Changes in bone mass and serum markers of bone metabolism after parathyroidectomy.
Primary hyperparathyroidism (PHPT) is associated with an increased bone turnover. The simultaneous use of biochemical and bone mass measurements before and after parathyroidectomy is sparsely reported. This study was carried out to evaluate changes in bone mass and markers of bone metabolism in postmenopausal women with PHPT after parathyroidectomy. Twelve women, mean age of 63 years, were investigated. Measurements of bone mineral density (total body, spine, hip, and forearm bone mineral density) with dual-energy x-ray absorptiometry were performed before operation and at follow-up at a median of 23 months. Concomitantly, changes in serum intact parathyroid hormone, bone-specific alkaline phosphatase (B-ALP), osteocalcin, carboxyterminal propeptide of type I procollagen, and the immunoactive carboxyterminal telopeptide of type I collagen were recorded. At follow-up a significant increase in bone mineral density of the spine (p < 0.05), femoral neck (p < 0.05), Ward's triangle (p < 0.05), and trochanter (p < 0.01) was observed. No significant changes in the forearm were registered. Levels of parathyroid hormone, B-ALP, and osteocalcin were elevated and intercorrelated before operation. The serum levels of these parameters decreased significantly after operation. Serum levels of carboxyterminal propeptide of type I procollagen and the immunoactive carboxyterminal telopeptide of type I collagen did not significantly differ from a reference population, and no major changes were observed at follow-up. Bone mineral density in the spine and hip is improved after parathyroidectomy in postmenopausal women with primary hyperparathyrodism. Serum levels of B-ALP and osteocalcin are elevated in PHPT and decrease after operation. The clinical usefulness of serum markers of collagen metabolism in investigating bone metabolism in PHPT seems limited.


[Competitive immunoassay and immunometric immunoassay].
Radioimmunoassays are simple and quite useful, being easily applied on a commercially serviceable basis. Furthermore radioimmunoassays are extremely sensitive and quite precise. Two site immunoradiometric assay in which one antibody was immobilized and another labelled with 125I becomes gradually popular, due to its higher sensitivity and the development of monoclonal antibody production by the hybridoma technique. Alternative analytical methods other than radioimmunoassays (radioimmunoassay, immunoradiometric assay) have been developed, in which the alternative labels to substitute for radioisotopes are enzymes, luminescent compounds and fluorescent probes.


[Digenea in Melanitta fusca and M. nigra (Mergini, Anseriformes) from the Baltic Sea].
Ten individuals of Melanitta fusca and M. nigra (Mergini, Anseriformes) each, wintering at the Polish Baltic coast, were examined for the presence of parasites. M. fusca yielded a total of 197 helminths, including 20 digeneans and 177 nematodes. The M. nigra individuals examined were found to support 923 helminths, including 62 digeneans, 860 nematodes, and a single cestode. M. fusca were hosts to the digeneans: Cryptocotyle concava, Notocotylus attenuatus and Psilostomum brevicolle. Digenea found in M. nigra represented: C. concava and Paramonostomum alveatum. The prevalence of P. brevicolle infection (60%) was higher than that of other digeneans; the maximum infection intensity was 40 C. concava individuals in a single M. nigra.


Endoscopic ultrasound in non-small cell lung cancer and negative mediastinum on computed tomography.
Despite technical advances in staging non-small cell lung cancer (NSCLC), accurate staging remains a challenge. Endoscopic ultrasound is useful in staging NSCLC when lymphadenopathy is present on a computed tomography (CT), but its role in the absence of lymphadenopathy on CT has not been well defined. Therefore, we sought to determine the clinical impact of endoscopic ultrasound (EUS) in staging NSCLC in absence of mediastinal lymphadenopathy on CT. Seventy-six patients with NSCLC with absence of mediastinal lymphadenopathy on CT were enrolled and followed prospectively. EUS-guided fine-needle aspiration was performed on sites that were suspicious for metastases. Surgical pathology after thoracotomy was used as the reference standard for assessing accuracy. Sixty-two (86%) patients underwent surgery, and 10 (13%) did not. EUS precluded surgery in 9 patients (12%) and influenced management in 18 (25%) of all patients in this study. EUS detected malignant mediastinal lymphadenopathy more frequently in patients with lower lobe and hilar cancers combined compared with upper lobe cancers (p = 0.004). EUS played a significant role in identifying patients with unresectable (N3) NSCLC when adenopathy was not present on CT imaging and appears to be more sensitive in detecting lymph node metastases in lower lobe and hilar NSCLC compared with upper lobe NSCLC.


The effect of isoflurane anesthesia on the electroencephalogram assessed by harmonic wavelet bicoherence-based indices.
Bicoherence quantifies the degree of quadratic phase coupling among different frequency components within a signal. Previous studies, using Fourier-based methods of bicoherence calculation (FBIC), have demonstrated that electroencephalographic bicoherence can be related to the end-tidal concentration of inhaled anesthetic drugs. However, FBIC methods require excessively long sections of the encephalogram. This problem might be overcome by the use of wavelet-based methods. In this study, we compare FBIC and a recently developed wavelet bicoherence (WBIC) method as a tool to quantify the effect of isoflurane on the electroencephalogram. We analyzed a set of previously published electroencephalographic data, obtained from 29 patients who underwent elective abdominal surgery under isoflurane general anesthesia combined with epidural anesthesia. Nine potential indices of the electroencephalographic anesthetic effect were obtained from the WBIC and FBIC techniques. The relationship between each index and end-tidal concentrations of isoflurane was evaluated using correlation coefficients (r), the inter-individual variations (CV) of index values, the coefficient of determination (R(2)) of the PKPD models and the prediction probability (P(K)). The WBIC-based indices tracked anesthetic effects better than the traditional FBIC-based ones. The DiagBic_En index (derived from the Shannon entropy of the diagonal bicoherence values) performed best [r = 0.79 (0.66-0.92), CV = 0.08 (0.05-0.12), R(2) = 0.80 (0.75-0.85), P(K) = 0.79 (0.75-0.83)]. Short data segments of ∼10-30 s were sufficient to reliably calculate the indices of WBIC. The wavelet-based bicoherence has advantages over the traditional Fourier-based bicoherence in analyzing volatile anesthetic effects on the electroencephalogram.


The effects of ascorbic acid on in vitro heterophil function.
As a feed additive, ascorbic acid has been shown to have a protective effect against bacterial and viral diseases and to reduce the impact of detrimental stress in chickens. This study examined the effect of ascorbic acid treatment on in vitro heterophil function by examining random migration and phagocytosis and bacterial killing of Staphylococcus aureus. Heterophils were evaluated in broiler chickens ranging from 5 to 16 wk of age, and age differences were seen. Significant increases in bacterial killing were found in heterophils treated with ascorbic acid, and this difference tended to be greater in chickens from 5 to 10.5 wk of age. No significant differences were found in phagocytosis or random migration, but ascorbic acid tended to decrease random migration. The most significant effect on in vitro heterophil function was an increase in bacterial killing.


Development and Clinical Application of Phosphorus-Containing Drugs.
Phosphorus-containing drugs belong to an important class of therapeutic agents and are widely applied in daily clinical practices. Structurally, the phosphorus-containing drugs can be classified into phosphotriesters, phosphonates, phosphinates, phosphine oxides, phosphoric amides, bisphosphonates, phosphoric anhydrides, and others; functionally, they are often designed as prodrugs with improved selectivity and bioavailability, reduced side effects and toxicity, or biomolecule analogues with endogenous materials and antagonistic endoenzyme supplements. This review summarized the phosphorus-containing drugs currently on the market as well as a few promising molecules at clinical studies, with particular emphasis on their structural features, biological mechanism, and indications.


Global, regional, and national estimates of pneumonia morbidity and mortality in children younger than 5 years between 2000 and 2015: a systematic analysis.
Global child mortality reduced substantially during the Millennium Development Goal period (2000-15). We aimed to estimate morbidity, mortality, and prevalence of risk factors for child pneumonia at the global, regional, and national level for developing countries for the Millennium Development Goal period. We estimated the incidence, number of hospital admissions, and in-hospital mortality due to all-cause clinical pneumonia in children younger than 5 years in developing countries at 5-year intervals during the Millennium Development Goal period (2000-15) using data from a systematic review and Poisson regression. We estimated the incidence and number of cases of clinical pneumonia, and the pneumonia burden attributable to HIV for 132 developing countries using a risk-factor-based model that used Demographic and Health Survey data on prevalence of the various risk factors for child pneumonia. We also estimated pneumonia mortality in young children using data from multicause models based on vital registration and verbal autopsy. Globally, the number of episodes of clinical pneumonia in young children decreased by 22% from 178 million (95% uncertainty interval [UI] 110-289) in 2000 to 138 million (86-226) in 2015. In 2015, India, Nigeria, Indonesia, Pakistan, and China contributed to more than 54% of all global pneumonia cases, with 32% of the global burden from India alone. Between 2000 and 2015, the burden of clinical pneumonia attributable to HIV decreased by 45%. Between 2000 and 2015, global hospital admissions for child pneumonia increased by 2·9 times with a more rapid increase observed in the WHO South-East Asia Region than the African Region. Pneumonia deaths in this age group decreased from 1·7 million (95% UI 1·7-2·0) in 2000 to 0·9 million (0·8-1·1) in 2015. In 2015, 49% of global pneumonia deaths occurred in India, Nigeria, Pakistan, Democratic Republic of the Congo, and Ethiopia collectively. All key risk factors for child pneumonia (non-exclusive breastfeeding, crowding, malnutrition, indoor air pollution, incomplete immunisation, and paediatric HIV), with the exception of low birthweight, decreased across all regions between 2000 and 2015. Globally, the incidence of child pneumonia decreased by 30% and mortality decreased by 51% during the Millennium Development Goal period. These reductions are consistent with the decrease in the prevalence of some of the key risk factors for pneumonia, increasing socioeconomic development and preventive interventions, improved access to care, and quality of care in hospitals. However, intersectoral action is required to improve socioeconomic conditions and increase coverage of interventions targeting risk factors for child pneumonia to accelerate decline in pneumonia mortality and achieve the Sustainable Development Goals for health by 2030. Bill & Melinda Gates Foundation.


Blockade of central histaminergic H2 receptors aggravates ischemic neuronal damage in gerbil hippocampus.
Histaminergic H2 antagonists have been reported to provoke central nervous system dysfunction in humans. They also aggravate ischemic neuronal damage in experimental animals. Because energy failure and glutamate release are crucial factors in ischemic neuronal damage, the effects of ranitidine on energy state and the extracellular concentration of glutamate were investigated in gerbil brain. Prospective, randomized, controlled animal study. University animal laboratory. Male Mongolian gerbils. The changes in the direct-current potential shift in the hippocampal CA1 area produced by transient forebrain ischemia for 2.5 mins were compared in gerbils pretreated with saline or ranitidine (10 nmol) intracerebroventricularly. The histologic outcome was evaluated 7 days after ischemia by observing the delayed neuronal death in these animals. In a second study, brain concentrations of adenosine 5'-triphosphate after various durations of decapitation ischemia were determined, and the effect of ranitidine was evaluated. In a third experiment, changes in the extracellular concentrations of excitatory amino acids during forebrain ischemia were examined by a microdialysis procedure. The forebrain ischemia produced a sudden shift in the membrane potential 62 +/- 5 secs (mean +/- sd, n = 6) after the start of ischemia. The preischemic administration of ranitidine facilitated onset of depolarization (38 +/- 8 secs; p <.01). The histologic outcome was aggravated by ranitidine (p <.01). Decapitation ischemia reduced brain adenosine 5'-triphosphate concentration rapidly. Ranitidine facilitated the ischemic reduction in adenosine 5'-triphosphate, and the value after 1 min was 55% of that in the corresponding saline group (p <.01). Ranitidine enhanced the ischemic increase in the glutamate concentration, and the peak value in the ranitidine group was 316% of that in the saline group (p <.05). The deleterious effect of ranitidine on ischemic neuronal damage may involve the increase in the extracellular concentration of glutamate and facilitation of energy depletion in an anaerobic state.


Secretory patterns of LH and FSH during development and hypothalamic and hypophysial characteristics following development of steroid-induced ovarian follicular cysts in dairy cattle.
Two experiments were conducted to (1) investigate developmental endocrinology of ovarian follicular cysts (cysts) in cattle and (2) evaluate effects of cysts on hypothalamic and hypophysial characteristics. Cysts were induced with oestradiol-17 beta (15 mg) and progesterone (37.5 mg) dissolved in alcohol and injected s.c. twice daily for 7 days. Cysts were defined as the presence of follicular structures (which may or may not have been the same structure) of 2.0 cm in diameter or greater that were present for 10 days without ovulation and corpus luteum development. In Exp. 1,22 non-lactating, non-pregnant Holstein cows were allocated to 3 groups. Beginning on Day 5 (oestrus = Day 0) of the oestrous cycle, 7 cows (Controls) were treated with twice daily s.c. injections of ethanol (2 ml/injection) for 7 days. Luteolysis was then induced with PGF-2 alpha and blood samples were collected daily every 15 min for 6 h from the morning after the PGF-2 alpha injection (Day 13) until oestrus. Steroids to induce cysts were injected as previously described into the remaining cows (N = 15). Three blood samples were collected at 15-min intervals every 12 h throughout the experimental period. Additional blood samples were collected every 15 min for 6 h on a twice weekly basis. After steroid injections, follicular and luteal structures on ovaries were not detected via rectal palpation for a period of 36 +/- 4 days (static phase). Then follicles developed which ovulated within 3-7 days (non-cystic; N = 7) or increased in size with follicular structures present for 10 days (cystic; N = 8). Mean (+/- s.e.m.) concentrations of LH, FSH, oestradiol-17 beta and progesterone in serum remained low and were not different during the static phase between cows that subsequently developed cysts or ovulated. During the follicular phase, mean serum concentration of LH (ng/ml) was higher (P less than 0.1) in cows with cysts (2.9 +/- 0.2) than in cows without cysts (1.1 +/- 0.1) or control cows (1.4 +/- 0.2). In addition, LH pulse frequency (pulses/6 h) and amplitude (ng/ml) were higher (P less than 0.1) in cows with cysts (3.6 +/- 0.3 and 2.2 +/- 0.3, respectively) than in non-cystic (2.3 +/- 0.2 and 1.0 +/- 0.2, respectively) and control (1.8 +/- 0.1 and 1.1 +/- 0.2, respectively) groups during the follicular phase. There were no differences in the FSH, oestradiol-17 beta or progesterone characteristics in cows of any of the 3 groups during the follicular phase.(ABSTRACT TRUNCATED AT 400 WORDS)


Deep peroneal nerve palsy due to osteochondroma arising from fibular head and proximal lateral tibia.
Following median and ulnar nerves, peroneal nerve entrapment is the most frequent nerve involvement in the body Katirji and Wilbourn (1998) [1]. Osteochondromas are the most common benign bone tumors comprising 9% of all bone tumors and 35% of benign bone tumors Porter (2000) [2]. Hereditary exostoses (HME) is an autosomal dominant disorder with variable penetrance characterized by multiple osteochondromas near joints. It is one of the most commonskeletal dysplasias with a frequency of about 1.18%. In this study, we aimed to present a case with a drop foot resulting from osteochondromas of proximal tibia and fibula and help to guide the clinicians in differential diagnosis according to SCARE criteria Agha (2016) [3].


Weaving the invisible thread: design of an optically invisible metamaterial fibre.
We present the design of an invisible metamaterial fibre operating at optical frequencies, which could be fabricated by adapting existing fibre drawing techniques. The invisibility is realised by matching the refractive index of the metamaterial fibre with the surroundings. We present a general recipe for the fabrication of such fibres, and numerically characterise a specific example using hexagonally arranged silver nanowires in a silica background. We find that invisibility is highly sensitive to details of the metamaterial boundary, a problem that is likely to affect most invisibility and cloaking schemes.


Bifurcations and chaos in a Lorenz-like pilot-wave system.
A millimetric droplet may bounce and self-propel on the surface of a vertically vibrating fluid bath, guided by its self-generated wave field. This hydrodynamic pilot-wave system exhibits a vast range of dynamics, including behavior previously thought to be exclusive to the quantum realm. We present the results of a theoretical investigation of an idealized pilot-wave model, in which a particle is guided by a one-dimensional wave that is equipped with the salient features of the hydrodynamic system. The evolution of this reduced pilot-wave system may be simplified by projecting onto a three-dimensional dynamical system describing the evolution of the particle velocity, the local wave amplitude, and the local wave slope. As the resultant dynamical system is remarkably similar in form to the Lorenz system, we utilize established properties of the Lorenz equations as a guide for identifying and elucidating several pilot-wave phenomena, including the onset and characterization of chaos.


Enantioselective degradation of tebuconazole in cabbage, cucumber, and soils.
The enantioselective degradation of tebuconazole has been investigated to elucidate the behaviors in agricultural soils, cabbage, and cucumber fruit. Rac-tebuconazole was fortified into three types of agricultural soils and sprayed foliage of cabbage and cucumber, respectively. The degradation kinetics, enantiomer fraction and enantiomeric selectivity were determined by reverse-phase high-performance liquid chromatography (HPLC) and liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS) on a Lux amylose-2 chiral column. The process of the degradation of tebuconazole enantiomers followed first-order kinetic in the test soils and vegetables. It has been shown that the degradation of tebuconazole was enantioselective. The results indicated that the (+)-S-tebuconazole showed a faster degradation in cabbage, while the (-)-R-tebuconazole dissipated faster than (+)-S-form in cucumber fruit and the test soils.


An evidence of group discussion and problem-solving skills in MBBS freshers: Implications and applications.
Teachers need to follow adult learning principles and students need to have discussion and problem-solving skills for the use of active learning methods in classroom. We aimed to find out whether MBBS freshers had group discussion and problem-solving skills. A free group discussion session for problem-solving using adult learning principles was held during the foundation course for MBBS freshers. The task for group discussion was to give suggestions to improve the situation indicated by the given general medical professional problem. Qualitative deductive thematic analysis was used to analyze suggestions which could be grouped under the themes of seven roles of CanMEDS Physician Competency Framework. The results of deductive thematic analysis of suggestions of student groups are described under seven themes of the roles of the CanMEDS Physician Competency Framework. MBBS freshers showed excellent group discussion, plenary presentation, and problem-solving skills for the given problem. They also had relevant general knowledge about medical profession. Their problem-oriented thinking skills were facilitated using adult learning principles. It is recommended that the use of group discussion for problem-solving with facilitation by using adult learning principles should be emphasized in undergraduate medical education to promote the use of active learning methods in classroom.


Protective Effects of Sonic Hedgehog Against Ischemia/Reperfusion Injury in Mouse Skeletal Muscle via AKT/mTOR/p70S6K Signaling.
Skeletal muscle ischemia/reperfusion (I/R) injury is a common and severe disease. Sonic hedgehog (Shh) plays a critical role in post-natal skeletal muscle regeneration. In the present study, the role of Shh in skeletal muscle I/R injury and the mechanisms involved were investigated. The expression of Shh, AKT/mTOR/p70S6K and apoptosis pathway components were evaluated following tourniquet-induced skeletal muscle I/R injury. Then, mice were subjected to systemic administration of cyclopamine or one-shot treatment of a plasmid encoding the human Shh gene (phShh) to examine the effects of Shh on I/R injury. Moreover, mice were subjected to systemic administration of NVP-BEZ235 to investigate the role of the AKT/mTOR/p70S6K pathway in Shh-triggered skeletal muscle protection. We found that the levels of Shh, AKT/mTOR/p70S6K pathway components and Cleaved Caspase 3 and the Bax/Bcl2 ratio initially increased and then decreased at different time points post-I/R injury. Moreover, Shh protected skeletal muscle against I/R injury by alleviating muscle destruction, reducing interstitial fibrosis and inhibiting apoptosis, and these protective effects were abrogated when the AKT/mTOR/p70S6K pathway was inhibited. Collectively, these data suggest that Shh signaling exerts a protective role through the AKT/mTOR/p70S6K signaling pathway during skeletal muscle I/R injury. Thus, Shh signaling may be a therapeutic target for protecting skeletal muscle from I/R injury.


[Positional cloning--current status and future directions].
Several strategies for isolating disease genes have been developed. In functional cloning, the gene is isolated based on information on the function of gene products (proteins). In contrast, positional cloning is based on the isolation of the disease gene, starting from the knowledge of its location on the genome. The flow chart of positional cloning was described as follows; 1) identification of the location of the disease gene by linkage analysis. 2) construction of the physical map spanning the region. 3) isolation of the candidate genes from the region. 4) identification of mutations in the candidate genes, which is specific to the disease. The current concept and strategies on the positional cloning is discussed.


[Myelodysplastic syndrome developing acute myelocytic leukemia with gastric mucormycosis].
80-year-old female was admitted to our hospital because of pancytopenia. Her peripheral and bone marrow examinations were performed. According to the criteria of FAB classification, the diagnosis was myelodysplastic syndrome (refractory anemia with excess of blasts in transformation). Etoposide was administered to decrease leukemic blasts. However, she still had high fever and increasing of CRP. Hematological data also showed the increasing of WBC count, blast cells, and LDH enzyme. Antibiotics and anti fungal drugs were also not effective. She died of respiratory failure, although the cautions and extensive treatment was tried. Autopsy findings revealed proliferation of mucor in the mucosa of stomach. So, we reported here a very rare case of gastric mucormycosis, localizing exclusively in the stomach which was difficult to diagnose while she was alive.


Constitutive short telomere length of chromosome 17p and 12q but not 11q and 2p is associated with an increased risk for esophageal cancer.
Shortened telomere length may cause chromosomal instability in Barrett's esophagus and thus promote tumorigenesis. However, whether short telomere length in all chromosomes or just some of them is associated with increased esophageal cancer (EC) risk is largely unknown. To address this question, we examined the overall and chromosome-specific telomere lengths of 17p, 12q, 2p, and 11q and assessed their associations with EC risk. In a case-control study with 94 EC cases and 94 matched controls, the overall telomere length and the chromosome-specific telomere lengths of 17p, 12q, 2p, and 11q in peripheral blood lymphocytes were determined by a real-time PCR and a modified single telomere length analysis assay, respectively. Multivariate logistic regression analysis was used to assess the association between telomere length and EC risk. Compared with controls, EC patients had significantly shorter overall telomere lengths (P = 0.004) and chromosome-specific telomere lengths of 17p (P = 0.003) and 12q (P = 0.006) but not of 11q (P = 0.632) and 2p (P = 0.972). Furthermore, the multivariate logistic regression analysis showed that the short overall telomere length and chromosome-specific telomere lengths of 17p and 12q were associated with a dose-dependent increase in EC risk. Our study provides the first epidemiologic evidence that short telomere length of 17p and 12q plays an important role in esophageal carcinogenesis, suggesting that short telomere length of specific chromosomes is associated with the etiology of different cancer types.


Double-staining artefact observed in certain individuals during dual-colour immunophenotyping of lymphocytes by flow cytometry.
An unusual double-staining artefact has been repeatedly observed in certain individuals (both HIV-positive and healthy laboratory controls) during 2-colour immunophenotyping of lymphocytes by flow cytometry after red cell lysis. This artefact can falsely suggest co-expression of CD4 and CD8, as well as some of the other monoclonal antibody pairs commonly used in the typing of lymphocytes. It is caused by a serum factor associated with the ammonium-sulphate-precipitated and gamma-globulin fractions. It appears to be fairly common in the population (being found in 6 out of 105 of our healthy laboratory controls and in 42 out of 247 of our HIV-1 seropositive subjects); it may be genetically determined, but may be acquired in some. It is a potential source of error in lymphocyte immunophenotyping, which can be avoided by simple adjustments to the recommended techniques.


[25 years "Anesthesiology and Reanimation"--a historical review].
The 25th anniversary of the foundation of the journal "Anaesthesiology und Reanimation" seems to be a good occasion, first of all, to look back at the special situation regarding the opportunities open to East German anaesthetists for publishing anaesthesiological papers before and after the Berlin Wall was built and then to give a review of the history of this journal. As the author's own publication list shows, East Germans could publish papers in West German journals without any problems before a major reform of the universities, bringing drastic changes, was introduced in East Germany in 1969. It became practically impossible to publish papers in West German journals because the "Directorates of International Relations", which had been installed at all universities in 1969, supervised the entire correspondence with persons and institutions in all foreign countries, in particular West Germany, the other West European countries and the countries of North and South America. Thus, East German anaesthetists were forced to publish in non-anaesthesiological East German journals because there was no journal of anaesthesiology in East Germany until "Anaesthesiologie und Reanimation" was founded as journal of the "Society of Anaesthesiology and Reanimation of the GDR" in 1976. The problems arising from the introduction of this journal under socialist conditions, including political pressure and control through the "General Secretariat of the Medical Scientific Societies of the Ministry of Health of the GDR" as well as technical problems with the publisher and the printers, are described. In spite of all these problems, which were overcome by the editor-in-chief with the aid of his colleagues on the editorial board and the scientific advisory council, this journal was initially published with a circulation of 1,200 copies in 1976 and its circulation increased to 1,600 copies in 1989. The journal proved to be of great benefit to East German anaesthetists and anaesthetists from other East European countries. It was included in an international exchange programme of anaesthesiological journals, which was particularly helpful for East German anaesthetists because they could not subscribe to West German, West European or American journals due to a lack of hard currency. The international exchange of the journal led to an increasing number of authors from West Germany and other West European countries and even from the USA and Canada who published papers in "Anaesthesiology und Reanimation". The "silent revolution" in 1989 brought new problems. The journal was primarily an organ of the "Society of Anaesthesiology and Intensive Therapy of the GDR", but with the end of the GDR, this society was dissolved on 23rd October 1990. Fortunately, "Anaesthesiologie und Reanimation" was taken over by the "German Society of Anaesthesiology and Intensive Medicine" as an organ of this society, in which the former members of the East German society were gathered. The next problem was that the publisher "VEB Verlag Volk und Gesundheit", Berlin and "Verlag Gesundheit GmbH", Berlin respectively ceased to exist in 1992 and we had to look for another publisher. We were very happy that "Selecta Verlagsgesellschaft mbH", Munich, later Wiesbaden, was interested in this journal and took it on in the same year and has now published it since that time with a circulation of 1,000 copies. The chequered history of "Anaesthesiology und Reanimation", the subtitle of which has been changed to "Journal of Anaesthesiology, Intensive Therapy, Emergency Medicine and Pain Therapy" in 1991, clearly shows, on the one hand, the difficult political circumstances under which the development of anaesthesiology took place in East Germany, and demonstrates, on the other, the special problems of the foundation of a medical journal under socialist conditions with which the editorial board in general and the editor-in-chief in particular were confronted and how they tried to overcome the


Mobile patient simulator for resuscitation training with automatic external defibrillators.
Resuscitation training has to be performed under most realistic conditions. This includes both usual CPR measures (breathing and chest compressions) and advanced measures, e.g. the usage of an Automatic External Defibrillator (AED). Almost all currently available simulators for ECG signals used in such trainings have a rather limited variety of available ECG signals. The trainer also has to change between different rhythms manually, resulting in a less realistic training environment. The development will result in mobile ECG simulator which can automatically react to events in the resuscitation process according to pre-programmed scenarios. It also has potential to simulate other physiological parameters like thorax impedance in the future.


Sound velocity and absorption in a coarsening foam.
We present experimental measurements of sound velocity and absorption in a commercial shaving foam. We observe that both quantities evolve with time as the foam coarsens increasing its mean bubble radius <R>. By varying the acoustic frequency we probe the foam from the large wavelength regime, lambda approximately 1500<R>, down to the scale lambda approximately 20<R>. Sound absorption alpha varies significantly with both the foam age and the excitation frequency. After an initial transition time of 20 min, the attenuation per wavelength, alphalambda, varies linearly with the foam age. In addition, for evolution times smaller than approximately 90 min, we observe that alphalambda scales linearly with both foam age and frequency. From these scalings we show that the thermal dissipation mechanism is the dominant one. Sound velocity c is initially frequency independent but the medium becomes slightly dispersive as the foam coarsens. We observe that sound velocity depends on the evolution of the structure of the foam, even in the large wavelength regime. After 2 h of foam coarsening, c decreases at least by a factor of 20%, due to the softening of the foam. These facts are explained by considering the liquid matrix elasticity, due to the presence of surfactant molecules. A simple model of foam structure, combined with results of Biot's theory for porous media, gives both good qualitative and quantitative agreement with our experimental results in the low frequency regime.


Experimental antitumor activity of the amsacrine analogue CI-921.
CI-921 is a di-substituted analogue of amsacrine currently in phase 1 clinical trial. CI-921 was developed to clinical trial largely on the basis of a series of studies at five cancer research laboratories that demonstrated its improved spectrum and degree of activity relative to those of amsacrine against murine tumor models. The tumor models studied included lung, colon, and mammary carcinomas and encompassed a wide range of biologic properties and chemosensitivities. CI-921 had significant activity against 16 of 19 (84%) tumor models examined. The activity of CI-921 was superior to that of amsacrine in 10 of 14 tumor systems that were sensitive to at least one of the agents and for which comparable data existed. In the remaining four systems, CI-921 and amsacrine were equivalent in activity. CI-921 was found to be roughly equipotent with amsacrine on a milligram-per-kilogram (body wt) basis and was found to have significantly higher activity when given orally.


Molecular and functional characterization of three odorant binding proteins from the oriental fruit moth Grapholita molesta (Busck) (Lepidoptera: Tortricide).
Odorant binding proteins (OBPs) act in recognizing odor molecules and their most well-studied functions are transporting odors across the sensillum lymph to olfactory receptor neurons within the insect antennal sensillum. The adults of Grapholita molesta highly depend on olfactory cues in locating host plants and selecting oviposition sites, in which OBPs play an important role in perceiving and recognizing host plant volatiles. Exploring the physiological function of OBPs could facilitate our understanding of their importance in insects' chemical communication. In this study, three OBP genes were cloned and named GmolOBP4, GmolOBP5, and GmolOBP10. Quantitative real-time PCR results indicated that GmolOBP4 and GmolOBP10 were predominantly expressed in adult antennae and GmolOBP5 was expressed in multiple tissues, including head, legs, and wings in addition to antennae. The binding affinities of the three recombinant GmolOBPs (rGmolOBPs) with four sex pheromone components and twenty-nine host plant volatiles were measured using 1-N-Phenyl-naphthylamine as a fluorescence probe. The three rGmolOBPs exhibited specific binding properties to potential ligands, GmolOBP4 and GmolOBP10 bound to minor sex pheromone components, such as (Z)-8-dodecenyl alcohol and dodecanol, respectively. rGmolOBP4 showed intermediate binding ability with hexanal, benzyl alcohol, and pear ester, rGmolOBP5 had a weak affinity for benzaldehyde, pear ester and, methyl jasmonate, and rGmolOBP10 showed strong binding capacity toward hexanol, decanol, and α-ocimene. We speculate that the GmolOBP4 and GmolOBP10 have dual functions in perception and recognition of host plant volatiles and sex pheromone components, while GmolOBP5 may serve other function(s).


Perinatal depression among black Caribbean women.
The present paper describes findings from a mixed-method, longitudinal cohort study into perinatal depression among black Caribbean women. Using symptom scores from the Edinburgh Postnatal Depression Scale (EPDS), 101 black Caribbean and 200 white British women accessing maternity services in Manchester, UK, were screened for depressive symptoms in the last trimester of pregnancy and 6 weeks following delivery. The purpose of the study, which was undertaken between February 2000 and February 2001, was to estimate the prevalence of depressive symptoms during and after pregnancy among black Caribbean women compared to white British women in the same geographical area, and to explore black Caribbean women's beliefs about perinatal depression and their attitudes to help-seeking. Despite higher levels of self-reported risk, black Caribbean women were less likely than white British women to score above threshold (EPDS > or = 12) during pregnancy (chi2 = 4.16, d.f. = 1, P = 0.041). Although equally likely to score above threshold postnatally, they were less likely to receive treatment (chi2 = 4.20, d.f. = 1, P = 0.040) and more likely to be referred to secondary care (Fisher's Exact Test, P = 0.049). Qualitative findings suggest important differences between black Caribbean women's beliefs, attitudes and associated help-seeking practices, and those previously reported. Lower rates of depressive symptoms might partly be accounted for by conceptualisations of mental illness which differ from those of white British and South Asian women, and mistrust of the mental health services. This study showed that black Caribbean ethnicity is an important dimension in understanding the social patterning of mental illness. The findings have implications for the equitable provision of primary care services since black Caribbean women experienced depressive symptoms in pregnancy and early motherhood, but were less likely than their white British counterparts to receive treatment.


Expression and significance of vWF, GMP-140 and ADAMTS13 in patients with aneurysmal subarachnoid hemorrhage.
The aim of this study was to investigate the role of the von Willebrand factor (vWF) in patients with aneurysmal subarachnoid hemorrhage (aSAH), platelet membrane glycoprotein-140 (GMP-140). The aim is also to discover the expression and clinical significance of von Willebrand factor (vWF) cleaving protease (ADAMTS13). 83 patients with aSAH were selected from January 2014 to December 2016. The patients were divided into cerebral vasospasm group (CVS group) (n = 37) and no convulsion group (non-CVS group) (n = 46); delayed cerebral ischemia group (DCI group) (n = 31) and non-delayed cerebral ischemia group (non-DCI group) (n = 52). Also, the different aneurysm diameter group included 43 patients in < 5 mm group, 29 patients in 5-10 mm group, 11 patients in > 10 mm group. The number of patients in the good prognosis group and the poor prognosis group were 49 and 34, respectively. Enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of vWF, GMP-140, and ADAMTS13 in plasma of aSAH patients, and the correlation between the indexes was analyzed. The repeated measures analysis of variance showed that there was no significant difference in plasma vWF, GMP-140, and ADAMTS13 levels in each group of the aSAH patients (p < 0.05). The vWF level of the CVS group was higher than that of the non-CVS group on day 4 and day 10. The GMP-140 level of the CVS group was higher than that of the non-CVS group on day 1, day 4 and day 10. And the ADAMTS13 level was lower than that of the non-CVS group on day 1 and day 10. The difference was statistically significant (p < 0.05). The plasma vWF level of DCI group was higher than that of the non-DCI group on day 1 and day 4. The plasma GMP-140 level at day 4 was higher than that of the non-DCI group. The plasma ADAMTS13 level at day 1 was lower than that in the non-DCI group. The difference was significant (p < 0.05). The plasma vWF level in > 10 mm group was higher than that in < 5 mm group and 5-10 mm group at day 1 and day 4. The plasma vWF level in 5-10 mm group was higher than that in < 5 mm group at day 4. The plasma GMP-140 levels in > 10 mm group were higher than that in < 5 mm group and 5-10 mm group at day 1 and d ay 4. The plasma GMP-140 level in 5-10 mm group was higher than that in < 5 mm group at day 1. The plasma ADAMTS13 level in > 10 mm group was lower than that in < 5 mm group and 5-10 mm group on day 1. Moreover, the plasma ADAMTS13 level in 5-10 mm group was lower than that in < 5 mm group: p < 0.05. The plasma vWF level in the good prognosis group was lower than that in the poor prognosis group on day 4 and day 10. On day 1, day 4, and day 10, the level of GMP-140 was lower than that of the poor prognosis group. The ADAMTS13 level on day 1 and day 4 was higher than that in the poor prognosis group. The difference was statistically significant (p < 0.05). Pearson product moment correlation analysis showed that the plasma vWF level was positively correlated with GMP-140 at day 1 (r = 0.334, p < 0.05), negatively correlated with ADAMTS13 (r = -0.426, p < 0.05), and GMP-140 was negatively correlated with ADAMTS13 (r = -0.398, p < 0.05). At day 4, plasma vWF was positively correlated with GMP-140 (r = 0.278, p < 0.05), negatively correlated with ADAMTS13 (r = -0.311, p < 0.05), and GMP-140 was negatively correlated with ADAMTS13 (r = -0.235, p < 0.05). At day 10, there was no significant correlation between vWF, GMP-140, and ADAMTS13 (p > 0.05). VWF, GMP-140, and ADAMTS13 were correlated with the diameters and prognoses of CVS, DCI, aneurysms. Combined detection can help to evaluate the condition of patients with aSAH, so as to provide a guide for clinical treatment and prognosis.


Photoelectrochemical Reduction of Carbon Dioxide with a Copper Graphitic Carbon Nitride Photocathode.
Research on the photoreduction of CO2 often has been dominated by the use of sacrificial reducing agents. A pathway that avoids this problem would be the development of photocathodes for CO2 reduction that could then be coupled to a photoanodic oxygen evolution reaction. Here, we present the use of copper-substituted graphitic carbon nitride (Cu-CN) on a fluorinated tin oxide (FTO) electrode for the photoelectrochemical two-electron reduction of CO2 to CO as a major product (>95 %) and formic acid (<5 %). The results show that at a potential of -2.5 V versus Fc\Fc+ the CO2 reduction activity of Cu-CN on FTO electrode improves by 25 % upon illumination by visible light with a faradaic efficiency of nearly 100 %. Independently, X-ray photoelectron spectroscopy conclusively shows a pronounced increase in the electrical conductivity of the Cu-CN upon white light illumination under vacuum and a contactless measuring configuration. This photo-assisted charge mobility is shown to play a key role in the increased reactivity and faradaic efficiency for the reduction of CO2 .


Evolutionary significance of isopreneemission from mosses.
Isoprene emission has been documented and characterized from species in all major groups of vascular plants. We report in our survey that isoprene emission is much more common in mosses and ferns than later divergent land plants but is absent in liverworts and hornworts. The light and temperature responses of isoprene emission from Sphagnum capillifolium (Ehrh.) Hedw. are similar to those of other land plants. Isoprene increases thermotolerance of S. capillifolium to the same extent seen in higher plants as measured by chlorophyll fluorescence. Sphagnum species in a northern Wisconsin bog experienced large temperature fluctuations similar to those reported in tree canopies. Since isoprene has been shown to help plants cope with large, rapid temperature fluctuations, we hypothesize the thermal and correlated dessication stress experienced by early land plants provided the selective pressure for the evolution of light-dependent isoprene emission in the ancestors of modern mosses. As plants radiated into different habitats, this capacity was lost multiple times in favor of other thermal protective mechanisms.


Safety and feasibility of two-dimensional echocardiography and myocardial perfusion imaging in patients with chest pain.
The accurate identification of patients at high risk for acute coronary syndromes among those seen in the emergency department with possible myocardial ischemia and nonischernic electrocardiograms is a problem. Two-dimensional echocardiography and myocardial perfusion imaging with 99m-technetium sestamibi can identify patients at low and high risk; however, comparative studies are lacking. The authors studied 555 patients considered at low or moderate risk for myocardial ischemia in our emergency department on the basis of the presenting history, and results of physical examination and electrocardiography. These patients underwent echocardiography and myocardial perfusion imaging within 4 hours of presentation. Endpoints included myocardial infarction, percutaneous transluminal coronary angioplasty, and positive results on stress perfusion imaging. Both imaging procedures were performed in the emergency department on 370 patients. Overall agreement between the two techniques was high (concordance, 89%) in the patients who had myocardial infarction or underwent coronary angiography. Agreement between the two techniques is high when used in patients with possible myocardial ischemia. Both techniques helped identify patients at high risk who required admission and those who could be safely discharged.


Regulation of cellular processes by PPARgamma ligands in neuroblastoma cells is modulated by the level of retinoblastoma protein expression.
Neuroblastoma is a childhood cancer, which spontaneously regresses. This has led to a search for agents that mimic this process. We show that both natural and synthetic ligands of PPARgamma (peroxisome-proliferator-activated receptor gamma) inhibit the growth of neuroblastoma cells in vitro. The degree of PPAR activation was attenuated however in the presence of the retinoblastoma protein. Addition of trichostatin A, a histone deacetylase inhibitor, abolished retinoblastoma protein repression of PPAR activity. Moreover, enhanced growth inhibition was observed when neuroblastoma cells were treated with a PPARgamma ligand and a histone deacetylase inhibitor, suggesting a combination therapy to treat neuroblastoma might prove more effective than using either agent alone.


DNA methylation regulates adenosine A(2A) receptor cell surface expression levels.
Adenosine A(2A) receptors (A(2A)Rs) appear to play important roles in inflammation and in certain diseases of the nervous system. Pharmacological modulation of A(2A)Rs is particularly useful in Parkinson's disease and has been tested in schizophrenia. However, little is known about the regulation of A(2A)R gene (ADORA2A). A bioinformatic analysis revealed the presence of three CpG islands in the 5' UTR region of human ADORA2A. Next, HeLa, SH-SY5Y and U87-MG cells were treated for 48 h with 5 muM 5-azacytidine (Aza). Increased A(2A)R levels were demonstrated in HeLa and SH-SY5Y cells when compared with non-treated cells. No modifications were seen in U87-MG cells. The increased A(2A)R mRNA and protein levels were accompanied by a loss of DNA methylation pattern in HeLa and SH-SY5Y cells, as measured with the SEQUENOM MassArray platform. The Aza treatment also reduced the affinity of a methyl-CpG-binding protein for ADORA2A by quantitative chromatin immunoprecipitation in HeLa cells. Interestingly, A(2A)R levels were reduced by S-adenosyl-l-methionine treatment in U87-MG and methyl-CpG-binding protein affinity was increased for ADORA2A by quantitative chromatin immunoprecipitation. Therefore, these results show for the first time that DNA methylation plays a role in ADORA2A transcription and, subsequently, in constitutive A(2A)R cell surface levels.


Effects of vegetation on soil cyanobacterial communities through time and space.
Photoautotrophic soil cyanobacteria play essential ecological roles and are known to exhibit large changes in their diversity and abundance throughout early succession. However, much less is known about how and why soil cyanobacterial communities change as soil develops over centuries and millennia, and the effects that vegetation have on such communities. We combined an extensive field survey, including 16 global soil chronosequences across contrasting ecosystems (from deserts to tropical forests), with molecular analyses to investigate how the diversity and abundance of photosynthetic and nonphotosynthetic soil cyanobacteria are affected by vegetation change during soil development, over time periods from hundreds to thousands of years. We show that, in most chronosequences, the abundance, species richness and community composition of soil cyanobacteria are relatively stable as soil develops (from centuries to millennia). Regardless of soil age, forest chronosequences were consistently dominated by nonphotosynthetic cyanobacteria (Vampirovibrionia), while grasslands and shrublands were dominated by photosynthetic cyanobacteria. Chronosequences undergoing drastic vegetation shifts (e.g. transitions from grasslands to forests) experienced significant changes in the composition of soil cyanobacterial communities. Our results advance our understanding of the ecology of cyanobacterial classes, and of the understudied nonphotosynthetic cyanobacteria in particular, and highlight the key role of vegetation as a major driver of their temporal dynamics as soil develops.


Optimization of whispering gallery resonator design for biosensing applications.
Whispering gallery modes (WGMs) within microsphere cavities enable highly sensitive label-free detection of changes in the surrounding refractive index. This detection modality is of particular interest for biosensing applications. However, the majority of biosensing work utilizing WGMs to date has been conducted with resonators made from either silica or polystyrene, while other materials remain largely uninvestigated. By considering characteristics such as the quality factor and sensitivity of the resonator, the optimal WGM sensor design can be identified for various applications. This work explores the choice of resonator refractive index and size to provide design guidelines for undertaking refractive index biosensing using WGMs.


[Correlative factors analysis and predictive model construction of intestinal flora imbalance during acute exacerbation of chronic obstructive pulmonary disease].
Objective: To explore correlative factors and construct predictive model of intestinal flora imbalance in patients with acute exacerbation of Chronic Obstructive Pulmonary Disease (COPD). Methods: The patients in acute exacerbation stage of COPD (AECOPD) hospitalized in Yixing People's Hospital from January 1 to December 31, 2019 were included. According to the clinical symptoms and results of fecal examination, the subjects were divided into case group (n=45) and control group (n=83). Multivariate logistic regression was used to analyze the correlative factors of intestinal flora imbalance in AECOPD patients. The prediction model of intestinal flora imbalance in patients with AECOPD was constructed according to the results of factor logistic regression analysis, and the effectiveness of the prediction model was evaluated by receiver operating characteristic (ROC) curve analysis. Results: The ages of subjects in case group and control group were (76±9) and (74±8) years old, respectively, among which males accounted for 80.0% (36/45) and 69.9% (58/83), respectively. The multivariate logistic regression model analysis showed that serum albumin concentration, frequency of acute exacerbation ≥2 times/year, complicated with chronic cor pulmonale and diabetes mellitus were correlative factors of intestinal flora imbalance in patients with AECOPD. The OR (95%CI) were 0.98 (0.80-0.97), 3.70 (1.79-11.72), 2.62 (1.46-10.80) and 3.85 (1.17-8.58), respectively. The prediction model of intestinal flora imbalance was logit P=3.858-0.13×serum albumin consentration+1.52×acute exacerbation ≥2 times/year+1.379×chronic cor pulmonale+1.155×diabetes mellitus. The area under the ROC curve of this model was 0.847 and the sensitivity and specificity of the prediction model were 88.9% and 71.1%, respectively. Conclusions: Serum albumin, frequency of acute exacerbation ≥2 times/year, complicated with chronic cor pulmonale and diabetes mellitus are correlative factors of intestinal flora imbalance in patients with AECOPD. The predictive model shows high clinical value in predicting intestinal flora imbalance in patients with AECOPD.


PDGF upregulates delayed rectifier via Src family kinases and sphingosine kinase in oligodendroglial progenitors.
An increase in the expression of the delayed rectifier current (I(K)) has been shown to correlate with mitogenesis in many cell types. However, pathways involved in the upregulation of I(K) by growth factors in oligodendroglial progenitors (OPs) have not been well-elucidated. In this study, we found that treatment with platelet-derived growth factor (PDGF) and basic fibroblast growth factor but not ciliary neurotrophic factor resulted in increased I(K) density and upregulation of Kv1.5 and Kv1.6 mRNA transcripts. The effect of PDGF on I(K) was blocked by mimosine, a cell cycle inhibitor, and by genistein, a tyrosine kinase inhibitor. Using inhibitors of PDGF-activated pathways, we found that PDGF-induced upregulation of Kv1.5 and I(K) density involves Src family tyrosine kinases, sphingosine kinase, and intracellular Ca(2+) but not ERK1/2 or phosphatidylinositol 3-kinase pathways. Furthermore, agents that were effective inhibitors of PDGF-induced I(K) upregulation also attenuated OP proliferation, supporting the concept that I(K) is an important link between PDGF-activated signaling cascades and cell cycle progression.


Short communication: A low-cost method for analyzing nevirapine levels in hair as a marker of adherence in resource-limited settings.
The measurement of antiretroviral concentrations in hair is emerging as an important technology to objectively quantify adherence to combination antiretroviral therapy. Hair levels of antiretrovirals are the strongest independent predictor of virologic success in large prospective cohorts of HIV-infected patients and surpass self-report in predicting outcomes. Hair is easy to collect and store, but validated methods to analyze antiretroviral levels in hair using liquid chromatography tandem mass spectrometry (LC-MS/MS) are expensive. We report here on the development of a thin-layer chromatography (TLC) assay for the semiquantitative analysis of nevirapine in hair. TLC assay results from 11 samples were consistent with results using LC-MS/MS [Spearman correlation coefficient 0.99 (95% CI 0.95-0.996)]. This simple, low-cost method of analyzing nevirapine concentrations in hair may provide a novel monitoring tool for antiretroviral adherence in resource-limited settings and merits further study in clinical settings.


Locating Exceptional Points on Multidimensional Complex-Valued Potential Energy Surfaces.
We present a method for locating non-Hermitian degeneracies, called exceptional points (EPs), and minimum-energy EPs between molecular resonances using the complex absorbing potential equation-of-motion coupled-cluster (CAP-EOM-CC) method. EPs are the complex-valued analogue of conical intersections (CIs) and have a similar impact on nonadiabatic processes between resonances as CIs have on nonradiative transitions between bound states. We demonstrate that the CAP-EOM-CC method in the singles and doubles approximation (CAP-EOM-CCSD) yields crossings of the correct dimensionality. The use of analytic gradients enables applications to multidimensional problems. Results are presented for hydrogen cyanide and chloroethylene, for which the location of the crossings of anionic resonances is crucial for understanding the dissociative electron attachment process.


[The treatment of adult glioma is multiphasic].
The prognosis of glioma has improved. Even patients with glioblastoma surviving over two years is not rare. The quality of life has improved because of earlier diagnosis and more precise surgical and radiotherapy techniques. In grade 3-4 gliomas treatment modalities are combined. In grade 2 there are several options for postoperative treatment. Recurrencies are treated actively irrespective of the initial histological grade of the tumor. Chemotherapy is used both combined with radiotherapy and as a single treatment at recurrence. The best results are achieved with close co-operation among different specialities in neuro-oncology, most effectively in weekly meetings. Fluent flow of information between health care units promotes the best quality of life for glioma patients.


Prevalence of urinary incontinence after brain injury.
There is little reported in the literature describing the prevalence of voiding dysfunction after brain injury. A prospective study was conducted, 54 consecutive admissions to our brain injury unit from September 1992 through January 1993 were screened for signs and symptoms of voiding dysfunction. Signs and symptoms were noted in 24 patients (44.4%). There was no statistically significant difference in symptom prevalence based on age, sex, hemisphere (right or left) injured, or presence or absence of a frontal lobe injury. Those functioning at a lower cognitive level (Rancho Los Amigos Scale VI or less) had a higher symptom prevalence than the VII-VIII group (p = 0.004, Chi Square Test).


High toxicity, low receptor density, and low integration frequency severely impede the use of adenovirus vectors for production of transgenic mice.
Although many methods are available for introducing genes into the mammalian germ line, none is ideal for genetic manipulation of livestock or primates. These organisms produce relatively few offspring in each reproductive cycle and they have long generation times. For these reasons, a recent report that adenovirus vectors can efficiently insert genes into the mouse germ line by embryo infection is of considerable interest. Adenovirus vectors have a high cloning capacity, can be produced in high titers, and can infect a wide variety of cell types. We have investigated in more detail the potential for such vectors to infect embryos and integrate their DNA into the genome. We exposed mouse embryos to adenovirus vectors that express bacterial beta-galactosidase (LacZ), and studied expression in the preimplantation period, toxicity of the vectors, and the frequency with which fetuses and pups integrate vector DNA. Our findings indicate that fully functional adenovirus receptor does not appear until the two-cell stage of development. Successful infection is associated with high toxicity, such that viral titers must be balanced to achieve high infection with tolerable levels of toxicity. Screening of 94 animals after embryo infection revealed a single positive polymerase chain reaction signal, which is indicative of the presence of the lacZ gene. This finding could not be confirmed by Southern blotting, which indicates that the founder animal was a genetic mosaic for the exogenous DNA. We conclude from these experiments that adenovirus gene transfer vectors are not readily usable for germ line gene insertion.


A chondrogenic gene expression signature in mesenchymal stem cells is a classifier of conventional central chondrosarcoma.
Phenotypic and molecular parallels between the development of chondrosarcoma and the differentiation of chondrocytes in normal growth plate suggest that chondrosarcoma may arise from mesenchymal precursor cells driven towards chondrogenesis. We hypothesized that a comparison between cartilaginous tumours and their possible physiological cells of origin, mesenchymal stem cells (MSCs), might have biological and clinical relevance. MSCs from eight donors were submitted to chondrogenic differentiation in spheroid cultures. Expression profiles of MSCs at days 0, 7, 14, 28 and 42 of chondrogenesis and of 18 chondrosarcomas with different histological grades were studied using a customized cDNA array. Hierarchical clustering of MSC gene expression during chondrogenesis allowed the classification of samples in a pre-chondrogenic and a chondrogenic cluster corresponding to the phenotypes of early and late differentiation stages. The 74 genes differentially expressed between the two clusters were defined as chondrogenesis-relevant genes. Gene expression profiles of chondrosarcoma were submitted to hierarchical clustering on the basis of these chondrogenesis-relevant genes. This analysis allowed clear distinction between grade I and grade III chondrosarcoma and separated grade II chondrosarcoma into two groups. All grade II chondrosarcomas with occurrence of metastasis were found together with the grade III chondrosarcomas in the pre-chondrogenic cluster. This analysis shows that a molecular approach based on the comparison of tumour samples to an in vitro model for chondrogenic differentiation allows a new classification of chondrosarcoma in two clusters. These data suggest that the identification of a pre-chondrogenic and a chondrogenic phenotype for chondrosarcoma by gene expression profiling could develop into a useful tool to predict the clinical behaviour of chondrosarcoma.


Phylogenetic analysis of the family Megalopodidae (Coleoptera: Chrysomeloidea): better taxon-sampling facilitates detection of new relationships and new taxa.
The systematics of Megalopodidae is not adequately known, in spite of it being a relatively small group of phytophagous beetles. The first phylogenetic analysis of Megalopodidae with a comprehensive generic representation (25 genera of 30 described, 10 subgenera and 77 species) is undertaken. A parsimony analysis under equal and implied weights was carried out based on 147 adult and larval morphological characters. Subfamilies Palophaginae and Zeugophorinae were recovered as monophyletic, by contrast with Megalopodinae, which proved to be paraphyletic. Atelederinae are proposed as a new subfamily. Also, three tribes and three subtribes within Megalopodinae are proposed: Leucasteini trib.n., Sphondyliini trib.n. and Megalopodini, the latter including Macrolophina subtrib.n., Temnaspidina subtrib.n. and Megalopodina. The genera Macrolopha, Kuilua, Poecilomorpha, Temnaspis, Antonaria, Agathomerus, Megalopus and Bothromegalopus were recovered as non-monophyletic. New delimitations of the polyphyletic genera Poecilomorpha and Macrolopha are proposed, Clythraxeloma is resurrected, and the subgenera of Agathomerus are suppressed. The following new combinations are proposed: Kuilua apicata (Fairmaire), K. nyassae (Jacoby), Poecilomorpha cribricollis (Pic), P. minuta (Pic), Clythraxeloma assamensis (Jacoby), C. bipartita (Lacordaeri), C. discolineata (Pic), C. downesii (Baly), C. gerstaeckeri (Westwood), C. laosensis (Pic), C. maculata (Pic), C. mouhoti (Baly), C. nigrocyanea (Motschulsky), C. pretiosa (Reineck), Temnaspis tricoloripes (Pic) and Barticaria faciatus (Dalman). Clythraxeloma cyanipennis Kraatz is a restored combination. Distribution patterns of Megalopodidae largely conform to the breakup of Gondwanaland, with its main clades having particular distributions: Andean-Australian (Palophaginae), Ethiopian (Leucasteini, Sphondyliini, and Macrolophina), Neotropical (Ateledrinae and Megalopodina) and Ethiopian-Oriental-Palaearctic (Temnaspidina the result of a secondary expansion. Zeugophorinae present a worldwide distribution, except for the Neotropical and Andean regions, which may be the result of geodispersal. The findings of the present study also shed light on groups with taxonomic issues, where phylogenetic analyses are strongly needed.


Leukapheresis increases circulating tumour cell yield in non-small cell lung cancer, counts related to tumour response and survival.
Circulating tumour cells (CTCs) can be used to monitor cancer longitudinally, but their use in non-small cell lung cancer (NSCLC) is limited due to low numbers in the peripheral blood. Through diagnostic leukapheresis (DLA) CTCs can be obtained from larger blood volumes. Patients with all stages of NSCLC were selected. One total body blood volume was screened by DLA before and after treatment. Peripheral blood was drawn pre- and post DLA for CTC enumeration by CellSearch. CTCs were detected in the DLA product (volume equalling 2 × 108 leucocytes) and after leucocyte depletion (RosetteSep, 9 mL DLA product). Single-cell, whole-genome sequencing was performed on isolated CTCs. Fifty-six patients were included. Before treatment, CTCs were more often detected in DLA (32/55, 58%) than in the peripheral blood (pre-DLA: 18/55, 33%; post DLA: 13/55, 23%, both at p < 0.01). CTCs per 7.5 mL DLA product were median 9.2 times (interquartile range = 5.6-24.0) higher than CTCs in 7.5 mL blood. RosetteSEP did not significantly improve CTC detection (pretreatment: 34/55, 62%, post treatment: 16/34, 47%) and CTCs per mL even decreased compared to DLA (p = 0.04).. Patients with advanced-stage disease with DLA-CTC after treatment showed fewer tumour responses and shorter progression-free survival (PFS) than those without DLA-CTC (median PFS, 2.0 vs 12.0 months, p < 0.01). DLA-CTC persistence after treatment was independent of clinical factors associated with shorter PFS (hazard ratio (HR) = 5.8, 95% confidence interval (CI), 1.4-35.5, p = 0.02). All evaluable CTCs showed aneuploidy. DLA detected nine times more CTCs than in the peripheral blood. The sustained presence of CTCs in DLA after treatment was associated with therapy failure and shortened PFS. The study was approved by the Medical Ethical Committee (NL55754.042.15) and was registered in the Dutch trial register (NL5423).


Effects of sacrocaudal spinal cord transection and transplantation of fetal spinal tissue on withdrawal reflexes of the tail.
Reflex responses to electrocutaneous stimulation of the tail were characterized in awake cats, before and after transection of the spinal cord at sacrocaudal levels S3-Ca1. Consistent with effects of spinal transection at higher levels, postoperative cutaneous reflexes were initially depressed, and the tail was flaccid. Recovery ensued over the course of 70-90 days after sacrocaudal transection. Preoperative and chronic postlesion reflexes elicited by electrocutaneous stimulation were graded in amplitude as a function of stimulus intensity. Chronic postlesion testing of electrocutaneous reflexes revealed greater than normal peak amplitudes, peak latencies, total amplitudes (power), and durations, particularly for higher stimulus intensities. Thus, sacrocaudal transection produced effects representative of the spastic syndrome. In contrast, exaggerated reflex responsivity did not develop for a group of cats that received transplants of fetal spinal cord tissue within sacrocaudal transection cavities at the time of injury, in conjunction with long-term immunosuppression by cyclosporine. We conclude that gray matter replacement and potential neuroprotective actions of the grafts and/or immunosuppression prevent development of the spastic syndrome. This argues that the spastic syndrome does not result entirely from interruption of long spinal pathways.


Ulcerative colitis: prevention of relapse.
The clinical management of ulcerative colitis (UC) involves first treating the acute symptoms to induce remission, and then successfully maintaining it. Oral 5-aminosalicylic acids are safe and useful for maintaining remission in patients with UC. In terms of adherence, a once-daily form of 5-aminosalicylic acid is superior in maintaining remission as compared with split dosing. Patients at high risk of relapse may be candidates for treatment with thiopurines and/or biologics in the early stages of UC. Calcineurin inhibitors, such as cyclosporine and tacrolimus, are effective for severe, steroid-refractory UC patients. It is suggested that these patients use thiopurines as their maintenance therapy once they achieve remission with calcineurin inhibitors. Recent studies have confirmed that biologics are effective for inducing clinical and endoscopic remission of UC, and thus they may improve long-term prognosis of UC.


Case report: SARS-CoV-2-induced urticaria or just a concomitance?
The association between urticaria and different virus infections has been reported in many studies. Different virus infections have been reported to be comorbidities of spontaneous urticaria. In this paper, we report the case of a male patient with acute urticaria 7 days after he left the hospital where he was treated for coronavirus disease 2019 (COVID-19). This infection may act as a causative or a facilitating factor for the initiation of acute urticaria and additional cofactors such as stress may contribute for the urticaria phenotype to be expressed. Additional facts for severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) virus in future will clarify if urticarial rash is one of the COVID's multiple faces.


Moderate alcohol use and health: a consensus document.
The aim of this consensus paper is to review the available evidence on the association between moderate alcohol use, health and disease and to provide a working document to the scientific and health professional communities. In healthy adults and in the elderly, spontaneous consumption of alcoholic beverages within 30 g ethanol/d for men and 15 g/d for women is to be considered acceptable and do not deserve intervention by the primary care physician or the health professional in charge. Patients with increased risk for specific diseases, for example, women with familiar history of breast cancer, or subjects with familiar history of early cardiovascular disease, or cardiovascular patients should discuss with their physician their drinking habits. No abstainer should be advised to drink for health reasons. Alcohol use must be discouraged in specific physiological or personal situations or in selected age classes (children and adolescents, pregnant and lactating women and recovering alcoholics). Moreover, the possible interactions between alcohol and acute or chronic drug use must be discussed with the primary care physician. The choice to consume alcohol should be based on individual considerations, taking into account the influence on health and diet, the risk of alcoholism and abuse, the effect on behaviour and other factors that may vary with age and lifestyle. Moderation in drinking and development of an associated lifestyle culture should be fostered.


Dietary supplement use among elite young German athletes.
Little is known about the prevalence and motives of supplement use among elite young athletes who compete on national and international levels. Therefore, the current survey was performed to assess information regarding the past and present use of dietary supplements among 164 elite young athletes (16.6 +/- 3.0 years of age). A 5-page questionnaire was designed to assess their past and present (last 4 weeks) use of vitamins, minerals, carbohydrate, protein, and fat supplements; sport drinks; and other ergogenic aids. Furthermore, information about motives, sources of advice, supplement sources, and supplement contamination was assessed. Eighty percent of all athletes reported using at least 1 supplement, and the prevalence of use was significantly higher in older athletes (p < .05). Among supplement users, minerals, vitamins, sport drinks, energy drinks, and carbohydrates were most frequently consumed. Only a minority of the athletes declared that they used protein/amino acids, creatine, or other ergogenic aids. Major motives for supplement use were health related, whereas performance enhancement and recommendations by others were less frequently reported. Supplements were mainly obtained from parents or by athletes themselves and were mostly purchased in pharmacies, supermarkets, and health-food stores. Among all athletes, only 36% were aware of the problem of supplement contamination. The survey shows that supplement use is common and widespread among German elite young athletes. This stands in strong contrast to recommendations by leading sport organizations against supplement use by underage athletes.


Detection beyond the Debye screening length in a high-frequency nanoelectronic biosensor.
Nanosensors based on the unique electronic properties of nanotubes and nanowires offer high sensitivity and have the potential to revolutionize the field of Point-of-Care (POC) medical diagnosis. The direct current (dc) detection of a wide array of organic and inorganic molecules has been demonstrated on these devices. However, sensing mechanism based on measuring changes in dc conductance fails at high background salt concentrations, where the sensitivity of the devices suffers from the ionic screening due to mobile ions present in the solution. Here, we successfully demonstrate that the fundamental ionic screening effect can be mitigated by operating single-walled carbon nanotube field effect transistor as a high-frequency biosensor. The nonlinear mixing between the alternating current excitation field and the molecular dipole field can generate mixing current sensitive to the surface-bound biomolecules. Electrical detection of monolayer streptavidin binding to biotin in 100 mM buffer solution is achieved at a frequency beyond 1 MHz. Theoretical modeling confirms improved sensitivity at high frequency through mitigation of the ionic screening effect. The results should promise a new biosensing platform for POC detection, where biosensors functioning directly in physiologically relevant condition are desired.


Post-capillary Immobilon-P membrane fraction collection for capillary electrophoresis.
A simple, cost-effective and efficient method of continuous fraction collection for capillary electrophoresis is described. The method employs a membrane, such as polyvinylidene difluoride, onto which the separated components from a capillary electrophoresis capillary are directly collected to overcome the problem of analyte dilution and to facilitate the fraction collection process. Model proteins are separated and collected onto a polyvinylidene difluoride membrane.


Immunocharacterization of NADH-Glutamate Dehydrogenase from Vitis vinifera L.
Rabbit antiserum was raised against NADH-glutamate dehydrogenase (GDH) isoenzyme 1, purified from leaves of Vitis vinifera L. cv Soultanina and its specificity was tested. This antiserum was used for immunocharacterization of the GDH from leaf, shoot, and root tissues. The antiserum recognized the seven isoenzymes of NADH-GDH and precipitated all the enzyme activity from the three tissues tested. Western blot following SDS-PAGE revealed the same protein band for the three tissues, with a molecular mass of 42.5 kilodaltons corresponding to NADH-GDH subunit. Results, based on the immunological studies, revealed that NADH-GDH from leaf, shoot, and root tissues are closely related proteins. Furthermore, addition of ammonium ions to the culture medium of in vitro grown explants resulted in a significant increase in NADH-GDH activity in root, shoot, and leaf tissues.


[Open versus percutaneous repair of abdominal aortic aneurysm].
The mortality in aortic abdominal aneurysm surgery remains in the 2-7% range. The aim of the study was to compare the results and safety of surgical aneurysm resection with grafting under general anaesthesia, using percutaneous insertion of a stent under local anaesthesia and intravenous analgesic sedation. The data from patients scheduled for elective subrenal abdominal aortic treatment was analysed retrospectively. Patients were allocated to two groups, according to their general condition, ASA status, presence of other pathologies and anatomical conditions. Patients in group I underwent open surgery with general anaesthesia; patients in group II received stents implanted using local anaesthesia and intravenous analgesic sedation. One houndred twenty-seven patients were allocated either to group I (n=87) or to group II (n=40). Blood pressure, heart rate, the need for catecholamines, blood loss and fluid replacement were all higher in group I. More than 50% of patients from this group required mechanical ventilation in the early postoperative period, as well as longer hospitalization. All patients in group II survived, while 6 patients from group I died from postoperative complications. Endovascular repair of aortic abdominal aneurysms under local anaesthesia combined with i.v. sedation is a safe alternative in high-risk patients.


[Endoscopic transluminal drainage for infected pancreatic necrosis].
To evaluate the effectiveness of intraluminal drainage of acute fluid accumulations for infected pancreatic necrosis. There were 848 patients with acute pancreatitis between January 2018 and December 2020 at the Sklifosovsky Research Institute for Emergency Care. Necrotizing pancreatitis was detected in 232 (27.4%) patients. Among necrotic forms, pancreatic parenchymal necrosis was detected in 56 (24.1%) patients, its combination with peripancreatic necrosis - in 176 (75.9%) patients. All patients underwent transabdominal ultrasound, CT of the abdomen and retroperitoneal space, esophagogastroduodenoscopy, endo-ultrasonography of pancreatobiliary zone. Dimensions and localization of acute necrotic accumulations were established using ultrasound and CT data. Endoscopic transluminal drainage was performed in 22 patients with necrotizing pancreatitis and fluid accumulations attached to the stomach or duodenum. There were 12 men (55%) and 10 women (45%) aged 48.5 [39; 56] (35; 88) years. Effectiveness of endoscopic treatment was assessed considering clinical, endoscopic data and reduction of fluid accumulations confirmed by ultrasound and CT data. Among 22 patients, connection with pancreatic ductal system was detected in 3 patients (13.6%) that required pancreaticoduodenal stenting. Early postoperative period was complicated by bleeding from the area of pancreatogenic destruction in 4 patients (18.1%). Therefore, angiography and endovascular embolization of a. gastroduodenalis were required in 2 (9.1%) cases. In 1 (4.5%) case, we performed endoscopic hemostasis using Hemoblock hemostatic solution (4 ml). Combination of both methods was used in 1 (4.5%) patient. In 11 (50%) patients, endoscopic drainage was the final method of surgical treatment of necrotizing pancreatitis. Four patients (18.1%) died. Multiple organ failure caused mortality in 3 patients (13.6%). One (4.5%) patient died from severe nosocomial pneumonia developed in 32 days after drainage. Spurs not drained into the stomach with US-confirmed suspension and sequestration were observed in 11 (50%) out of 22 patients. These accumulations required additional ultrasound-assisted percutaneous drainage. Endoscopic transluminal drainage is a perspective minimally invasive method for necrotizing pancreatitis.


Cultured Ovules as Models for Cotton Fiber Development under Low Temperatures.
Cotton fibers (Gossypium hirsutum L.) developing in vitro responded to cyclic temperature change similarly to those of field-grown plants under diumal temperature fluctuations. Absolute temperatures and rates of temperature change were similar under both conditions. In vitro fibers exhibited a "growth ring" for each time the temperature cycled to 22 or 15 degrees C. Rings were rarely detected when the low point was 28 degrees C. The rings seemed to correspond to alternating regions of high and low cellulose accumulation. Fibers developed in vitro under 34 degrees C/22 degrees C cycling developed similarly to constant 34 degrees C controls, but 34 degrees C/22 degrees C and 34 degrees C/15 degrees C cycling caused delayed onset and prolonged periods of elongation and secondary wall thickening. Control fiber length and weight were finally achieved under 34 degrees C/22 degrees C cycling, but both parameters were reduced at the end of the experiment under 34 degrees C/15 degrees C cycling. Fibers developed under all conditions had equal bundle tensile strength. These results demonstrate that: (a) cool temperature effects on fiber development are at least partly fiber/ovule-specific events; they do not depend on whole-plant physiology; and (b) cultured ovules are valid models for research on the regulation of the field cool temperature response.


Interactions of substrate and product with cytochrome P450 2B4.
Interactions of the substrate(s) benzphetamine and the product (P) desmethylbenzphetamine with cytochrome P450 2B4 were studied by difference spectrophotometry. A two-sites model in which site 1 binding, causing Type I transition (low- to high-spin) must precede site 2 binding, causing Type II transition (high- to low-spin), gave an acceptable fit to the spectral titration data. The equilibrium association constant of substrate for site 1 (K1) was greater than that for site 2 (K2), and the K2 for the product was greater than K1, indicating that the substrate binds preferentially to site 1 and the product prefers site 2. In addition, competition between P and a strong Type II ligand (1-benzylimidazole) and a noncompetitive type of interaction between S and the same Type II ligand was observed. This indicates that P binds to the same site as the Type II ligand and S binds to a different site. The observed high-spin maxima for both P (EP1HSmax) and S (ES1HSmax) were similar to those calculated using the K1 and K2 values obtained from the curve-fitting procedure, indicating that the equilibrium concentration of the high-spin species is controlled entirely by K1 and K2. Simultaneous presence of the substrate and product decreased K1 of the substrate and K2 of the product, indicating that there is interaction between the substrate-preferred and the product-preferred sites. A possible functional significance of the differences in the site preferences of the substrate and product is discussed.


[Comparative pharmacokinetics of the beta-1 receptor blookader celiprolol after a single oral administration in subjects with health kidneys and in patients with impaired renal function].
Pharmacokinetic parameters were determined after the oral administration of a single tablet containing 200 mg celiprolol HCl to 8 healthy volunteers with normal kidney function and 6 patients with stable impaired renal function of different degrees of severity. The plasma levels and the urinary excretion of celiprolol were followed up for 48 hours after administration with the help of specific chemo-analytical methods. The substance was equally well absorbed both by healthy volunteers and patients with renal disease. While the cumulative renal excretion (0 to 48 hours after administration) was reduced from 18.2% in healthy volunteers to 2.3% of the applied dose in kidney patients, the global elimination constant k fell from 0.104 h-1 in healthy volunteers to 0.072 h-1 in the patients with renal disease. It can be assumed that in patients with impaired renal function at least a part of the lacking renal elimination of celiprolol can be taken over by "extrarenal elimination". According to the method of Dettli a reduction in dosage of the beta 1-blocker, celiprolol is not necessary in patients with more or less impaired kidney function.


HFLD: A Nonempirical London Dispersion-Corrected Hartree-Fock Method for the Quantification and Analysis of Noncovalent Interaction Energies of Large Molecular Systems †.
A nonempirical quantum mechanical method for the efficient and accurate quantification and analysis of intermolecular interactions is presented and tested on existing benchmark sets. The leading idea here is to focus on the intermolecular part of the correlation energy that contains the all-important London dispersion (LD) interaction. To keep the cost of the method low, essentially at the level of a Hartree-Fock (HF) calculation, the intramolecular part of the correlation energy is neglected. We also neglect the nondispersive parts of the intermolecular correlation energy. This scheme that we denote as Hartree-Fock plus London dispersion (HFLD) can be readily realized on the basis of the recently reported multilevel implementation of the domain-based local pair natural orbital coupled-cluster (DLPNO-CC) theory in conjunction with the well-established local energy decomposition (LED) analysis. The accuracy and efficiency of the HFLD method are evaluated on rare gas dimers, on the S66 and L7 benchmark sets of noncovalent interactions, and on an additional set (LP14) consisting of bulky Lewis pairs held together by intermolecular interactions of various strengths, with interaction energies ranging from -8 to -107 kcal/mol. It is first shown that the LD energy calculated with this approach is essentially identical to that obtained from the full DLPNO-CCSD(T)/LED calculation, with a mean absolute error of 0.2 kcal/mol on the S66 benchmark set. Moreover, in terms of the overall interaction energies, the HFLD method shows an efficiency that is comparable to that of the HF method, while retaining an accuracy between that of the DLPNO-CCSD and DLPNO-CCSD(T) schemes. Since the underlying DLPNO-CCSD method is linear scaling with respect to the system size, the HFLD approach also does not lead to new bottlenecks for large systems. As an illustrative example of its efficiency, the HFLD scheme was applied to the interaction between the substrate and the residues in the active site of the cyclohexanone monooxygenase enzyme. The excellent cost/performance ratio indicates that the HFLD method opens new avenues for the accurate calculation and analysis of noncovalent interaction energies in large molecular systems.


Determination of 5-fluorouracil in hospital effluents.
Cytostatic anticancer drugs are an increasingly important issue in the environmental debate, mainly due to the lack of knowledge about the fate of these toxic substances. Over the last decades, 5-fluorouracil (5-FU) has been one of the most frequently used antineoplastic agents and may, therefore, be regarded as one of the pilot substances for environmental contamination. As a prerequisite for these investigations, a method for the determination of 5-FU in hospital effluents has been developed. Waste water samples were enriched by solid-phase extraction on ENV(+) columns (concentration factor 500) and analysed by capillary electrophoresis using a buffer containing 80% 160 mM sodium borate buffer (pH 9.5) and 20% acetonitrile (v/v). This method is applicable within the range 5-500 microg 5-FU L(-1). The standard curve (correlation coefficient >0.99) was linear with recovery rates from 80 to 96% and an accuracy from 9.0 to 20% (intra-assay standard deviation 0.7-8.9%; inter-assay standard deviation 2.2-9.5%). Based on the consumption of 5-FU in oncologic departments and the detection limit of 1.7 microg L(-1), this method covers the range necessary to evaluate 5-FU in hospital effluents. The applicability of the method was proven by chemical analysis of real hospital waste water samples. Obtained over a time period of 1 month (range 20-122 microg 5-FU L(-1)), the results were similar to those calculated by an input-output model. The presented method provides an analytical tool necessary to face the monitoring of environmental contamination problems.


Frustrated chaos in biological networks.
The behaviour of three biologically inspired networks is investigated: Immune Idiotypic Network (IIN), Hopfield Network (HN) and Coupled Map Lattice (CML), mainly the effect on the dynamics induced by connecting the network in a frustrated way. Frustration occurs when the global structure is such that local connectivity patterns responsible for stable behaviour are intertwined, leading to mutually competing attractors and chaotic itinerancy among brief appearance of these attractors. Frustration destabilizes the network and provokes an unpredictable "wavering" among the stable dynamic regimes which characterize the same network when it is interconnected in a non-frustrated way. As the main contribution of this paper, an immune idiotypic network in which the prevailing behaviour is oscillatory is studied in detail. It is shown how connecting an elementary three-clone network in a frustrating way transforms the oscillatory regime into a chaotic one. This chaotic regime is further analysed and several interesting aspects are discussed such as the variable homogeneity, the intrinsic chaotic itinerancy among brief oscillatory regimes and the strong unpredictability. In addition, dynamical regimes obtained by frustrating the connectivity of HN and CML are presented and the similarities as well as the differences with the IIN dynamics are emphasized. Common to all these networks is the description of the frustrated chaos as a succession of attempts to relax the network into one of the oscillatory regimes given by a weaker and non-frustrated connectivity, an impossible achievement making the dynamics rambling over brief but repelling orbits.


Analysis of the Research Hotspot of Drug Treatment of Tuberculosis: A Bibliometric Based on the Top 50 Cited Literatures.
The objective of the current study was to analyze the research hotspot of drug treatment for tuberculosis via top literatures. A retrospective analysis was performed on June 7th, 2021. Literatures were searched on the Web of Science Core Collection to identify the top 50 cited literatures related to drug treatment of tuberculosis. The characteristics of the literatures were identified. The outcomes included authorship, journal, study type, year of publication, and institution. Cooccurrence network analysis and visualization were conducted using the VOS viewer (Version 1.6.16; Leiden University, Leiden, The Netherlands). The top 50 cited literatures were cited 308 to 2689 times and were published between 1982 and 2014. The most studied drugs were the first-line drugs such as isoniazid and rifampicin (n = 22), and drug-resistant tuberculosis was most frequently reported (n = 16). They were published in 18 journals, and the New England Journal of Medicine published the most literatures (n = 18), followed by the American Journal of Respiratory and Critical Care Medicine (n = 7), and the Lancet (n = 6). The authors were from 13 countries, and the authors from the USA published most of the literatures (n = 30), while authors from other countries published less than five literatures. The CDC in the USA (n = 4), the World Health Organization (WHO) (n = 3), and the American Philosophical Society (n = 3) were the leading institutions, and only two authors published at least two top-cited literatures as first authors. This study provides insights into the development and most important literatures on drug therapy for tuberculosis and evidence for future research on tuberculosis treatment.


Surface immunoglobulin-mediated signal transduction involves rapid phosphorylation and activation of the protooncogene product Raf-1 in human B-cells.
The protooncogene product, Raf-1, is a serine/threonine kinase and has been implicated as an intermediate in signal transduction mechanisms. We examined neoplastic and normal B cells for phosphorylation and activation of Raf-1 protein in response to anti-immunoglobulin antibody (anti-Ig). Anti-Ig induced rapid phosphorylation of Raf-1 protein in both neoplastic B-cells of hairy cell leukemia and normal tonsillar B-cells which proliferated well in response to anti-Ig. The increase in phosphorylation was due primarily to an increase in phosphoserine. The immune complex kinase assay using Histone V-S as an exogenous substrate also showed an increase in Raf-1-associated kinase activity. An inhibitor of protein kinase C, H7, inhibited the proliferation as well as the Raf-1 phosphorylation in response to the proliferative signal of anti-Ig. Further, downregulation of protein kinase C by the treatment with 12-phorbol 13-myristic acid significantly abrogated the induction of Raf-1 phosphorylation. These results suggest that, in human B-cells, Raf-1 protein may be involved in the signal transduction pathway mediated by surface immunoglobulin, and that it may be, at least partially, phosphorylated by activated PKC.


Improved Comprehensive Photovoltaic Performance and Mechanisms by Additive Engineering of Ti3C2Tx MXene into CsPbI2Br.
CsPbI2Br is promising in the application of perovskite solar cells (PSCs) owing to its reasonable bandgap and good thermal stability. However, the reported power conversion efficiency (PCE) of the CsPbI2Br solar cells is still much lower than that of the organic-inorganic hybrid PSCs, mainly due to relatively poor CsPbI2Br crystal quality. Herein, additive engineering to the photoactive layer of CsPbI2Br using the Ti3C2Tx MXene nanosheets is reported. Thanks to the improved crystallinity/reduced defect density, together with the formation of the Schottky junction between the MXene nanosheets and CsPbI2Br, enhanced separation and transfer of the photogenerated electron-hole pairs can be achieved for optimal MXene addition. A simple device configuration of ITO/SnO2/Ti3C2Tx-added CsPbI2Br/P3HT/Ag can thus deliver a significantly boosted PCE of 15.10%, i.e., a ∼16.69% relative increment compared with that (12.94%) of the control device without adding MXene. In addition, the enhanced humidity resistance is achieved for the MXene-added CsPbI2Br layers.


Molecular basis of transferrin polymorphism in goldfish (Carassius auratus).
Transferrin (TF) polymorphism was investigated in a color variety of goldfish (Carassius auratus), and its molecular basis analyzed. Three TF variants (A1, A2 and B1) were identified from an inbred strain of the goldfish, of which A1 and B1 displayed a large electrophoretic difference on both native and SDS-PAGE gels. The TF cDNAs corresponding to variants A1 and B1 were cloned and sequenced from A1A1, A1B1 and B1B1 individuals, and their deduced amino acid sequences were analyzed. Substantial amino acid variation occurred between variants A1 and B1, with significant differences in peptide length, theoretical molecular weight (Mw) and isoelectric point (pI). No potential glycosylation sites were observed in the two amino acid sequences, which excluded the possibility that carbohydrate difference might cause electrophoretic variation among the TF variants. Further analysis suggested that the distinct electrophoretic mobility of the two variants A1 and B1 by SDS-PAGE resulted from their Mw difference, while the difference by the native PAGE could be explained by their pI variation. Furthermore, genomic DNA fragments containing the transferrin alleles were amplified and subjected to RFLP analysis in A1A1, A1B1 and B1B1 individuals. The data revealed characteristic banding patterns for each TF genotype, and demonstrated that the TF alleles A1 and B1 could be used as a co-dominant marker system. The initial work relating to the goldfish TF variants will benefit the understanding of the evolutionary and functional significance of TF polymorphism in fish.


Experience Managing Adult Patients on Continuous Ambulatory Peritoneal Dialysis in Bangladesh.
Continuous ambulatory peritoneal dialysis (CAPD) is becoming increasingly known to the patients of Bangladesh, and patient numbers are increasing. Here, we report our experience and clinical outcomes in this field.Our analysis included all CAPD patients managed in a tertiary care hospital in Bangladesh between 2003 and 2015. All patients received a Tenckhoff double-cuff catheter by mini-laparotomy, and twin bags were used in most patients. In acute cases, regular exchanges were started manually with small-volume dwells the same or the next day.During the study period, 500 patients (mean age: 62 ± 18 years; 62% men; 86% percent with diabetes) were managed. Selection of CAPD was made by choice (47%) or for hemodynamic instability (32%), remote residence (17%), or poor vascular access (4%). Total duration of follow-up was 9364 patient-months (range: 1 - 78 months). The peritonitis rate was 1 episode in 30 patient-months. Fewer than 5% of patients required catheter removal. Similarly, the percentages of catheter tip migration and fluid leak were at the lower end. Patient survival was 68%, 48%, 38%, 22%, and 8% at 1, 2, 3, 5, and 7 years. Deaths were mostly attributable to vascular events.In a population with predominantly diabetic patients, CAPD was shown to be a viable mode of renal replacement therapy. The rates of peritonitis and catheter-related complications were low. Survival in the initial years can be considered acceptable.


A Rapid, Stability Indicating RP-UPLC Method for Simultaneous Determination of Ambroxol Hydrochloride, Cetirizine Hydrochloride and Antimicrobial Preservatives in Liquid Pharmaceutical Formulation.
A stability indicating reversed phase ultra performance liquid chromatography (RP-UPLC) method was developed for simultaneous determination of ambroxol hydrochloride (AMB), cetirizine hydrochloride (CTZ), methylparaben (MP) and propylparaben (PP) in liquid pharmaceutical formulation. The desired chromatographic separation was achieved on an Agilent Eclipse plus C18, 1.8 μm (50 × 2.1 mm) column using gradient elution at 237 nm detector wavelength. The optimized mobile phase consists of a mixture of 0.01 M phosphate buffer and 0.1 % triethylamine as a solvent-A and acetonitrile as a solvent-B. The developed method separates AMB, CTZ, MP and PP in presence of twelve known impurities/degradation products and one unknown degradation product within 3.5 min. Stability indicating capability was established by forced degradation experiments and seperation of known and unknown degradation products. The lower limit of quantification was established for AMB, CTZ, MP and PP. The developed RP-UPLC method was validated according to the International Conference on Harmonization (ICH) guidelines. This validated method is applied for simultaneous estimation of AMB, CTZ, MP and PP in commercially available syrup samples. Further, the method can be extended for estimation of AMB, CTZ, MP, PP and levo-cetirizine (LCTZ) in various commercially available dosage forms.