthetic antennas drastically alters the adiabatic framework, in which electronic energy transfer has been conventionally studied, and suggests the possibility of exploiting non-adiabatic dynamics for directed energy transfer. Here, a generalized dimer model incorporates asymmetries between pigments, coupling to the environment, and the doubly excited state relevant for nonlinear spectroscopy. For this generalized dimer model, the vibrational tuning vector that drives energy transfer is derived and connected to decoherence between singly excited states. A correlation vector is connected to decoherence between the ground state and the doubly excited state. Optical decoherence between the ground and singly excited states involves linear combinations of the correlation and tuning vectors. Excitonic coupling modifies the tuning vector. The correlation and tuning vectors are not always orthogonal, and both can be asymmetric under pigment exchange, which affects energy transfer. For equal pigment vibrational frequencies, the nonadiabatic tuning vector becomes an anti-correlated delocalized linear combination of intramolecular vibrations of the two pigments, and the nonadiabatic energy transfer dynamics become separable. With exchange symmetry, the correlation and tuning vectors become delocalized intramolecular vibrations that are symmetric and antisymmetric under pigment exchange. Diabatic criteria for vibrational-excitonic resonance demonstrate that anti-correlated vibrations increase the range and speed of vibronically resonant energy transfer (the Golden Rule rate is a factor of 2 faster). A partial trace analysis shows that vibronic decoherence for a vibrational-excitonic resonance between two excitons is slower than their purely excitonic decoherence.


Determination of cetirizine dihydrochloride, related impurities and preservatives in oral solution and tablet dosage forms using HPLC.
An HPLC method was developed and validated for the determination of cetirizine dihydrochloride (CZ) as well as its related impurities in commercial oral solution and tablet formulations. Furthermore, two preservatives associated with the drug formulations, namely, propyl (PP) and butylparabens (BP) were successfully determined by this method. The chromatographic system used was equipped with a Hypersil BDS C18, 5 microm column (4.6 x 250 mm) and a detector set at 230 nm in conjunction with a mobile phase of 0.05 M dihydrogen phosphate:acetonitrile:methanol:tetrahydrofuran (12:5:2:1, v/v/v/v) at a pH of 5.5 and a flow rate of 1 ml min(-1). The calibration curves were linear within the target concentration ranges studied, namely, 2 x 10(2) - 8 x 10(2) microg ml(-1) and 1-4 microg ml(-1) for CZ, 20-100 microg ml(-1) for preservatives and 1-4 microg ml(-1) for CZ related impurities. The limits of detection (LOD) and quantitation (LOQ) for CZ were, respectively, 0.10 and 0.34 microg ml(-1) and for CZ related impurities were in the ranges of 0.08-0.26 microg ml(-1) and 0.28-0.86 microg ml(-1), respectively. The method proved to be specific, stability indicating, accurate, precise, robust and could be used as an alternative to the European pharmacopoeial method set for CZ and its related impurities.


Membrane lipid integrity relies on a threshold of ATP production rate in potato cell cultures submitted to anoxia
In this paper we report on our study of the changes in biomass, lipid composition, and fermentation end products, as well as in the ATP level and synthesis rate in cultivated potato (Solanum tuberosum) cells submitted to anoxia stress. During the first phase of about 12 h, cells coped with the reduced energy supply brought about by fermentation and their membrane lipids remained intact. The second phase (12-24 h), during which the energy supply dropped down to 1% to 2% of its maximal theoretical normoxic value, was characterized by an extensive hydrolysis of membrane lipids to free fatty acids. This autolytic process was ascribed to the activation of a lipolytic acyl hydrolase. Cells were also treated under normoxia with inhibitors known to interfere with energy metabolism. Carbonyl-cyanide-4-trifluoromethoxyphenylhydrazone did not induce lipid hydrolysis, which was also the case when sodium azide or salicylhydroxamic acid were fed separately. However, the simultaneous use of sodium azide plus salicylhydroxamic acid or 2-deoxy-D-glucose plus iodoacetate with normoxic cells promoted a lipid hydrolysis pattern similar to that seen in anoxic cells. Therefore, a threshold exists in the rate of ATP synthesis (approximately 10 &mgr;mol g-1 fresh weight h-1), below which the integrity of the membranes in anoxic potato cells cannot be preserved.


The transitional dynamics of caloric ecosystems: changes in the food supply around the world.
Changes to the global food supply have been characterized by greater availability of edible oils, sweeteners, and meats-a profound "nutrition transition" associated with rising obesity, type 2 diabetes, and cardiovascular disease. Through an analysis of three longitudinal databases of food supply, sales and economics across the period 1961-2010, we observed that the change in global food supply has been characterized by a dramatic rise in pig meat consumption in China and poultry consumption in North America. These changes have not been experienced by all rapidly-developing countries, and are not well explained by changes in income. The changes in food supply include divergence among otherwise similar neighboring countries, suggesting that the changes in food supply are not an inevitable result of economic development. Furthermore, we observed that the nutrition transition does not merely involve an adoption of "Western" diets universally, but can also include an increase in the supply of edible oils that are uncommon in Western countries. Much of the increase in sales of sugar-sweetened beverages and packaged foods is attributable to a handful of multinational corporations, but typically from products distributed through domestic production systems rather than foreign importation. While North America and Latin America continued to have high sugar-sweetened beverage and packaged food sales in recent years, Eastern Europe and the Middle East have become emerging markets for these products. These findings suggest further study of natural experiments to identify which policies may mitigate nutritional risk factors for chronic disease in the context of economic development.


A role for calcium in auxin transport.
The basipetal transport of the auxin, indoleacetic acid, in sunflower stem sections is markedly suppressed by washing the tissue in ethylenediaminetetraacetate, and transport is restored by subsequent application of calcium solutions. The ethylenediaminetetraacetate treatment is shown to result in the removal of substantial amounts of calcium from the tissue, and the restoration of transport is distinctive for calcium solutions, lesser effects being observed for magnesium and lanthanum, and little effect for monovalent cations. The calcium effects are interpreted as indicating that the auxin transport system depends upon structural or functional features of cellular membranes which involve calcium in a manner analogous to the transport of inorganic ions.


Nontraditional Transesophageal Echocardiographic Views to Evaluate Hepatic Vasculature in Orthotopic Liver Transplantation and Liver Resection Surgery.
Utilization of intraoperative transesophageal echocardiography (TEE) during orthotopic liver transplantation (OLT) is expanding annually in high-volume transplant centers. During OLT intraoperative TEE is used to gather real-time information on cardiovascular function and intravascular volume status. Although standardized TEE views exist, there are nontraditional views described in the literature which have the potential to diagnose evolving pathology and define normal variants of hepatic vasculature. A literature review was completed utilizing the PubMed database for English-only, peer-reviewed publications discussing nontraditional use of intraoperative TEE during OLT and hepatic vascular-related surgeries from 2009 to 2019. Both case reports and review articles were considered. The PubMed literature search offered 8 publications for analysis, including 7 case reports and 1 article review, revealing several nontraditional TEE views not included in a comprehensive transesophageal echocardiographic examination. These nontraditional views were generally obtained using modifications to the transgastric and bicaval views to visualize liver vasculature. We present the various techniques for obtaining these views from the 8 articles identified. At high-volume transplant centers, TEE use during OLT is increasing. Intraoperative TEE is a valuable tool to assess hepatic vascular structures critical to allograft/organ function without interruption of the surgical procedure. Nontraditional use of TEE to diagnose intraoperative noncardiac pathology in OLT appears underutilized and underreported. The modified hepatic and modified transgastric views we describe can be used to evaluate hepatic vasculature, influence surgical decision-making and ultimately improve patient care.


Investigating genome reduction of Bordetella pertussis using a multiplex PCR-based reverse line blot assay (mPCR/RLB).
The genetic composition of the bacterium causing whooping cough, Bordetella pertussis, has been investigated using microarray studies in order to examine potential genetic contributors to the disease re-emergence in the past decade. Regions of difference (RDs) have been previously identified as clusters of genes flanked by insertion sequences which are variably present in different sets of isolates, and have also been shown to be potential markers of B. pertussis evolution.This study used microarray data to identify and select a panel of RDs; primers and probes for these RDs were then designed to test for the presence or absence of these regions in a novel and less expensive multiplex PCR-based reverse line blot (mPCR/RLB) assay. By comparing the presence or absence of RDs, we aimed to determine the genomic variability of a diverse collection of B. pertussis strains and how they have changed over time. A B. pertussis specific mPCR/RLB using 43 genes representing 30 RDs, was developed and used to characterise a set of 42 B. pertussis isolates. When mapped against the previously identified evolutionary relationships of the strains, the losses of two RDs--BP0910A--BP00930 and BP1948-BP1962--were found to be associated with significant events in B. pertussis history: the loss of BP0910A--BP00930 coincided with introduction of whole cell vaccines in the 1950s while that of BP1948-BP1962 occurred after the introduction of acellular vaccines. The loss of BP1948-BP1962 also coincided with expansion of the most recent B. pertussis strains. The mPCR/RLB assay offers an inexpensive and fast method of determining the gene content of B. pertussis strains and also confirms that gene losses are an ongoing feature of B. pertussis evolution.


Vitamin E as an antioxidant of the lung: mechanisms of vitamin E delivery to alveolar type II cells.
Oxidants play an important role in the development of acute and chronic lung injuries. Alveolar surfactant is the first target of air-borne oxidants. Surfactant contains, besides dipalmitoyl phosphatidylcholine, cholesterol and polyunsaturated phospholipids that play an important functional role. Therefore, vitamin E could be important for protecting surfactant lipids against oxidation and subsequent lung injury. Alveolar type II cells play a central role in synthesis and secretion of surfactant lipids and also supplement the surfactant with vitamin E during intracellular assembly. High density lipoprotein (HDL) is the primary source of vitamin E for type II cells. The uptake of vitamin E by specific lipid transfer is mediated by at least three HDL-specific receptors (scavenger receptor BI, membrane dipeptidase, and HDL-binding protein-2). In addition, cubilin and megalin mediate in a cooperative manner HDL-holoparticle uptake by alveolar type II cells. A temporary vitamin E deficiency induces a reversible change of the expression of pro- and antiinflammatory markers and of markers defining apoptosis, and reduces surfactant lipid synthesis in alveolar type II cells. These metabolic changes of type II cells may prime the lung to develop clinically manifest injury in response to an additional insult, e.g., hyperoxia.


[Perinatal mortality in Austria: an analysis of social risk factors].
Social factors related to perinatal mortality are analyzed using log-linear models and data for a sample of 215 perinatal deaths that occurred in hospitals in Vienna, Austria, during 1978. A sample of 210 surviving children is used as a control group. "The findings indicate that perinatal mortality decreases with higher education of mothers. Furthermore, the risk of perinatal mortality is considerably higher for those who have mothers above age 35.... For illegitimate births, the risk of death is twice that of legitimate births even when accounting for differential medical control during pregnancy." (summary in ENG)


Crystal structure of the yeast cell-cycle control protein, p13suc1, in a strand-exchanged dimer.
p13(suc1) from fission yeast is a member of the CDC28 kinase specific (CKS) class of cell-cycle control proteins, that includes CKS1 from budding yeast and the human homologues CksHs1 and CksHs2. p13(suc1) participates in the regulation of p34(cdc2), a cyclin-dependent kinase controlling the G1-S and the G2-M transitions of the cell cycle. The CKS proteins are believed to exert their regulatory activity by binding to the kinase, in which case their function may be governed by their conformation or oligomerization state. Previously determined X-ray structures of p13(suc1), CksHs1 and CksHs2 show that these proteins share a common fold but adopt different oligomeric states. Monomeric forms of p13(suc1) and CksHs1 have been solved. In addition, CksHs2 and p13(suc1) have been observed by X-ray crystallography in assemblies of strand-exchanged dimers. Analysis of various assemblies of the CKS proteins, as found in different crystal forms, should help to clarify their role in cell-cycle control. We report the X-ray crystal structure of p13(suc1) to 1.95 A resolution in space group C2221. It is present in the crystals as a strand-exchanged dimer. The overall monomeric fold is preserved in each lobe of the dimer but a single beta-strand (Ile94-Asp102) is exchanged between the central beta-sheets of each molecule. Strand exchange, which has been observed for p13(suc1) in two different space groups, and for CksHs2, is now confirmed to be an intrinsic feature of the CKS family. A switch between levels of assembly may serve to coordinate the function of the CKS proteins in cell-cycle control.


Scientific bases of acupuncture analgesia.
The present paper was to review the physiological bases of acupuncture analgesia (AA) on normal subjects, patients, and animals. Effect of acupuncture on pain perception in normal subjects was studied and compared with sham acupuncture. It was shown that the analgesic effect of acupuncture has its physiological basis. Using neurophysiological, neuropharmacological, neurobiochemical and neuromorphological methods, the neurohumoral mechanism of AA was studied from the peripheral neural pathway of acupuncture sensation (De-Qi sensation in Chinese traditional medicine) to the central neuromodulatory effect of AA. It was indicated that needling of acupuncture point could activate the afferent fibers of peripheral nerves to elicit De-Qi sensation, then ascended mainly through the ventro-lateral funiculi, which conducted pain and temperature sensation upward to the brain, activated the antinociceptive system including certain brain nuclei. modulators (opioid peptides), neurotransmitters, through the descending inhibitory pathway resulting in analgesia. Especially the clinical and laboratory results indicated that the endogenous opiate peptides (EOP) participated in AA from the presynaptic level to the receptor sites, which provided a scientific basis for understanding the mechanism of AA. Substantial evidences have been accumulated that acupuncture has prominent analgesic effect; but it fails to give sufficient analgesia during operation. Some effective measures to improve the therapeutic effect of acupuncture, such as the combination of acupuncture with drugs, the selection of suitable EA parameters and optimal time spacing should be adopted.


Granulysin produced by uterine natural killer cells induces apoptosis of extravillous trophoblasts in spontaneous abortion.
Immune changes are known to occur in recurrent spontaneous abortion, but it is unclear whether either maternal natural killer (NK) cells or T cells attack fetus-derived trophoblasts. To clarify the immunological causes of spontaneous abortion, we examined the relationship between cytotoxic granule proteins in decidual lymphocytes, such as granulysin, granzyme B, and perforin, and the induction of apoptosis in extravillous trophoblasts (EVTs). The number of granulysin-positive CD56(bright) NK cells increased significantly in the decidua basalis during spontaneous abortion compared with normal pregnancy; however, granzyme B- and perforin-positive cells did not change. Interestingly, the expression of granulysin was also detected in the nuclei of EVTs in spontaneous abortion samples. When IL-2-stimulated CD56(bright) NK cells were cocultured with EVT cells (HTR-8/SV40neo), granulysin was found initially in the cytoplasm and then accumulated in the nuclei of the HTR-8/SV40neo cells. Furthermore, transfected cells expressing a GFP-granulysin fusion protein induced apoptosis in HTR-8/SV40neo cells independently of caspases. Our results suggest that granulysin-positive uterine NK cells attack EVTs; subsequently, the uNK-derived granulysin actively accumulates in the nuclei of EVTs, causing the death of EVTs due to apoptosis. These data support a new apoptosis pathway for trophoblasts via uNK-derived granulysin, suggesting that granulysin is involved in spontaneous abortion.


Autonomic failure in hydrencephaly.
Autonomic functions were studied in three patients with hydrencephalus and five with hydrocephalus. Autonomic failure of central origin was found in the patients with hydrencephalus; whereas, those suffering from hydrocephalus had essentially normal autonomic function. In two patients with hydrencephalus, the hypothalamus was markedly abnormal but the rest of the autonomic nervous system was histologically normal. From this it is concluded that in some patients with mental and motor retardation, autonomic failure may be of cerebral origin but that this is not a feature of patients with hydrocephalus.


The effect of image alterations on identification using palmar flexion creases.
Palmprints are identified using matching of minutia points, which can be time consuming for fingerprint experts and in database searches. This article analyzes the operational characteristics of a palmar flexion crease (PFC) identification software tool, using a dataset of 10 replicates of 100 palms, where the user can label and match palmar line features. Results show that 100 palmprint images modified 10 times each using rotation, translation, and additive noise, mimicking some of the characteristics found in crime scene palmar marks, can be identified with a 99.2% genuine acceptance rate and 0% false acceptance rate when labeled within 3.5 mm of the PFC. Partial palmprint images can also be identified using the same method to filter the dataset prior to traditional matching, while maintaining an effective genuine acceptance rate. The work shows that identification using PFCs can improve palmprint identification through integration with existing systems, and through dedicated palmprint identification applications.


Single-Layer Triboelectric Nanogenerators Based on Ion-Doped Natural Nanofibrils.
As emerging ambient energy harvesting technology, triboelectric nanogenerators (TENGs) have proven to be a robust power source and have demonstrated the unique ability to power micro-nano electronics autonomously to form self-powered devices. Although four working modes of TENGs have been developed to promote the feasibility of self-powered micro-nano systems, the relatively complicated structure composed of multilayer and movable components limits the practical applications of TENGs. Herein, we propose a single-layer triboelectric nanogenerator (SL-TENG) based on ion-doped natural nanofibrils. Compared with the simplest mode of currently existing TENGs, i.e., the single-electrode type, this novel single-electrode TENG further simplifies the configuration by the removal of the dielectric layer. The underlying mechanism of the proposed SL-TENG is comprehensively investigated through electrical measurements and the analysis of the effect of ion species at different concentrations. In contrast to conventional TENGs that require electrodes to realize charge transfer, it is revealed that the ions doped into natural nanofibrils effectively realize charge transfer due to the separation and migration of cations and anions. This new working principle based on the combination of electrons and ions enables TENGs to show greater potential for applications since the ultrasimple single-layer configuration enables them to be more easily integrated with other electronic components; additionally, the whole device of the proposed SL-TENG is biodegradable because the natural nanofibrils are completely extracted from carrots.


Weight-Based Victimization and Physical Activity Among Adolescents With Overweight or Obesity: A Scoping Review of Quantitative and Qualitative Evidence.
Increased physical activity engagement plays a vital role in preventing and treating overweight or obesity in children and adolescents. Research has found that adolescents who are overweight or obese tend to participate in less physical activity than adolescents of average weight. Weight-based victimization (victimization related to weight or body size) is highly prevalent in adolescence and seems to be a factor that might negatively impact engagement in physical activity. This scoping review's objective was to identify the nature and extent of research evidence on links between weight-based victimization and physical activity among community-based or primary health care samples of adolescents who are overweight or obese. Following established scoping review methods, we searched electronic databases PubMed, Web of science, SportDiscuss, and Cinahl from 23 Nov 2020 to 02 Dec 2020. Published studies with community-based or primary health care samples of adolescents who were overweight or obese (aged 13-18 years, Iso-BMI ≥ 25, i.e., age and gender specific percentiles based on specified cut-off value for overweight and obesity) and that were peer-reviewed and published were included in the analysis. Data from the included studies were put into a table and analyzed descriptively and numerically in terms of the extent and nature of the studies. After full text review, 12 articles were included, equally distributed in the qualitative and quantitative paradigm. There was a homogeneity of the research designs applied. Articles revealed high frequency of weight-based victimization. Among quantitative studies the reported links between weight-based victimization and physical activity were somewhat mixed, with three studies reporting weight-based victimization to negatively impact physical activity, while three studies report no significant impact. Qualitative studies reported experiences of teasing and bullying by peers, humiliation, and feelings of insecurity about appearance as barriers to engagement in physical activity. The empirical evidence on the links between weight-based victimization and physical activity among community-based or primary-health care samples of adolescents who are overweight or obese is sparse. The results revealed a high presence of weight-based victimization in physical activity which seems to act as barriers for activity engagement. There is a need for more research to advance the understanding of the links between weight-based victimization and physical activity among community-based or primary-health care samples of adolescents who are overweight or obese.


Metabolic profiling of flavonol metabolites in human urine by liquid chromatography and tandem mass spectrometry.
Twenty-one flavonol metabolites have been identified by LC/ESI-MS/MS in human urine, including isomers, after the consumption of cooked onions. Metabolites identified include quercetin monoglucuronides, methyl quercetin monoglucuronides, a quercetin monoglucuronide sulfate, quercetin diglucuronides, a methyl quercetin diglucuronide, quercetin glucoside sulfates, methyl quercetin, quercetin, and kaempferol monoglucuronides. The fragmentation patterns of flavonol metabolites obtained by MS/MS were distinctive for some isomers, indicating that fragmentation patterns may be useful predictors of conjugation position. Two isomers of sulfate quercetin glucosides were also found in urine, suggesting that many of the quercetin glucosides in onion are absorbed intact and undergo metabolism to the sulfate conjugate. Additionally, the interindividual variation in urinary quercetin metabolite profiles was determined by comparing the relative level of six different quercetin metabolites excreted in the urine of healthy volunteers. The ranges of quercetin metabolites excreted were similar among volunteers, yet notable differences in the levels of metabolites among individuals were observed. This study demonstrates the potential of monitoring the range of quercetin metabolites to reveal information on interindividual biotransformation capacity in response to dietary manipulations and as a biomarker for flavonol consumption.


Low-intensity pulsed ultrasound stimulation for mandibular condyle osteoarthritis lesions in rats.
This study evaluated low-intensity pulsed ultrasound effects for temporomandibular joint osteoarthritis in adult rats. Osteoarthritis-like lesions were induced in 24 adult rats' temporomandibular joints with low-dose mono-iodoacetate injections. The rats were divided into four groups: control and mono-iodoacetate groups, injected with contrast media and mono-iodoacetate, respectively, at 12 weeks and observed until 20 weeks; and low-intensity pulsed ultrasound and mono-iodoacetate + low-intensity pulsed ultrasound groups, injected with contrast media and mono-iodoacetate, respectively, at 12 weeks with low-intensity pulsed ultrasound performed from 16 to 20 weeks. Condylar bone mineral density, bone mineral content and bone volume were evaluated weekly with microcomputed tomography. Histological and immunohistochemical staining for matrix metalloproteinases-13 was performed at 20 weeks. At 20 weeks, the mono-iodoacetate + low-intensity pulsed ultrasound group showed significantly higher bone mineral density, bone mineral content and bone volume than the mono-iodoacetate group; however, these values remained lower than those in the other two groups. On histological and immunohistochemical analysis, the chondrocytes were increased, and fewer matrix metalloproteinases-13 immunopositive cells were identified in the mono-iodoacetate + low-intensity pulsed ultrasound group than mono-iodoacetate group. Low-intensity pulsed ultrasound for 2 weeks may have therapeutic potential for treating temporomandibular joint osteoarthritis lesions.


[Incorporation of odd-numbered fatty acids into the hepatic lipids of Wistar rats].
Isolated Wistar rat livers are perfused with a recirculating medium which contain even- and odd- numbered fatty acids provided by yeast Candida tropicalis grown on n-paraffins. After perfusions odd- numbered fatty acids (OFA) (15:0, 17:0, 17:1) are mainly present in hepatic triacylglycerols, the latter are secreted in the circulating medium. Then OFA can participate in lipidic metabolism as even- numbered fatty acids.


Magnetic resonance imaging 4-D flow-based analysis of aortic hemodynamics in Turner syndrome.
Cardiovascular surveillance is important in Turner syndrome because of the increased risk of aortic dilation and dissection with consecutively increased mortality. To compare 4-D flow MRI for the characterization of aortic 3-D flow patterns, dimensions and vessel wall parameters in pediatric patients with Turner syndrome and age-matched controls. We performed 4-D flow MRI measuring in vivo 3-D blood flow with coverage of the thoracic aorta in 25 patients with Turner syndrome and in 16 female healthy controls (age mean ± standard deviation were 16 ± 5 years and 17 ± 4 years, respectively). Blood flow was visualized by time-resolved 3-D path lines. Visual grading of aortic flow in terms of helices and vortices was performed by two independent observers. Quantitative analysis included measurement of aortic diameters, quantification of peak systolic wall shear stress, pulsatility index and oscillatory shear index at eight defined sites. Patients with Turner syndrome had significantly larger aortic diameters normalized to BSA, increased vortices in the ascending aorta and elevated helix flow in the ascending and descending aorta compared to controls (all P<0.03). Patients with abnormal helical or vortical flow in the ascending aorta had significantly larger diameters of the ascending aorta (P<0.03). Peak systolic wall shear stress, pulsatility index and oscillatory shear index were significantly lower in Turner patients compared to controls (p=0.02, p=0.002 and p=0.01 respectively). Four-dimensional flow MRI provides new insights into the altered aortic hemodynamics and wall shear stress that could have an impact on the development of aortic dissections.


Immediate functional and cosmetic open rhinoplasty following acute nasal fractures: our experience with Asian noses.
Closed reduction and splinting are generally recommended in the acute management of nasal fractures. Although open reduction is recommended for more severe nasal fractures, immediate functional and cosmetic open rhinoplasty following nasal fractures has not been described for Asian noses. The authors document their experiences with combining open reduction of acute nasal fractures with simultaneous cosmetic correction of preexisting aesthetic concerns in an Asian population. Twenty-five Asian patients underwent primary functional and cosmetic open rhinoplasty immediately following acute nasal fracture. Grafts consisted of autologous material, including septum, concha, rib, and deep temporal fascia. Prior to opening the nose, anatomical reduction of the bony vault fractures was performed. Spreader grafts were used to stabilize the fractured or dislocated dorsal septum as well as to straighten the nose. Aesthetic refinement of the nose included lengthening, refining the tip, and increasing tip projection and was performed according to the patients' aesthetic desires. Patient satisfaction was subjectively reported on a 1 to 10 scale. Mean follow-up was 17 months (range, 10-24 months). Twenty-three patients rated the results of their procedures as 7 or higher. Functionally, all patients were breathing as well or better postoperatively compared with their preinjury functional state. One patient (4%) underwent a secondary filler procedure for a slight dorsal irregularity. Immediate cosmetic and functional open rhinoplasty is safe, predictable, and effective in Asian patients. 4.


Generation of Hydrogen from Water: A Pd-Catalyzed Reduction of Water Using Diboron Reagent at Ambient Conditions.
Production of hydrogen from renewable sources, particularly from water, is an intensive area of research, which has far-reaching relevance in hydrogen economy. A homogeneous catalytic method is presented for producing clean hydrogen gas from water, in a reaction of water with a diboron compound as the reductant, under ambient reaction conditions. The Pd-catalytic system is stable in water and displays excellent recyclability. Hydroxy analogues such as alcohols are compatible with the Pd/B2Pin2 system and generate hydrogen gas efficiently. The B2Pin2-H2O system, in the presence of palladium, is an excellent catalytic system for selective hydrogenation of olefins.


Diagnosis of adult GH deficiency.
The current guidelines for the diagnosis of adult GHD are mainly based on the statements from the GH Research Society Consensus from Port Stevens in 1997. It is stated that diagnosis of adult GHD must be shown biochemically by provocative tests within the appropriate clinical context. The insulin tolerance test (ITT) was indicated as that of choice and severe GHD defined by a GH peak lower than 3 microg/L. The need to rely on provocative tests is based on evidence that that the measurement of IGF-I as well as of IGFBP-3 levels does not distinguish between normal and GHD subjects. Hypoglycemia may be contraindicated; thus, alternative provocative tests were considered, provided they are used with appropriate cut-off limits. Among classical provocative tests, arginine and glucagon alone were indicated as alternative tests, although less discriminatory than ITT. Testing with the combined administration of GHRH plus arginine was recommended as an alternative to ITT, mostly taking into account its marked specificity. Based on data in the literature in the last decade, the GRS Consensus Statements should be appropriately amended. Regarding the appropriate clinical context for the suspicion of adult GHD, one should evaluate patients with hypothalamic or pituitary disease or a history of cranial irradiation, as well as those with childhood-onset GHD are at obvious risk as adults for severe GHD. Brain injuries (trauma, subarachnoid hemorrage, tumours of the central nervous system) very often cause acquired hypopituitarism, including severe GHD. Given the epidemiology of brain injuries, the important role of the endocrinologist in providing major clinical benefit to brain injured patients who are still undiagnosed should be underscored. From the biochemical point of view, although normal IGF-I levels do not rule out severe GHD, very low IGF-I levels in patients highly suspected for GHD (i.e. patients with childhood-onset, severe GHD or with multiple hypopituitarism acquired in adulthood) can be considered as definitive evidence for severe GHD; thus, these patients would skip provocative tests. Patients suspected for adult GHD with normal IGF-I levels must be investigated by provocative tests. ITT remains a test of reference but it should be recognized that other tests are as reliable as ITT. Glucagon as classical test and, particularly, new maximal tests such as GHRH in combination with arginine or GH secretagogues (GHS) (i.e. GHRP-6) have well defined cut-off limits, are reproducible, able to distinguish between normal and GHD subjects. Overweight and obesity have confounding effect on the interpretation of the GH response to provocative tests. In adults cut-off levels of GH response below which severe GHD is demonstrated must be appropriate to lean, overweight and obese subjects to avoid false positive diagnosis in obese adults and false negative diagnosis in lean GHD patients. Finally, normative values of GH response to provocative tests may depend on age, particularly in the transitional age; the normative cut-off levels of GH response to ITT in this phase of life are now available.


Successful Management of Pulmonary Arterial Hypertension by Monitoring N-Terminal Pro-B-Type Natriuretic Peptide Serum Levels in a Preterm Infant with Chronic Lung Disease: A Case Report.
We measured the serial changes in N-terminal probrain natriuretic peptide (NT-proBNP) levels in a 6-month-old male infant with chronic lung disease (CLD) complicated by pulmonary arterial hypertension (PAH). The patient was born at the 24th week of gestation weighing 695 g. At 1 month after birth, an echocardiogram confirmed the diagnosis of CLD with PAH. He was treated with inhaled nitric oxide (iNO) and oral sildenafil and discharged from the hospital. At 190 days of age, the patient was readmitted to our department because of a viral upper respiratory infection. At 195 days of age, his respiratory condition worsened with pulmonary edema and his NT-proBNP level was determined to be 10,117 pg/mL. The patient was immediately administered iNO, and his respiratory condition improved, and NT-proBNP levels decreased. However, he experienced repeated severe cyanosis attacks. Before the attacks, his NT-proBNP level was > 1,000 pg/mL. Therefore, we continuously administered iNO until his NT-proBNP level decreased to < 1,000 pg/mL. We safely discontinued iNO administration at 473 days of age. In conclusion, serial change in NT-proBNP is a surrogate marker with prognostic value in patients with PAH associated with CLD.


DNA and Histone Methylation Regulates Different Types of Fruit Ripening by Transcriptome and Proteome Analyses.
Methylation affects different aspects of genetic material stability, gene expression regulation, and histone modification. The previous reports depicted that DNA and histone methylation regulates plant growth and development. In this study, we evaluated the effects of DNA and histone methylation on 'Hongjia' strawberry and 'Lichun' tomato. We investigated the transient transformation system for arginine methyltransferase (FvPRMT1.5) overexpression and interference and assessed the phenotypic appearance and mRNA and protein expression levels. Results depicted that changes in methylation levels caused inhibition of carotenoids and anthocyanins. Furthermore, the profiling of aroma components was altered in response to 5-azacytidine. DNA hypomethylation induced the expression levels of genes involved in photosynthesis, flavonoid biosynthesis, and hormone signal transduction pathways, while the expression levels of related proteins showed a downward trend. Overall, we proposed a model that reveals the possible regulatory effects of DNA and histone methylation during fruit ripening.


Mast cell degranulation in rat mesenteric venule: effects of L-NAME, methylene blue and ketotifen.
Mast cells are present in proximity to the microvessels, and on stimulation with inhibition of NO synthesis, are a rich source of numerous inflammatory mediators. A microcirculatory study was undertaken to clarify whether nitric oxide (NO) and activation of guanylate cyclase is involved in degranulation of perivascular mast cells in the rat mesenteric venule, and whether oral administration of ketotifen suppress the degranulation. Intravital microscopy was used to monitor the rates of adherence and extravasation of leukocytes in single unbranched venules with diameters between 25 and 35 microm of rat mesentery. Leukocyte rolling velocity, red blood cell velocity, vessel diameter and blood pressure were also measured. Mast cell degranulation was quantified within 30 microm from the venule. NG-nitro-L-arginine methyl ester (L-NAME) at an intravenous dose of 30 mg kg-1 increased the number of degranulated cells, while its enantiomer, D-NAME at the same dose had no effect. Superfusion with methylene blue (MB), an inhibitor of soluble guanylate cyclase, at 50 microm elicited similar degranulation of the mast cells. The degranulation was associated with increased adhesion of leukocytes to the endothelium and the slowed rolling. Pretreatment with ketotifen at an oral dose of 1 mg kg-1 inhibited mast cell degranulation in responses to either L-NAME or MB. It is conceivable that guanylate cyclase for NO production pathway in endothelial and/or mast cells is involved in the mast cell degranulation process, and the process or subsequent action of NO may be preserved by ketotifen, eliciting down-modulation of mast cell activation.


Spatial optical solitons in nonlinear photonic crystals.
We study spatial optical solitons in a one-dimensional nonlinear photonic crystal created by an array of thin-film nonlinear waveguides, the so-called Dirac-comb nonlinear lattice. We analyze modulational instability of the extended Bloch-wave modes and also investigate the existence and stability of bright, dark, and "twisted" spatially localized modes in such periodic structures. Additionally, we discuss both similarities and differences of our general results with the simplified models of nonlinear periodic media described by the discrete nonlinear Schrödinger equation, derived in the tight-binding approximation, and the coupled-mode theory, valid for shallow periodic modulations of the optical refractive index.


Abdominal cerclage in a patient with a neocervix with planned cesarean hysterectomy at delivery.
Pregnancies complicated by congenital uterine anomalies (CUA) with a neocervix present a variety of challenges for the obstetrician. Abdominal cerclage can be utilized to help prevent preterm delivery in a patient with a neocervix. A 14-year-old female presented with right adnexal pain and was found to have a complex uterine anomaly resembling a noncommunicating unicornuate uterus with a cervix embedded in the rudimentary horn. A neocervix was created during surgical removal of the rudimentary horn. The patient became pregnant at age 24, and a transabdominal cerclage served an important role in the prevention of preterm delivery. Although limited data exists regarding the outcomes for the use of abdominal cerclage after the creation of a neocervix, term delivery is possible with said intervention.


[Effects of different wavelet filters on correlation and diagnostic performance of radiomics features].
To investigate the effects of different wavelet filters on correlation and diagnostic performance of radiomics features. Methods: A total of 143 colorectal cancer (CRC) patients (64 positive in lymph node metastasis and 79 negative) with contrast-enhanced CT examination were recruited. After labeling the tumor area by experienced radiologists, radiomics wavelets features based on 48 different wavelets were extracted using in-house software coded by Matlab. The correlation coefficients of the features with same names between different wavelets were calculated and got the distribution of high-correlation features between each wavelet. The least absolute shrinkage and selection operator (LASSO) was used to build signatures between lymph node metastasis and wavelet features data set based on different wavelets. The numbers of features in signatures and diagnostic performance were compared using Delong's test. Results: With the difference of wavelet order increased, the number of high-correlation features between two wavelets decreased. Some features were prone to high correlation between different wavelets. When building radiomics signature based on single wavelet, signatures built from 'rbio2.2', 'sym7' and 'db7' did well in predicting lymph node metastasis. The signature based on Daubechies wavelet feature set had the highest performance in predicting lymph node metastasis, while the signature from Biorthogonal wavelet features was worst. Improvement was significant in diagnostic performance after excluding the high-correlation features in the whole features set (P=0.004). Conclusion: In order to reduce the data redundancy of features, it is recommended to select wavelets with large differences in wavelet orders when calculating radiomics wavelet features. It is necessary to remove high correlation features for improving the diagnostic performance of radiomics signature.


Umbilical cord cleansing with chlorhexidine in neonates: a systematic review.
We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to evaluate the efficacy of chlorhexidine application to the umbilical cord in neonates. We searched MEDLINE and other electronic databases, and included all RCTs that evaluated the effect of single or multiple chlorhexidine cord applications on the neonatal mortality rate (NMR) and/or the incidence of systemic sepsis and omphalitis. A total of six RCTs-four community-based cluster RCTs and two hospital-based trials-were included in the review. Of the four cluster RCTs, three were conducted in South Asia in settings with high rates of home births (>92%) while the fourth, available only as an abstract, was conducted in Africa. Pooled analysis by the 'intention-to-treat' principle showed a significant reduction in NMR after chlorhexidine application (four studies; relative risk (RR) 0.85; 95% confidence interval (CI) 0.76 to 0.95; fixed effects (FE) model). On subgroup analysis, only multiple applications showed a significant effect (four studies; RR 0.88; 95% CI 0.78 to 0.99) whereas a single application did not (one study; RR 0.86; 0.73 to 1.02). Similarly, only the community-based trials showed a significant reduction in NMR (three studies; RR 0.86; 95% CI 0.77 to 0.95), while the hospital-based study did not find any effect (RR 0.11; 0.01 to 2.03). Since all the studies were conducted in high-NMR settings (⩾30 per 1000 live births), we could not determine the effect in settings with low NMRs. Only one study-a hospital-based trial from India-reported the incidence of neonatal sepsis; it did not find a significant reduction in any sepsis (RR 0.67; 95% CI 0.35 to 1.28). Pooled analysis of community-based studies revealed significant reduction in the risk of omphalitis in infants who received the intervention (four studies; RR 0.71; 95% CI 0.62 to 0.81). The hospital-based trial had no instances of omphalitis in either of the two groups. Chlorhexidine application delayed the time to cord separation (four studies; mean difference 2.11 days; 95% CI 2.07 to 2.15; FE model). Chlorhexidine application to the cord reduces the risk of neonatal mortality and omphalitis in infants born at home in high-NMR settings. Routine chlorhexidine application, preferably daily for 7 to 10 days after birth, should therefore be recommended in these infants. Given the paucity of evidence, there is presently no justification for recommending this intervention in infants born in health facilities and/or low-NMR settings.


Efficient coding of natural scenes in the lateral geniculate nucleus: experimental test of a computational theory.
A recent computational theory suggests that visual processing in the retina and the lateral geniculate nucleus (LGN) serves to recode information into an efficient form (Atick and Redlich, 1990). Information theoretic analysis showed that the representation of visual information at the level of the photoreceptors is inefficient, primarily attributable to a high degree of spatial and temporal correlation in natural scenes. It was predicted, therefore, that the retina and the LGN should recode this signal into a decorrelated form or, equivalently, into a signal with a "white" spatial and temporal power spectrum. In the present study, we tested directly the prediction that visual processing at the level of the LGN temporarily whitens the natural visual input. We recorded the responses of individual neurons in the LGN of the cat to natural, time-varying images (movies) and, as a control, to white-noise stimuli. Although there is substantial temporal correlation in natural inputs (Dong and Atick, 1995b), we found that the power spectra of LGN responses were essentially white. Between 3 and 15 Hz, the power of the responses had an average variation of only +/-10.3%. Thus, the signals that the LGN relays to visual cortex are temporarily decorrelated. Furthermore, the responses of X-cells to natural inputs can be well predicted from their responses to white-noise inputs. We therefore conclude that whitening of natural inputs can be explained largely by the linear filtering properties (Enroth-Cugell and Robson, 1966). Our results suggest that the early visual pathway is well adapted for efficient coding of information in the natural visual environment, in agreement with the prediction of the computational theory.


Bone tissue reactions to demineralized freeze-dried bone in conjunction with e-PTFE barrier membranes in man.
Demineralized freeze-dried bone (DFDB) has been demonstrated to be osteoinductive in rodents, while no new bone formation has been reported at ectopic sites in goats, dogs and monkeys. In the present study, DFDB was used in connection with dental implant placement and expanded polytetrafluorethylene (e-PTFE) membranes. Histological examination showed that DFDB particles near the host bone underwent a partial remineralization, while DFDB distant from pre-existing bone was slowly resorbed and showed no remineralization, no osteoinduction, and no osteoconduction. This could be due either to the fact that the response to osteoinductive stimuli is lower in higher species, or to the fact that large quantities of DFDB are required to provide sufficient quantities of bone morphogenetic protein.


Candidemia in the critically ill: initial therapy and outcome in mechanically ventilated patients.
Mortality among critically ill patients with candidemia is very high. We sought to determine whether the choice of initial antifungal therapy is associated with survival among these patients, using need for mechanical ventilatory support as a marker of critical illness. Cohort analysis of outcomes among mechanically ventilated patients with candidemia from the 24 North American academic medical centers contributing to the Prospective Antifungal Therapy (PATH) Alliance registry. Patients were included if they received either fluconazole or an echinocandin as initial monotherapy. Of 5272 patients in the PATH registry at the time of data abstraction, 1014 were ventilated and concomitantly had candidemia, with 689 eligible for analysis. 28-day survival was higher among the 374 patients treated initially with fluconazole than among the 315 treated with an echinocandin (66% versus 51%, P < .001). Initial fluconazole therapy remained associated with improved survival after adjusting for non-treatment factors in the overall population (hazard ratio .75, 95% CI .59-.96), and also among patients with albicans infection (hazard ratio .62, 95% CI .44-.88). While not statistically significant, fluconazole appeared to be associated with higher mortality among patients infected with glabrata (HR 1.13, 95% CI .70-1.84). Among ventilated patients with candidemia, those receiving fluconazole as initial monotherapy were significantly more likely to survive than those treated with an echinocandin. This difference persisted after adjustment for non-treatment factors.


Secreted form of EphA7 in lung cancer.
EPHA7 is a member of the EPHA family of receptor kinases, among which several members are known to be involved in human lung carcinogenesis. We report here a novel spliced variant, the so-called secreted form of EPHA7, recently reported in malignant lymphoma, in human lung cancer cell lines and primary lung cancer. In contrast to the EPHA7 down-regulation in colorectal cancer by promoter hypermethylation, EPHA7 is expressed at a substantial level in most human lung cancers and the secreted form of EPHA7 mRNA was found in a fraction of primary lung cancer tissues, lung cancer cell lines, and immortalized bronchogenic epithelial cell lines. Interestingly, the secreted form of EPHA7 message was predominantly detected in non-adeno type lung carcinoma. The mechanistic role of the secreted form of EPHA7 in human lung carcinogenesis is not clear, but the presence of this form could distinctly exclude adenocarcinoma of the lung from the other categories, i.e., squamous cell carcinoma, small cell carcinoma and large cell carcinoma, which have strong association with smoking. This is the first study to detect the secreted form of EPHA7 in human epithelial tissues. EPHA7 warrants further investigation to determine its possible involvement in smoking related lung carcinogenesis.


An algorithm for the assembly of robust physical maps based on a combination of multi-level hybridization data and fingerprinting data.
We have developed an algorithm which combines data obtained from restriction digestion experiments and hybridization experiments to construct robust physical maps of whole chromosomes. The algorithm has been incorporated into a program which accepts hybridization data consisting of an unordered hybridization matrix and fingerprinting data containing band coordinates for each clone. The combined data is used to produce a non-redundant, ordered matrix which can be further reduced to represent a minimum tile coverage of the chromosome. In addition, the method also takes into account multi-level hybridization events which allows for an improved treatment of the hybridization data. The program is evaluated against several other contig building programs using simulated and real data sets. Finally, it is applied to construct a physical map of the 4.1 Mb genome of Ochrobactrum anthropi based on 1387 clones and 70 probes, as well as 624 fingerprints.


Effects of adenosine on NANC bronchoconstriction in anaesthetized guinea-pigs.
The present work assesses the effects of the acute administration of adenosine on tachykinergic bronchoconstriction induced in different ways (exogenously administered capsaicin or substance P and vagal electrical stimulation) in anaesthetized and curarized guinea-pigs. Adenosine (30-3000 micrograms kg-1, i.v.) enhanced significantly and dose-relatedly the airway narrowing induced by a single dose of capsaicin (0.5-2 micrograms kg-1, i.v.), both in normal and in vagotomized animals. A smaller and less dose-dependent enhancement by the nucleoside of the pulmonary resistance increase induced by substance P (5-15 micrograms kg-1, i.v.) was observed. This effect was almost completely prevented by the H1 antagonist diphenhydramine (1 mg kg-1, i.v.), which also unmasked an inhibitory action of adenosine at the highest doses. Diphenhydramine, on the contrary, did not significantly modify the potentiation by adenosine of capsaicin-mediated bronchoconstriction. Finally, the nucleoside dose-dependently inhibited the atropine-resistant bronchospasm following vagal electrical stimulation. The use of the selective adenosinic agonists R-N6-[2-phenylisopropyl]adenosine (1-100 micrograms kg-1, i.v.) and 5'-N-methylcarboxamidoadenosine (1-100 micrograms kg-1, i.v.) before the administration of capsaicin, revealed the ability of the first to reproduce the enhancement induced by adenosine, while the second had an inhibitory effect. It is concluded that adenosine has both excitatory and inhibitory modulatory effects on airway responsiveness to excitatory non-adrenergic non-cholinergic (e-NANC) stimuli. The excitatory effects, revealed with substance P and capsaicin, support the hypothesis that adenosine may play a role as an asthma mediator.


Synthesis, structures and spin crossover properties of infinite 3D frameworks of iron(II) containing organodinitrile bridging ligands.
Four new Fe(II) coordination polymers of formulation [Fe(L)(3)][MCl(4)](2), M = Fe(III), In(III) have been synthesized and structurally and magnetically characterized. They contain organodinitrile bridging ligands where L is 1,1'-azobiscyclopentanecarbonitrile (ACCN) or 2,2'-azobisisobutyronitrile (AIBN). The compounds are [Fe(AIBN)(3)][InCl(4)](2) (1), [Fe(AIBN)(3)][FeCl(4)](2) (2), [Fe(ACCN)(3)][InCl(4)](2) (3), and [Fe(ACCN)(3)][FeCl(4)](2) (4). Compounds 1 and 2 were first reported many years ago, elsewhere, but not then structurally characterized. All four compounds adopt an "open framework" α-Po type 3D lattice structure with the [M(III)Cl(4)](-) anions held in the channels thereof. There are two crystallographically independent, distorted octahedral Fe(II)N(6) sites in 1 and 2, but only one Fe(II) site in 3 and 4. These are the first open framework systems containing covalently linked dinitrile bridging ligands and join a related class of [Fe(L)(3)](2+) frameworks known with ditriazole and ditetrazole linkers and exhibiting spin crossover behaviour. Indeed, compounds 1 and 2 display a 'half' spin transition in their magnetic susceptibility vs. temperature plots, this being due to the fact that only half of the Fe(II) d(6) centres in the framework changed spin from HS → LS as the temperature decreased, as also evidenced by the structural details around the Fe(II) centres, determined below T(1/2) (118 and 170 K for 1 and 2, respectively). Mössbauer spectra confirmed these spin changes. The weak cooperativity between the SCO centres led to a lack of thermal hysteresis. When the ACCN ligand was used instead of the AIBN ligand, in compounds 3 and 4, only one crystallographically unique Fe(II) centre was observed in an otherwise similar framework. No SCO transition was observed in 3 and 4 as evidenced by temperature independent moment data, backed up by single crystal X-ray crystallographic analysis at 123 K. Thus the HS Fe(II) ions remain in this spin state at all temperatures, presumably because the ligand field, at the nitrile N-donors, is weaker in ACCN than in AIBN. In addition, the crystal structure of a minor phase of an aqua complex, [Fe(AIBN)(2)(H(2)O)(2)][FeCl(4)](2) (2a), obtained from the reaction that produced 2, showed a 2D layer motif, with trans-Fe(N)(4)(H(2)O)(2) ligation.


Novel agent-based salvage autologous stem cell transplantation for relapsed multiple myeloma.
High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) is a standard frontline therapy for multiple myeloma (MM). Therapeutic options for patients with relapsed MM after ASCT include novel agents in different combos, salvage ASCT (sASCT), and allogeneic transplant, with no unique standard of care. We retrospectively analyzed 66 MM patients who relapsed after up-front single or double ASCT(s) and received novel agent-based sASCT at five Italian centers. Median event-free survival from up-front ASCT(s) to first relapse (EFS1) was 44 months. Seventy-three percent of patients received sASCT at first disease progression. Re-induction regimens were bortezomib based in 87% of patients. Response to re-induction therapy included complete response (CR) 18%, ≥ very good partial response (VGPR) 48%, and overall response rate (ORR) 83%. Response to sASCT included CR 44%, ≥ VGPR 77%, and ORR 94%. With a median follow-up of 24 months after sASCT, 39 patients experienced disease progression. Median EFS from sASCT (EFS2) was 17 months. Median overall survival from ASCT (OS1) and sASCT (OS2) was 166 and 43 months, respectively. EFS2 and OS2 were significantly shorter in patients with EFS1 ≤ 24 months, in patients who did not receive sASCT at first disease progression and in patients with extramedullary disease (EMD). In multivariate analysis, EFS1 ≤ 24 months was associated with shorter EFS2 and OS2, EMD was associated with shorter EFS2, and < CR after sASCT was associated with shorter OS2. Novel agent-based sASCT is a safe and effective procedure for relapsed MM.


MiR-421 is a functional marker of circulating tumor cells in gastric cancer patients.
The detection of circulating tumor cells (CTCs) has recently received great attention. To evaluate if miR-421 could be used as a specific marker for CTCs, the level of miR-421 in mononuclear cells (MNCs) from peripheral blood were determined by reverse transcription-polymerase chain reaction. Transfection of miR-421 inhibitor significantly suppressed tumor growth in vivo. The level of miR-421 in MNCs from gastric cancer was significantly higher than in those from healthy controls. The area under the receiver operating characteristic curve was 0.773 ± 0.0736. In conclusion, miR-421 may be used as a biomarker for monitoring CTCs in patients with gastric cancer.


Antinociceptive effects of lead acetate in sciatic nerve chronic constriction injury model of peripheral neuropathy in male Wistar rats.
The toxicological effects of lead and its compounds have overshadowed its possible health beneficial effects. Currently, the success rate for treating neuropathic pain has been very low. This study investigated the antinociceptive effects of orally administered low dose lead acetate in sciatic nerve ligated Wistar rats. Thirty Wistar rats randomly divided into five groups were used for this study. Chronic constriction injury (CCI) was used to induce neuropathic pain in Wistar rats. Allodynic and hyperalgesic signs were investigated using von Frey filaments and hotplate, respectively. Morris water maze test was used to assess the memory functions of the rats. The study revealed that oral administration of low-dose lead acetate significantly (p < 0.05) increased pain thresholds of ligated rats. CCI enhanced memory function in Wistar rats which was significantly decreased following lead acetate administration. The findings suggest that lead acetate possesses antinociceptive effects in peripherally induced neuropathic pain model in Wistar rats.


Measuring dipolar and J coupling between quadrupolar nuclei using double-rotation NMR.
Among the interactions which govern NMR spectra, spin-spin coupling interactions provide the most direct form of structural information which is of interest to chemists. Dipolar coupling may be used to measure internuclear distances directly and J coupling may be used to identify bonding interactions and provide insights into the nature of the bonds. It is well known that the presence of a quadrupolar interaction reintroduces the dipolar interaction in spinning samples; however, similarly to the J coupling, this information is often lost if the observed nucleus is quadrupolar due to quadrupolar spectral broadening. Here we show for multiple spin pairs that double-rotation (DOR) NMR fully removes the effects of the quadrupolar interaction on the NMR spectrum leaving only the effects of dipolar and J couplings. We also demonstrate that the J coupling multiplets do not disappear for quadrupolar A2 spin pairs as they do for spin-1/2 nuclei. With DOR NMR, it is then straightforward to measure homonuclear J coupling constants between magnetically equivalent quadrupolar nuclei. A deeper understanding of the origins of the magnitudes and dominant mechanisms of J coupling for quadrupolar spin pairs in a series of related compounds is obtained by decomposing computed J coupling constants into their major molecular orbital contributions.


Is deep brain stimulation a treatment option for anorexia nervosa?
Anorexia nervosa (AN) is a severe psychiatric disorder with high rates of morbidity, comorbidity and mortality, which in a subset of patients (21%) takes on a chronic course. Since an evidence based treatment for AN is scarce, it is crucial to investigate new treatment options, preferably focused on influencing the underlying neurobiological mechanisms of AN. The objective of the present paper was to review the evidence for possible neurobiological correlates of AN, and to hypothesize about potential targets for Deep brain stimulation (DBS) as a treatment for chronic, therapy-refractory AN. One avenue for exploring new treatment options based on the neurobiological correlates of AN, is the search for symptomatologic and neurobiologic parallels between AN and other compulsivity- or reward-related disorders. As in other compulsive disorders, the fronto-striatal circuitry, in particular the insula, the ventral striatum (VS) and the prefrontal, orbitofrontal, temporal, parietal and anterior cingulate cortices, are likely to be implicated in the neuropathogenesis of AN. In this paper we will review the few available cases in which DBS has been performed in patients with AN (either as primary diagnosis or as comorbid condition). Given the overlap in symptomatology and neurocircuitry between reward-related disorders such as obsessive compulsive disorder (OCD) and AN, and the established efficacy of accumbal DBS in OCD, we hypothesize that DBS of the nucleus accumbens (NAc) and other areas associated with reward, e.g. the anterior cingulated cortex (ACC), might be an effective treatment for patients with chronic, treatment refractory AN, providing not only weight restoration, but also significant and sustained improvement in AN core symptoms and associated comorbidities and complications. Possible targets for DBS in AN are the ACC, the ventral anterior limb of the capsula interna (vALIC) and the VS. We suggest conducting larger efficacy studies that also explore the functional effects of DBS in AN.


A secondary active transport mechanism modelling.
A sustained effort in biochemical, biophysical and physiological research is devoted to the characterization of the transfer of ions and molecules between biological membranes and their aqueous environment. The transported molecules include compounds with substantial structural and physico-chemical differences. It is widely assumed that the biological activity of these compounds arises as a result of binding to active sites in membrane-bound proteins, while the lipid background is considered to play a more passive role. In the simple, symmetric, four-state carrier model for transport of a single solute, transport is down the concentration gradient of that solute. However, a simple modification of this model results in transport up the solute concentration gradient.


Functional oligomerization of poliovirus RNA-dependent RNA polymerase.
Using a hairpin primer/template RNA derived from sequences present at the 3' end of the poliovirus genome, we investigated the RNA-binding and elongation activities of highly purified poliovirus 3D polymerase. We found that surprisingly high polymerase concentrations were required for efficient template utilization. Binding of template RNAs appeared to be the primary determinant of efficient utilization because binding and elongation activities correlated closely. Using a three-filter binding assay, polymerase binding to RNA was found to be highly cooperative with respect to polymerase concentration. At pH 5.5, where binding was most cooperative, a Hill coefficient of 5 was obtained, indicating that several polymerase molecules interact to retain the 110-nt RNA in a filter-bound complex. Chemical crosslinking with glutaraldehyde demonstrated physical polymerase-polymerase interactions, supporting the cooperative binding data. We propose a model in which poliovirus 3D polymerase functions both as a catalytic polymerase and as a cooperative single-stranded RNA-binding protein during RNA-dependent RNA synthesis.


The air-kerma rate constant of 192Ir.
The air-kerma rate constant gamma delta (and its precursors), as one of the basic radiation characteristics of 192Ir, was determined by many authors. Analysis of accessible data on this quantity led us to the conclusion that published data strongly disagree. That is the reason we calculated this quantity on the basis of our and many other authors' gamma-ray spectral data and the latest data for mass energy-transfer coefficients for air. In this way, a value was obtained for gamma delta of 30.0 +/- 0.9 a Gy m2 s-1 Bq-1 for an unshielded 192Ir source and 27.8 +/- 0.9 a Gy m2s -1Bq-1 for a standard packaged radioactive source taking into account attenuation of gamma rays in the platinum source wall.


An Investigation of Multidimensional Voice Program Parameters in Three Different Databases for Voice Pathology Detection and Classification.
Automatic voice-pathology detection and classification systems may help clinicians to detect the existence of any voice pathologies and the type of pathology from which patients suffer in the early stages. The main aim of this paper is to investigate Multidimensional Voice Program (MDVP) parameters to automatically detect and classify the voice pathologies in multiple databases, and then to find out which parameters performed well in these two processes. Samples of the sustained vowel /a/ of normal and pathological voices were extracted from three different databases, which have three voice pathologies in common. The selected databases in this study represent three distinct languages: (1) the Arabic voice pathology database; (2) the Massachusetts Eye and Ear Infirmary database (English database); and (3) the Saarbruecken Voice Database (German database). A computerized speech lab program was used to extract MDVP parameters as features, and an acoustical analysis was performed. The Fisher discrimination ratio was applied to rank the parameters. A t test was performed to highlight any significant differences in the means of the normal and pathological samples. The experimental results demonstrate a clear difference in the performance of the MDVP parameters using these databases. The highly ranked parameters also differed from one database to another. The best accuracies were obtained by using the three highest ranked MDVP parameters arranged according to the Fisher discrimination ratio: these accuracies were 99.68%, 88.21%, and 72.53% for the Saarbruecken Voice Database, the Massachusetts Eye and Ear Infirmary database, and the Arabic voice pathology database, respectively.


Single nucleotide polymorphism analysis reveals heterogeneity within a seedling tree population of a polyembryonic mango cultivar.
Within a polyembryonic mango seedling tree population, the genetic background of individuals should be identical because vigorous plants for cultivation are expected to develop from nucellar embryos representing maternal clones. Due to the fact that the mango cultivar 'Hôi' is assigned to the polyembryonic ecotype, an intra-cultivar variability of ethylene receptor genes was unexpected. Ethylene receptors in plants are conserved, but the number of receptors or receptor isoforms is variable regarding different plant species. However, it is shown here that the ethylene receptor MiETR1 is present in various isoforms within the mango cultivar 'Hôi'. The investigation of single nucleotide polymorphisms revealed that different MiETR1 isoforms can not be discriminated simply by individual single nucleotide exchanges but by the specific arrangement of single nucleotide polymorphisms at certain positions in the exons of MiETR1. Furthermore, an MiETR1 isoform devoid of introns in the genomic sequence was identified. The investigation demonstrates some limitations of high resolution melting and ScreenClust analysis and points out the necessity of sequencing to identify individual isoforms and to determine the variability within the tree population.


Treatment of ischemic optic neuropathy.
Ischemic damage of the optic nerve has no proven effective treatment. While ischemia related to vasculitis (arteritic) is treated with systemic corticosteroids, the primary goal is to prevent further damage, either in the affected or fellow eye. Thrombolytic or anticoagulation supplementive therapy may be considerations for the future. In the more common idiopathic (nonarteritic) form (NAION), multiple attempts at therapy, including systemic corticosteroids, anticoagulants and antiplatelet agents, diphenylhydantoin, hyperbaric oxygen, and optic nerve sheath decompression have been unsuccessful. The use of levodopa has been proposed but is unproven. Megadose intravenous corticosteroid therapy has not been studied in a systematic way. Neuroprotective strategies are under intense investigation for optic neuropathies including NAION, and clinical trials in humans are in progress. Optic nerve regeneration studies are ongoing in animals. Prophylaxis in NAION is unproven.


Management of impacted third molars among Nigerian dentists.
Seventy-five Nigerian dentists were interviewed on their approach to the management of impacted third molars. The mean age of the dentists was 34.8 years, with a male/female ratio of 3.4:1. Most of the female dentists were found in the training institutions (p = 0.005). More than half of the dentists (58.7%) practiced in institutions with dental schools (training institutions), majority preferred the buccal approach (92%), and all the dentists (100%) preferred third molar disimpaction under local analgesia. Most dentists (88%) prescribe antibiotics following third molar surgery. Fifty dentists (66.7%) routinely reviewed all patients postoperatively while 12 dentists (16%) were of the opinion that all impacted third molars should be extracted. Only 21 dentists (28%) were aware of any protocol on the management of impacted teeth. More dentists in the training institutions performed third molar surgery less frequently than dentists in other hospitals (p = 0.07) who tend to employ chisels/mallet for bone removal (p = 0.0004). The need for continuing education and the formulation of guidelines in order to assist dentists to make informed decisions is emphasised. This will help conserve scarce resources and enhance the operation of the newly introduced National Health Insurance Scheme.