Morphologic Characteristics of Myelodysplastic Syndromes.
Morphologic characterization remains a cornerstone in the diagnosis and classification of myelodysplastic syndromes (MDS) in the updated International Consensus Classification (ICC) and 5th edition World Health Organization Classification of Myeloid Neoplasms (Arber, Orazi, & Hasserjian, 2022; Khoury & Solary, 2022). The presence of dysplasia is one of the key diagnostic criteria required for establishing a diagnosis of MDS, and the percentage of myeloblasts in the blood and bone marrow impacts both disease classification and prognostication. Morphologic features also aid in distinguishing MDS from a myriad of other myeloid neoplasms and non-neoplastic mimics. Additional key morphologic features that should be recorded in any MDS case are the bone marrow cellularity and the degree of reticulin fibrosis. In this review, the morphologic assessment of the bone marrow biopsy, bone marrow aspirate, and peripheral blood smear as it pertains to the diagnosis and up-to-date classification of MDS will be described. The implications of the findings on classification and prognosis will also be discussed.


[Facial paralysis of infectious origin in patients receiving cochlear implants].
Peripheral facial paralysis during cochlear implant surgery appears in 0.43 % of adults and 0.39 % of children. Peripheral facial paralysis secondary to acute otitis media is very rare in adults, while the incidence in children remains between 0.19 % and 0.45 %. We present 3 cases of patients who underwent cochlear implant surgery at our department, and who presented peripheral facial paralysis secondary to acute otitis media. The procedure is similar to facial paralysis secondary to acute otitis media in children. Treatment consists of parenteral antibiotic and corticosteroid treatment. Prognosis is favourable, with a total recovery of facial function in 1 or more months.


i-Tracker: for quantitative proteomics using iTRAQ.
iTRAQ technology for protein quantitation using mass spectrometry is a recent, powerful means of determining relative protein levels in up to four samples simultaneously. Although protein identification of samples generated using iTRAQ may be carried out using any current identification software, the quantitation calculations have been restricted to the ProQuant software supplied by Applied Biosciences. i-Tracker software has been developed to extract reporter ion peak ratios from non-centroided tandem MS peak lists in a format easily linked to the results of protein identification tools such as Mascot and Sequest. Such functionality is currently not provided by ProQuant, which is restricted to matching quantitative information to the peptide identifications from Applied Biosciences' Interrogator software. i-Tracker is shown to generate results that are consistent with those produced by ProQuant, thus validating both systems. i-Tracker allows quantitative information gained using the iTRAQ protocol to be linked with peptide identifications from popular tandem MS identification tools and hence is both a timely and useful tool for the proteomics community.


Multimodal encoding in a simplified model of intracellular calcium signaling.
Many cells use calcium signaling to carry information from the extracellular side of the plasma membrane to targets in their interior. Since virtually all cells employ a network of biochemical reactions for Ca(2+) signaling, much effort has been devoted to understand the functional role of Ca(2+) responses and to decipher how their complex dynamics is regulated by the biochemical network of Ca(2+)-related signal transduction pathways. Experimental observations show that Ca(2+) signals in response to external stimuli encode information via frequency modulation (FM) or alternatively via amplitude modulation (AM). Although minimal models can capture separately both types of dynamics, they fail to exhibit different and more advanced encoding modes. By arguments of bifurcation theory, we propose instead that under some biophysical conditions more complex modes of information encoding can also be manifested by minimal models. We consider the minimal model of Li and Rinzel and show that information encoding can occur by AM of Ca(2+) oscillations, by FM or by both modes (AFM). Our work is motivated by calcium signaling in astrocytes, the predominant type of cortical glial cells that is nowadays recognized to play a crucial role in the regulation of neuronal activity and information processing of the brain. We explain that our results can be crucial for a better understanding of synaptic information transfer. Furthermore, our results might also be important for better insight on other examples of physiological processes regulated by Ca(2+) signaling.


Why do different people choose different university degrees? Motivation and the choice of degree.
Different people choose undergraduate degrees to study at university for different reasons. To date, there have been limited attempts to identify individual differences in motivation that drive undergraduate degree choice. We identified that people choose university degrees for four reasons: career concerns (Career), intrinsic interest in the subject (Interest), an opportunity to help others (Helping) and because they are looking for an easy option to get into higher education (Loafing). We investigated whether these motivations apply to the choice of undergraduate degree in two samples: (1) undergraduate (N = 989) and (2) prospective (N = 896) students. We developed the Motivations Influencing Course Choice (MICC) questionnaire to measure these motivations. Scales of Helping, Career, Loafing, and Interest showed good psychometric properties, showed validity with respect to general life goals and personality traits, and predicted actual and prospective degree choices. We demonstrated that medical degrees were chosen due to a mixture of Helping and Career, while engineering degrees were associated with Career and low Interest in the degree. The choice of arts and humanities degrees was driven by Interest and low concern about future career, accompanied with high Loafing. We also demonstrated gender differences: females were high in Helping (both samples) and Interest (only in the undergraduate sample) motivation, while males scored higher in Career (only in the undergraduate sample) and Loafing (both samples). The findings can feed into both theoretical accounts of proximal motivation as well as provide help to improve degree programmes at universities and support better career advice.


Residues within transmembrane domains 4 and 6 of the Na,K-ATPase alpha subunit are important for Na+ selectivity.
The Na,K- and H,K-ATPases are plasma membrane enzymes responsible for the active exchange of extracellular K(+) for cytoplasmic Na(+) or H(+), respectively. At present, the structural determinants for the specific function of these ATPases remain poorly understood. To investigate the cation selectivity of these ATPases, we constructed a series of Na,K-ATPase mutants in which residues in the membrane spanning segments of the alpha subunit were changed to the corresponding residues common to gastric H,K-ATPases. Thus, mutants were created with substitutions in transmembrane domains TM1, TM4, TM5, TM6, TM7, and TM8 independently or together (designated TMAll). The function of each mutant was assessed after coexpression with the beta subunit in Sf-9 cells using baculoviruses. The enzymatic properties of TM1, TM7, and TM8 mutants were similar to the wild-type Na,K-ATPase, and while TM5 showed modest changes in apparent affinity for Na(+), TM4, TM6, and TMAll displayed an abnormal activity. This resulted in a Na(+)-independent hydrolysis of ATP, a 2-fold higher K(0.5) for Na(+) activation, and the ability to function at low pH. These results suggest a loss of discrimination for Na(+) over H(+) for the enzymes. In addition, TM4, TM6, and TMAll mutants exhibited a 1.5-fold lower affinity for K(+) and a 4-5-fold decreased sensitivity to vanadate. Altogether, these results provide evidence that residues in transmembrane domains 4 and 6 of the alpha subunit of the Na,K-ATPase play an important role in determining the specific cation selectivity of the enzyme and also its E1/E2 conformational equilibrium.


Emulsifying and physicochemical properties of soy hull hemicelluloses-soy protein isolate conjugates.
Protein-polysaccharide conjugates could potentially combine the excellent emulsification properties of the protein with the stabilizing effect of the polysaccharide. The investigation aimed to prepare soy hull hemicelluloses-soy protein isolate (SHH-SPI) conjugates by Maillard reaction in a controlled dry state condition and assess the suitability of the conjugates in stabilizing oil-in-water (O/W) emulsion. Results indicated that Maillard reactions occurred between amino groups and carbonyl, resulting in consumption of some functional groups and the appearance of new groups in the conjugates. The conjugates of SHH-SPI obtained at the SPI content of 30% and 40% exhibited substantially improved emulsification capacity in maintaining the physical stability of O/W emulsions for a prolong storage period at heat treatment, compared with SHH and SPI alone. Overall, these results demonstrated that SHH and SPI could generate novel emulsions with improved physical and chemical stability by Mallsird reaction for application in food and pharmaceutical products.


Insulin resistance in Japanese adolescents with type 2 diabetes mellitus.
An oral glucose tolerance test (O-GTT) was conducted in 22 patients with type 2 diabetes mellitus whose ages at onset were less than 18 years old. They were classified into 2 groups, obese and non-obese at onset, and insulin secretory function was compared with that of a non-obese healthy group. The results show that, in the group of obese subjects with type 2 diabetes mellitus, both values of fasting IRI and sigmaIRI were significantly higher than those in the healthy group. In the non-obese adolescent group with type 2 diabetes mellitus, both values of fasting IRI and sigmaIRI were also significantly higher than those in the healthy group, although the difference was not as prominent as in the obese subjects with type 2 diabetes mellitus. It was revealed that insulin resistance is present not only in obese adolescents with type 2 diabetes mellitus, but also in non-obese adolescents with type 2 diabetes mellitus.


Influence of food and of age on nitrazepam kinetics.
The influence of food intake and of age on the kinetics of nitrazepam was examined in eight young and eight elderly healthy volunteers after single-dose administration of the drug. Serial blood samples were obtained during 0-24 hr, and the serum concentrations of nitrazepam were determined by gas chromatography. Concomitant food intake had no apparent influence on the absorption rate or on the bioavailability of nitrazepam in the young subjects, and there was no significant difference in nitrazepam kinetics between young and elderly subjects. Accordingly, nitrazepam may be taken together with food as well as on an empty stomach, at least in young subjects, and the increased nitrazepam sensitivity often seen in elderly subjects does not seem secondary to age-dependent pharmacokinetic differences.


Chloroplast phylogeny indicates that bryophytes are monophyletic.
Opinions on the basal relationship of land plants vary considerably and no phylogenetic tree with significant statistical support has been obtained. Here, we report phylogenetic analyses using 51 genes from the entire chloroplast genome sequences of 20 representative green plant species. The analyses, using translated amino acid sequences, indicated that extant bryophytes (mosses, liverworts, and hornworts) form a monophyletic group with high statistical confidence and that extant bryophytes are likely sisters to extant vascular plants, although the support for monophyletic vascular plants was not strong. Analyses at the nucleotide level could not resolve the basal relationship with statistical confidence. Bryophyte monophyly inferred using amino acid sequences has a good statistical foundation and is not rejected statistically by other data sets. We propose bryophyte monophyly as the currently best hypothesis.


Sensation seeking in long-term abstinent alcoholics, treatment-naïve active alcoholics, and nonalcoholic controls.
Elevated sensation seeking is associated with the development of alcohol dependence; however, it has not been studied in long-term abstinent alcoholics. In the current study, we examine sensation seeking in middle-aged long-term abstinent alcoholics (LTAA) and in younger actively drinking treatment-naïve alcoholics (TxN). A modified version of the Sensation Seeking Scale (SSS) was administered to 52 middle-aged LTAA (average age = 46.6 years) and 86 younger TxN (average age = 31.2 years), each study with its own age and gender comparable nonalcoholic controls (NAC). The SSS was modified to remove items specifically associated with alcohol or drug use. The associations between the SSS and alcohol use and deviance proneness were examined. The 2 NAC samples did not differ on the SSS, allowing the 2 NAC samples to be combined into a single control group (NAC = 118), and the LTAA and TxN samples to be directly compared without concern for cohort effects. LTAA did not differ from NAC on the SSS; however, the TxN group had higher SSS scores compared with NAC on all subscales except Boredom Susceptibility. Sensation seeking was comparably associated with lower socialization in each group. The results suggest that either sensation seeking normalizes with long-term abstinence or that relatively normal levels of sensation seeking predict the ability to achieve long-term abstinence. In either case, the results have important implications for our understanding of long-term abstinence.


Self-Grouping Multi-Network Clustering.
Joint clustering of multiple networks has been shown to be more accurate than performing clustering on individual networks separately. Many multi-view and multi-domain network clustering methods have been developed for joint multi-network clustering. These methods typically assume there is a common clustering structure shared by all networks, and different networks can provide complementary information on this underlying clustering structure. However, this assumption is too strict to hold in many emerging real-life applications, where multiple networks have diverse data distributions. More popularly, the networks in consideration belong to different underlying groups. Only networks in the same underlying group share similar clustering structures. Better clustering performance can be achieved by considering such groups differently. As a result, an ideal method should be able to automatically detect network groups so that networks in the same group share a common clustering structure. To address this problem, we propose a novel method, ComClus, to simultaneously group and cluster multiple networks. ComClus treats node clusters as features of networks and uses them to differentiate different network groups. Network grouping and clustering are coupled and mutually enhanced during the learning process. Extensive experimental evaluation on a variety of synthetic and real datasets demonstrates the effectiveness of our method.


Toxic effect of nonylphenol on the marine macroalgae Gracilaria lemaneiformis (Gracilariales, Rhodophyta): antioxidant system and antitumor activity.
The objective of the present work was to evaluate the toxic effect of nonylphenol (NP) on the antioxidant response and antitumor activity of Gracilaria lemaneiformis. An obvious oxidative damage was observed in this study. The thallus exposed to NP showed 1.2-2.0-fold increase in lipid peroxide and displayed a maximum level of 16.58 μmol g-1 Fw on 0.6 mg L-1 for 15-day exposure. The activities of antioxidant enzymes such as superoxide dismutase (SOD) and catalase (CAT) enhanced significantly by 1.1-3.2-fold and subsequently diminished at the high concentrations and prolonged exposure. The results of DNA damage in comet assay also supported that NP was obviously toxic on G. lemaneiformis with increasing the percentage of tail DNA in a dose-dependent manner. Furthermore, the ethanol extract of G. lemaneiformis (EEGL) did exhibit antitumor potential against HepG-2 cells. While decreased in cell inhibition, ROS generation, apoptosis, and caspase-3 in HepG-2 cells treated with the EEGL were observed when G. lemaneiformis was exposed to NP for 15 days, and which were related to exposure concentration of NP. These suggested that NP has strongly toxic effect on the antitumor activity of G. lemaneiformis. The results revealed in this study imply that macroalgae can be useful biomarkers to evaluate marine pollutions.


Spliced leader RNA-mediated trans-splicing in a dinoflagellate, Karenia brevis.
Spliced leader (SL) trans-splicing is a form of mRNA processing originally described in parasitic kinetoplastids. During this reaction, a short RNA sequence is transferred from the 5'-end of an SL transcript to a splice acceptor site on pre-mRNA molecules. Here we report numerous mRNAs from a dinoflagellate, Karenia brevis, which contain an identical leader sequence at their 5'-terminal end. Furthermore, we have isolated a gene from K. brevis encoding a putative SL RNA containing the conserved splice donor site immediately following the leader sequence. A 1,742-bp DNA fragment encoding a K. brevis 5S gene repeat was found to encode the SL RNA gene, as well as a U6 small nuclear RNA (snRNA) gene, and binding sites for the core components of the splicesome (Sm proteins) involved in RNA splicing. Therefore the K. brevis SL RNA appears to be in a genomic arrangement typical of SL genes in a number of species known to mature their mRNAs by trans-splicing. Additionally, we show that the SL gene exists as a stable snRNA and has a predicted secondary structure typical of SL RNAs. The data presented here support the hypothesis that an SL RNA is present in K. brevis and that maturation of a percentage of mRNAs in K. brevis occurs via a trans-splicing process in which a common SL sequence is added to the 5'-end of mature mRNAs. The occurrence of SL trans-splicing in a dinoflagellate extends the known phylogenetic range of this process.


[Proton beam therapy: clinical indications and summary of the Swiss experience].
Compared to conventional radiotherapy, proton beam therapy provides a superior distribution of radiation dose due to the physical characteristics of protons. Protons administer a uniform dose across the target and then virtually zero deep to the target and lower dose proximal to the target (for non-superficial lesions). The result is a smaller treatment volume, and therefore a lower incidence and frequency of treatment-related morbidity. Moreover, the reduction in treatment volume permits a higher dose to the tumor. This means an improved local control probability and lower normal tissue complication probability. Evidence-based medicine has demonstrated that clinical gains have been realized in the treatment of patient with uveal melanoma, skull-base or spinal sarcoma and prostate cancer. In the future, more extensive prospective studies are required to assess more completely the potential clinical benefit of proton beam therapy in many anatomical sites in children and adults.


Nutritional and volatile profiles of pulp and flavedo from four local pummelo cultivars grown in Fujian province of China.
The nutritional and volatile profiles of pulp and flavedo samples from four distinct local pummelo landraces ("Siji," "Pingshan," "Wendan," and "Guanxi") cultivated in Fujian province of China were investigated. "Guanxi" pummelo exhibited relatively high contents of vitamin C (42.01 mg/100 mL) and phenols (360.61 mg/L) and displayed a robust antioxidant capacity (41.15 mg/100 mL). Conversely, the red pulp from "Pingshan" demonstrated relatively high values of carotenoids (55.96 µg/g) and flavonoids (79.79 mg/L). Considerable differences were observed in volatile compositions between the two fruit tissues and among the four genotypes. A total of 166 and 255 volatile compounds were detected in the pulp and flavedo samples, respectively. Notably, limonene and β-myrcene were identified as the principal volatile compounds in flavedo, whereas hexanal was highly abundant in the pulp of "Siji," "Pingshan," and "Guanxi." "Wendan" displayed distinct separation from the other three pummelo cultivars in principal component analysis based on the pulp volatile compositions. This distinction was attributed to the higher number and content of volatile compounds in "Wendan" pulp, particularly the remarkable enrichment of β-myrcene. The newly characterized pummelo landraces and genotype/tissue-dependent variations in volatiles provide essential information for the genetic improvement of pummelo aroma, as well as for fruit processing and utilization.


[Alpha-adrenergic regulation of two calcium signal pathways in adipocytes].
Using selective receptor's agonist and antagonists we show that mouse white fat cells express alpha1A-, alpha2-adrenergic receptors, which activation with noradrenaline is capable of causing calcium responses different by formation mechanism. Adipocyte's calcium responses to alpha1-adrenoreceptor agonists are caused by alpha1A-type adrenoreceptor and suppressed by inhibitors of PLC-dependent pathway. Calcium responses to alpha2-adrenoreceptors agonists are realized only in the presence of more than 200 microM of L-arginine and suppressed by inhibitors of NOS-PKG-RyR pathway. The incubation of cells with L-arginine creates conditions for switching on the signal pathway with participation of eNOS --> NO --> sGC --> cGMP --> PKG --> CD38 --> RyR --> Ca2+ and for switching of the PLC - IP3R-dependent pathway. Adipocyte's calcium response to L-arginine represents a sharp impulse of the big amplitude and is mediated by alpha2-adrenoreceptors. L-arginine activating alpha2-adrenoreceptors and being the substrate of eNOS, realizes two functions in this pathway.


Race-based and sex-based differences in bioactive lipid mediators after myocardial infarction.
Leucocyte-directed specialized pro-resolving mediators (SPMs) are essential for cardiac repair, and their biosynthesis coincides with the expression of pro-inflammatory mediators; however, the precise quantitation during an acute myocardial infarction (MI) event is poorly understood in race-specific and sex-specific manner. Coronary heart disease is the leading cause of death and disability in the USA. Although the prevalence of coronary heart disease is similar between Black and White patients, cardiovascular events (including MI), rehospitalization, and mortality are disproportionately higher in Black patients. Therefore, understanding differences in inflammation and resolution can enable the development of predictive, personalized, and precise treatment and attenuate sex/racial disparities. Thus, herein, we assess differences in bioactive lipids and SPMs, between Black and White patients experiencing an acute MI. From the PRiME-GGAT cohort, we collected plasma after MI within 24-48 h from 22 Black (15 male and 7 female) and 31 White (23 male and 8 female) subjects for a comparative race-based and sex-based analyses. MI was confirmed using a biochemical measurement of plasma troponin and ST elevation. Plasma levels of three essential polyunsaturated fatty acids [arachidonic acid (AA), docosahexaenoic acid (DHA), and eicosapentaenoic acid (EPA)] and a set of 40 bioactive lipid mediators with major emphasis on SPMs were quantified by liquid chromatography-mass spectrometry. AA and DHA were higher in White male and female patients, and EPA was noted higher only in White male patients compared with White female and Black male and female patients. Lipoxygenase-mediated AA-derived 12-hydroxyeicosatetraenoic acid (29-63%) and 15-hydroxyeicosatetraenoic acid (3-9%) and DHA-derived 17-hydroxydocosahexaenoic acid (3-22%) and 14-hydroxydocosahexaenoic acid (7-10%) were major bioactive lipid mediators in plasma. The SPM signature resolvin E1 was significantly lower in Black patients compared with White male and female patients, whereas protectin D1 was lower in White male patients compared with White female and Black male and female patients. Our comparative analyses of fatty acids and respective cyclooxygenase-derived and lipoxygenase-derived SPM signatures capture the heterogeneity of disease pathology and elucidate potential mechanisms underlying sex-based and race-based differences following MI.


Antioxidant Sulfated Polysaccharide from Edible Red Seaweed Gracilaria birdiae is an Inhibitor of Calcium Oxalate Crystal Formation.
The genus Gracilaria synthesizes sulfated polysaccharides (SPs). Many of these SPs, including those synthesized by the edible seaweed Gracilaria birdiae, have not yet been adequately investigated for their use as potential pharmaceutical compounds. Previous studies have demonstrated the immunomodulatory effects of sulfated galactans from G. birdiae. In this study, a galactan (GB) was extracted from G. birdiae and evaluated by cell proliferation and antioxidant tests. GB showed no radical hydroxyl (OH) and superoxide (O2-) scavenging ability. However, GB was able to donate electrons in two further different assays and presented iron- and copper-chelating activity. Urolithiasis affects approximately 10% of the world's population and is strongly associated with calcium oxalate (CaOx) crystals. No efficient compound is currently available for the treatment of this disease. GB appeared to interact with and stabilize calcium oxalate dihydrate crystals, leading to the modification of their morphology, size, and surface charge. These crystals then acquired the same characteristics as those found in healthy individuals. In addition, GB showed no cytotoxic effect against human kidney cells (HEK-293). Taken together, our current findings highlight the potential application of GB as an antiurolithic agent.


Stimulation of secretory antibody following oral administration of antigen.
IgA antibodies produced by plasma cells in secretory tissues associated with mucosal surfaces represent a major host defense against infectious agents. Precursors of these IgA-producing cells originate in gut-associated lymphoid tissue and, to a lesser extent, in bronchial-associated lymphoid tissue and migrate via the blood not only to gut but also to other mucosal tissues, forming a common mucosal immune system. Oral administration of antigen leads to priming of precursor cells in the gut and subsequent occurrence of specific secretory IgA (S-IgA) antibody in saliva, milk, tears, and the respiratory and genital tracts. On the basis of a review of the world literature, it has been concluded that oral live vaccines elicit higher antibody titers in remote-site secretions and in serum than do oral killed vaccines, which usually stimulate only relatively low levels of local secretory antibody. Oral immunization induces S-IgA in children and adults (including the elderly) without detectable adverse effects. Despite a number of remaining questions, oral immunization against extraintestinal infections is a promising area for future clinical studies.


Aspergillus osteomyelitis after heart-lung transplantation.
Aspergillus osteomyelitis is a severe complication of invasive aspergillosis. Fewer than 15 cases have been observed after solid organ transplantation. We describe a case of Aspergillus osteomyelitis of the ilium after heart-lung transplantation with favorable outcome after medical treatment.


New filarial nematode from Japanese serows (Naemorhedus crispus: Bovidae) close to parasites from elephants.
A new onchocercid species, Loxodontofilaria caprini n. sp. (Filarioidea: Nematoda), found in subcutaneous tissues of 37 (33%) of 112 serows (Noemorhedus crispus) examined in Japan, is described. The female worm had the characteristics of Loxodontofilaria, e.g., the large body size, well-developed esophagus with a shallow buccal cavity, and the long tail with three caudal lappets. The male worm of the new species, which was first described in the genus, had unequal length of spicules, 10 pairs of pre- and post-caudal papillae, and three terminal caudal lappets. Deirids were present in both sexes. Among four species of the genus loxodontofiloria: one from the hippopotamus and three from the Elepantidae, L. caprini n. sp. appears close to L. asiatica Bain, Baker & Chabaud, 1982, a subcutaneous parasite of Elephas indicus in Myanmar (Burma). However, L. caprini n. sp. is distinct from L. asiatica in that the Japanese female worm has an esophagus half as long and the microfilariae also half as long with a coiled posterior. The microfilariae were found in the skin of serows. The new parasite appears to clearly illustrate a major event in the evolution of onchocercids: the host-switching. This might have occurred on the Eurasian continent, where elephantids and the lineage of rupicaprines diversified during the Pliocene-Pleistocene, or in Japan, into which some of these hosts migrated.


Obesity, energy balance and spermatogenesis.
Obesity has grown to pandemic proportions. It affects an increasing number of children, adolescents and young adults exposed to the silent comorbidities of this disorder for a longer period. Infertility has arisen as one important comorbidity associated with the energy dysfunction promoted by obesity. Spermatogenesis is a highly regulated process that is determined by specific energetic requirements. The reproductive potential of males relies on hormonal-dependent and -independent stimuli that control sperm quality. There are conflicting data concerning the impact of male overweight and obesity on sperm quality, as well as on the possible paternal-induced epigenetic trait inheritance of obesity. In addition, it remains a matter of debate whether massive weight loss induced by lifestyle interventions, drugs or bariatric surgery may or may not benefit obese men seeking fatherhood. Herein, we propose to discuss how energy balance may modulate hormonal signalling and sperm quality in overweight and obese men. We also discuss some molecular mechanisms that mediate obesity-related dysfunction in male reproductive system and how paternal obesity may lead to trait inheritance. Finally, we will discuss how lifestyle modifications and sustained weight loss, particularly the loss achieved by bariatric surgery, may revert some of the deleterious effects of obesity in men and their offspring.


Leiomyosarcoma of stomach: a case report.
We report a rare case of leiomyosarcoma of stomach infiltrating into the spleen and tail of pancreas, which presented at the age of 28 years of age with haematemesis and was diagnosed after exploratory laparotomy. En block excision of tail of pancreas, spleen and part of the greater curvature of stomach containing the mass was done.


Simplifying contrast-induced acute kidney injury prediction after primary percutaneous coronary intervention: the age, creatinine and ejection fraction score.
Contrast-induced acute kidney injury (CI-AKI) is a common event after percutaneous coronary intervention (PCI). Presently, the main strategy to avoid CI-AKI lies in saline hydration, since to date none pharmacologic prophylaxis proved beneficial. Our aim was to determine if a low complexity mortality risk model is able to predict CI-AKI in patients undergoing PCI after ST elevation myocardial infarction (STEMI). We have included patients with STEMI submitted to primary PCI in a tertiary hospital. The definition of CI-AKI was a raise of 0.3 mg/dL or 50% in post procedure (24-72 h) serum creatinine compared to baseline. Age, glomerular filtration and ejection fraction were used to calculate ACEF-MDRD score. We have included 347 patients with mean age of 60 years. In univariate analysis, age, diabetes, previous ASA use, Killip 3 or 4 at admission, ACEF-MDRD and Mehran scores were predictors of CI-AKI. After multivariate adjustment, only ACEF-MDRD score and diabetes remained CI-AKI predictors. Areas under the ROC curve of ACEF-MDRD and Mehran scores were 0.733 (0.68-0.78) and 0.649 (0.59-0.70), respectively. When we compared both scores with DeLong test ACEF-MDRDs AUC was greater than Mehran's (P = 0.03). An ACEF-MDRD score of 2.33 or lower has a negative predictive value of 92.6% for development of CI-AKI. ACEF-MDRD score is a user-friendly tool that has an excellent CI-AKI predictive accuracy in patients undergoing primary percutaneous coronary intervention. Moreover, a low ACEF-MDRD score has a very good negative predictive value for CI-AKI, which makes this complication unlikely in patients with an ACEF-MDRD score of <2.33.


In vitro digestibility study of some plant protein sources as aquafeed for carps Labeo rohita and Cyprinus carpio using pH-Stat method.
Aquaculture, as a promising food industry, is expected to meet the demand for quality food from the increasing human population. As the diet is critical for feeding farm fish, such a faster growth in the industry is destined to create stress in the fishmeal market to supply diets to the tune. In this context, here, we studied the protein content of 20 plant ingredients, including aquatic weeds, cereals, pulses and oil-cakes using micro-Kjeldahl method and evaluated in vitro digestibility of these ingredients for rohu Labeo rohita and common carp Cyprinus carpio using pH-Stat method. The protein contents of water fern, duckweed, almond oil-cake and soybean product were 20.81, 39.75, 47.78 and 57.48%, respectively. Species-specific digestibility was found for the same plant ingredient. The degree of hydrolysis for water fern, duck weed, almond oil-cake and soybean product were 14.17, 4.80, 17.30 and 3.57%, respectively for rohu and 4.58, 6.03, 12.17 and 3.35%, respectively for common carp. This study showed that incorporation of water fern and almond oil-cake in the diet of rohu, and duck weed and almond oil-cake in the diet of common carp are beneficial considering their protein content and digestibility. These are cost-effective, protein-rich feed ingredients for aquafeed.


Access to and patterns of use of behavioral health services among children and adolescents in TennCare.
This study assessed trends in access to and use of behavioral health services for school-aged children in TennCare, Tennessee's Medicaid managed care program, between state fiscal years 1995 and 2000. Claims, encounter, and enrollment data from the Bureau of TennCare were used. The data analyzed were restricted to services and enrollment periods for children and adolescents between the ages of four and 17 years at the time of service or enrollment. Measures were calculated in four areas: overall access to behavioral health services, use of inpatient services, use of outpatient specialty treatment services, and use of supportive services like case management and medication management. The number of youths who received a behavioral service increased by nearly 50 percent between state fiscal years 1995 and 2000. At the same time, the number of youths enrolled in TennCare increased by 19 percent. The annual access rate increased from 72.7 youths per 1000 enrollees to 91.7. However, the volume of services for children fell. Access rates were low relative to estimates of need in this population. The system made less use of inpatient services and relied more on outpatient services, particularly case management and medication management services. Children's access rates for behavioral health services improved even as the TennCare program expanded to cover more children. The system served more youths in part by reducing the volume of services for children receiving treatment and substituting more supportive services. Ongoing performance monitoring for policy making will require enhancements of data monitoring activities by the state.


Endoscopic ultrasound imaging of insulinomas: limitations and clinical relevance.
Compared to other imaging methods, endoscopic ultrasound is the best procedure to localize insulinomas preoperatively. Positive finding furthermore confirms endocrinological diagnosis, especially considering the differential diagnosis of hypoglycaemia factitia by oral antidiabetics. However, it always has to be considered that endoscopic ultrasound imaging may reveal false positive and false negative results, and quality of the findings obtained by endoscopic ultrasound imaging depends to a large extent on the examiner's experience. An important issue of endoscopic ultrasound imaging in insulinomas nowadays is planning surgical strategy. As illustrated by three cases, endoscopic ultrasound imaging enables to identify patients that qualify for laparoscopic, minimal invasive surgery.


Paternal Expressed Gene 10 (PEG10) is decreased in early-onset preeclampsia.
Preeclampsia is a severe complication of pregnancy which is attributed to placental dysfunction. The retrotransposon, Paternal Expressed Gene 10 (PEG10) harbours critical placental functions pertaining to placental trophoblast cells. Limited evidence exists on whether PEG10 is involved in preeclampsia pathogenesis. This study characterised the expression and regulation of PEG10 in placentas from patients with early-onset preeclampsia compared to gestation-matched controls. PEG10 expression was measured in plasma and placentas collected from patients with early-onset preeclampsia (< 34 weeks') and gestation-matched controls using ELISA (protein) and RT-qPCR (mRNA). First-trimester human trophoblast stem cells (hTSCs) were used for in vitro studies. PEG10 expression was measured during hTSC differentiation and hTSC exposure to hypoxia (1% O2) and inflammatory cytokines (IL-6 and TNFα) using RT-qPCR. Functional studies used PEG10 siRNA to measure the effect of reduced PEG10 on canonical TGF-[Formula: see text] signalling and proliferation using luciferase and xCELLigence assays, respectively. PEG10 mRNA expression was significantly reduced in placentas from patients with early-onset preeclampsia (< 34 weeks' gestation) relative to controls (p = 0.04, n = 78 vs n = 18 controls). PEG10 protein expression was also reduced in preeclamptic placentas (p = 0.03, n = 5 vs n = 5 controls, blinded assessment of immunohistochemical staining), but neither PEG10 mRNA nor protein could be detected in maternal circulation. PEG10 was most highly expressed in hTSCs, and its expression was reduced as hTSCs differentiated into syncytiotrophoblasts (p < 0.0001) and extravillous trophoblasts (p < 0.001). Trophoblast differentiation was not altered when hTSCs were treated with PEG10 siRNA (n = 5 vs n = 5 controls). PEG10 was significantly reduced in hTSCs exposed to hypoxia (p < 0.01). PEG10 was also reduced in hTSCs treated with the inflammatory cytokine TNF [Formula: see text] (p < 0.01), but not IL-6. PEG10 knocked down (siRNA) in hTSCs showed reduced activation of the canonical TGF-β signalling effector, the SMAD binding element (p < 0.05) relative to controls. PEG10 knockdown in hTSCs however was not associated with any significant alterations in proliferation. Placental PEG10 is reduced in patients with early-onset preeclampsia. In vitro studies suggest that hypoxia and inflammation may contribute to PEG10 downregulation. Reduced PEG10 alters canonical TGF-[Formula: see text] signalling, and thus may be involved in trophoblast dysfunction associated with this pathway.


Thermo-kinetic Study of Genetically Different Carbon-Source Materials.
A nonisothermal thermogravimetric analysis (TGA) technique was applied to determine the devolatilization kinetic parameters of completely different genesis samples of four groups: coal, biomass, lignite, and petcoke. The physical and chemical characteristics were determined using the proximate and ultimate analysis and the ash composition profile using the X-ray fluorescence method. Heating rates of 10, 15, and 20 °C/min were used in the temperature range of 25-1000 °C during the slow pyrolysis under an inert gas atmosphere. A widely used and proposed first-order Coats-Redfern kinetic model was applied, which showed the highest values of activation energies (Ea) for the petcoke sample from 57.17 to 67.58 kJ/mol at three different heating rates, while the lignite sample represented the lowest Ea values between 12.84 and 16.03 kJ/mol. The thermo-kinetic behavior was explained based on the catalytic effect of the ash composition profile, morphology, and structure of the substances determined using different analytical techniques. For the TGA process, the application of scanning electron microscopy, Fourier-transform infrared spectroscopy, etc., for the physiochemical analysis of the four genetically different carbon-source materials represented the novelty of the present work.


Differential requirements for Tousled-like kinases 1 and 2 in mammalian development.
The regulation of chromatin structure is critical for a wide range of essential cellular processes. The Tousled-like kinases, TLK1 and TLK2, regulate ASF1, a histone H3/H4 chaperone, and likely other substrates, and their activity has been implicated in transcription, DNA replication, DNA repair, RNA interference, cell cycle progression, viral latency, chromosome segregation and mitosis. However, little is known about the functions of TLK activity in vivo or the relative functions of the highly similar TLK1 and TLK2 in any cell type. To begin to address this, we have generated Tlk1- and Tlk2-deficient mice. We found that while TLK1 was dispensable for murine viability, TLK2 loss led to late embryonic lethality because of placental failure. TLK2 was required for normal trophoblast differentiation and the phosphorylation of ASF1 was reduced in placentas lacking TLK2. Conditional bypass of the placental phenotype allowed the generation of apparently healthy Tlk2-deficient mice, while only the depletion of both TLK1 and TLK2 led to extensive genomic instability, indicating that both activities contribute to genome maintenance. Our data identifies a specific role for TLK2 in placental function during mammalian development and suggests that TLK1 and TLK2 have largely redundant roles in genome maintenance.


[1993: the centenary of artificial pneumoperitoneum].
Artificial pneumoperitoneum (introduction of gas in the peritonea cavity) has been tried for the first time in medical practice, by the Austrian surgeon Mosetig-Moorhof, in January and July 1893. This method was utilized in turns to therapeutic or diagnostic ends, especially in the treatment of pulmonary tuberculosis (collapsotherapy) since 1930 till the advent of isoniazid in 1952. Today, pneumoperitoneum remains an ultimate indication; it is the first step of coelioscopy.


Raised maternal serum alpha-fetoprotein levels and low birth weight babies.
In a retrospective study of low birth weight babies (less than 2.5 kg) born in one year it was found that statistically more maternal serum alpha-fetoprotein levels were above twice the median level than a control group of mothers producing larger babies (more than 3 kg). However, from the results the test cannot be accepted as being a prospective indicator or as a screening test of low birth weight in pregnant women.


Effects of carrot pomace powder and a mixture of pectin and xanthan on the quality of gluten-free batter and cakes.
Carrot pomace powder (CPP) is a valuable by-product of carrot processing containing nutrients and fiber and can be utilized for enrichment of gluten-free products. The main purpose of this study was to determine the effects of various levels of CPP (0, 10, 20, and 30%) and a mixture of hydrocolloids (HC) including pectin and xanthan (1.5% of each) on the quality of batter and gluten-free cakes. With increasing the level of CPP and inclusion of HC the viscosity of the batter increased significantly from 87 mPa s for the control to >7000 mPa s for 30%CCP + HC sample. The density of the control batter was 1.2 g/cm3 which reduced significantly to 0.899 g/cm3 for HC sample. The pH of the cake reduced from 7.23 to 6.78 with addition of CPP but increased slightly with inclusion of HC. The density of the cake reduced from 0.510 g/cm3 for the control to 0.395 g/cm3 for 20%CCP + C sample. The texture of the cakes became softer, more springy and chewable with addition of CPP, CPP + HC, and HC. The control sample had the lowest uniformity index (0.178) which improved with addition of CPP and CPP + HC and a highly uniform cake with a uniformity index of 0.045 was obtained for the 30%CCP + HC cake. Addition of CPP increased the dark color of the cakes while inclusion of HC had no effect on the appearance of the cake and color. It was concluded that inclusion of maximum 30%CCP and 20%CPP + HC promoted the quality and sensory attributes of gluten-free cakes. Although different types of gluten-free products are available in the market, most of them contain insufficient amount of fiber and nutrients. Despite popularity, gluten-free cakes are poor in fiber and nutrient contents. Therefore, improving the nutritional value of these products has received an increasing attention by the food industry. Carrot pomace powder (CPP) is an available source of fiber and nutrients and hence can be utilized for enrichment of gluten-free products. This study showed that the inclusion of up to 30% CPP or 20% CPP with a mixture of xanthan and pectin (3%, 1:1) improved the quality and sensory attributes of the cakes. Industrial implications of this study may lead to new product development and improved marketing due to the enhancement of quality, sensory attributes, and nutritional value of the products.


Multidrug- and metal-resistant strains of Klebsiella pneumoniae isolated from Penaeus monodon of the coastal waters of deltaic Sundarban.
Marine shrimp of the species Penaeus monodon were collected from the coastal region (Haroa) of the deltaic Sundarbans of West Bengal, India during the premonsoon period in 1996. Klebsiella pneumoniae was isolated from the alimentary canal and gills of the shrimp as the sole isolate. All 10 isolated strains were resistant to erythromycin (30 micrograms/mL), ampicillin (100 micrograms/mL), furazolidone (100 micrograms/mL), and penicillin (100 IU). These strains were able to grow in the presence of silver (Ag+), cobalt (Co2+), cadmium (Cd2+), nickel (Ni2+), lead (Pb2+), copper (Cu2+), and zinc (Zn2+) at concentrations up to 10 mM. All the strains showed similar plasmid profiles, ranging in sizes from 1.8 to 120 kb. Resistance to lead, cobalt, nickel, and copper was encoded by a 3.5-kb plasmid of K. pneumoniae. Synthesis of a 14-kDa periplasmic protein was increased when they were grown in presence of 10 mM Cu2+.


Sulfonylurea Therapy Benefits Neurological and Psychomotor Functions in Patients With Neonatal Diabetes Owing to Potassium Channel Mutations.
Neonatal diabetes secondary to mutations in potassium-channel subunits is a rare disease but constitutes a paradigm for personalized genetics-based medicine, as replacing the historical treatment with insulin injections with oral sulfonylurea (SU) therapy has been proven beneficial. SU receptors are widely expressed in the brain, and we therefore evaluated potential effects of SU on neurodevelopmental parameters, which are known to be unresponsive to insulin. We conducted a prospective single-center study. Nineteen patients (15 boys aged 0.1-18.5 years) were switched from insulin to SU therapy. MRI was performed at baseline. Before and 6 or 12 months after the switch, patients underwent quantitative neurological and developmental assessments and electrophysiological nerve and muscle testing. At baseline, hypotonia, deficiencies in gesture conception or realization, and attention disorders were common. SU improved HbA1c levels (median change -1.55% [range -3.8 to 0.1]; P < 0.0001), intelligence scores, hypotonia (in 12 of 15 patients), visual attention deficits (in 10 of 13 patients), gross and fine motor skills (in all patients younger than 4 years old), and gesture conception and realization (in 5 of 8 older patients). Electrophysiological muscle and nerve tests were normal. Cerebral MRI at baseline showed lesions in 12 patients, suggesting that the impairments were central in origin. SU therapy in neonatal diabetes secondary to mutations in potassium-channel subunits produces measurable improvements in neuropsychomotor impairments, which are greater in younger patients. An early genetic diagnosis should always be made, allowing for a rapid switch to SU.


Transplantation of the postnatal rat myenteric plexus into the adult rat corpus striatum: an electron microscopic study.
Since the enteric nervous system (ENS) has been demonstrated to display many similarities with the central nervous system (CNS), we have undertaken investigations examining the possibility of using the ENS as a source of neurons for transplantation into the brain in neurodegenerative diseases. Grafts of freshly dissected myenteric plexus taken from young inbred Fischer rats were implanted in the corpus striatum of adult Fischer rats, some of which had received a quinolinic acid lesion 1 to 2 weeks prior to implantation. Brain sections from the grafted animals were examined electron microscopically 3 and 6 weeks after implantation. Grafts contained many enteric neurons and glial cells in ganglia morphologically similar to those seen within the intestine. Although a glia limitans could be observed in parts of the interface between graft and brain, ganglia at the surface of the graft were observed to be closely apposed to the surrounding striatum, with no intervening basal lamina. CNS axonal sprouts were identified in the corpus striatum near the interface with the grafted enteric ganglia and bundles of similar axons, some containing fibers that had enlarged and become myelinated, could be seen within the grafts. A smaller number of CNS axonal sprouts were also observed around the grafts in the quinolinic-acid-lesioned striata. This study confirms that even in the absence of surrounding layers of smooth muscle, enteric ganglia grafted into the corpus striatum survive and stimulate the production of axonal sprouts from striatal and other neurons, which subsequently grow into the grafts.


Reactive rise in blood pressure upon cuff inflation: cuff inflation at the arm causes a greater rise in pressure than at the wrist in hypertensive patients.
Cuff inflation at the arm is known to cause an instantaneous rise in blood pressure, which might be due to the discomfort of the procedure and might interfere with the precision of the blood pressure measurement. In this study, we compared the reactive rise in blood pressure induced by cuff inflation when the cuff was placed at the upper arm level and at the wrist. The reactive rise in systolic and diastolic blood pressure to cuff inflation was measured in 34 normotensive participants and 34 hypertensive patients. Each participant was equipped with two cuffs, one around the right upper arm (OMRON HEM-CR19, 22-32 cm) and one around the right wrist (OMRON HEM-CS 19, 17-22 cm; Omron Health Care Europe BV, Hoofddorp, The Netherlands). The cuffs were inflated in a double random order (maximal cuff pressure and position of the cuff) with two maximal cuff pressures: 180 and 240 mmHg. The cuffs were linked to an oscillometric device (OMRON HEM 907; Omron Health Care). Simultaneously, blood pressure was measured continuously at the middle finger of the left hand using photoplethysmography. Three measurements were made at each level of blood pressure at the arm and at the wrist, and the sequence of measurements was randomized. In normotensive participants, no significant difference was observed in the reactive rise in blood pressure when the cuff was inflated either at the arm or at the wrist irrespective of the level of cuff inflation. Inflating a cuff at the arm, however, induced a significantly greater rise in blood pressure than inflating it at the wrist in hypertensive participants for both systolic and diastolic pressures (P<0.01), and at both levels of cuff inflation. The blood pressure response to cuff inflation was independent of baseline blood pressure. The results show that in hypertensive patients, cuff inflation at the wrist produces a smaller reactive rise in blood pressure. The difference between the arm and the wrist is independent of the patient's level of blood pressure.


Circulating stem cells and tissue repair.
Stem cells are defined as cells that have clonogenic, self-renewing capacities and the capability to differentiate into multiple cell lineages. Whereas embryonic stem cells are derived from mammalian embryos in the blastocyst stage and can generate terminally differentiated cells of all 3 embryonic germ layers, adult human stem cells are capable of maintaining, generating, and replacing terminally differentiated cells within their own specific tissue as a consequence of physiologic cell turnover or tissue injury. The traditional idea of organ-restricted stem-cell differentiation is now being challenged by the suggestion that adult stem cells retain developmental plasticity. Preclinical and clinical studies described in this review provide evidence that within the blood circulate not only progenitor cells that differentiate into hematopoietic cells, but also stem/progenitor cells which can participate in the homeostasis, repair and replacement of solid organ tissues. In addition to the occurrence of cell fusion, there are 4 suggested mechanisms of adult stem cell differentiation into solid organ cells. Preclinical data support these models particularly that of transdifferentiation as the most likely model, allowing stem/progenitor cells to differentiate across lineage, tissue, and germ layer boundaries. There is increasing evidence that we can manipulate in vivo circulating adult stem cells to repair or regenerate solid organ tissue, which offers potential clinical benefit in the treatment of many hereditary and acquired diseases.


An exploratory study of the experiences of deceased-donor liver transplant recipients and their need for psychotherapeutic support.
This study aimed to explore the experiences of liver transplant recipients during their journey through the treatment and their need for psychotherapeutic support related to this process. Over time, measures of survival and quality of life in liver transplant recipients have continued to improve but their emotional needs remain under explored. In the longer-term recovery from transplantation, the focus shifts from physical health to psychological health. In the UK, there are no known embedded adult psychological services in liver transplant centres to react to this need. A qualitative descriptive design was used. Grounded theory analysis was used to study the narratives of six adult liver transplant recipients. Through a process of coding, conceptual categories were established to describe the participant experiences. The study adhered to the EQUATOR checklist, SRQR. Four categories emerged that were related to the experience of liver transplantation for the recipients. These were a process of adjustment, the phenomenon of waiting, liver transplant as a transformative experience and on the value of support. The participants identified a lack of psychotherapeutic support provided by the liver transplant service and felt that an embedded psychotherapeutic service would promote accessing such support during challenging times. Through the process of liver transplantation, recipients experience challenges with adjustment, waiting, feeling transformed and they value support with these feelings. In correlation with other studies, the findings of this study highlight the need for providing psychotherapeutic support within liver transplant services. The study provides evidence to support recommendations for a conjoined psychotherapy service within liver transplant services to support patients with their holistic needs.


Baclofen systemic toxicity: Experimental histopathological and biochemical study.
The present study was designed to highlight the toxic impact of baclofen on both biochemical and histopathological aspects in rats' liver, gastric, lung, kidney, and brain tissues. The study was performed on 30 healthy adult male albino rats divided into four groups with 5 rats in each control group, and 10 rats in either experimental groups (two experimental and two control groups). Five rats (negative control) were kept in a quite non-stressful environment, provided with food ad libitum and free access to water. Normal saline (1 ml) was given orally as placebo in the positive control group ( n = 5). Experimental group III, baclofen acute toxicity group (10 rats): Each animal received a single dose of lethal dose (LD50) of baclofen orally by gavage. It equals 145 mg/kg body weight. The rats were observed for acute toxicity manifestations as well as for LD50 deaths. Group IV, (baclofen-dependent group, 10 rats): Each animal received baclofen (1/10th LD50) in gradually increasing doses for 1 month. The levels of blood urea nitrogen, creatinine kinase, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, γ-glutamyl transpeptidase, cardiac troponin I, and prothrombin time in both baclofen-treated groups showed significant elevation when compared to controls. There were brain, lung, gastric, hepatic, and renal histopathological changes in baclofen-treated rats whose severity varied between the two experimental groups. Baclofen toxicity is an under diagnosed emergency. Physicians should consider baclofen toxicity in users having hepatorenal dysfunction, presenting with altered mental status, bradycardia, and hypotension.


Congenital lingual cyst: Expression of MUC protein and report of a new case.
Lingual congenital cysts are uncommon lesions that alter the functions of speech, swallowing and breathing when they have considerable dimension. They usually appear from birth and increase in size gradually in childhood and adolescence. While there are a considerable number of case reports, the nomenclature and origin of this lesion are controversial. Congenital lingual cysts are composed of an epithelial lining that can show heterogeneous histological features, such as globed, ciliated, squamous and parietal cells, while the wall presents mature connective tissue and eventually smooth muscle. In the present manuscript, we report a case of a congenital lingual cyst in a 13-year-old boy, as well as the immunoexpression of MUC family proteins (MUC-1 and MUC-5AC), hoping to provide data that will help to clarify the possible etiology of this lesion.


Enediyne-lexitropsin DNA-targeted anticancer agents. Physicochemical and cytotoxic properties in human neoplastic cells in vitro, and intracellular distribution.
Two series of hybrids of a dynemicin A model and DNA minor groove binding lexitropsins were synthesized and their cytotoxic activities were investigated in a panel of human normal and malignant cell lines using a colorimetric assay. Adriamycin was used as a control. Several of the agents demonstrated cytotoxic activity, the extent of which varied with tumor type. IC50s of the hybrids ranged from approximately 14-48 microM following 96 h incubation in the presence of test compound. Intracellular distribution studies were facilitated through endogenous fluorescence of the compounds. Evidence of nuclear uptake of the hybrid agents was demonstrated by confocal laser scanning microscopy. The results warrant further development of DNA-targeted enediyne-lexitropsin hybrids as potential anticancer agents.


Transferability of microsatellites for studies on the social behavior of the tufted capuchin monkey (genus Sapajus).
Because of relevant results that indicated that molecular techniques can provide increased knowledge of animal social systems, they usually complement observational field studies. Despite the great utility of microsatellites, they are not available for all species. Gathering genetic information using microsatellites that were originally designed for other species is a time-saving procedure. The aim of this study was to test the transferability of microsatellites and their usefulness in studies of social behavior of black capuchin monkeys (Sapajus nigritus). We noninvasively sampled adult and subadult black capuchins of three wild groups in southeastern Brazil. Seventeen microsatellites, which were previously designed for and successfully amplified in multiple Neotropical primate species, were tested. Nine of the 17 microsatellite loci tested produced an average of 6.22 alleles (range 2-12) per locus. The allelic richness and the expected heterozygosity for all loci was 5.93 and 0.70, respectively. The combined non-exclusion probability for one candidate parent across all loci was 0.01. The nine microsatellite loci optimized in this study have a great potential for application in studies of social structure and dispersal patterns in S. nigritus populations and in other Neotropical primate species.


Prevalence of respiratory syncytial virus infection in Italian infants hospitalized for acute lower respiratory tract infections, and association between respiratory syncytial virus infection risk factors and disease severity.
This study was designed to collect data on the prevalence of respiratory syncytial virus (RSV) infection in Italy in infants hospitalized for lower respiratory tract infections, and to evaluate which of the recognized risk factors might be associated with disease severity. Thirty-two centers throughout Italy participated in the study. Over a 6-month period (November 1,1999 to April 30, 2000), we evaluated all children < 2 years of age hospitalized for lower respiratory tract infections. All subjects were tested for RSV within 24 hr of hospitalization by using an immuno-enzymatic diagnostic test (Abbott Testpack, RSV). Logistic regression was used to identify the factors that might be associated with more severe disease or could increase the likelihood of RSV positivity in hospitalized infants. Out of a total of 1,232 children enrolled, 40.6% were found to be RSV-positive (RSV+). The peak of the RSV epidemic occurred in February, while the lowest prevalence of RSV positivity was seen in November (P < 0.05). A high proportion of study subjects had low birth weight and low gestational age. The clinical diagnosis at hospitalization was bronchiolitis in 66.7%, pneumonia in 15.3%, and wheezy bronchitis in 18.1%. In the bronchiolitis group, a higher prevalence of RSV+ was found in patients with gestational age <or= 33 weeks or 34-35 weeks, as compared to those with a gestational age >or= 36 weeks (P < 0.04). No differences were found in the proportion of RSV+ patients in the three gestational age subgroups with pneumonia and wheezy bronchitis (P > 0.05, each comparison). Independent of the clinical diagnosis at admission, RSV infection was associated with more severe respiratory impairment. Environmental smoke exposure was higher in subjects with bronchiolitis than in those with wheezy bronchitis (P < 0.04), and RSV+ was positively related with the birth order (P < 0.05). The presence of older siblings and birth order plays an important role in RSV infection. The collected data show that, in Italy, RSV is an important cause of lower respiratory tract infection in infants. Gestational age, birth order, birth weight, and exposure to tobacco smoke affected the prevalence and severity of RSV-related lower respiratory tract disease.


Nucleotide sequence of the bovine parainfluenza 3 virus genome: its 3' end and the genes of NP, P, C and M proteins.
We present the nucleotide sequence of bovine parainfluenza 3 virus (BPIV3) genome from its 3' end to the opening region of the F gene, through the NP, P plus C, and M genes. Comparison of the sequence with those reported for other paramyxoviruses indicated that BPIV3 was most similar to human parainfluenza 3 virus (HPIV3), and also very similar to Sendai virus in the structural make-up of its genome and the amino acid sequences of its gene products, suggesting that these three viruses constitute a paramyxovirus subgroup from which Newcastle disease and measles viruses are separable. In BPIV3 and Sendai virus, the NP and M proteins, the main structural elements, were more highly conserved than the functionally important P and C proteins. This tendency was also observed even in BPIV3 and HPIV3. Virus-specific amino acid sequences of the NP and M proteins were found at the carboxyl and amino terminal regions, respectively. BPIV3 M mRNA was found to have aberrations in its poly A attachment site.


Insulin modulates early-phase noradrenaline response to glucose ingestion in humans.
To clarify the relationship between the early-phase insulin response and the early-phase noradrenaline (NA) response to glucose ingestion in humans, serum NA, adrenaline, immunoreactive insulin (IRI), C-peptide immunoreactivity, potassium, nonesterified fatty acid and plasma glucose levels were measured in 8 non-diabetics and 10 diabetics without autonomic disturbance after oral 75 g glucose load. Following results were obtained: 1) In non-diabetics, the maximal NA response was observed at 30 min after glucose ingestion, but in diabetics, mean serum NA levels remained unchanged. The effect of glucose ingestion on the NA response was significantly different between non-diabetics and diabetics by the repeated measurements analysis of variance (F ratio = 5.72, P less than 0.05). 2) In total group (n = 18), at early-phase after glucose ingestion (at 30 min), positive correlation was found between dIRI level and dNA level (r = 0.52, P less than 0.05), between dIRI level and %dNA level (r = 0.56, P less than 0.05), between dIRI/dglucose ratio (insulinogenic index) and dNA level (r = 0.70, P less than 0.01). 3) In four diabetics, NA responses to glucose ingestion were studied again after mild energy restriction for 2 wk. In three of them, both early-phase IRI response and early-phase NA response to glucose ingestion improved after diet therapy, but in the remainder, early-phase NA response to glucose ingestion remained unchanged in accordance with sustained impaired early-phase insulin response to glucose ingestion.(ABSTRACT TRUNCATED AT 250 WORDS)


Review of vorapaxar for the prevention of atherothrombotic events.
Atherosclerosis is frequently caused by clot blockage of the coronary or peripheral arteries, and may lead to myocardial infarction (MI) or peripheral arterial disease (PAD). Despite advancements in management of atherosclerosis, mortality and ischemic rates remain high. Vorapaxar is a protease activated receptor-1 (PAR-1) antagonist, and prevents thrombin activation of PAR-1 receptors on platelets. Vorapaxar was studied in 2 landmark trials in patients with acute coronary syndrome (ACS) and in those with history of atherosclerosis. For patients with ACS, vorapaxar did not significantly reduce rates of the primary efficacy outcome as compared to placebo. For patients with a history of atherosclerosis, vorapaxar significantly reduced rates of primacy outcome. However, in both landmark trials, vorapaxar significantly increased risks of bleeding, and significantly increases risks of intracranial hemorrhage in patients with a history of stroke. Vorapaxar was approved in 2014 in the US for patients with a history of MI or PAD, and in the European Union for patients with a history of MI. Use of vorapaxar may be limited due to its high potential for causing bleeding. Efficacy of vorapaxar in addition to aspirin and prasugrel or ticagrelor for the management of ACS should be studied in the future.


An economical Nanopore sequencing assay for human papillomavirus (HPV) genotyping.
Human papillomavirus (HPV) testing has been employed by several European countries to augment cytology-based cervical screening programs. A number of research groups have demonstrated potential utility of next-generation sequencing (NGS) for HPV genotyping, with comparable performance and broader detection spectrum than current gold standards. Nevertheless, most of these NGS platforms may not be the best choice for medium sample throughput and laboratories with less resources and space. In light of this, we developed a Nanopore sequencing assay for HPV genotyping and compared its performance with cobas HPV Test and Roche Linear Array HPV Genotyping Test (LA). Two hundred and one cervicovaginal swabs were routinely tested for Papanicolaou smear, cobas HPV Test and LA. Residual DNA was used for Nanopore protocol after routine testing. Briefly, HPV L1 region was amplified using PGMY and MGP primers, and PCR-positive specimens were sequenced on MinION flow cells (R9.4.1). Data generated in first 2 h were aligned with reference sequences from Papillomavirus Episteme database for genotyping. Nanopore detected 96 HPV-positive (47.76%) and 95 HPV-negative (47.26%) specimens, with 10 lacking β-globin band and not further analyzed (4.98%). Substantial agreement was achieved with cobas HPV Test and LA (κ: 0.83-0.93). In particular, Nanopore appeared to be more sensitive than cobas HPV Test for HPV 52 (n = 7). For LA, Nanopore revealed higher concordance for high-risk (κ: 0.93) than non-high risk types (κ: 0.83), and with similar high-risk positivity in each cytology grading. Nanopore also provided better resolution for HPV 52 in 3 specimens co-infected with HPV 33 or 58, and for HPV 87 which was identified as HPV 84 by LA. Interestingly, Nanopore identified 5 additional HPV types, with an unexpected high incidence of HPV 90 (n = 12) which was reported in North America and Belgium but not in Hong Kong. We developed a Nanopore workflow for HPV genotyping which was economical (about USD 50.77 per patient specimen for 24-plex runs), and with comparable or better performance than 2 reference methods in the market. Future prospective study with larger sample size is warranted to further evaluate test performance and streamline the protocol.


Correlation of polymer-like solution behaviors with electrospun fiber formation of hydroxypropyl-β-cyclodextrin and the adsorption study on the fiber.
In this paper, the formation of hydroxypropyl-β-cyclodextrin (HPCD) nanofibers in electrospinning and the adsorption of organic molecules on the HPCD nanofiber were studied. The properties of a polymer-like solution from the highly concentrated HPCD/N,N-dimethylformamide (DMF) solution revealed HPCD supramolecular aggregates formation. The entanglements of HPCD self-organized aggregates were one of the most important factors that significantly influenced fiber formation during cyclodextrin electrospinning. The HPCD self-organized aggregates entanglement concentration (C(e)) was investigated. Analyzing the dependence of specific viscosity (η(sp)) on concentration enabled the determination of the aggregates unentangled and entangled regimes for HPCD polymer-like solutions. The dynamic light scattering (DLS) measurements and the (1)H NMR spectra of the HPCD solutions confirmed the presence of considerable HPCD self-organized aggregates in high concentrated HPCD/DMF solutions due to the intermolecular hydrogen bonding. The scanning electron microscopy (SEM) showed the electrospinning morphology transitioned from regular beads to uniform fibers with increasing the HPCD concentration. The dependence of the fiber diameter on the zero shear rate viscosity (η(0)) was determined. The static adsorption behavior of the HPCD fibers was studied. Neutral red (NR) was used as a model organic molecule. The adsorption of NR onto HPCD fibers fitted the pseudo-second-order kinetic model. The equilibrium adsorption amount of NR was 18.41 mg g(-1), and the apparent adsorption rate constant was 9.83 × 10(-4) g mg(-1) min(-1) at 25 °C.


DREADD: a chemogenetic GPCR signaling platform.
Recently, we created a family of engineered G protein-coupled receptors (GPCRs) called DREADD (designer receptors exclusively activated by designer drugs) which can precisely control three major GPCR signaling pathways (Gq, Gi, and Gs). DREADD technology has been successfully applied in a variety of in vivo studies to control GPCR signaling, and here we describe recent advances of DREADD technology and discuss its potential application in drug discovery, gene therapy, and tissue engineering.


Osteoarthritis management of the knee--treatment options post the NSAID cardiotoxicity controversy.
This series of articles facilitated by the Cochrane Musculoskeletal Group (CMSG) aims to place the findings of recent Cochrane musculoskeletal reviews in a context immediately relevant to general practitioners. This article considers treatment options for osteoarthritis management of the knee post the 'NSAID cardiotoxicity controversy'.


Birth of cloned pigs from zona-free nuclear transfer blastocysts developed in vitro before transfer.
The objective of this work was to obtain cloned pig offspring by uterine transfer of blastocysts produced by zona-free manipulation. We started by defining the most suitable culture media for growing pig nuclear transfer embryos produced by zona-free micromanipulation comparing NCSU-23aa with Synthetic Oviduct Fluid (SOFaa) and with in vivo culture in the sheep oviduct. We found that parthenogenetic development to day 7 blastocyst in NCSU-23aa and sheep oviduct was significantly superior as compared to SOFaa (61.8%, 64% and 42.4 respectively) although blastocyst cell number was higher in the latter. Interestingly, when we compared the two media for the culture of nuclear transfer (NT) embryos derived from 3 different donor cell lines, we observed lower rates of development with NCSU-23aa (from 24.5% to 32.4%) while with SOFaa the development was significantly higher for two donor cell lines as compared to the third (44.4%, 48.9% and 20.6% respectively). A total of 244 blastocysts grown in SOFaa were transferred in four synchronized sows on day 5 or 6 of development. Two recipients farrowed 6 and 8 piglets corresponding to an efficiency of development to term of 8% and 16% of the transferred embryos respectively. Eleven pigs are now 10 month of age and those that have reached puberty have been proven to be fertile. Finally, this is the first report on the production of cloned pigs derived from the transfer of NT embryos at the blastocyst stage.


Non-operative management of ulnar collateral ligament injuries in the throwing athlete.
Medial ulnar collateral ligament (UCL) injuries have become increasingly prevalent in overhead athletes. The orthopaedic literature contains a wealth of information on operative management of these injuries. However, there are few high-quality longitudinal studies on non-operative care of UCL injuries. The purpose of this review is to describe the non-operative approach to managing UCL injuries, including recommended rehabilitation strategies and predictors of successful non-operative treatment.


Unmasking artifactual increases in creatine kinase isoenzymes in patients with renal failure.
Previous reports have suggested that creatine kinase isoenzymes are elevated in patients with chronic renal failure and thus are less useful in the evaluation of chest pain in such patients. Our data in 88 patients with chronic renal failure receiving maintenance dialysis confirm this observation for total plasma creatine kinase. However, elevations in MB and BB creatine kinase, although statistically significant, were biologically unimpressive (5.9 +/- 0.05 [SEM] IU/L compared with 4.8 +/- 0.04 IU/L for MB creatine kinase [p less than 0.02], and 5.5 +/- 0.08 ng/ml compared with 3.2 +/- 0.05 ng/ml for BB creatine kinase [p less than 0.0002] ), and were unlikely to cause diagnostic confusion. In 92% of patients with chronic renal failure, plasma MB creatine kinase activity was within the normal range (less than 13 IU/L). Eight percent of patients manifested abnormal MB creatine kinase values; the highest was 20 IU/L. The glass bead method for measuring MB creatine kinase was used to avoid the potential confusion induced by non-creatine kinase-mediated fluorescence, which occurs in the region of MB and BB creatine kinase on electrophoresis. The infrequent and modest increases in plasma MB creatine kinase observed in patients with chronic renal failure should be appreciated, but it should not cause diagnostic confusion, because acute myocardial infarction usually results in more substantial elevations of MB creatine kinase.


Binding abstract concepts.
Binding theories assume that a stimulus and the response made to it are bound together in an event file (Hommel et al., Behav Brain Sci 24(05):849-937, 2001). Such bindings can occur even after single encounters. If the stimulus or parts of its features are repeated within the time frame in which the event file is still intact, the previously integrated response is retrieved. Stimulus-response binding can exist at a perceptual, conceptual or a response selection level (Henson et al., Trends Cogn Sci 18(7):376-384, 2014). The current experiments test whether the observed binding of concepts with responses can be extended from concrete to abstract concepts (detailedness) and whether abstract concepts can retrieve the previous response, in the absence of perceptual repetition. In the present experiment participants responded to a target feature (colour) while the detailedness of the stimulus was irrelevant to the task. The results showed a significant interaction of response relation and detailedness relation, even in the absence of perceptual repetition. This interaction is interpreted as evidence for response-retrieval due to abstract concept repetition. Thus, our data suggest a broader impact of binding mechanism on performance as even abstract concepts can be integrated into event-files and later modulate behaviour.


Ligand Binding Site Comparison - LiBiSCo - a web-based tool for analyzing interactions between proteins and ligands to explore amino acid specificity within active sites.
Interaction between protein and ligands are ubiquitous in a biological cell, and understanding these interactions at the atom level in protein-ligand complexes is crucial for structural bioinformatics and drug discovery. Here, we present a web-based protein-ligand interaction application named Ligand Binding Site Comparison (LiBiSCo) for comparing the amino acid residues interacting with atoms of a ligand molecule between different protein-ligand complexes available in the Protein Data Bank (PDB) database. The comparison is performed at the ligand atom level irrespectively of having binding site similarity or not between the protein structures of interest. The input used in LiBiSCo is one or several PDB IDs of protein-ligand complex(es) and the tool returns a list of identified interactions at ligand atom level including both bonded and non-bonded interactions. A sequence profile for the interaction for each ligand atoms is provided as a WebLogo. The LiBiSco is useful in understanding ligand binding specificity and structural promiscuity among families that are structurally unrelated. The LiBiSCo tool can be accessed through https://albiorix.bioenv.gu.se/LiBiSCo/HomePage.py.


Large amplitude capillary-gravity solitary waves in a stratified fluid sandwiched between two deep homogeneous layers.
The study addresses the propagation of plane capillary gravity solitary waves of permanent form in a three layer formulation. The intermediate fluid is assumed to be stratified, while the upper and lower ones are homogeneous and infinitely deep. One or both interfaces separating these layers are subject to capillarity. The research can be applied to the case of two deep fluids when one of these fluids is stratified near the interface. The latter formulation is relevant to studies of capillary gravity waves in the transitional area between sea water and liquid carbon dioxide in the deep ocean. This has become an issue of importance for the secure storage of carbon dioxide, which is an environmental/technological problem in modern days. Therefore, we address a capillary-gravity wave motion beyond the well-examined cases of a free surface or two fluid flows. It is shown that in the considered formulation, capillary-gravity solitary waves of finite amplitude obey an integro-differential equation. This equation contains both Korteweg-de Vries (KdV) and Benjamin-Ono (BO) dispersion laws and a specific nonlinearity, which depends on the properties of the stratified layer. Capillary (KdV-type) dispersion dominates if the thickness of the stratified layer is d≪d∗. When d≫d∗, the gravitational (BO-type) dispersion determines the flow. The value d∗ depends on the mode number, gravitational acceleration, and capillarity effects. Analytical solutions for the amplitude function and the streamline patterns are presented.


Malignant Catatonia Warrants Early Psychiatric-Critical Care Collaborative Management: Two Cases and Literature Review.
Malignant catatonia (MC) is a life-threatening manifestation which can occur in the setting of an underlying neuropsychiatric syndrome or general medical illness and shares clinical and pathophysiological features and medical comorbidities with the Neuroleptic Malignant Syndrome (NMS). The subsequent diagnosis and definitive therapy of MC are typically delayed, which increases morbidity and mortality. We present two cases of MC and review recent literature of MC and NMS, illustrating factors which delay diagnosis and management. When clinical features suggest MC or NMS, we propose early critical care consultation and stabilization with collaborative psychiatric management.


Pesticide residues in total diet samples, Spain--1971-72.
Average pesticide residue levels were determined for the 17 main food groups in the average Spanish diet. Using these levels and the estimated average intake of these foods, authors computed an individual's average daily consumption of pesticides from each of these food groups and her/his total diet. Foods were acquired over a 1-year period from the market of Valencia, a city that gets supplies from an agricultural area where pesticide consumption is appreciably higher than that of the rest of the country. Thus average residue levels found must be higher than the national average. Except for fruits and vegetables, the different items composing each food group were sampled in proportion to the amount consumed in the average Spanish diet. Foods forming each group were homogenized into composite samples. All foods were analyzed raw. The most frequently detected pesticides were DDT and BHC. Malathion was detected at levels less than 0.10 ppm in some samples of vegetable oils, pears, and apples. DDT and BHC levels varied from undetectable to amounts less than 1.0 ppm. Highest levels were found in lard. An individual's average daily intake of pesticides was calculated to be 78 mug DDT, a sum which includes residues of o,p'-DDT, p,p'-DDT, and p,p'-DDE, and 13.8 mug gamma-BHC. These levels are much lower than the maximum acceptable daily limits established by the United Nations Food Agricultural Organization and World Health Organization.


A modulation of the anaphylactic basophil histamine release by selective H2 histamine agonists.
Two selective H2-histamine agonists, dimaprit and impromidine, have been tested for their action on histamine release from human basophils and rat mast cells. IgE-mediated basophil histamine release was inhibited by stimulation of histamine H2-receptors. However, differences between the actions of both dimaprit and impromidine were noticed. Both impromidine and dimaprit had no specific effect on 48/80-induced histamine release from rat mast cells, although the latter in higher concentrations either slightly increased spontaneous histamine release or non-specifically inhibited compound 48/80-induced release. The results are consistent with the view that activation of adenylate cyclase via H2-histamine receptors might be an important regulatory mechanism of histamine release from human basophils but not from rat mast cells.


Lung and bone metastases patterns in limb osteosarcoma: Surgical treatment of primary site improves overall survival.
Osteosarcoma (OS) is one of the most prevalent malignant bone tumors. The proportion of patients with limb OS was relatively high. Lung metastasis (LM) and bone metastasis are the first and second most common metastatic types of OS, respectively. A total of 270 new cases of LM, 55 new cases of bone metastases (BM), and 36 new cases of lung and BM were diagnosed in the surveillance, epidemiology and end results database from 2010 to 2019. Univariate and multivariate logistic regression analyses were used to identify the risk factors for lung and/or BM, and Cox regression analyses were performed to identify the prognostic factors for lung and/or BM. Kaplan-Meier curves and log-rank tests were used to analyze the overall survival of limb OS patients with lung and/or BM. Female sex, telangiectatic OS type, central OS type, T3 stage, N1 stage, BM, surgical treatments, radiotherapy and chemotherapy were significantly correlated with LM. T3 stage, LM, liver metastases, and radiotherapy significantly correlated with BM. The small cell OS type, T2 stage, T3 stage, N1 stage, liver metastases, and radiotherapy were significantly correlated with lung and BM. Among limb OS patients with LM, the mean survival months of older age, black race, N1 stage, BM, brain metastases, no surgery, and no chemotherapy were lower than those of the control group. In limb OS patients with LM and BM, the mean survival months in the no surgery group was lower than in the surgery group. T stage and radiotherapy significantly influence the occurrence of limb OS with lung and/or BM. Surgery at the primary site has been shown to be effective in improving the survival rate of patients with lung and/or BM.


The IBS-36: a new quality of life measure for irritable bowel syndrome.
We aimed to develop and validate a quality of life instrument for patients with irritable bowel syndrome (IBS). Using focus groups, existing questionnaires, and literature reviews, five IBS patients and nine gastroenterologists compiled and pilot tested for content validity a 70-item questionnaire. The questionnaire was then administered to 107 IBS patients, and using these data, the 70-item questionnaire was reduced to 36 questions through statistical and consensus methodology. The IBS-36 questionnaire was tested for construct validity, reliability, reproducibility, and responsiveness using a gold standard of structured interviews by three gastroenterologists, the Medical Outcomes Study Short Form Quality of Life Questionnaire, and the Coping Resource Inventory. The IBS-36 consists of 36 questions scored on a 7-point Likert scale. It has a very high internal consistency (Cronbach's alpha = 0.95) and a high test-retest reliability (Spearman's r = 0.92) and correlates as hypothesized with the Medical Outcomes Study Short Form Quality of Life Questionnaire (p < 0.001), McGill pain scores (p < 0.001), and IBS patient-reported sleep, symptom, and pain scores (ps = 0.030, <0.001, and <0.001, respectively). The IBS-36 addresses all areas of quality of life affected by IBS and is easy to administer and score. The IBS-36 is a well-validated, condition-specific quality of life measure for IBS patients that is sensitive to clinical intervention and highly correlated with established quality of life measures and patient-reported symptom scores.


Postoperative visceral hypotension the common cause for gastrointestinal complications after cardiac surgery.
In order to identify peroperative risk factors and to evaluate different etiological factors in developing postoperative gastrointestinal complications, clinical variables were studied in 3493 patients undergoing adult cardiac surgery. There were 86 gastrointestinal complications, 2.9%, with an overall morality among these of 22.1%: the mortality rate was 3.9% for all patients undergoing cardiac surgery at our institution (p < 0.001). Paralytic ileus, intestinal ischemia, and acute cholecystitis were the most frequently seen complications. Arterial hypertension, smoking and poor preoperative cardiac function, clinical instability, and the need for an emergency operation were distinct clinical risk factors. Cardiopulmonary bypass time was, by itself, not an important factor. Embolic etiology was also ruled out. The incidence of peroperative myocardial infarction, low postoperative cardiac output necessitating massive use of vasopressor substances and/or intraaortic balloon pumping were significantly more often observed in patients who subsequently developed gastrointestinal complications. The common etiological factor in developing gastrointestinal complications of any kind, after cardiac surgery, seems to be postoperative splanchnic hypoperfusion with visceral ischemia. In order to reduce postoperative morbidity and mortality it is essential to identify patients at risk, support preoperative poor cardiac function, and to carefully monitor these patients postoperatively for abdominal complications to reach an early diagnosis.


Co-delivery of hydrophilic and hydrophobic drugs by micelles: a new approach using drug conjugated PEG-PCLNanoparticles.
Co-delivery strategy has been proposed to minimize the amount of each drug and to achieve the synergistic effect for cancer therapies. A conjugate of the antitumor drug, doxorubicin, with diblock methoxy poly (ethylene glycol)-poly caprolactone (mPEG-PCL) copolymer was synthesized by the reaction of mPEG-PCL copolymer with doxorubicin in the presence of p-nitrophenylchloroformate. The conjugated copolymer was characterized in vitro by 1H-NMR, FTIR, DSC and GPC techniques. Then, the doxorubicin conjugated mPEG-PCL(DOX-mPEG-PCL) was self-assembled into micelles in the presence of curcumin in aqueous solution. The resulting micelles were characterized further by various techniques such as dynamic light scattering (DLS) and atomic force microscopy (AFM).The encapsulation efficiency of doxorubicin and curcumin were 82.31 ± 3.32 and 78.15 ± 3.14%, respectively. The results revealed that the micelles formed by the DOX-mPEG-PCL with and without curcumin have spherical structure with average size of 116 and 134 nm respectively. The release behavior of curcumin and doxorubicin loaded to micelles were investigated in a different media. The release rate of micelles consisted of the conjugated copolymer was pH dependent as it was higher at lower pH than in neutral condition. Another feature of the conjugated micelles was a sustained release profile. The cytotoxicity of micelles were evaluated by MTT (3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide, atetrazole) assay on lung cancer A549 cell lines. In vitro cytotoxicity assay showed that the mPEG-PCL copolymer did not affect the growth of A549 cells. The cytotoxic activity of the micelles against A549 cells was greater than free doxorubicin and free curcumin.


Complete genome sequence of Neisseria gonorrhoeae NCCP11945.
Neisseria gonorrhoeae is an obligate human pathogen that is the etiological agent of gonorrhea. We explored variations in the genes of a multidrug-resistant N. gonorrhoeae isolate from a Korean patient in an effort to understand the prevalence, antibiotic resistance, and importance of horizontal gene transfer within this important, naturally competent organism. Here, we report the complete annotated genome sequence of N. gonorrhoeae strain NCCP11945.


Progress in targeting the BCL-2 family of proteins.
The network of protein-protein interactions among the BCL-2 protein family plays a critical role in regulating cellular commitment to mitochondrial apoptosis. Anti-apoptotic BCL-2 proteins are considered promising targets for drug discovery and exciting clinical progress has stimulated intense investigations in the broader family. Here, we discuss recent developments in small molecules targeting anti-apoptotic proteins and alternative approaches to targeting BCL-2 family interactions. These studies advance our understanding of the role of BCL-2 family proteins in physiology and disease, providing unique tools for dissecting these functions. The BCL-2 family of proteins is a prime example of targeting protein-protein interactions and further chemical biology approaches will increase opportunities for novel targeted therapies in cancer, autoimmune and aging-associated diseases.


Control of recurrent supraventricular tachycardia with amiodarone hydrochloride.
Amiodarone hydrochloride, a new antiarrhythmic agent, controlled a recurrent supraventricular arrhythmia, refractory to conventional medical treatment, in a 57-year-old patient with an anomalous conduction system and idiopathic cardiomyopathy. For the 11 months that the patient has been taking the drug her arrhythmia has not recurred. This drug has produced no important side effects in this patient.


Unmyelinated axons in the rat hippocampus hyperpolarize and activate an H current when spike frequency exceeds 1 Hz.
The mammalian cortex is densely populated by extensively branching, thin, unmyelinated axons that form en passant synapses. Some thin axons in the peripheral nervous system hyperpolarize if action potential frequency exceeds 1-5 Hz. To test the hypothesis that cortical axons also show activity-induced hyperpolarization, we recorded extracellularly from individual CA3 pyramidal neurons while activating their axon with trains consisting of 30 electrical stimuli. Synaptic excitation was blocked by kynurenic acid. We observed a positive correlation between stimulation strength and the number of consecutive axonal stimuli that resulted in soma spikes, suggesting that the threshold increased as a function of the number of spikes. During trains without response failures there was always a cumulative increase in the soma response latency. Intermittent failures, however, decreased the latency of the subsequent response. At frequencies of > 1 Hz, the threshold and latency increases were enhanced by blocking the hyperpolarization-activated H current (Ih)by applying the specific Ih blocker ZD7288 (25 microM) or 2 mM Cs+. Under these conditions, response failures occurred after 15-25 stimuli, independent of the stimulation strength. Adding GABA receptor blockers (saclofen and bicuculline) and a blocker of metabotropic glutamate receptors did not change the activity-induced latency increase in recordings of the compound action potential. We interpret these results as an activity-induced hyperpolarization that is partly counteracted by Ih. Such a hyperpolarization may influence transmitter release and the conduction reliability of these axons.


A review of the adverse side effects associated with antipsychotics as related to their efficacy.
Since the introduction of antipsychotic medication for the treatment of psychosis, a wide range of different types of antipsychotic drugs have been developed while their side effects have become evident. The side effects of both the typical and atypical generation of antipsychotics have important consequences for the quality of life of recipients, stigma experienced and also the level of care of patients. It is well acknowledged that the side effects of antipsychotics reduce compliance with the medication. In this review the data for an association between typical and atypical antipsychotics and the main side effects that are well-supported in the literature was explored: weight gain and associated metabolic effects; extrapyramidal symptoms and tardive dyskinesia; prolactin elevation and associated sexual effects; QTc elongation; and a group of miscellaneous side effects. It has been demonstrated that the production of adverse effects following the use of antipsychotic medication differs widely both between atypical and typical drugs but also within these subgroups. Considering the wide range of antipsychotics available amongst both groups and the differing effects they have on patients in terms of side effects, there is reason to believe that a more personalised approach to antipsychotic treatment should be considered. Additionally, screening for risk factors, screening for the appearance of side effects, as well as good communication with patients about the side effects and other options available are important tasks for clinicians in order to optimise concordance with medication.


Regiodivergent Intermolecular [3+2] Cycloadditions of Vinyl Aziridines and Allenes: Stereospecific Synthesis of Chiral Pyrrolidines.
The first rhodium-catalyzed intermolecular [3+2] cycloaddition reaction of vinyl aziridines and allenes for the synthesis of enantioenriched functionalized pyrrolidines was realized. [3+2] cycloaddition with the proximal C=C bond of N-allenamides gave 3-methylene-pyrrolidines in high regio- and diastereoselectivity, whereas, 2-methylene-pyrrolidines were obtained as the major products by the cycloadditions of vinyl aziridines with the distal C=C bond of allenes. Use of readily available starting materials, a broad substrate scope, high selectivity, mild reaction conditions, as well as versatile functionalization of the cycloadducts make this approach very practical and attractive.


The chemistry and biochemistry of heme c: functional bases for covalent attachment.
A discussion of the literature concerning the synthesis, function, and activity of heme c-containing proteins is presented. Comparison of the properties of heme c, which is covalently bound to protein, is made to heme b, which is bound noncovalently. A question of interest is why nature uses biochemically expensive heme c in many proteins when its properties are expected to be similar to heme b. Considering the effects of covalent heme attachment on heme conformation and on the proximal histidine interaction with iron, it is proposed that heme attachment influences both heme reduction potential and ligand-iron interactions.