Treatment of quinine resistant falciparum malaria in Thai children.
A study was carried out to assess the efficacy of a modified 7 day course of quinine in children with falciparum malaria, in comparison with those of a 7 day course of quinine at standard dosage and a combination of a 7 day course of quinine and sulfadoxine-pyrimethamine, and in relation to the MIC, and to the serum levels of quinine during the course of treatment. Seventy seven children aged 2 years to 12 years with falciparum malaria were randomly treated with one of the 3 regimens. Group I, quinine 10 mg base per kg body wt. 8 hourly for 7 days, 21 of 28 cases (75%) were cured, while 6 cases (21%) showed RI and 1 case (4%) RII failure. Group II, quinine 10 mg base per kg body wt. 8 hourly for the first 4 days then 15 mg base per kg body wt. 8 hourly for the next 3 days, 20 of 23 cases (87%) were cured, while 3 cases (13%) showed RI failure. Group III, quinine 10 mg base per kg body wt. 8 hourly for 7 days and then sulfadoxine 30 mg per kg body wt. and pyrimethamine 1.5 mg per kg body wt., 16 of 26 cases (62%) were cured and 10 cases (38%) showed RI failure. The cure rates in the 3 groups were not statistically different. The three groups had similar serum quinine concentration profiles. Treatment with quinine was successful in cases in which serum quinine levels could be maintained above MIC for 7 days. There was no additional effect of sulfadoxine-pyrimethamine on quinine.


Evaluation of a new calibration method for bilirubinometers measurements.
Although bilirubin meters are still continuously widely used to screen neonatal jaundice worldwide, they still need a metrological calibration method to evaluate the measurement accuracy of these kinds of devices. In this article, the author describes a new calibration method for evaluation of the bilirubinometers measurements and evaluates the results with one of the most common statistical metrological techniques to establish and evaluate the calibration method; the techniques are x̄ and R control charts. The method mainly depends on establishing a correlation between two units, the bilirubin unit (mg/dl) and one of the metrological standard SI units, the irradiance (W/cm2), experimentally to achieve the calibration method. The study results showed that the estimated correlation coefficient of irradiance response to the bilirubinometer under test was around 0.80, which is a primary indication that the method is a considerably valid technique. In addition, the calibration method was evaluated by the statistical parameters x̄ and R control charts, and the results concluded that the variability calibration process is stable, controlled, and hence could be promisingly utilized to evaluate various bilirubinometers with satisfied accuracy and precision in measurements.


Efficacy of iodine water purification tablets against Cryptosporidium oocysts and Giardia cysts.
The ability to control water-borne diseases is critical for soldiers, hikers, and others who may need to drink directly from an outdoor source. Water-borne protozoan parasites that are specifically of concern are Giardia and Cryptosporidium because of their resistance to halogen disinfection. The purpose of this study was to determine the effectiveness of iodine tablets against Giardia and Cryptosporidium under general- and worst-case water conditions that might be found in the field. Giardia cysts and Cryptosporidium oocysts were exposed to iodine according to manufacturer's instructions (two tablets/L = 13-18 mg/L for 20 minutes). This dose inactivated 3-log10 of Giardia in general-case water and pH 9. In worst-case water, however, only about 35% of cysts were inactivated at pH 5. Fifty minutes were required to achieve a 3-log10 reduction at pH 5. Cryptosporidium oocysts were more difficult to inactivate. Only 10% were inactivated after a 20-minute exposure to iodine according to manufacturer's instructions; even after 240 minutes of exposure to iodine only 66-81% oocysts were inactivated. These data strongly suggest that iodine disinfection is not effective in inactivating Cryptosporidium oocysts in water. Because this organism is common in all surface waters, it is recommended that another method of treatment be used before ingestion.


Carbon and hydrogen isotopic fractionation during biodegradation of methyl tert-butyl ether.
Carbon and hydrogen isotopic fractionation during aerobic biodegradation of MTBE by a bacterial pure culture (PM1) and a mixed consortia from Vandenberg Air Force Base (VAFB) were studied in order to assess the relative merits of stable carbon versus hydrogen isotopic analysis as an indicator of biodegradation. Carbon isotopic enrichment in residual MTBE of up to 8.1/1000 was observed at 99.7% biodegradation. Carbon fractionation was reproducible in the PM1 and VAFB experiments, yielding similar enrichment factors (epsilon) of -2.0/1000 +/- 0.1/1000 to -2.4/1000 +/- 0.3/1000 for replicates in the PM1 experiment and -1.5/1000 +/- 0.1/1000 to -1.8/1000 +/- 0.1/1000 for replicates in the VAFB experiment. Hydrogen isotopic fractionation was highly reproducible for the PM1 pure cultures, with epsilon values of -33/1000 +/- 5/1000 to -37/1000 +/- 4/1000 for replicate samples. In the VAFB microcosms, there was considerably more variability in epsilon values, with values of -29/1000 +/- 4/1000 and -66/1000 +/- 3/1000 measured for duplicate sample bottles. Despite this variability, hydrogen isotopic fractionation always resulted in 2H enrichment of the residual MTBE of >80/1000 at 90% biodegradation. The reproducible carbon fractionation suggests that compound-specific carbon isotope analysis may be used to estimate the extent of biodegradation at contaminated sites. Conversely, the large hydrogen isotopic fractionation documented during biodegradation of MTBE suggests that compound-specific hydrogen isotope analysis offers the most conclusive means of identifying in-situ biodegradation at contaminated sites.


Dinotefuran induces oxidative stress and autophagy on Bombyx mori silk gland: Toxic effects and implications for nontarget organisms.
Dinotefuran, a third-generation neonicotinoid insecticide, is widely utilized in agriculture for pest control; however, its environmental consequences and risks to non-target organisms remain largely unknown. Bombyx mori is an economically important insect and a good toxic detector for environmental assessments. In this study, ultrastructure analysis showed that dinotefuran exposure caused an increase in autophagic vesicles in the silk gland. Dinotefuran exposure triggered elevated levels of oxidative stress in silk glands. Reactive oxygen species, oxidized glutathione disulfide, glutathione peroxidase, the activities of UDP glucuronosyl-transferase and carboxylesterase were induced in the middle silk gland, while malondialdehyde, reactive oxygen species, superoxide dismutase , oxidized glutathione disulfide were increased in the posterior silk gland. Global transcription patterns revealed the physiological responses were induced by dinotefuran. Dinotefuran exposure substantially induced the expression levels of many genes involved in the mTOR and PI3K - Akt signaling pathways in the middle silk gland, whereas many differentially expressed genes involved in fatty acid and pyrimidine metabolism were found in the posterior silk gland. Additionally, functional, ultrastructural, and transcriptomic analysis indicate that dinotefuran exposure induced an increase of autophagy in the silk gland. This study illuminates the toxicity effects of dinotefuran exposure on silkworms and provides new insights into the underlying molecular toxicity mechanisms of dinotefuran to nontarget organisms.


Postanesthetic Cold Sensibility Test as an Indicator for the Efficacy of Inferior Alveolar Nerve Block in Patients with Symptomatic Irreversible Pulpitis of Mandibular Molars.
This study was conducted on the mandibular first molars of 54 patients (35 males and 19 females) with signs and symptoms of SIP. To anesthetize the affected molars, all patients received a single carpule of 2% lidocaine with 1 : 100000 epinephrine using a standardized inferior alveolar nerve block (IANB) technique. The cold test was conducted before beginning the endodontic procedures and after gaining lip numbness, and the results were reported as either positive or negative response. The root canal preparation (RCP) was then initiated and the patients' responses were documented (Gold standard test). True pulpal anesthetic failure was described as a pain perception during the access cavity and pulp tissue removal. True pulpal anesthesia was defined as no pain or discomfort during the access cavity and pulp extirpation. The qualitative variables frequencies and percentages of patients with true/false positive and negative responses were determined and then compared using the Chi-square test. The pain perception of male and female patients during the cold test and gold standard was compared using the Fisher exact test. The following diagnostic parameters were calculated using an online statistical calculator: sensitivity, specificity, predictive values, accuracy, and Youden index. In addition, a receiver operating characteristic curve (ROC) was constructed and the area under the curve (AUC) was calculated. The overall percentage of actual failure of pupal anesthesia was 57%. The sensitivity, specificity, positive predictive value, negative predictive value, accuracy, and Youden index for the cold test were 0.87, 0.91, 0.93, 0.84, 0.89, and 0.78, respectively. There was no statistically significant difference between male and female patients regarding their responses to cold testing and the gold standard test (P > 0.05). Besides, the patients' reactions to the cold test were significantly matched with their reactions to the gold standard test (P < 0.05). The area under the ROC was mostly 0.9. The cold test could be a valuable and accurate method for predicting the potential pupal anesthesia before beginning the endodontic treatment of mandibular molars with symptomatic irreversible pulpitis, particularly after obtaining postanesthetic soft tissue numbness.


Recent advances progress in radiotherapy for breast cancer after breast-conserving surgery: a review.
Adjuvant radiotherapy after breast-conserving surgery has become an integral part of the treatment of breast cancer. In recent years, the development of radiotherapy technology has made great progress in this field, including the comparison of the curative effects of various radiotherapy techniques and the performance of the segmentation times. The choice of radiotherapy technology needs to be co-determined by clinical evidence practice and evaluated for each individual patient to achieve precision radiotherapy. This article discusses the treatment effects of different radiotherapy, techniques, the risk of second cancers and short-range radiation therapy techniques after breast-conserving surgery such as hypo fractionated whole breast irradiation and accelerated partial breast irradiation. The choice of radiotherapy regimen needs to be based on the individual condition of the patient, and the general principle is to focus on the target area and reduce the irradiation of the normal tissues and organs. Short-range radiotherapy and hypofractionated are superior to conventional radiotherapy and are expected to become the mainstream treatment after breast-conserving surgery.


Photochemical reaction of 2-(3-benzoylphenyl)propionic acid (ketoprofen) with basic amino acids and dipeptides.
Photoreaction of 2-(3-benzoylphenyl)propionic acid (ketoprofen, KP) with basic amino acids (histidine, lysine, and arginine) and dipeptides (carnosine and anserine) including a histidine moiety in phosphate buffer solution (pH 7.4) has been investigated with transient absorption spectroscopy. With UV irradiation KP(-) gave rise to a carbanion through a decarboxylation reaction, and the carbanion easily abstracted a proton from the surrounding molecule to yield a 3-ethylbenzophenone ketyl biradical (EBPH). The dipeptides as well as the basic amino acids were found to accelerate the proton transfer reaction whereas alanine and glycine had no effect on the reaction, revealing that these amino acids having a protonated side chain act as a proton donor. The formation quantum yield of EBPH was estimated to be fairly large by means of an actinometrical method with benzophenone, and the bimolecular reaction rate constant for the proton transfer between the carbanion and the protonated basic amino acids or the protonated dipeptides was successfully determined. It has become apparent that the bimolecular reaction rate constant for the proton transfer depended on the acid dissociation constant for the side chain of the amino acids for the first time. This reaction mechanism was interpreted by difference of the heat of reaction for each basic amino acid based on the thermodynamical consideration. These results strongly suggest that the side chain of the basic amino acid residue in protein should play an important role for photochemistry of KP in vivo.


Crystal structures of Aedes aegypti alanine glyoxylate aminotransferase.
Mosquitoes are unique in having evolved two alanine glyoxylate aminotransferases (AGTs). One is 3-hydroxykynurenine transaminase (HKT), which is primarily responsible for catalyzing the transamination of 3-hydroxykynurenine (3-HK) to xanthurenic acid (XA). Interestingly, XA is used by malaria parasites as a chemical trigger for their development within the mosquito. This 3-HK to XA conversion is considered the major mechanism mosquitoes use to detoxify the chemically reactive and potentially toxic 3-HK. The other AGT is a typical dipteran insect AGT and is specific for converting glyoxylic acid to glycine. Here we report the 1.75A high-resolution three-dimensional crystal structure of AGT from the mosquito Aedes aegypti (AeAGT) and structures of its complexes with reactants glyoxylic acid and alanine at 1.75 and 2.1A resolution, respectively. This is the first time that the three-dimensional crystal structures of an AGT with its amino acceptor, glyoxylic acid, and amino donor, alanine, have been determined. The protein is dimeric and adopts the type I-fold of pyridoxal 5-phosphate (PLP)-dependent aminotransferases. The PLP co-factor is covalently bound to the active site in the crystal structure, and its binding site is similar to those of other AGTs. The comparison of the AeAGT-glyoxylic acid structure with other AGT structures revealed that these glyoxylic acid binding residues are conserved in most AGTs. Comparison of the AeAGT-alanine structure with that of the Anopheles HKT-inhibitor complex suggests that a Ser-Asn-Phe motif in the latter may be responsible for the substrate specificity of HKT enzymes for 3-HK.


Origin of Surface Reconstruction in Lattice Oxygen Oxidation Mechanism Based-Transition Metal Oxides: A Spontaneous Chemical Process.
A fundamental understanding of surface reconstruction process is pivotal to developing highly efficient lattice oxygen oxidation mechanism (LOM) based electrocatalysts. Traditionally, the surface reconstruction in LOM based metal oxides is believed as an irreversible oxygen redox behavior, due to the much slower rate of OH- refilling than that of oxygen vacancy formation. Here, we found that the surface reconstruction in LOM based metal oxides is a spontaneous chemical reaction process, instead of an electrochemical reaction process. During the chemical process, the lattice oxygen atoms were attacked by adsorbed water molecules, leading to the formation of hydroxide ions (OH- ). Subsequently, the metal-site soluble atoms leached from the oxygen-deficient surface. This work also suggests that the enhancement of surface hydrophilicity could accelerate the surface reconstruction process. Hence, such a finding could add a new layer for the understanding of surface reconstruction mechanism.


Posterolateral Rotatory Apprehension Test in Tennis Elbow.
Tennis elbow is a syndrome that commonly diagnosed in patient who comes with lateral elbow pain. Instability pain in tennis elbow patient was observed and reported in many previous literatures. Posterolateral rotatory apprehension test was proposed for diagnosis of posterolateral rotatory instability of elbow. However, no review literatures that studied about posterolateral rotatory apprehensions test in tennis elbow. To find out the relationship between posterolateral rotatory apprehension test and tennis elbow. There were 44 patients that were recruited in this study. We examined the posterolateral rotatory apprehension test in tennis elbow patients. The examination was done in our outpatient clinic from March 2012 to April 2012. The data was collected to find out the ratio of negative test in tennis elbow patient. The results from the posterolateral rotatory apprehension test were negative in 43 patients. The ratio of the negative test result was 98%. A result from posterolateral rotatory apprehension test should be negative in general tennis elbow patients. If this test is used in a tennis elbow patients who are suspected with hidden instability and the result is positive, further evaluation is strongly suggested.


Diarrhea and Acute Tubular Necrosis Mimicking Hemolytic Uremic Syndrome in a Man With Immunoglobulin A (IgA) Nephropathy.
Immunoglobulin A (IgA) nephropathy is a heterogeneous disease with variable clinical presentations ranging from asymptomatic hematuria to advanced renal failure. A young male diagnosed with IgA vasculitis (skin, joints, and gastrointestinal) one month ago and placed on oral steroids presented with acute diarrhea, hemolytic anemia, renal failure (non-dialysis requiring), altered sensorium, and thrombocytopenia. The stool was found to be positive for Shiga toxin. He improved with methylprednisolone pulse alone, and renal biopsy showed acute tubular injury.


An assessment of the understanding of the offer of routine HIV testing among pregnant women in rural Zimbabwe.
The objective of this study is to assess the understanding of routine offer of HIV testing among women using antenatal care (ANC) services in a rural African district. A descriptive cross-sectional survey was conducted in Murewa district, Zimbabwe, among women consecutively enrolled during their first ANC visit in 10 health centres offering prevention of mother-to-child transmission (PMTCT) of HIV services including routine offer of HIV testing. Ninety-three (64%) of the 146 respondents had received some form of education on the importance of HIV testing before visiting the health centre on the day of their interview. Almost all respondents (n=139; 95%) felt that the information provided during the group education was sufficient to make a decision on whether or not they should have an HIV test. HIV testing uptake was high with 136 (93%) women being tested for HIV on the day of the interview. Of these, 128 (94%) were aware that they had been tested for HIV when interviewed before the time of receiving results. Fifty percent (n=67) of the women who accepted HIV testing directly after group education as part of their routine ANC blood tests were not aware, however, of the possibility of opting for individual pre-test counseling. The study found that in Zimbabwe, implementation of routine offer of HIV testing allowed women using ANC services to make an informed conscious decision to undertake an HIV test as part of the PMTCT package of services. There is a need to emphasize the availability of further individual pre-test counseling if necessary since a selected subgroup of women may still benefit from it.


A Comprehensive Study of Palate Development in Miniature Pig.
Palate development is an important morphogenetic event in facial development, including the fusion of the lateral and medial nasal portions of the frontonasal process and maxilla. Derailments of any of these events may result in cleft palate, the most frequent congenital craniofacial abnormality. Recent research has shown that the microanatomy of the miniature pig oral maxillofacial region is quite similar to that of humans, and the use of miniature pigs as a large animal model for dental and orofacial research is increasing. Little information is available, however, about the development of the miniature pig palate. Here, using histological and ultrastructural methods, we describe the developmental stages of the palate in miniature pigs. Sections from E26, E30, E35, E40, E45, and E50 embryos were stained with hematoxylin-eosin, and selected specimens were also processed for electron microscopy. The development of the miniature pig palate can be divided into four stages: growth of the bilateral palatal shelves alongside the tongue at E30; elevation of the horizontal position above the tongue at E35; establishment of bilateral shelf contact at the midline from E35-50; and a final fusion step at E50, similar to the mouse and human. The histological characteristics of the miniature pig palate at different developmental stages were synchronously verified at the ultrastructural level. Our study provides a piece of first-hand data regarding palate morphological organogenesis in the miniature pig and a foundation for further research with this model to explore mechanisms of cleft palate development. Anat Rec, 300:1409-1419, 2017. © 2017 Wiley Periodicals, Inc.


Dissociating compatibility effects and distractor costs in the additional singleton paradigm.
The interpretation of identity compatibility effects associated with irrelevant items outside the nominal focus of attention has fueled much of the debate over early versus late selection and perceptual load theory. However, compatibility effects have also played a role in the debate over the extent to which the involuntary allocation of spatial attention (i.e., attentional capture) is completely stimulus-driven or whether it is contingent on top-down control settings. For example, in the context of the additional singleton paradigm, irrelevant color singletons have been found to produce not only an overall cost in search performance but also significant compatibility effects. This combination of search costs and compatibility effects has been taken as evidence that spatial attention is indeed allocated in a bottom-up fashion to the salient but irrelevant singletons. However, it is possible that compatibility effects in the additional singleton paradigm reflect parallel processing of identity associated with low perceptual load rather than an involuntary shift of spatial attention. In the present experiments, manipulations of load were incorporated into the traditional additional singleton paradigm. Under low-load conditions, both search costs and compatibility effects were obtained, replicating previous studies. Under high-load conditions, search costs were still present, but compatibility effects were eliminated. This dissociation suggests that the costs associated with irrelevant singletons may reflect filtering processes rather than the allocation of spatial attention.


[Neuropsychology and forensic assessment in brain injured patients].
Neuropsychology, which deals with the relationships between upper mental functions and brain structures is directly involved with psychiatric and psychological disorders and thus constitutes one of the major domains of cognitive sciences. The impairment of upper mental functions is evident after severe brain injuries causing significant motor deficits. However, it is becoming increasingly evident that even mild or moderate brain injuries can cause sequelae which are difficult to analyze and quantify clinically. These sequelae constitute an "invisible handicap" which may greatly interfere with the patient's professional, relational and social life. The neuropsychological evaluation must be systematic and complete and has to be carried out with a sufficient hindsight (two to three years after the trauma) using neuropsychological and behavioural deficiency evaluation scales. Psychometric tests are also necessary. The data obtained from this evaluation must be correctly interpreted and constitutes the main exhibit in the forensic examination of the brain injured patient.


Antibiotic susceptibility of Streptococcus pneumoniae isolates in Portugal. A multicenter study between 1989 and 1993.
A total of 1,104 strains of Streptococcus pneumoniae were isolated from hospitalized patients (75.5%) and from colonization sites at the Public Health Institute (24.5%) during the last 4 years (1989-1993). Penicillin resistance (defined as MIC > or = 0.1 microgram/liter) was found to increase in time: 4.6% in 1989, 4.9% in 1990, 6.4% in 1991, 11.3% in 1992, and 17% in 1993. In 1992, 0.8% of the strains had penicillin MIC = 2 mg/liter. Increase in penicillin resistance was also evident among invasive strains [blood, cerebrospinal fluid (CSF), pleura]: 2/92 isolates from 1989-1992 (2.3%) were penicillin resistant as compared to 7/101 isolates from 1992 (6.9%). Multiresistance (resistance to three or more antibiotics) was 4.4% with penicillin, tetracycline, chloramphenicol being the predominant resistant phenotype at the end of 1992. In 1993, strains with resistance to penicillin plus chloramphenicol plus tetracycline increased further. Erythromycin resistance was usually associated with clindamycin resistance, but the majority of such strains remained susceptible to penicillin. Drift in the direction of increasing MIC values was also noted during this 3-year period among "susceptible" isolates: bacteria with MIC of 6-10 ng/ml representing the majority of isolates in 1990-1991 decreased and were replaced by cells with MIC of 20 ng/ml. The most frequent pneumococcal serotypes were 23, 19, 3, 6, 14, 9, and 8, with the frequency of type 9 increasing from 2.9% (in 1989) through 3.2% (1990) to 6.4% (1992). Among all antibiotic resistant strains, the prevalent serotypes were 23, 9, 14, and 6. The chromosomal backgrounds of resistant isolates tested by pulsed-field gel electrophoresis showed close resemblance to the background of the serotype 23F multiresistant clone first identified in Spain. The data suggest that the recent large increase in the frequency of penicillin-resistant pneumococci represents the import of this clone into Portugal during the early 1990s. The increased frequency of drug-resistant pneumococci highlights the importance of continued surveillance of these dangerous pathogens.


Multireference adaptive noise cancellation applied to somatosensory evoked potentials.
Somatosensory Evoked Potentials (SEP's) contain information that is useful in diagnosing various physiological disorders. However, surface measurements of these potentials suffer from very poor Signal-to-Noise ratio (SNR) resulting in imperceptible SEP waveforms. This factor motivates the employment of dedicated signal processing techniques to improve the quality of the waveform. The objective of this research work is to improve the SNR of SEP by eliminating the predominant myoelectric interference. The strategy followed to achieve this goal is to process the SEP signal by MultiReference Adaptive Noise Cancellation (MRANC). A theoretical model for the MRANC is presented and its performance under the influence of various factors is investigated and compared with other signal processing techniques. The performance of the MRANC is then evaluated by processing simulated and in vivo SEP data. It is found that the MRANC gives a significant improvement in the SNR of the SEP.


Ligand-Directed Signaling at the Delta Opioid Receptor.
Delta opioid receptors (δORs) regulate a number of physiological functions, and agonists for this receptor are being pursued for the treatment of mood disorders, chronic pain, and migraine. A major challenge to the development of these compounds is that, like many G-protein coupled receptors (GPCRs), agonists at the δOR can induce very different signaling and receptor trafficking events. This concept, known as ligand-directed signaling, functional selectivity, or biased agonism, can result in different agonists producing highly distinct behavioral consequences. In this chapter, we highlight the in vitro and in vivo evidence for ligand-directed signaling and trafficking at the δOR. A number of biological implications of agonist-directed signaling at the δOR have been demonstrated. Importantly, ligand-specific effects can impact both acute behavioral effects of delta agonists, as well as the long-term adaptations induced by chronic drug treatment. A better understanding of the specific signaling cascades that regulate these differential behavioral effects would help to guide rational drug design, ultimately resulting in δOR agonists with fewer adverse effects.


Recombinant human erythropoietin (rHuEPO): more than just the correction of uremic anemia.
Hematopoiesis is controlled by numerous interdependent humoral and endocrine factors. Erythropoietin (EPO), a hydrophobic sialoglycoproteic hormone, plays a crucial role in the regulation of hematopoiesis, and induces proliferation, maturation and differentiation of the erythroid cell line precursors. Thanks to recombinant DNA techniques, different recombinant hormones can now be produced at low cost and in large amounts. This has led to greater understanding of the pathophysiological factors regulating hematopoiesis. This in turn, hasprompted the search for new therapeutic approaches. EPO might also be used to treat patients with different types of anemia: uremics, newborns, patients with anemia from cancer or myeloproliferative disease, thalassemia, bone marrow transplants, chronic infectious diseases. Besides erythroid cells, EPO affects other blood cell lines, such as myeloid cells, lymphocytes and megakaryocytes. It can also enhance polymorphonuclear cell phagocytosis and reduce macrophage activation, thus modulating the inflammatory process. Hematopoietic and endothelial cells probably have the same origin, and the discovery of eyrthropoietin receptors also on mesangial, myocardial and smooth muscle cells has prompted research into the non-erythropoietic function of the hormone. EPO has an important, direct, hemodynamic and vasoactive effect, which does not depend only on an increase in hematocrit and viscosity. Moreover, EPO and its receptors have been found in the brain, suggesting a role in preventing neuronal death. Finally, the recently discovered interaction between EPO and vascular endothelial growth factor (VEGF), and the ability of EPO to stimulate endothelial cell mitosis and motility may be of importance in neovascularization and wound healing.


The acute effects of hemorrhagic shock on cerebral blood flow, brain tissue oxygen tension, and spreading depolarization following penetrating ballistic-like brain injury.
Traumatic brain injury (TBI) often occurs in conjunction with additional trauma, resulting in secondary complications, such as hypotension as a result of blood loss. This study investigated the combined effects of penetrating ballistic-like brain injury (PBBI) and hemorrhagic shock (HS) on physiological parameters, including acute changes in regional cerebral blood flow (rCBF), brain tissue oxygen tension (P(bt)O₂), and cortical spreading depolarizations (CSDs). All recordings were initiated before injury (PBBI/HS/both) and maintained for 2.5 h. Results showed that PBBI alone and combined PBBI and HS produced a sustained impairment of ipsilateral rCBF that decreased by 70% from baseline (p<0.05). Significant and sustained reductions in P(bt)O₂ (50% baseline; p<0.05) were also observed in the injured hemisphere of the animals subjected to both PBBI and HS (PBBI+HS). In contrast, PBBI alone produced smaller, more transient reductions in P(bt)O₂ levels. The lower limit of cerebral autoregulation was significantly higher in the PBBI+HS group (p<0.05, compared to HS alone). Critically, combined injury resulted in twice the number of spontaneous CSDs as in PBBI alone (p<0.05). It also lowered the propagation speed of CSD and the threshold of CSD occurrence [induced CSD at higher mean arterial pressure (MAP)]. However, rCBF and P(bt)O₂ were not responsive to the depolarizations. Our data suggest that PBBI together with HS causes persistent impairment of CBF and brain tissue oxygen tension, increasing the probability of CSDs that likely contribute to secondary neuropathology and compromise neurological recovery.


[The morphogenesis of tick-borne encephalitis in light of the new data on virus replication].
The analysis of the RNA virus spread of tick encephalitis in the course of infection has been performed. The virus RNA is detectable first, (as early as one day after the infection) in the lymph nodes. Later it is retained in the cells of T-dependent areas. Viral RNA is also the first to be detected in the vascular structures and ventricular system of the brain. The correlation between the time of the viral RNA replication and specific initial damage in the lymphoid tissue and central nervous system is established. The question is raised on the role of the lymphocyte recirculation in the spread of the virus in the body.


Nontraumatic myositis ossificans in healthy individuals.
Myositis ossificans has been subclassified into three categories: traumatic, progressive, or those cases associated with neuromuscular and chronic disease. Four cases of myositis ossificans occurred in otherwise healthy individuals without any history of trauma. These four patients illustrate a fourth and distinct subclassification of the disease.


Escitalopram in the treatment of depressed elderly patients.
Management of depression in elderly patients presents a significant medical challenge, and there is a need for further clinical trials. The authors examined the efficacy and tolerability of escitalopram and fluoxetine versus placebo in the treatment of elderly patients with major depressive disorder (MDD). This was an 8-week, randomized, double-blind comparison of the efficacy and tolerability of escitalopram (10 mg/day) and fluoxetine (20 mg/day), to placebo in elderly patients with MDD. The prospectively defined primary efficacy parameter was the change from baseline in mean Montgomery-Asberg Depression Rating Scale (MADRS) total score at endpoint, using last observation carried forward. The intent-to-treat set comprised 517 patients; the escitalopram group included 173 patients; fluoxetine, 164 patients; and placebo, 180 patients. Mean age was 75 years, with a range of 65 to 93. Formally, this was a "failed study" (i.e., neither active treatment was superior to placebo), and the efficacy results should, therefore, be interpreted with caution. On the basis of the primary efficacy parameter, fluoxetine showed significantly lower efficacy than both escitalopram and placebo, which were not significantly different from each other. Rates of withdrawal because of adverse events/lack of efficacy were: placebo (2.8%/4.4%, respectively), escitalopram (9.8%/1.7%, respectively), and fluoxetine (12.2%/1.8%, respectively). No single adverse event occurred at an incidence > or =10% in escitalopram-treated patients. Both escitalopram and fluoxetine were well tolerated by elderly patients with MDD. Neither demonstrated superior efficacy on primary endpoint versus placebo.


Photo-patternable titanium doped organic-inorganic hybrid gate dielectric in organic thin film transistors.
Solution processable and photo-patternable titanium doped organic-inorganic hybrid material (MDT hybrimer) was prepared by simple sol-gel reaction for the gate dielectrics in organic thin film transistors (OTFTs). The MDT hybrimer is a typical nanocomposite which is fabricated via UV crosslinking of the nano-sized organo-oligosiloxanes. The photo-patternability of the MDT thin films was investigated using the UV light. The surface and electrical properties of MDT thin film were also investigated. The pentacene-based OTFT with MDT gate dielectrics was fabricated by using the top contact geometry. It is found that the OTFT with the MDT gate dielectrics showed a small hysteresis and good performance. The filed-effect mobility, threshold voltage, subthreshold slope and on/off current ratio of OTFT with MDT gate dielectric were 0.66 cm2V(-1)s(-1), -14 V, 1.6 Vdec.(-1), and 3 x 10(6), respectively.


Extremely refractory Kawasaki disease with disseminated intravascular coagulation.
Disseminated intravascular coagulation is a rare complication of Kawasaki disease and appears in <0.1% of Kawasaki disease patients. We report a case of refractory Kawasaki disease complicated with disseminated intravascular coagulation and giant coronary aneurysm. A 5-month-old boy presented with Kawasaki disease with coagulopathy. Although the coagulopathy improved after fresh-frozen plasma and antithrombin-III administration, the fever persisted despite two rounds of intravenous immunoglobulin, along with intravenous methylprednisolone pulse therapy and infliximab administration. Despite all efforts to treatment, the patient had giant coronary aneurysms and died suddenly.


The impact of economic conditions on the disablement process: A Markov transition approach using SHARE data.
A growing number of studies underline the relationship between socioeconomic status and health at older ages. Following that literature, we explore the impact of economic conditions on changes in functional health overtime. Frailty, a state of physiological instability, has been identified in the public health literature as a candidate for disability prevention but received little attention from health economists. Using SHARE panel data, respondents aged 50 and over from ten European countries were categorised as robust, frail and dependent. The determinants of health states' changes between two interviews were analysed using multinomial Probit models accounting for potential sample attrition. A particular focus was made on initial socioeconomic status, proxied by three alternative measures. Concentration indices were computed for key transition probabilities. Across Europe, poorer and less educated elders were substantially more likely to experience health degradations and also less likely to experience health improvements. The economic gradient for the recovery from frailty was steeper than that of frailty onset, but remained lower than that of dependency onset. The existing social programs in favour of deprived and dependent elders could be widened to those diagnosed as frail to reduce the onset of dependency and economic inequalities in health at older ages.


Quadruplex formation by both G-rich and C-rich DNA strands of the C9orf72 (GGGGCC)8•(GGCCCC)8 repeat: effect of CpG methylation.
Unusual DNA/RNA structures of the C9orf72 repeat may participate in repeat expansions or pathogenesis of amyotrophic lateral sclerosis and frontotemporal dementia. Expanded repeats are CpG methylated with unknown consequences. Typically, quadruplex structures form by G-rich but not complementary C-rich strands. Using CD, UV and electrophoresis, we characterized the structures formed by (GGGGCC)8 and (GGCCCC)8 strands with and without 5-methylcytosine (5mCpG) or 5-hydroxymethylcytosine (5hmCpG) methylation. All strands formed heterogenous mixtures of structures, with features of quadruplexes (at pH 7.5, in K(+), Na(+) or Li(+)), but no feature typical of i-motifs. C-rich strands formed quadruplexes, likely stabilized by G•C•G•C-tetrads and C•C•C•C-tetrads. Unlike G•G•G•G-tetrads, some G•C•G•C-tetrad conformations do not require the N7-Guanine position, hence C9orf72 quadruplexes still formed when N7-deazaGuanine replace all Guanines. 5mCpG and 5hmCpG increased and decreased the thermal stability of these structures. hnRNPK, through band-shift analysis, bound C-rich but not G-rich strands, with a binding preference of unmethylated > 5hmCpG > 5mCpG, where methylated DNA-protein complexes were retained in the wells, distinct from unmethylated complexes. Our findings suggest that for C-rich sequences interspersed with G-residues, one must consider quadruplex formation and that methylation of quadruplexes may affect epigenetic processes.


The discovery of novel human androgen receptor antagonist chemotypes using a combined pharmacophore screening procedure.
Unraveling the mechanisms involved in castration- and therapy-resistant prostate cancer has led to a renewed interest in androgen receptor (AR)-targeted therapeutics. Anti-androgens that block the activity of the AR therefore remain a valid therapeutic option. However, they must be more effective than, or display a distinct mechanism of action or binding mode from those of bicalutamide and hydroxyflutamide, which are currently in clinical use. For that reason, the second-generation anti-androgen MDV3100 was developed. MDV3100, however, shares its 4-cyano-3-(trifluoromethyl)phenyl group with bicalutamide and hydroxyflutamide required for binding to the AR. In this work, we used a combined strategy to find new antagonist structures distinct from the 4-cyano-3-(trifluoromethyl)phenyl group to avoid cross-resistance for these compounds and to find structures without agonist activity on mutant ARs (AR W741C and AR T877A). We found two novel chemotypes with AR-antagonistic activity (IC(50): 3-6 μM) by virtual screening and confirmed their biological activity in an androgen-responsive reporter assay. The design of our computational approach was validated by the observation of strongly decreased or absence of agonistic activity on the two mutant ARs. Further structural derivatization to optimize the potency of these compounds can render these chemotypes into very promising, alternative AR antagonists for prostate cancer therapy.


Effects of anti-schistosomal chemotherapy on immune responses, protection and immunity. I. Changes in cellular and humoral responses.
The cellular and humoral immune responses of CF1 and C57BL/6 mice with schistosomiasis mansoni were evaluated before and after chemotherapeutic cure of their infections by praziquantel. Mice were infected for either 10 or 20 weeks prior to treatment and followed until 10 weeks after treatment. Peripheral blood eosinophilia, without concomitant general leukocytosis, was observed within 3 days of treatment and persisted for up to 4 weeks. By 6 and 10 weeks after treatment schistosomal-associated hepatosplenomegaly had greatly decreased. Delayed-type hypersensitivity to a soluble adult worm extract (SWAP) was modulated over 20 weeks of infection, and in C57BL/6 mice this modulation was alleviated by cure. In parallel studies of pulmonary egg granuloma formation, granuloma modulation was not effectively reversed. Antibodies against egg (SEA), cercarial (CAP) and adult worm (SWAP) extracts generally decreased by 10 weeks after chemotherapy of mice that were previously infected for 10 weeks. Mice infected for 20 weeks and then treated, generated increased levels of antibodies to SWAP and CAP by 10 weeks after treatment. Immunoglobulin isotypic analyses largely reflected the results of total antibody studies. These data demonstrate that the duration of infection prior to treatment is a determining factor in subsequent expression of immune reactivity, and provide the immunological background for experiments on resistance following chemotherapy of experimental murine schistosomiasis mansoni.


Correlations between slow-rate repetitive nerve stimulation and characteristics associated with amyotrophic lateral sclerosis in Chinese patients.
[Purpose] To clarify the features associated with decrements in compound muscle action potentials (CMAP) during slow-rate repetitive nerve stimulation (RNS) of muscles involved in amyotrophic lateral sclerosis (ALS) in mainland China. [Subjects and Methods] A retrospective study of decremental responses to slow-rate RNS was performed to compare patients with ALS to those with myasthenia gravis (MG). [Results] A significant decrement (>5%) was observed in at least one muscle in 54% of ALS patients. The trapezius muscle was the most commonly affected (67%). In the ALS group, the CMAP amplitude evoked by the first stimulus was negatively correlated with the CMAP decrement in ulnar but not accessory nerves. Additionally, a positive decrement was associated with disease progression but not gender, age at onset, disease duration, region of onset, ALSFRS-R scores, or ALS diagnostic subgroup in ALS. Furthermore, the incidence of positive decrements and the decremental percentages were significantly higher in myasthenia gravis (MG) than in ALS. [Conclusions] The lower CMAP amplitude by the first RNS stimulus was more likely to induce a positive decrement in the ulnar nerve in ALS patients. The positive decremental responses to RNS observed in ALS indicate the faster progress of the disease, which is helpful for evaluating prognoses.


Low-value clinical practices in adult traumatic brain injury: an umbrella review protocol.
Traumatic brain injury (TBI) leads to 50 000 deaths, 85 000 disabilities and costs $60 billion each year in the USA. Despite numerous interventions and treatment options, the outcomes of TBI have improved little over the last three decades. In a previous scoping review and expert consultation survey, we identified 13 potentially low-value clinical practices in acute TBI. The objective of this umbrella review is to synthesise the evidence on potentially low-value clinical practices in the care of acute TBI. Using umbrella review methodology, we will search Cochrane Central Register of Controlled Trials, Embase, Epistemonikos, International Prospective Register of Systematic Reviews (PROSPERO) and PubMed to identify systematic reviews evaluating the effect of potential intrahospital low-value practices using tailored population, intervention, comparator, outcome and study design questions based on the results of a previous scoping review. We will present data on the methodological quality of these reviews (Assessing the Methodological Quality of Systematic Reviews-2), reported effect sizes and strength of evidence (Grading of Recommendations, Assessment, Development and Evaluation). Ethics approval is not required as original data will not be collected. Knowledge users from five healthcare quality organisations and clinical associations are involved in the design and conduct of the study. Results will be disseminated in a peer-reviewed journal, at international scientific meetings and to clinical, healthcare quality and patient-partner associations. This work will support the development of metrics to measure the use of low-value practices, inform policy makers on potential targets for deimplementation and in the long term reduce the use of low-value clinical practices in acute TBI care. CRD42019132428.


Site-directed mutagenesis of the distal basic cluster of pancreatic bile salt-dependent lipase.
Previous studies have postulated the presence of two bile salt-binding sites regulating the activity of the pancreatic bile salt-dependent lipase. One of these sites, located in an N-terminal basic cluster, has been identified as the specific bile salt-binding site. Interaction of primary bile salts with this proximal site induces the formation of a micellar binding site from a pre-existing nonspecific or pre-micellar bile salt-binding site. Here we have investigated the functional significance of another basic cluster comprised of amino acid residues Arg(423), Lys(429), Arg(454), Arg(458), and Lys(462), distal from the catalytic site. For this purpose these residues were mutagenized in Ile or Ala residues. The mutagenized enzyme lost activity on both soluble and emulsified substrates in the presence of bile salts. However, in the absence of bile salts, the mutagenized enzyme displayed the same activity on soluble substrate as the wild-type recombinant enzyme. Consequently, the distal basic cluster may represent the nonspecific (or pre-micellar) bile salt-binding site susceptible to accommodate primary and secondary bile salts. According to the literature, tyrosine residue(s) should participate in this site. Therefore, two tyrosine residues, Tyr(427) and Tyr(453), associated with the distal basic cluster were also mutagenized. Each tyrosine substitution to serine did not inhibit the enzyme activity on soluble substrate, independently of the presence of primary or secondary bile salts. However, the enzyme activity on cholesteryl oleate solubilized in primary bile salt micelles was decreased by mutations substantiating that these residues are part of the nonspecific bile salt-binding site.


New insights into mechanisms of growth and beta-carotene production in Blakeslea trispora.
Blakeslea trispora (Mucorales) has economic importance because of its ability to produce large amounts of beta-carotene. To shed light on the actual point of induction and to shorten the following production process, germination and growth of its two mating types, (-) and (+), were observed separately, and the mating point was investigated in lab scale experiments. The (-) mating type showed much faster germination than the (+) type on solid medium and in Erlenmeyer flasks. However, after a first period, the (-) mating type grew clearly slower than the (+) type. In addition, the (-) type branched more vividly than the (+) type. A ratio of 30:1 of (-) and (+) type at an age of 20 h was found to achieve highest beta-carotene yields. Our results provide a comprehensive overview of Blakeslea trispora growth and its product synthesis.


Iatrogenic Transient Complete Heart Block in a Preexisting LBBB.
Catheter induced cardiac arrhythmia is a well-known complication encountered during pulmonary artery or cardiac catheterization. Injury to the cardiac conducting system often involves the right bundle branch which in a patient with preexisting left bundle branch block can lead to fatal arrhythmia including asystole. Such a complication during central venous cannulation is rare as it usually does not enter the heart. The guide wire or the cannula itself can cause such an injury during central venous cannulation. The length of the guide wire, its rigidity, and lack of set guidelines for its insertion make it theoretically more prone to cause such an injury. We report a case of LBBB that went into transient complete heart block following guide wire insertion during a central venous cannulation procedure.


A challenging twist in pulmonary renal syndrome.
Case. We report a rare case of hydralazine-induced anti-neutrophil cytoplasmic antibody-associated vasculitis. A 75-year-old African American woman with history of high blood pressure on hydralazine for 3 years presented with acute onset of shortness of breath and hemoptysis. Lab workup revealed a severe normocytic anemia and a serum creatinine of 5.09 mg/dL (baseline 0.9). Bronchoscopy demonstrated active pulmonary hemorrhage. A urine sample revealed red cell casts and a renal biopsy demonstrated pauci-immune, focally necrotizing glomerulonephritis with small crescents consistent with possible anti-neutrophil cytoplasmic antibody-positive renal vasculitis. Serologies showed high-titer MPO-ANCA and high-titer anti-histone antibodies. She was treated with intravenous steroids and subsequently with immunosuppression after cessation of hydralazine. The patient was subsequently discharged from hospital after a rapid clinical improvement. Conclusion. Hydralazine-induced anti-neutrophil cytoplasmic antibody-positive renal vasculitis is a rare adverse effect and can present as a severe vasculitic syndrome with multiple organ involvement. Features of this association include the presence of high titer of anti-myeloperoxidase anti-neutrophil cytoplasmic antibody with multiantigenicity, positive anti-histone antibodies, and the lack of immunoglobulin and complement deposition. Prompt cessation of hydralazine may be sufficient to reverse disease activity but immunosuppression may be needed.


Gigantic enlargement of the thymus gland.
True massive thymic hyperplasia is a very rare entity, characterized by an increase in the size and weight of the thymus gland, without an apparent cause. Surgery has been required in patients with severe respiratory distress. We present an idiopathic true massive thymic hyperplasia in a 5-month-old boy.


Cost-revenue analysis in the surgical treatment of the obstructed defecation syndrome.
The obstructed defecation syndrome is a frequent condition in the female population. Rectocele and rectal intussusception may cause symptoms of obstructed defecation. The aim of this study is to carry out an economic cost-revenue analysis comparing the rectocele and the rectal intussusception surgical techniques using a double-transanal, circular stapler (Stapled Trans-Anal Rectal Resection - STARR) with other techniques used to repair the same defects. The analysis involved the systematic calculation of the costs incurred during hospitalisation. The revenue estimate was obtained according to the rate quantification of the Diagnosis Related Group (DRG) associated with each hospitalisation. Our analysis confirmed that the global expenditure for the STARR technique amounts to 3,579.09 Euro as against 5,401.15 Euro for rectocele abdominal repair and 3,469.32 Euro for perineal repair. The intussusception repair cost according to Delorme's procedure amounts to 5,877.41Euro as against 3,579.09 Euro for the STARR technique. The revenue analysis revealed a substantial gain for the Health Authority as regards the treatment of rectocele and rectal intussusception for obstructed defecation syndrome. The highest revenue, 6,168. 52 Euro, was obtained with intussusception repair with STARR as compared to Delorme's procedure which presented revenue amounting to 2,359.04. Lower revenues are recorded if the STARR technique is intended for rectocele repair; in this case the revenue amounts to 1,778.12 Euro as against 869.67 Euro and 1,887.89 Euro for abdominal and perineal repair, respectively.


Lipid-induced colonic hypersensitivity in the irritable bowel syndrome: the role of bowel habit, sex, and psychologic factors.
Duodenal lipid infusion increases colonic hypersensitivity in irritable bowel syndrome (IBS). Whether this is affected by bowel habit, psychologic factors, or sex is unknown. We included 61 patients with IBS (50 women, 11 men), 25 with diarrhea-predominant IBS, 17 with constipation-predominant IBS, 19 with alternating-type IBS, and 20 healthy controls (15 women, 5 men). A colonic distension trial was performed with a barostat before and after a 1-hour duodenal lipid infusion (3 kcal/min). Colonic thresholds, colonic tone, and the viscerosomatic referral pattern were assessed and compared between groups. Patients also completed the Hospital Anxiety and Depression scale. The reduction in colonic pressure thresholds after vs before duodenal lipids was greater in patients than in controls for discomfort (P = .006) and pain (P < .0001). An increased viscerosomatic referral area for pain and discomfort during colonic distensions after vs before duodenal lipids was observed in patients but not in controls. The response was similar in IBS subgroups based on the predominant bowel habit, in patients with vs without anxiety and/or depression, and in women and men with IBS. The colonic tone response during lipid infusion was similar in IBS patients and controls, and in the different IBS subgroups. IBS patients show increased colonic sensitivity and altered viscerosomatic referral pattern after duodenal lipids. This response is largely unaffected by the predominant bowel habit, psychologic factors, or sex, but seems to be related to IBS per se.


Abdominal hysterectomy: a new approach for young gynaecologists.
Abdominal hysterectomy is performed for various gynaecological conditions. During operative procedures haemorrhage caused by trauma or slipping and retraction of uterine or ovarian artery has been a cause of great concern to gynaecologists specially in absence of adequate blood transfusion facilities. To overcome this problem, a new approach has been developed--ligation of the uterine artery and ovarian artery (in case of salpingo-oophorectomy) before going for conventional hysterectomy procedures. Abdominal hysterectomy was performed in 500 cases during last 7 years. Traumatic injury to left uterine vessels was seen in 2 cases (0.4%). No other injury to ovarian vessels, right uterine vessels, ureter and bladder was observed. Hence it is concluded that ligation of uterine artery, prior to conventional abdominal hysterectomy procedures, is an extremely safe procedure reducing the risk of haemorrhage and thus allowing young gynaecologists to perform this operation with less fear and more confidence.


Dopamine activity changes in cerebral cortex in the course of experimental acute pancreatitis.
Dopamine (DA) is biogenic amine that in the central (CNS) and peripheral nervous system plays an important role as a neurotransmitter and neuromediator. Dopamine neurones in CNS are responsible for regulating motor and emotional processes, higher psychological activities and hormone secretion. Acute pancreatitis (AP) is a general disease condition caused by pancreas extrasecretory cell damage which leads to self-digestion. One of its results is encephalopathy in consequence of shock symptoms, intravascular clotting, brain tissue ischaemia etc. The study has aimed at analysis of changes in the level of DA in rats' cerebral cortex in the course of experimental AP. The experiment was carried out on 102 rats. They were divided into three groups: Z - healthy (12), K - control (30), OP - experimental (60). The AP was induced in OP group according to Heinkel and Aho method. In K group the needle was only inserted into the common bile-pancreatic duct to analyse the effects of mechanical damage. The activity of pancreatic enzymes was determined to estimate the intensity of pancreatitis. The dopamine level was measured in rats << brain samples and to do so, the Brodie method modified by Chang was used. The statistical analysis was carried out. The greatest changes of DA level during experimental AP were noticed during the first 24 hours of experiment and they were in statistically significant way correlated with the level of lipase and amylase in blood serum. Peak DA concentration was detected between 6th and 12th hour of experiment.


Synthesis of novel polymerizable molecules bearing bisphosphonate.
In recent years, bisphosphonate chemistry has undergone an exponential growth due to the potential applications of these compounds in medicine and nanobiomaterial research. In this paper we describe the synthesis methods of different families of methacrylic monomers bearing a bisphosphonate with varying lengths of the chain, PEG linkers and more or less hydrolysable functions such as ester, carbamate or amide.


Development of an enzyme-linked immunosorbent assay-based test with a cocktail of nucleocapsid and spike proteins for detection of severe acute respiratory syndrome-associated coronavirus-specific antibody.
A new enzyme-linked immunosorbent assay (ELISA)-based immunoglobulin G (IgG)-plus-IgM antibody detection test for severe acute respiratory syndrome (SARS) has been developed by using a cocktail of four recombinant polypeptides as the antigen. These recombinant fragments were designed as parts of two different structural proteins from SARS-associated coronavirus (SARS-CoV). One recombinant polypeptide, S251-683, was designed as part of the spike glycoprotein, and the other three polypeptides comprised almost the whole nucleocapsid protein, avoiding the last 25 C-terminal amino acids. Immunization with a cocktail of these four polypeptides yielded a specific polyclonal antibody that is able to recognize SARS-CoV-infected cells by an immunofluorescence assay. This polypeptide cocktail was also used to set up an ELISA-based IgG-plus-IgM antibody detection test, which showed 99% specificity and 90% sensitivity upon evaluation using sera from 100 healthy negative controls and 20 SARS patients. Separate immunoreactivity assays with each recombinant polypeptide demonstrated that a combination of N and S protein fragments was more suitable than the individual peptides for developing a serological assay for SARS-CoV.


Nonadjacent Wireless Electrotherapy for Tissue Repair by a 3D-Printed Bioresorbable Fully Soft Triboelectric Nanogenerator.
Electrotherapy is a promising tissue repair technique. However, electrotherapy devices are frequently complex and must be placed adjacent to injured tissue, thereby limiting their clinical application. Here, we propose a general strategy to facilitate tissue repair by modulating endogenous electric fields with nonadjacent (approximately 44 mm) wireless electrotherapy through a 3D-printed entirely soft and bioresorbable triboelectric nanogenerator based stimulator, without any electrical accessories, which has biomimetic mechanical properties similar to those of soft tissue. In addition, the feasibility of using the stimulator to construct an electrical double layer with tissue for nonadjacent wireless electrotherapy was demonstrated by skin and muscle injury models. The treated groups showed significantly improved tissue repair compared with the control group. In conclusion, we developed a promising electrotherapy strategy and may inspire next-generation electrotherapy for tissue repair.


Disaccharide recognition by binuclear copper(II) complexes.
The sugar recognition by binuclear copper(II) complexes in solution is strongly dependent on secondary interactions and cannot be predicted from the intermetallic Cu...Cu distance.


[Seroprevalence of Helicobacter pylori infection and anti-CagA positivity in the county Szabolcs-Szatmár-Bereg].
The authors studied the seroprevalence of Helicobacter pylori infection and the risk factors for infection, among adult volunteers from Szabolcs-Szatmár-Bereg county, East Hungary in year 2000. Sera were collected from 756 adults (328 males, 428 females, m/f = 1.5:2; mean age 42.4 yrs.; range 18-69 yrs.). Anti-Helicobacter pylori IgG and anti-CagA IgG antibodies were identified serologically using a sensitive ELISA technique. A questionnaire was completed to obtain necessary informations. The overall rate of seropositivity was 58.6% (45.2% in those aged 18-29 and 69.6% in those aged 50-59). Seropositivity was significantly higher in rural population than in urban area (p < 0.001), sharing a bed (p < 0.001), if parents were manual workers (p < 0.001), between keepers of cat (p < 0.005). The authors found a significant inverse correlation between Helicobacter pylori infection and educational level (p < 0.001), income (p < 0.005), absence of water supply and sanitation (childhood: p < 0.001, adulthood: p < 0.05). There were no significant differences in Helicobacter pylori infection related to gender, subject's occupation, smoking and drinking habits, gastric symptoms, family history of ulcer or gastric cancer. 67.5% of Helicobacter pylori positives were anti-CagA positives too. Helicobacter pylori positivity is higher than in developed countries, and than in the more developed county Vas.


Functional Genomics for the Identification of Modulators of Platelet-Dependent Thrombus Formation.
Despite the absence of the genome in platelets, transcription profiling provides important insights into platelet function and can help clarify abnormalities in platelet disorders. The Bloodomics Consortium performed whole-genome expression analysis comparing in vitro-differentiated megakaryocytes (MKs) with in vitro-differentiated erythroblasts and different blood cell types. This allowed the identification of genes with upregulated expression in MKs compared with all other cell lineages, among the receptors BAMBI, LRRC32, ESAM, and DCBLD2. In a later correlative analysis of genome-wide platelet RNA expression with interindividual human platelet reactivity, LLRFIP and COMMD7 were additionally identified. A functional genomics approach using morpholino-based silencing in zebrafish identified various roles for all of these selected genes in thrombus formation. In this review, we summarize the role of the six identified genes in zebrafish and discuss how they correlate with subsequently performed mouse experiments.


Absolute rate constants of alkene addition reactions of a fluorinated radical in water.
Absolute rate constants of *R(f)SO(3)(-) radical addition to a series of water-soluble alkenes containing ionic, carboxylate substituents were measured by laser flash photolysis experiments in water. The observed rate constants were all considerably larger than those of structurally similar analogues in a nonpolar organic solvent, with rate factors of 3-9-fold being observed. It is concluded that such rate enhancements derive at least in part from stabilization of the polar transition state for addition of the electrophilic fluorinated radical to alkenes by the polar solvent water.


Investigation of the possible involvement of IgE anti-salicyloyl antibodies in patients with urticaria.
19 aspirin-sensitive and 14 non-aspirin-sensitive patients with chronic urticaria were tested for the presence of specific anti-salicyloyl-IgE antibodies by prick testing, RAST and in vitro histamine release using an aspirin-polylysine conjugate. Polylysine succinate served as a control. Negative results were obtained in all cases with the exception of 1 patient who gave a positive prick test response. However, this patient reacted to the control conjugate as well as aspirin polylysine. Skin prick test responses to the battery of environmental allergens revealed that the majority (90%) of the aspirin-sensitive patients were non-atopic. The findings suggest that the clinical symptoms and signs in patients with chronic urticaria associated with aspirin sensitivity are not mediated by specific IgE antibodies.


A comprehensive approach to stress in primary care.
Stress is a precipitant of many physical and emotional problems that patients present to their primary care physicians. Hans Selye's classic General Adaptation Syndrome is described as it relates to the body's response to stress. Techniques for assessing stress are presented. Stress management techniques that primary care physicians can employ in the office include prescribing relaxation and exercise, cognitive restructuring, dealing with negative thoughts, and setting appropriate goals. Severe or prolonged stress warrants consideration of a diagnosis of a mental disorder, use of a psychotropic medications, or referral to a psychiatrist or other mental health provider.


[Effect of furfural on the respiratory system].
Fifty-one workers of Butadien Plant, exposed to furfurol , had their respiratory system examined. Questionnaire studies demonstrated chronic bronchitis in 23.5% of subjects. Spirometric tests do not show subjective complaints. This seems to be related to hypercortisolemia, as experiments on animals indicate that furfurol inhalations increase corticosteroids concentrations in blood serum.


[The bacteriological and serological prevalence of Campylobacter spp. and Yersinia enterocolitica in fattening pig herds in Lower Saxony].
This article presents the results of a study on the occurrence of two bacteria that cause zoonoses, Campylobacter spp. and Yersinia enterocolitica. The study was carried out in 30 fattening herds in Lower Saxony, Germany, in 2004 and compares the results of bacteriological and serological methods of detection. Bacteriological findings of Campylobacter spp. in the faeces indicated that 69.7% of the fattening pigs were positive, but 81.2% tested positive serologically. All herds tested here were both bacteriologically and serologically positive for Campylobacter spp. Furthermore, only 8.4% tested positive for Yersinia enterocolitica in the faecal samples, but 66.8% of the animals were serologically positive for that bacterium. While bacteriological examination did not detect Yersinia enterocolitica in 56.7% of the herds tested, serological testing showed that only 16.7% of the units were without reacting animals. The great difference between the results of bacteriological and serological testing, especially in the case of Yersinia enterocolitica, can be explained by the intermittent intestinal excretion and predominance of this bacterium in the animals' tonsils. Low faecal excretion is also the reason for the low detection rate of 3.4% of Yersinia enterocolitica in the environmental samples, while that of Campylobacter spp. was 33.3%. These results indicate that the environment plays only a secondary role in the distribution of Yersinia enterocolitica in pig herds.


Mikulicz disease of a minor salivary gland.
The third recorded instance of Mikulicz disease of a minor salivary gland is described; this is the first case in which a surgical specimen, in addition to the biopsy specimen, was obtained for microscopic examination. A brief description of the disease and its treatment is also presented.


Physical effects of non-cavitated explorer probing on enamel smooth-surface carious lesions.
To assess the physical effects of explorer probing on non-cavitated smooth-surface enamel carious lesions. Extracted teeth with white enamel decalcification (ICDAS 2) were used. Indentations were made in decalcified and non-decalcified regions with a #23 explorer using "scratch" or "poke" application and 100g, 300g or 600g force. Specimens were imaged with SEM and polarizing light microscopy. Indentation widths were measured digitally. Two-way ANOVA with pair-wise comparisons was used to assess interactions of force and enamel condition (normal or carious) on indentation groove width. No or minimal effect was seen on normal enamel surface morphology. For the decalcified regions, defects were seen in SEM and polarizing light images. Findings included a smear layer, open clefts, lateral debris and micro-fractures. Two-way ANOVA for effects of force and enamel quality on mean groove width showed statistically significant differences for both variables for all teeth tested.


Helping older adults meet nutritional challenges.
Prevention of premature chronic diseases is an important component of healthy aging. Nutrition education can help to reduce the risk of premature chronic diseases in some older adults. Home delivered meals and congregate dining services assist vulnerable elderly persons by providing opportunities for nutritional and social support. Screening and assessment tools identify factors affecting nutritional health and can also provide specific directions for planning, implementation, and evaluation of tailored interventions. Dietitians and allied health professionals are well positioned to assist a heterogeneous population of older adults in securing nutritional adequacy.


[The Effect of Naldemedine Tosylate on the Postoperative Course of Robot-Assisted Radical Cystectomy].
Radical cystectomy is an invasive procedure frequently followed by postoperative complications. Although the protocol of enhanced recovery after surgery (ERAS) is used in the postoperative course, several components of the ERAS protocol may increase the workload of medical workers. In this study, we added naldemedine tosylate only to routine postoperative management instead of using the ERAS protocol and evaluated the effect on the postoperative course of robot-assisted radical cystectomy (RARC). We retrospectively investigated 58 patients who underwent RARC from May 2015 to February 2022 at our hospital and evaluated the postoperative complications, such as ileus and urinary tract infections, and, length of hospital stay (LOS). We used naldemedine tosylate for the patients who underwent RARC after November 2019. As a result, naldemedine tosylate reduced 26.8% of postoperative complications within 30 days after the operation (p=0.041) and shortened LOS 8 days (p=0.018). Naldemesine tosylate improved the postoperative course of RARC.


Induction of active (REM) sleep and motor inhibition by hypocretin in the nucleus pontis oralis of the cat.
Hypocretin (orexin)-containing neurons in the hypothalamus, which have been implicated in the pathology of narcolepsy, project to nuclei in the brain stem reticular formation that are involved in the control of the behavioral states of sleep and wakefulness. Among these nuclei is the nucleus pontis oralis (NPO). Consequently, the present study was undertaken to determine if the hypocretinergic system provides regulatory input to neurons in the NPO with respect to the generation of the states of sleep and wakefulness. Accordingly, polygraphic recordings and behavioral observations were obtained before and after hypocretin-1 and -2 were microinjected into the NPO in chronic, unanesthetized cats. Microinjections of either hypocretin-1 or -2 elicited, with a short latency, a state of active [rapid eye movement (REM)] sleep that appeared identical to naturally occurring active sleep. The percentage of time spent in active sleep was significantly increased. Dissociated states, which are characterized by the presence of muscle atonia without one or more of the electrophysiological correlates of active sleep, also arose following the injection. The effect of juxtacellular application of hypocretin-1 on the electrical activity of intracellularly recorded NPO neurons was then examined in the anesthetized cat. In this preparation, the application of hypocretin-1 resulted in the depolarization of NPO neurons, an increase in the frequency of their discharge and an increase in their excitability. These latter data represent the first description of the in vivo action of hypocretin on intracellularly recorded neuronal activity and provide evidence that the active sleep-inducing effects of hypocretin are due to a direct excitatory action on NPO neurons. Therefore we suggest that hypocretinergic processes in the NPO may play a role in the generation of active sleep, particularly muscle atonia and therefore are likely to be involved in the pathology of narcolepsy.


Osteocrin attenuates inflammation, oxidative stress, apoptosis, and cardiac dysfunction in doxorubicin-induced cardiotoxicity.
Inflammation, oxidative stress, and apoptosis contribute to the evolution of doxorubicin (DOX)-induced cardiotoxicity. Osteocrin (OSTN) is a novel secretory peptide mainly derived from the bone and skeletal muscle, and plays critical roles in regulating bone growth and physical endurance. Inspiringly, OSTN was also reported to be abundant in the myocardium that functioned as a therapeutic agent against cardiac rupture and congestive heart failure in mice after myocardial infarction. Herein, we investigated the role and potential mechanism of OSTN in DOX-induced cardiotoxicity. Cardiac-restrict OSTN overexpression was performed by the intravenous injection of a cardiotropic AAV9 vector, and subsequently the mice received 15 mg/kg DOX injection (i.p., once) to induce acute cardiac injury. Besides, H9C2 cell lines were used to assess the possible role of OSTN in vitro by incubating with recombinant human OSTN or small interfering RNA against Ostn (siOstn). To clarify the involvement of protein kinase G (PKG), KT5823 and siPkg were used in vivo and in vitro. Mice were also administrated intraperitoneally with 5 mg/kg DOX weekly for consecutive 3 weeks at a cumulative dose of 15 mg/kg to mimic the cardiotoxic effects upon chronic DOX exposure. OSTN treatment notably attenuated, whereas OSTN silence exacerbated inflammation, oxidative stress, and cardiomyocyte apoptosis in DOX-treated H9C2 cells. Besides, cardiac-restrict OSTN-overexpressed mice showed an alleviated cardiac injury and malfunction upon DOX injection. Mechanistically, we found that OSTN activated PKG, while PKG inhibition abrogated the beneficial effect of OSTN in vivo and in vitro. As expected, OSTN overexpression also improved cardiac function and survival rate in mice after chronic DOX treatment. OSTN protects against DOX-elicited inflammation, oxidative stress, apoptosis, and cardiac dysfunction via activating PKG, and cardiac gene therapy with OSTN provides a novel therapeutic strategy against DOX-induced cardiotoxicity.


Threshing efficiency as an incentive for rapid domestication of emmer wheat.
The harvesting method of wild and cultivated cereals has long been recognized as an important factor in the emergence of domesticated non-shattering ear genotypes. This study aimed to quantify the effects of spike brittleness and threshability on threshing time and efficiency in emmer wheat, and to evaluate the implications of post-harvest processes on domestication of cereals in the Near East. A diverse collection of tetraploid wheat genotypes, consisting of Triticum turgidum ssp. dicoccoides - the wild progenitor of domesticated wheat - traditional landraces, modern cultivars (T. turgidum ssp. durum) and 150 recombinant (wild × modern) inbred lines, was used in replicated controlled threshing experiments to quantify the effects of spike brittleness and threshability on threshing time and efficiency. The transition from a brittle hulled wild phenotype to non-brittle hulled phenotype (landraces) was associated with an approx. 30 % reduction in threshing time, whereas the transition from the latter to non-brittle free-threshing cultivars was associated with an approx. 85 % reduction in threshing time. Similar trends were obtained with groups of recombinant inbred lines showing extreme phenotypes of brittleness and threshability. In tetraploid wheat, both non-brittle spike and free-threshing are labour-saving traits that increase the efficiency of post-harvest processing, which could have been an incentive for rapid domestication of the Near Eastern cereals, thus refuting the recently proposed hypothesis regarding extra labour associated with the domesticated phenotype (non-brittle spike) and its presumed role in extending the domestication episode time frame.


Complete Genome Sequence of Helicobacter pylori Strain ATCC 43504, a Type Strain That Can Infect Gerbils.
Helicobacter pylori ATCC 43504 is a type strain isolated from a gastric cancer patient in Australia and is commonly used for pathogenicity studies. In this study, we report the complete genome sequence of a strain that can infect gerbils. The data provide a basis for future H. pylori research.


Three new earthworm species of the tokioensis-group in the genus Amynthas (Oligochaeta: Megascolecidae) from Guangxi Province, China.
Three new species of the genus Amynthas are described from Guangxi Province, China. They are named A. dissimilis sp. nov., A. anteporus sp. nov. and A. marsupiformis sp. nov. All of them have two pairs of spermathecal pores in 6/7-7/8, and belong to the tokioensis-group. Their morphological characteristics are compared to similar species in tokioensis-group from China and other Asian countries. In addition, the mitochondrial COI and 12S-tRNA-Val-16S sequence of three new species were determined, then pairwise distances between species were calculated. Both morphological and molecular evidences could easily distinguish the new species from earthworms previously reported in the tokioensis-group.


[Sodium, potassium, calcium and magnesium metabolism in patients with allergic-infectious bronchial asthma].
A total of 126 patients with infectious -- allergic bronchial asthma were studied, 56 males and 67 females, aged from 16 to 58 (average age 38,5), with a duration of the disease from 1 to 20 years, distributed into four groups: group 1 -- 33 patients with light stage of the disease, group II - 36 patients with moderately severe stage of the disease, group III -- severe stage of the disease (32 patients), group IV -- 25 patients with moderately severe and severe stage, treated with Ketotifen. Disorder of electrolyte metabolism was found in all patient groups with infectious-allergic bronchial asthma. Hyperpotassemia , hypermagnesiemia , hypernatremia and hypocalcemia were established with statistical significance. Various mechanisms participate in the pathogenesis-of those disorders, the allergic reaction being at the root. The electrolytic alterations depend on the stage and severity of the bronchial asthma. The electrolyte metabolism was favourably influenced after the treatment in all patient groups and pronounced - in the patients from group IV. That requires a proper drug treatment with a consideration given to the disturbed electrolytic balance.


Synthesis and functions of well-defined polymer-drug conjugates as efficient nanocarriers for intravesical chemotherapy of bladder cancer(a).
Novel poly(ethylene glycol) and poly(N-(2-hydroxypropyl)methacrylamide) block copolymer (PEG-b-PHPMA) with well-defined composition was synthesized by RAFT polymerization. Folate and doxorubicin (DOX) were quantitatively introduced into the copolymer. The influences of folate content and pH value on folate receptor (FR) mediated cell endocytosis and pH-responsive DOX release were studied. It has been demonstrated that minimum folate content is needed for the enrichment of hydrophobic folate on the hydrophilic part of polymer conjugates. The cytotoxicity of targetable polymer drug conjugates was much higher than that of non-targetable ones and free DOX. It could be concluded that the folate plays a significant role in targeting and internalization of the conjugates against bladder cancer cells.


[First experiences with the incontinence operation Kaufman III (implantation of a silicongel prothesis covered with polyurethanfoam) (author's transl)].
For operative treatment of urinary incontinence after TUR of the prostate, radical prostatectomy and meningocele operation the silicongel prothesis described by Kaufman was implanted. By compression of the bulbus urethrae a sealing effect was achieved. The pressure of the detrusor opens the urethra enough to enable urination. Seven patients were operated. The results directly after the operations were: three very good, two good and two bad. We achieved very good results by implantation of the prothesis "large" -in the case of the two bad operative results we used the "medium" size prothesis. By filling these protheses with 5 ml liquid they proved to be leaky. One of these was operatively removed and replaced by the size "large". This patient later developed a urethra stricture in the implantation region with overflow bladder after having been continent. By internal urethrotomy this condition was restored; except for minor dripping after miction the patient was continent. The prothesis of a direct postoperative continent patient had to be filled. This led to and infection with the development of fistula. The prothesis had to be removed. A further patient who sat on a hard object developed a lesion of the prothesis with resulting incontinence. At least six months after the operations four patients remained continent and three incontinent.


Chronic plasma exchange in systemic lupus erythematosus nephritis.
Thirty-nine patients with systemic lupus erythematosus (SLE) and diffuse proliferative glomerulonephritis have been enrolled in a multi-centre randomised controlled prospective study of chronic 4L plasma exchange therapy performed every three to four weeks. In the patients randomised to the pheresis (P) group and who received either albumin or plasma as replacement, there was a difference of 33 per cent better renal function at this time in the study. This difference did not achieve a significance with a p value of less than 0.05. However, the 30 patients randomised into the P group to receive albumin replacement did demonstrate a 50 per cent difference from the C group which was significant at a p value of less than 0.045. This also correlated with a statistically significant reduction in immune complex titres in the P versus the C groups. Chronic 4L plasma exchange with albumin replacement may be a useful therapeutic adjunct in patients with SLE and diffuse proliferative glomerulonephritis.


Optimal diagnosis of the skin cancer using a hybrid deep neural network and grasshopper optimization algorithm.
When skin cells divide abnormally, it can cause a tumor or abnormal lymph fluid or blood. The masses appear benign and malignant, with the benign being limited to one area and not spreading, but some can spread throughout the body through the body's lymphatic system. Skin cancer is easier to diagnose than other cancers because its symptoms can be seen with the naked eye. This makes us to provide an artificial intelligence-based methodology to diagnose this cancer with higher accuracy. This article proposes a new non-destructive testing method based on the AlexNet and Extreme Learning Machine network to provide better results of the diagnosis. The method is then optimized based on a new improved version of the Grasshopper optimization algorithm (GOA). Simulation of the proposed method is then compared with some different state-of-the-art methods and the results showed that the proposed method with 98% accuracy and 93% sensitivity has the highest efficiency.


NPY Y1 receptor like immunoreactivity exists in a subpopulation of beta-endorphin immunoreactive nerve cells in the arcuate nucleus: a double immunolabelling analysis in the rat.
Double immunolabelling immunohistochemistry in the arcuate nucleus of the rat demonstrates that neuropeptide Y (NPY) Y1 receptor like immunoreactivity is strongly present in a subpopulation of beta-endorphin immunoreactive nerve cell bodies, while the small NPY immunoreactive nerve cell bodies located medially lack NPY Y1 receptor like immunoreactivity. The NPY Y1 like immunoreactive nerve cell bodies lie in an arcuate area rich in NPY immunoreactive nerve terminals forming an uniform plexus. It is postulated that NPY Y1 receptors in beta-endorphin neurons may mediate some actions of NPY on motivational processes and pain control as well as on hypophyseal hormone secretion, involving at the least in part a regulation of the tubero-infundibular DA neurons.


Effectiveness of resistance exercise in functional fitness in women with primary Sjögren's syndrome: randomized clinical trial.
Objective: The purpose of this study was to analyse the effectiveness of resistance exercise in functional fitness in women with primary Sjögren's syndrome (pSS).Method: This is a randomized controlled clinical trial with 51 volunteers: 26 allocated to the exercise group (GEX) and 25 to the control group. The GEX underwent a supervised resistance-training programme for 16 weeks, with two sessions per week. The outcomes measured were: functional capacity (FC), by the Fullerton Functional Fitness Test; Daily Motor Activity Index (DMAI), evaluated by an actigraph; disease activity, by the ESSDAI; and quality of life, by the 36-item Short Form Health Survey (SF-36). The evaluations were performed by a blind evaluator at baseline (TØ) and after 16 weeks (T16wk).Results: In the GEX, all FC parameters demonstrated improvement, except for the upper limb flexibility test (p = 0.866): upper and lower limb strength, flexibility, aerobic capacity, and agility (all p < 0.01). A similar situation occurred in the SF-36, where all domains demonstrated improvement except for the emotional aspect (p = 0.710): FC, physical aspects limitation, general health status, vitality, social aspects, and mental health (all p < 0.01). The DMAI (p = 0.2) and EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) (p = 0.284) did not change. No significant improvement was observed in the control group.Conclusion: The supervised resistance exercise programme did not worsen the DMAI or disease activity, demonstrating the safety of the intervention, and was effective in improving FC and quality of life in women with pSS.Registry identifier (clinical trials.gov): NCT03130062.


Anatomy and physiology of the lower urinary tract.
The lower urinary tract has two main functions: storage and periodic elimination of urine. These functions are regulated by a complex neural control system located in the brain and spinal cord. This control system performs like a simple switching circuit to maintain a reciprocal relation between the reservoir (bladder) and outlet (urethra and urethral sphincter) components of the urinary tract. Spinal cord injury disrupts voluntary control and the normal reflex pathways that coordinate bladder and sphincter function. Studies in animals indicate that recovery of bladder function after spinal injury is dependent on the reorganization of reflex pathways in both the peripheral and the central nervous system. Part of this reorganization may be influenced by neural-target organ interactions that are mediated by neurotrophic factors released by the peripheral organs.


In-Phase and Quadrature Analysis for Amplitude and Frequency Modulations Due to Vibrations on a Surface-Acoustic-Wave Resonator.
Surface-acoustic-wave resonators (SAWRs) have found widespread usage in various modern consumer radio frequency (RF) communications electronics, such as cellular phones, wireless devices, GPS devices, frequency control, and sensing applications. External mechanical vibrations modify an SAWR relative dimensions and the substrate's elastic properties, which alter the device's acoustic wave propagation velocity and ultimately cause the SAWR RF response to change. Detecting vibrations are desirable for dynamic strain or vibration sensing applications, whereas external mechanical excitations can result in spurious signals which compromise SAW-based filters and oscillators used in RF communication, frequency control, and sensors targeting measurands such as temperature and pressure. Therefore, understanding and characterizing the SAWR's response to external vibration is relevant for establishing device operation, and assisting in device design and packaging to either mitigate the impact of vibrations for RF communications and frequency control or enhance the SAWR response for sensor applications. This paper presents an in-phase and quadrature demodulation technique (I-Q technique) to detect, quantify, and analyze the effect of externally induced mechanical vibrations on an SAWR. The I-Q technique disclosed reveals that the mechanical vibrations cause both frequency and amplitude modulations of the SAWR RF response, which can be separated by this technique. Furthermore, the procedure also allows the direct measurement of vibration frequencies and vibration magnitude. The technique, measured results, and analysis established here provide a better understanding of the impact of external mechanical vibrations on an SAWR response, which is important in contemporary communications, frequency control, and sensing applications.


High variation and strong phylogeographic pattern among cpDNA haplotypes in Taxus wallichiana (Taxaceae) in China and North Vietnam.
We studied the phylogeography of Chinese yew (Taxus wallichiana), a tree species distributed over most of southern China and adjacent regions. A total of 1235 individuals from 50 populations from China and North Vietnam were analysed for chloroplast DNA variation using polymerase chain reaction-restriction fragment length polymorphism of the trnL-F intron-spacer region. A total of 19 different haplotypes were distinguished. We found a very high level of population differentiation and a strong phylogeographic pattern, suggesting low levels of recurrent gene flow among populations. Haplotype differentiation was most marked along the boundary between the Sino-Himalayan and Sino-Japanese Forest floristic subkingdoms, with only one haplotype being shared among these two subkingdoms. The Malesian and Sino-Himalayan Forest subkingdoms had five and 10 haplotypes, respectively, while the relatively large Sino-Japanese Forest subkingdom had only eight. The strong geography-haplotype correlation persisted at the regional floristic level, with most regions possessing a unique set of haplotypes, except for the central China region. Strong landscape effects were observed in the Hengduan and Dabashan mountains, where steep mountains and valleys might have been natural dispersal barriers. The molecular phylogenetic data, together with the geographic distribution of the haplotypes, suggest the existence of several localized refugia during the last glaciation from which the present-day distribution may be derived. The pattern of haplotype distribution across China and North Vietnam corresponded well with the current taxonomic delineation of the three intraspecific varieties of T. wallichiana.


Massive postglacial gene flow between European white oaks uncovered genes underlying species barriers.
Oaks are dominant forest tree species widely distributed across the Northern Hemisphere, where they constitute natural resources of economic, ecological, social and historical value. Hybridisation and adaptive introgression have long been thought to be major drivers of their ecological success. Therefore, the maintenance of species barriers remains a key question, given the extent of interspecific gene flow. In this study, we made use of the tremendous genetic variation among four European white oak species (31 million single nucleotide polymorphisms (SNPs)) to infer the evolutionary history of these species, study patterns of genetic differentiation and identify reproductive barriers. We first analysed the ecological and historical relationships among these species and inferred a long-term strict isolation followed by a recent and extensive postglacial contact using approximate Bayesian computation. Assuming this demographic scenario, we then performed backward simulations to generate the expected distributions of differentiation under neutrality to scan their genomes for reproductive barriers. We finally identified important intrinsic and ecological functions driving the reproductive isolation. We discussed the importance of identifying the genetic basis for the ecological preferences between these oak species and its implications for the renewal of European forests under global warming.


Bromperidol radioimmunoassay: human plasma levels.
A sensitive radioimmunoassay (RIA) procedure was developed to assay for bromperidol levels in human plasma after therapeutic drug administration. The antisera used in the RIA procedure was generated in rabbits against a haloperidol-bovine serum albumin conjugate. Tritiated haloperidol was used as the radioligand in the assay. A single ether extraction of alkalinized plasma was used to separate bromperidol from its more polar metabolites and to reduce assay variability encountered with a direct plasma assay. The lower limit of detection was approximately 0.5 ng/mL of parent drug in plasma. The assay exhibited within- and between-assay variabilities of approximately 9 and 14%, respectively. A 103-106% recovery of bromperidol from quality control plasma samples was observed over the concentration range of 1-150 ng/mL. A correlation coefficient of 0.9999 with respect to measured versus expected bromperidol content in the quality control plasma samples was exhibited. Cross-reactivity characteristics of the antisera indicated that dehydrobromperidol could significantly interfere (approximately 25% cross-reactivity) with the RIA procedure. However, biotransformation studies have not suggested this compound as a metabolite of bromperidol. Predose ( Cmin ) plasma levels of bromperidol in schizophrenic patients maintained on drug therapy are also reported.


Effect of Hypoxia on Self-Renewal Capacity and Differentiation in Human Tendon-Derived Stem Cells.
BACKGROUND Hypoxic conditions play roles in functioning of human tendon-derived stem cells (hTSCs). The goal of this study was to investigate the effect of various hypoxic conditions in self-renewal capacity and differentiation of TSCs. MATERIAL AND METHODS hTSCs was obtain from supraspinatus tendon donors. Colony formation and cell proliferation assay were used to assess the self-renewal of hTSCs. qRT-PCT and Western blot analysis were used to examine stemness and multi-differentiation potential of hTSCs. RESULTS We found that culturing at 5% O2 is more beneficial for the self-renewal of hTSCs than the other 3 culture conditions, with larger colony size and numbers. The proliferation of hTSCs in 5%, 10%, and 20% O2 cultures increased after seeding. The number of cells in the 5% O2 condition was higher than that in other culture; however, self-renewal capacity of hTSCs in 0.5% O2 was inhibited. The expression levels of stem cell markers, including NS, Nanog, Oct-4, and SSEA-4, were highest in 0.5% O2 culture. Furthermore, hTSCs cultured in 20% O2 exhibited significantly higher expression of the 3 markers (PPAR-γ, Sox-9, and Runx-2). CONCLUSIONS Hypoxic condition of culture encouraged self-renewal capacity of hTSCs, but inhibited their multi-differentiation potential, compared to normoxic condition of culture. Moreover, excessively low oxygen concentration impaired the capacity of hTSCs.


Comparative in vitro acitvity of chloramphenicol and thiamphenicol on common aerobic and anaerobic gram-negative bacilli(Salmonella and Shigella excluded).
The antibacterial activity of thiamphenicol was compared to that of chloramphenicol against 313 strains of gram-negative bacilli isolated from various clinical specimens. These two antiboitics were equally active against the 106 isolates of Haemophilus MIC equals 0.1 minus 1.56 mu g/ml) and against 40 strains of Bacteroides fragilis (almost all strains being inhibited by 12.5 mug/ml of the two drugs). In contrast, when compared with chloramphenicol, 2-16 times as much of thiamphenicol was required to inhibit Enterobacteriacae, making prediction of the susceptibility of these strains to thiamphenicol on the basis of chloramphenicol testing alone likely to be hazardous. Disc diffusion test using 30-mug discs and 12 mm as cut-off point was a reliable technique to determine susceptibility of bacteria either to chloramphenicol or thiamphenicol. When thiamphenicol discs of greater potency (50 mug) were employed, many strains exhibited wide zones of inhibition although most of them were resistant by the agar dilution method (MIC is greater than 12.5 mug/ml). This practice is not advisable for testing organisms isolated outside of the urinary tract.