Drug resistance profiles of new- and previously treated patients with pulmonary tuberculosis in Ibadan, Nigeria.
Information on TB drug resistance profiles and its' associated risk factors are scarce in Nigeria despite the large burden of disease in the country. The study was designed to report drug resistance profiles of new- and previously treated patients with pulmonary tuberculosis (TB) in Ibadan, Nigeria. Sputum from consenting pulmonary TB patients were collected and cultured for Mycobacterium tuberculosis (Mtb) at the TB laboratory of the University College Hospital, Ibadan, Nigeria using standard method. Mtb were stored and sent for drug susceptibility testing against first and second-line anti-TB drugs at the MRC Unit, The Gambia and at the Institute of Tropical Medicine, Antwerp, Belgium using BACTEC MGIT 960 and proportion method on solid medium respectively. Of 238 Mtb collected, 124 (52.1%) were viable, 102 (59.65%) non-viable while 12 (7.02%) were contaminated. About half (58.87%) of the Mtb were from previously treated patients, 40 (32.26%) were from new patients while treatment history of 1.1 (8.87%) were unknown. Forty-seven (37.90%) of the 124 Mtb. tested were multidrug resistant (MDR) out of which, 40 (85.10%) were from previously treated patients.. HIV prevalence was 8.69%. Of the 17 MDR-TB from previously treated cases tested for second-line drugs, four (23.53%) were resistant to fluoroquinolones or injectable agents, 13 (76.47%) were susceptible while none was resistant to both of these classes of drugs. MDR-TB in Ibadan already demonstrates resistance to second line anti-TB drugs hence management of MDR-TB patients should be strengthened to prevent emergence of extensively drug-resistant TB (XDR-TB).


Uptake and biotransformation of 2,2',4,4'-tetrabromodiphenyl ether (BDE-47) in four marine microalgae species.
Hydroxylated- and methoxylated- polybrominated diphenyl ethers (OH-PBDEs and MeO-PBDEs) are more toxic than PBDEs and occur widely in the marine environment, and yet their origins remain controversial. In this study, four species of microalgae (Isochrysis galbana, Prorocentrum minimum, Skeletonema grethae and Thalassiosira pseudonana) were exposed to BDE-47, which is synthetic and is the predominant congener of PBDEs in the environment. By chemical analysis after incubation of 2 to 6 days, the efficiency of uptake of BDE-47 and, more importantly, the potential of undergoing biotransformation to form OH-PBDEs and MeO-PBDEs by the microalgae were investigated. Growth rates of these axenic microalgae were not affected upon exposure to environmentally relevant concentrations (0.2-20 μg BDE-47 L-1), and accumulation ranged from 0.772 ± 0.092 μg BDE-47 g-1 lipid to 215 ± 54 μg BDE-47 g-1 lipid within 2 days. Debromination of BDE-47 and formation of BDE-28 occurred in all microalgae species (0.01 to 0.87%), but biotransformation to OH-PBDEs was only found in I. galbana upon exposure to extremely high concentration. The results of this study showed that biotransformation of microalgae species is unlikely an explanation for the OH-PBDEs and MeO-PBDEs found in the marine environment.


Novel phases and superconductivity of tin sulfide compounds.
Tin sulfides, Sn x S y , are an important class of materials that are actively investigated as novel photovoltaic and water splitting materials. A first-principles evolutionary crystal structure search is performed with the goal of constructing the complete phase diagram of Sn x S y and discovering new phases as well as new compounds of varying stoichiometry at ambient conditions and pressures up to 100 GPa. The ambient phase of SnS2 with P 3 ¯ m 1 symmetry remains stable up to 28 GPa. Another ambient phase, SnS, experiences a series of phase transformations including α-SnS to β-SnS at 9 GPa, followed by β-SnS to γ-SnS at 40 GPa. γ-SnS is a new high-pressure metallic phase with P m 3 ¯ m space group symmetry stable up to 100 GPa, which becomes a superconductor with a maximum T c = 9.74 K at 40 GPa. Another new metallic compound, Sn3S4 with I 4 ¯ 3 d space group symmetry, is predicted to be stable at pressures above 15 GPa, which also becomes a superconductor with relatively high T c = 21.9 K at 30 GPa.


Diabetes Alters Diurnal Rhythm of Electroretinogram in db/db Mice.
Diabetic retinopathy (DR) is the most common complications of diabetes and a leading cause of blindness in the United States. The retinal neuronal changes precede the vascular dysfunction observed in DR. The electroretinogram (ERG) determines the electrical activity of retinal neural and non-neuronal cells. The retinal ERG amplitude is reduced gradually on the progression of DR to a more severe form. Circadian rhythms play an important role in the physiological function of the body. While ERG is known to exhibit a diurnal rhythm, it is not known whether a progressive increase in the duration of diabetes affects the physiological rhythm of retinal ERG. To study this, we determined the ERG rhythm of db/db mice, an animal model of type 2 diabetes at 2, 4, and 6 months of diabetes under a regular light-dark cycle and constant dark. Our studies demonstrate that the diurnal rhythm of ERG amplitude for retinal a-wave and b-wave was altered in diabetes. The implicit time was increased in db/db mice while the oscillatory potential was reduced. Moreover, there was a progressive decline in an intrinsic rhythm of ERG upon an increase in the duration of diabetes. In conclusion, our studies provide novel insights into the pathogenic mechanism of DR by showing an altered circadian rhythm of the ERG.


The Effects of the COVID-19/SARS-CoV-2 Pandemic Outbreak on Otolaryngology Activity in Italy.
The coronavirus disease 2019 (COVID-19) pandemic during the first months of 2020 is causing profound changes in worldwide health care systems, resulting in a major reduction of surgical interventions and routine non-urgent outpatient diagnostic procedures. The lockdown due to the COVID-19 pandemic in Italy, one of the most affected countries in Europe, is having severe effects on the otolaryngology medical and surgical activities. The main changes are represented by the postponement of outpatient visits and scheduled surgery, while the only guaranteed service is reserved to diagnostics and surgery for oncology and urgent patients. In these cases, given the sites of action typical of the otolaryngology practice, physicians and nurses are exposed to a high risk of contagion through virus aerosol transmission. Furthermore, as the current measures of lockdown continue, it will be difficult to perform scheduled and new diagnostic assessments, medical treatments and surgical procedures in a timely manner favoring the risk of diagnostic and therapeutic delays with severe impact on patients' health.


Adult Burkitt leukemia and lymphoma.
The World Health Organization Classification of Lymphoid Neoplasms identifies Burkitt lymphoma/leukemia as a highly aggressive mature B-cell neoplasm consisting of endemic, sporadic, and immunodeficiency-associated variants. These subtypes share many morphologic and immunophenotypic features, but differences exist in their clinical and geographic presentations. All of these subtypes possess chromosomal rearrangements of the c-myc oncogene, the genetic hallmark of Burkitt lymphoma that contributes to lymphomagenesis through alterations in cell cycle regulation, cellular differentiation, apoptosis, cellular adhesion, and metabolism. Brief-duration, high-intensity chemotherapy regimens containing aggressive central nervous system prophylaxis have had remarkable success in the treatment of this disease, with complete remission rates of 75% to 90% and overall survivals reaching 50% to 70% in adults. Although Burkitt lymphoma cells are extremely chemosensitive, biologically targeted therapies should be developed because current treatment options are suboptimal for patients with poor prognostic features or in the setting of relapsed disease.


Mineralocorticoid-receptor signalling in vascular smooth muscle.
Human data suggest that eplerenone and spironolactone lowers blood pressure by mechanisms independent of the distal tubule. Now, a novel inducible conditional knockout model of the mineralocorticoid receptor (MR) in vascular smooth muscle cells (VSMCs) brings out understanding further.


Biosynthesis and oligosaccharide processing of human Tamm-Horsfall glycoprotein permanently expressed in HeLa cells.
Human Tamm-Horsfall glycoprotein (T-H) is produced by renal cells of ascending limb of loop of Henle and is largely excreted in urine. N-linked glycans account for close to 30% of the weight of T-H. We studied the biosynthesis of recombinant T-H permanently expressed in HeLa cells. The conversion from the precursor (84 kDa) to the mature form (97 kDa) mainly depends on the processing of glycans from the high-mannose to polyantennary type. The conversion from precursor to mature form is very slow and the glycan structure of precursor appears to be that of a glycoprotein not yet processed by Golgi alpha 1,2 mannosidase. Since T-H has a very high number of disulfide bridges (more than 50 cysteine residues/mol) one may infer that the rate limiting step for the precursor export out of ER is the formation of a correct set of disulfide bonds. Mature T-H isolated from HeLa cells retained one N-linked chain with the high-mannose structure similarly to urinary T-H. This result indicates that the occurrence of one unprocessed high-mannose chain in mature T-H is host-cell independent and very likely related to the T-H primary structure.


High-Rota Synthesis of Single-/Double-/Multi-Unit-Cell Ti-HSZ Nanosheets To Catalyze Epoxidation of Large Cycloalkenes Efficiently.
This work first reports high-efficiency epoxidation of large cycloalkenes (carbon number ≥ 7) with tert-butyl hydroperoxide (TBHP) over single-/double-/multi-unit-cell nanosheet-constructed hierarchical zeolite, which is synthesized by one-step hydrothermal crystallization using piperidine as the structure-directing agent of the microporous structure. The excellent catalytic property of the material is ascribed to its unique structural characteristic. Plenty of surface titanols or silanols on the surface of MWW nanosheets are beneficial for the formation of transition-state intermediates; a large number of intercrystalline mesopores in the shell of the material not only facilitate the formation of the intermediate for TBHP but also have nearly no hindrance for the diffusion and mass transfer of bulky cycloalkene to the above intermediates; the 12-MR side cups penetrating into the crystals from the external surface are exposed as much as possible to the reaction system because of the single-/double-/multi-unit-cell MWW nanosheet, serving as the primary reaction space for the epoxidation of bulky cyclic alkene and oxidants and providing enough space for the transition state of Ti-OOtBu and bulky cycloalkane. Moreover, an efficient calcination-free catalytic reaction-regeneration method is developed to overcome the challenge for the recyclability of microporous Ti-zeolite in the catalytic epoxidation of bulky cycloalkenes.


The impact of gravidity, symptomatology and timing of infection on placental malaria.
Placental malaria is associated with increased risk of adverse perinatal outcomes. While primigravidity has been reported as a risk factor for placental malaria, little is known regarding the relationship between gravidity, symptomatology and timing of Plasmodium falciparum infection and the development of placental malaria. The aim of this study was to investigate the relationship between the development of placental malaria and gravidity, timing of infection, and presence of symptoms. This is a secondary analysis of data from a double-blind randomized control trial of intermittent preventive therapy during pregnancy in Uganda. Women were enrolled from 12 to 20 weeks gestation and followed through delivery. Exposure to malaria parasites was defined as symptomatic (fever with positive blood smear) or asymptomatic (based on molecular detection of parasitaemia done routinely every 4 weeks). The primary outcome was placental malaria diagnosed by histopathology, placental blood smear, and/or placental blood loop-mediated isothermal amplification. Multivariate analyses were performed using logistic regression models. Subgroup analysis was performed based on the presence of symptomatic malaria, gravidity, and timing of infection. Of the 228 patients with documented maternal infection with malaria parasites during pregnancy, 101 (44.3%) had placental malaria. Primigravidity was strongly associated with placental malaria (aOR 8.90, 95% CI 4.34-18.2, p < 0.001), and each episode of malaria was associated with over a twofold increase in placental malaria (aOR 2.35, 95% CI 1.69-3.26, p < 0.001). Among multigravid women, the odds of placental malaria increased by 14% with each advancing week of gestation at first documented infection (aOR 1.14, 95% CI 1.02-1.27, p = 0.02). When stratified by the presence of symptoms, primigravidity was only associated with placental malaria in asymptomatic women, who had a 12-fold increase in the odds of placental malaria (aOR 12.19, 95% CI 5.23-28.43, p < 0.001). Total number of P. falciparum infections in pregnancy is a significant predictor of placental malaria. The importance of timing of infection on the development of placental malaria varies based on gravidity. In primigravidas, earlier asymptomatic infections were more frequently identified in those with placental malaria, whereas in multigravidas, parasitaemias detected later in gestation were associated with placental malaria. Earlier initiation of an effective intermittent preventive therapy may help to prevent placental malaria and improve birth outcomes, particularly in primigravid women.


750 nm 1.5 W frequency-doubled semiconductor disk laser with a 44 nm tuning range.
We demonstrate 1.5 W of output power at the wavelength of 750 nm by intracavity frequency doubling a wafer-fused semiconductor disk laser diode-pumped at 980 nm. An optical-to-optical efficiency of 8.3% was achieved using a bismuth borate crystal. The wavelength of the doubled emission could be tuned from 720 to 764 nm with an intracavity birefringent plate. The beam quality parameter M2 of the laser output was measured to be below 1.5 at all pump powers. The laser is a promising tool for biomedical applications that can take advantage of the large penetration depth of light in tissue in the 700-800 nm spectral range.


[Diagnostic image (290). A woman with painful finger joints and swelling].
A 38-year-old woman with chronic pain of and swelling located at the proximal interphalangeal (PIP) finger joints suffered from 'knuckle pads' or 'Garrod's fatty pads'.


High-Flow, Heated, Humidified Air Via Nasal Cannula Treats CPAP-Intolerant Children With Obstructive Sleep Apnea.
Continuous positive airway pressure (CPAP) is effective but challenging for children with obstructive sleep apnea (OSA). High-flow air via open nasal cannula (HFNC) as treatment in children remains controversial. We report the efficacy of HFNC in children with OSA and CPAP intolerance, a titration protocol, and a discussion of potential mechanisms. Patients aged 1 to 18 years with OSA (defined by obstructive apnea-hypopnea index [OAHI] greater than 1 event/h) and CPAP intolerance were enrolled. Routine polysomnography data obtained during 1 night wearing HFNC was compared with diagnostic data by Wilcoxon rank-sum test. Ten school-age subjects (representing all patients attempting HFNC at our institution to date) with varied medical conditions, moderate to severe OSA, and CPAP intolerance wore HFNC from 10 to 50 L/min of room air with oxygen supplementation if needed (room air alone for 6 of the 10). HFNC reduced median OAHI from 11.1 events/h (interquartile range 8.7-18.8 events/h) to 2.1 events/h (1.7-2.2 events/h; P = .002); increased oxyhemoglobin saturation (SpO2) mean from 91.3% (89.6% to 93.5%) to 94.9% (92.4% to 96.0%; P < .002); increased SpO2 nadir from 76.0% (67.3% to 82.3%) to 79.5% (77.2% to 86.0%; P = .032); decreased SpO2 desaturation index from 19.2 events/h (12.7-25.8 events/h) to 6.4 events/h (4.7-10.7 events/h; P = .013); and reduced heart rate from 88 bpm (86-91 bpm) to 74 bpm (67-81 bpm; P = .004). Stratified analysis of the 6 subjects with only room air via HFNC, the OAHI, obstructive hypopnea index, and mean SpO2 still demonstrated improvements (P = .031). High-flow nasal cannula reduces respiratory events, improves oxygenation, reduces heart rate, and may be effective for CPAP intolerant children with moderate to severe OSA. Our data suggest HFNC warrants further study and consideration by payers as OSA therapy.


Characterization of the biochemical properties of recombinant ribonuclease III.
An Escherichia coli double strand specific endoribonuclease, RNase III, was cloned, expressed in large amounts, and purified to homogeneity. Enzyme activity was monitored by assaying fractions for the ability to correctly process exogenous RNA containing specific RNase III cleavage sites. DEAE-Sepharose ion exchange chromatography in the presence of a linear KCl gradient (from 0.02 M to 0.75 M) demonstrated that RNase III exists as two distinct forms. One form elutes at a KCl concentration of 0.13 M and the other elutes at 0.33 M. The presence of stoichiometric amounts of the GTP-binding protein Era during purification results in the conversion of the low salt form into the high salt form. Size exclusion chromatography demonstrated that both forms exist as a dimer in solution. In order to investigate the nature of the dimer, protein cross-linking was performed and cross-linked products were detected by silver staining. The protein-protein dimer can be visualized at protein:cross-linker molar ratios as low as 1:15 within 1 minute of exposure to cross-linker in 0.1 M KCl. Upon addition of substrate RNA to the cross-linking reaction a second form of the protein-protein dimer (with a slightly smaller apparent molecular weight) becomes prominent. Induction of the new form is absolutely dependent upon the addition of substrate mRNA to the reaction mixture. We postulate that the RNase III dimer undergoes a dramatic conformational change upon recognition of RNA which we are able to trap by cross-linking.


Vaccines for the elderly need to be introduced into the immunization program in India.
The population in India over age 60 years has tripled in the past 50 years and will relentlessly increase in the near future. According to census 2011, elderly people were 8.1% of the total population, and the projections for population over 60 years over the next 4 censuses are 133 million (2021) expanding to 301 million (2051). In developing countries, the elderly have suffered from both communicable and non-communicable diseases. Moreover, advancing age is associated with decreased immunity along with physiological changes, and poor health leads to increased risk of infectious diseases. Infections such as pneumococcal, influenza, tetanus, and zoster are more common among elderly population. These infections are major causes of morbidity and mortality among the elderly and are responsible for a large number of deaths and hospitalizations. Communicable diseases like influenza and pneumonia are the fifth leading cause of death among elderly persons. A study reported the incidence of nosocomial infections in geriatric patients in India to be ~20%. Pseudomonas aeruginosa was the most common microbe associated with Urinary Tract Infection, while Staphylococcus aureus was frequently observed in cases of pneumonia among hospitalized elderly population. In India, because of many reasons, preventive care for elderly persons is often neglected. Among the many infections to which the elderly are prone, some can be prevented by administration of appropriate vaccines. Vaccination of the elderly is one of the most effective means of preventing disease, disability, and death from infectious diseases.


Protein glycation and aggregation inhibitory potency of biomolecules from black gram milled by-product.
Persistent hyperglycaemia causes increased advanced glycation end products (AGEs), which contribute to the pathogenesis of diabetic complication. Therefore, effect of black gram milled by-product (BGBP) extract on inhibition of AGE formation in a bovine serum albumin (BSA)/glucose system was investigated. BGBP extract had a total polyphenol content of 82 mg GAE g-1 and flavonoid content of 46 mg CE g-1 . Ferulic acid, protocatechuic acid, gallic acid, gentisic acid, isovitexin, vitexin and epicatechin were the major bioactives in the extract. BGBP extract exhibited an effective Fe2+ chelating activity. Size exclusion-high-performance liquid chromatographic studies indicated that upon BSA-AGE formation the BSA monomer content was 38%; however, in the presence of BGBP extract at 50 and 100 µg levels, the monomer content increased and it was found to be 48% and 73%, respectively. BGBP extract at 50 and 100 µg levels decreased the protein carbonyl and fructosamine contents, and quenched the fluorescence intensity of glycated BSA in a dose-dependent manner. Further, fluorescence and transmission electron microscopic studies confirmed the decrease in formation of AGEs by BGBP extract. As BGBP extract inhibited the formation of AGEs, the extract can be used as a nutraceutical or it can be incorporated into food products to obtain functional foods. © 2016 Society of Chemical Industry.


Spatial distribution of phagolysosomes is independent of the regulation of lysosome position by Rab34.
Within a cell, the regulation of organelle positioning is considered to be critical in spatio-temporal responses. The position of late endocytic organelles (named here lysosomes for simplicity) is tightly controlled and has a functional impact on processes like endocytosis, phagocytosis and autophagocytosis. The cytoplasmic distribution profile of lysosomes can be easily determined in cells where the cytoplasm/nuclear ratio in a cross-section area is high. However, determining lysosomal position in cells with lower cytoplasm/nuclear ratio, such as macrophages is more challenging. Here, we describe a method that can be efficiently and accurately used to determine the position of organelles in macrophages using confocal microscopy in two-dimensional (2D) images. Using this approach in macrophages, we confirmed previous observations in epithelial cells that both changes in cytoplasmic pH and the levels of active Rab34 induced a re-distribution of lysosomes to the cell centre or periphery. Noteworthy is that this Rab34-dependent re-distribution of lysosomes did not significantly affect the spatial distribution profile of phagolysosomes in the cytoplasm. We conclude that although Rab34 regulates both lysosomal positioning and lysosome to phagosome fusion, the latter effect is not due to the regulation of the cytoplasmic accessibility of lysosomes to phagosomes by Rab34.


Functional organization of ascending and descending connections of the cochlear nucleus of horseshoe bats.
The ascending projections of the cochlear nucleus (CN) and the sources of descending inputs to the CN were investigated in horseshoe bats (Rhinolophus rouxi) by tracing the anterograde and retrograde transport of horseradish peroxidase (HRP or WGA-HRP) injected into the CN. The tracer was iontophoretically deposited into physiologically characterized regions of the cochlear nucleus (Feng and Vater, '85). We report the course and termination of pathways arising from the anteroventral (AVCN), posteroventral (PVCN), and dorsal (DCN) cochlear nucleus. The projection fields within the auditory brainstem centers (superior olivary complex [SOC]; lateral lemniscus complex [LLC]; and inferior colliculus [IC]) and their tonotopic organization according to the frequency representations at the injection sites are described. While the projection pattern is generally in accordance with other mammals, several species-characteristic features are noted: i) the lateral superior olive (LSO) receives tonotopically organized input from both the AVCN and PVCN; ii) the CN-projections to medial nuclear groups of the SOC located between the LSO and the medial nucleus of the trapezoid body do not support previously suggested homologies; iii) the ventral nucleus of the LLC can be subdivided into two divisions with distinct input patterns from the AVCN and PVCN, respectively.


[Cytokines and the nervous system: the relationship between seizures and epilepsy].
INTRODUCTION. The immune system and the peripheral and central nervous system are in constant communication by means of messengers and signalling molecules released, such as cytokines, neuropeptides, neurohormones and neurotransmitters, among others. Seizures are defined as the transitory appearance of signs and symptoms that trigger an abnormally excessive neuronal activity in the brain. Following seizures the generation of a neuroinflammatory process has been observed to occur, with the consequent release of proinflammatory cytokines and inflammation-mediating molecules, which make the patient more prone to epilepsy. AIM. To offer evidence suggesting and supporting the role of cytokines in the appearance of seizures and in epilepsy, since these molecules have proven to have dual properties. DEVELOPMENT. The central nervous system, by means of the blood-brain barrier, restricts the flow of activated cells and inflammation mediators released from the peripheral system towards the brain parenchyma. Moreover, there is also another series of mechanisms that contributes to the 'selective and modified' immunity of the central nervous system. The purpose of all this series of events is to limit the responses of the immune system at central level, although it has been shown that in the central nervous system they are permanently under the control and regulation of the immune system. CONCLUSIONS. Cytokines in epilepsy play a dual role with pro- and anti-convulsive properties. Seizures do not induce the expression of cytokines only inside the brain, but also peripherally.


Ultrasonic assessment of fetal activity.
Modern ultrasound techniques enable dynamic studies of fetal activity in utero to be studied and quantified. Real-time B-mode scanning has become the method of choice for this purpose because of its ease of use and precision. Fetal movements can be visualized as early as in the seventh week of pregnancy and the development of the movement patterns can be followed throughout the pregnancy. Up to 16 types of movements have been described by several research groups. In early pregnancy, the finding of normal fetal movements is a good prognostic sign in cases of threatened abortion. A decrease in the movement incidence or a qualitative change of the movements are associated with poor outcome. In late pregnancy, the mean incidence of general fetal movements has been found on average to be 9 to 18 per cent of observation time. Fetal breathing movements, mainly with typical "see-saw' configurative changes of the fetal trunk, occur episodically: both long-term and short-term periodicity have been revealed. For recognition of the time incidence pattern of fetal movements or breathing, a sufficiently long observation time (80 to 100 minutes) is necessary. The incidence of fetal breathing movements increases with gestational age and breathing movements become more regular in mature fetuses. Fetal motor activity is subject to several external influences: glucose given to the mother causes an increase in the fetal breathing movement incidence; maternal hypercarbia stimulates the fetal breathing movements; alcohol administered to the mother abolishes fetal breathing; maternal smoking changes the time spacing of breathing and increases the fetal breathing rate; and exposure of the fetus to sound causes an increase in the number of movements. Real-time ultrasonography enables detection and recording of several other fetal activities: hiccups, swallowing and changes in the stomach volume, micturition, and fetal eye movements. The latter fetal activity is used together with fetal movements, fetal mouth movements and fetal heart rate for the identification of the fetal behavioural states. Quantification of fetal activity as a clinical test of fetal well-being was expected to give an alarm signal in cases of fetal hypoxia and imminent asphyxia. In general, the predictive value of a negative result (i.e., a finding of normal fetal activity) was high; the predictive value of decreased or abnormal fetal activity was found to be much less predictive of fetal compromise.(ABSTRACT TRUNCATED AT 400 WORDS)


The significance of cell-bound antigen-specific IgE in chronic urticaria.
Radioallergosorbent test (RAST) was performed on the sera obtained from chronic urticarial patients from whose leucocytes significant histamine release by mite antigen was observed. In 14 out of 19 cases investigated, no mite-antigen-specific IgE was detected in their sera by RAST, in spite of significant mite-antigen-induced histamine release from their leucocytes. The results suggest that type I reaction may be involved in chronic urticaria and the cell-bound, antigen-specific IgE may be important rather than the circulating antigen-specific IgE in this disease.


Stochastic thermodynamics under coarse graining.
A general formulation of stochastic thermodynamics is presented for open systems exchanging energy and particles with multiple reservoirs. By introducing a partition in terms of "mesostates" (e.g., sets of "microstates"), the consequence on the thermodynamic description of the system is studied in detail. When microstates within mesostates rapidly thermalize, the entire structure of the microscopic theory is recovered at the mesostate level. This is not the case when these microstates remain out of equilibrium, leading to additional contributions to the entropy balance. Some of our results are illustrated for a model of two coupled quantum dots.


Computational Calorimetry of PNIPAM Cononsolvency in Water/Methanol Mixtures.
We revisit the mechanism for cononsolvency of PNIPAM in water/methanol mixtures. Using extensive molecular dynamics simulations, we calculate the calorimetric enthalpy of the PNIPAM collapse transition and observe a unique fingerprint of PNIPAM cononsolvency which is analyzed in terms of microscopic interactions. We find that polymer hydration is the determining factor for PNIPAM collapse in the cononsolvency regime. In particular, it is shown that methanol frustrates the ability of water to form hydrogen bonds with the amide proton and therefore causes polymer collapse.


Ineffectiveness of heparin treatment in burn shock in the guinea pig.
The cardiovascular and metabolic responses during burn shock were characterized in 10 guinea pigs burned to the xyphoid process for 3 s in boiling water. This produced a burn of approximately 70% of the body surface. Their responses were compared to the values obtained at corresponding times in a group of unburned controls (n=10). The effect of Heparin treatment on burn shock was evaluated in another group (n=8) of guinea pigs burned to the xyphoid process and injected subcutaneously with 50,000 U Heparin/kg immediately after being burned. In the burned, untreated (BUT) animals, cardiac output was reduced more than 50% at 15 mins post-burn, and cardiac output remained depressed for the next 8 h. Mean arterial blood pressure was initially maintained in the BUT animals, but started to fall after 3 h. Heart rate, oxygen consumption and core temperature all decreased progressively in the BUT group. Hemoconcentration was evident in the BUT animals, and there was an elevation in the post-burn glucose and lactate levels, a decrease in pH, and no change in free fatty acids. Heparin treatment did not significantly modify 24-h survival, and the post-burn cardiovascular responses of the Heparin-treated animals were similar to those of the BUT animals. Metabolically, the Heparin-treated animals had a significant elevation in free fatty acids post-burn, but otherwise closely resembled the BUT animals.


Nasotracheal intubation--a modality in the management of acute epiglottitis in adults.
Acute epiglottitis in adults is usually treated by close observation or tracheostomy. In the last decade, this therapeutic attitude has been challenged by the impressive results obtained by nasotracheal intubation in the treatment of pediatric cases. Many authors have suggested the use of nasotracheal intubation in adults as well as in children: it would be a natural complement to close observation when airway shunting becomes advisable thus rendering tracheostomy unnecessary. Three conditions have to be met before safe nasotracheal intubation can be considered: interested anesthesiological service, supportive otolaryngological assistance, and dependable nursing care. The case of a young woman treated by close observation proceeding to nasotracheal intubation, as the sole way to secure the airway is presented.


Role of myoglobin in regulating respiration.
The 1H NMR Val E11 signal provides a unique opportunity to observe carbon monoxide (CO) inhibition of Mb in the in vivo myocardium and to assess the functional role of Mb in regulating respiration. Upon carbon monoxide infusion, the MbO2 Val E11 signal at -2.76 ppm gradually disappears, and a new signal at -2.26 ppm, corresponding to MbCO, emerges. These signals yield the intracellular partial pressure of both O2 and CO and the extent of Mb inactivation, since CO binds more tightly to Mb than O2. Although contractile function decreases slightly to a steady state level, it shows no dose dependence on pCO. Up to 80% MbCO saturation, the contractile function remains at the steady state level. Neither the PCr concentration nor the oxygen consumption rate is significantly perturbed. Above 80% MbCO saturation, the oxygen consumption rate starts to decline. The experimental observations raise provocative questions about the functional role of Mb in the cell.


Partial deletion of both the spermine synthase gene and the Pex gene in the X-linked hypophosphatemic, gyro (Gy) mouse.
Gy, along with Hyp, is a dominant mutation of the normal gene Pex causing X-linked hypophosphatemia in the mouse. Hemizygous Gy male mice, however, have greater defects in survival, bodily growth, skeletal mineralization, and neurological function than those found in heterozygous Gy females or in Hyp mice. Since the gene for spermine synthase is immediately upstream of the homologous human gene PEX, we compared the effects of the Gy and Hyp mutations on both the spermine synthase gene and the Pex gene. Barely detectable levels of spermine (< 5% of normal) with elevated levels of its precursor, spermidine, were found in organs of Gy male mice compared to normal male littermates. Neither Gy females nor Hyp male mice were significantly affected. Four missing introns of the spermine synthase gene were identified in Gy male mice, suggesting extensive gene disruption. A pseudogene for spermine synthase was also identified in the mouse genome. Pex mRNA was found in several but not all tissues studied in adult normal mice. Pex mRNA was altered in both Gy and Hyp mice. All male Hyp mice were lacking the 3' end of the Pex message, whereas all male Gy mice were deficient at the 5' end. In summary, the Gy mutation is associated with a recessively expressed mutation of the spermine synthase gene, leading to spermine deficiency, and a dominantly expressed mutation of the Pex gene, leading to hypophosphatemia. Alterations in two contiguous genes in Gy may explain the additional phenotypic abnormalities present in the Gy male mouse.


Kinase insert domain-containing receptor kinase inhibitors as anti-angiogenic agents.
A variety of data accumulated during the past 10 years indicates that vascular endothelial growth factor-mediated angiogenesis is a key process in the growth of solid tumours. Efficacious and specific modulation of that signalling event through the inhibition of the cognate tyrosine kinase kinase insert domain-containing receptor (Flk-1) has been reported. A variety of small molecule kinase-domain-containing receptor kinase inhibitors, including SU-5416, SU-6668, PTK-787, midostaurin, ZD4190 and ZD6474, have progressed to the clinical testing stage and this has allowed the direct and critical inspection of preclinical and clinical behaviour. The variety of potency, kinase selectivity and pharmacokinetic profiles offered by this group of compounds is providing important guidance for the efficacious use of these agents today and the design of second and third generation compounds for the future.


Characterization of testudine melanomacrophage linear, membrane extension processes--cablepodia--by phase and atomic force microscopy.
Melanomacrophages (MMs) are a component of an internal, pigmented cell system in liver and splenic tissues of some fishes, anurans, and reptiles. The cells have been found in centers or aggregates in sinusoids and are associated with cells capable of producing a peptide cytokine and immunoglobulins. A unique cell extension process has been observed in turtle MMs placed into cell culture, and this process has been studied by light and atomic force microscopy. These structures, referred to as cablepodia, are uniquely straight, narrow, and unbranching and appear to originate from growth cones opposite lamellipodia. Cablepodia were found to connect with other turtle MMs and fibroblasts forming cell networks. Dividing fibroblasts to which a cablepodium attached ceased cell division. The observations collectively suggest that a principal reason for aggregations of MMs in internal organs of lower vertebrates is their ability to form interconnected networks of cell processes for trapping and processing of particulate matter, cells, and infectious organisms and, possibly, for the communication of cell signals and transfer of intracellular materials.


Oxygenation and deoxygenation velocity factors of chorioallantoic capillary blood.
The oxygenation and deoxygenation rates of capillary blood of chicken embryo were measured precisely with a microphotometric reaction apparatus. The velocity factors expressed as Fcox and Fcdeox in ml O2-ml RBC-1-S-1-mmHg-1 were calculated as functions of oxygen saturation. They were similar to results previously obtained in human blood using the rapid flow apparatus. The continuous registration of the reaction with oxygen enables us to estimate the equilibrium time of blood when passing through the chorioallantoic capillary. The value obtained was almost identical to the contact time indirectly assessed from the CO reaction. The diffusing capacity of the chorioallantoic capillary plexus of the 16-day-old embryos was estimated as 7.3 x 10(-3) ml-min-1mmHg-1 by using the values of the Fcox and the equilibrium time determined here together with the values of the blood flow and hematocrit which had been obtained in the previous experiments.


Isolation of a thyroid hormone-responsive gene by immunoprecipitation of thyroid hormone receptor-DNA complexes.
Thyroid hormone (T3) receptor (TR) is a ligand-dependent transcription factor that acts through specific binding sites in the promoter region of target genes. In order to identify new genes that are regulated by T3, we used anti-TR antiserum to immunoprecipitate TR-DNA complexes from GH4 cell nuclei that had previously been treated with a restriction enzyme. Screening of the immunopurified, cloned DNA for TR binding sites by electrophoretic mobility shift assay yielded 53 positive clones. A subset of these clones was specifically immunoprecipitated with anti-TR antiserum and may therefore represent biologically significant binding sites. One of these clones, clone 122, was characterized in detail. It includes sequences highly related to the NICER long terminal repeat-like element and contains three TR binding sites as determined by DNase I footprinting. Two of the clone 122 TR binding sites are located upstream of the TATA box, and one is located downstream. The TR binding site downstream from the promoter was necessary and sufficient to confer T3-dependent regulation in transient transfection experiments. Expression of a reporter construct under the control of the clone 122 promoter region was activated by TR in the absence of ligand and returned to basal levels after T3 addition. Clone 122 sequences hybridize to at least two different mRNAs of approximately 6 and 10 kb from GH4 cells. The levels of both of these mRNAs increased upon removal of T3. Our studies suggest that specific immunoprecipitation of chromatin allows identification of binding sites and target genes for transcription factors.


Uptake of fluorine-18-fluorodeoxyglucose in sarcoidosis.
Whole-body PET scanning was performed using 18F-fluorodeoxyglucose (FDG) in two patients with hilar lymphadenopathy in whom the clinical differential diagnosis was between sarcoidosis and lymphoma. Both patients were later proven to have sarcoidosis. Uptake of 18FDG was seen in both intra- and extrathoracic lesions as well as in associated erythema nodosum. One patient underwent a repeat scan after steroid therapy where a marked decrease in hilar uptake was seen. Fluorine-18-fluorodeoxyglucose uptake is observed in lymph nodes with sarcoid involvement. Further investigation is necessary to assess if quantitative differences exist between sarcoid and malignant lymphadenopathy.


Serum metabolome changes in adult patients with severe dengue in the critical and recovery phases of dengue infection.
Dengue virus (DENV) is the most prevalent arbovirus leading to an estimated 100 million symptomatic dengue infections every year. DENV can cause a spectrum of clinical manifestations, ranging from mild dengue fever (DF) to more life threatening forms such as dengue hemorrhagic fever (DHF). The clinical symptoms of DHF become evident typically at the critical phase of infection (5-7 days after onset of fever), yet the mechanisms that trigger transition from DF to DHF are not well understood. We performed a mass spectrometry-based metabolomic profiling of sera from adult DF and DHF patients at the critical and recovery phases of infection. There were 29 differentially expressed metabolites identified between DF and DHF at the critical phase. These include bile acids, purines, acylcarnitines, phospholipids, and amino acids. Bile acids were observed up to 5 fold higher levels among DHF compared to DF patients and were significantly correlated to the higher levels of aspartate transaminase (AST) and alanine transaminase (ALT), suggestive of liver injury among DHF. Uric acid, the most abundant antioxidant in the blood, was observed to be 1.5 fold lower among DHF compared to DF patients. This could result in decreased capacity of endogenous antioxidant defense and elevated oxidative stress among DHF patients. In the recovery phase, the levels of eight metabolites were still significantly higher or lower among DHF patients, including chenodeoxyglycocholic acid, one of the bile acids observed at the critical phase. This indicates potential prolonged adverse impact on the liver due to DENV infection in DHF patients. Our study identified altered metabolic pathways linked to DHF in the critical and recovery phases of dengue infection and provided insights into the different host and DENV interactions between DF and DHF. The results advance our understanding on the mechanisms of DHF pathogenesis, alluding to possible novel therapeutic targets to dengue management.


Bone marrow graft-versus-host disease: early destruction of hematopoietic niche after MHC-mismatched hematopoietic stem cell transplantation.
Disrupted hematopoiesis and delayed immune reconstitution are life-threatening complications of allogeneic hematopoietic stem cell transplantation (allo-HSCT). Although graft-versus-host disease (GVHD) is a major risk factor for the bone marrow (BM) insufficiency, how GVHD impairs BM hematopoiesis has been largely unknown. We hypothesized that BM stromal niche could be a target of GVHD. In major histocompatibility complex (MHC)-mismatched murine models of GVHD, we have demonstrated the early destruction of osteoblasts that especially affected B-cell lineages. The defective B lymphopoiesis was due to the impaired ability of BM stroma and osteoblasts to support the hematopoiesis, as evidenced by the failure of GVHD-affected BM to reconstitute the hematopoietic cells. The administration of anti-CD4 monoclonal antibody (mAb) ameliorated these effects and improved B lymphopoiesis while preserving graft-versus-tumor effects. Genetic ablation of Fas-Fas ligand signaling also partially restored B lymphopoiesis. Our present study provided evidence of BM GVHD, with the identification of osteoblasts as the main target for GVHD in BM. Moreover, our data showed the potential for mAb therapies to enhance immune reconstitution in vivo for patients undergoing allo-HSCT.


Epimerization of 2'-carbonylalkyl-C-glycosides via enolation, beta-elimination and intramolecular cycloaddition.
Treatment of 2'-carbonyl-alpha-C-glycopyranosides of gluco, galacto, manno, 2-deoxy, and 2-azido sugars with 4% NaOMe resulted in anomeric epimerization to give their respective beta-anomers in good to excellent yields. The epimerization of the 2'-aldehyde of alpha-C-galactopyranoside (10) in deuterium methanol, which afforded the beta-anomer with exclusive deuterium replacements at the 1'-position, excluded the possibility of the exo-glycal as being involved as an intermediate. When 2'-aldehyde (36) and 2'-ketone (41) of 2,3-di-O-benzyl-alpha/beta-l-C-arabinofuranoside were used as substrates we were able to obtain the respective equatorial alpha-C-arabinopyranosides (37 and 42). These observations confirmed that the epimerization involves an acyclic alpha,beta-unsaturated aldehyde or ketone, which is formed by the enolation of 2'-carbonyl-alpha-C-glycoside with subsequent beta-elimination. Thereafter an intramolecular hetero-Michael cycloaddition occurs, leading to the formation of thermodynamically controlled stable products, which were exclusively the equatorial C-glycopyranosides, except in the case of 2'-carbonyl-C-furanosides, where a mixture of two anomers was obtained.


Comparison of different extraction methods for polysaccharides from Dendrobium officinale stem.
The purpose of this study was to screen the optimum extraction of polysaccharides (DOP) from Dendrobium officinale stem. Firstly, different methods, including hot water extraction (HWE), cold-pressing (CP), freeze-thawing cold-pressing (FTCP), ultrasonic-assisted hot water extraction (UHWE), microwave-assisted hot water extraction (MHWE) and enzyme-assisted hot water extraction (EHWE), were employed to extract DOP under their respective best parameters. Then, the extraction yield, structure and antioxidant activity of the polysaccharides from different extraction methods were compared under the same condition. The data implied that UHWE and FTCP possessed higher extraction yield than the other extraction methods. Besides, DOPCP and DOPFTCP had higher molecular weight than the other polysaccharide samples. More importantly, DOPFTCP had the highest antioxidant activity. Overall, DOPFTCP exhibit high extraction yield, well-preserved molecular chains and best antioxidant activity, all these indicated FTCP was the most suitable method to extract DOP.


Membrane potential dependent modulations of calcium oscillations in insulin-secreting INS-1 cells.
This study was undertaken to examine the role of K(+) channels on cytosolic Ca(2+) ([Ca(2+)](i)) in insulin secreting cells. [Ca(2+)](i) was measured in single glucose-responsive INS-1 cells using the fluorescent Ca(2+) indicator Fura-2. Glucose, tolbutamide and forskolin elevated [Ca(2+)](i) and induced [Ca(2+)] oscillations. Whereas the glucose effect was delayed and observed in 60% and 93% of the cells, in a poorly and a highly glucose-responsive INS-1 cell clone, respectively, tolbutamide and forskolin increased [Ca(2+)](i) in all cells tested. In the latter clone, glucose induced [Ca(2+)](i) oscillations in 77% of the cells. In 16% of the cells a sustained rise of [Ca(2+)](i) was observed. The increase in [Ca(2+)](i) was reversed by verapamil, an L-type Ca(2+) channel inhibitor. Adrenaline decreased [Ca(2+)](i) in oscillating cells in the presence of low glucose and in cells stimulated by glucose alone or in combination with tolbutamide and forskolin. Adrenaline did not lower [Ca(2+)](i) in the presence of 30mM extracellular K(+), indicating that adrenaline does not exert a direct effect on Ca(2+) channels but increases K(+) channel activity. As for primary b-cells, [Ca(2+)](i) oscillations persisted in the presence of closed K(ATP) channels; these also persisted in the presence of thapsigargin, which blocks Ca(2+) uptake into Ca(2+) stores. In contrast, in voltage-clamped cells and in the presence of diazoxide (50mM), which hyperpolarizes the cells by opening K(ATP) channels, [Ca(2+)](i) oscillations were abolished. These results support the hypothesis that [Ca(2+)](i) oscillations depend on functional voltage-dependent Ca(2+) and K(+) channels and are interrupted by a hyperpolarization in insulin-secreting cells.


Medical care for interned enemy aliens: a role for the US Public Health Service in World War II.
During World War II, the US Public Health Service (USPHS) administered health care to 19 000 enemy aliens and Axis merchant seamen interned by the Justice Department through its branch, the Immigration and Naturalization Service (INS). The Geneva Prisoners of War Convention of 1929, which the United States applied to civilian internees, provided guidelines for belligerent nations regarding humanitarian treatment of prisoners of war, including for their health. The INS forged an agreement with the USPHS to meet these guidelines for the German, Italian, and Japanese internees and, in some cases, their families. Chronic shortages and crowded camps continuously challenged USPHS administrators. Nevertheless, the USPHS offered universal access to care and provided treatment often exceeding care received by many American citizens.


Rules and trends of metal cation driven hydride-transfer mechanisms in metal amidoboranes.
Group I and II metal amidoboranes have been identified as one of the promising families of materials for efficient H(2) storage. However, the underlying mechanism of the dehydrogenation of these materials is not well understood. Thus, the mechanisms and kinetics of H(2) release in metal amidoboranes are investigated using high level ab initio calculations and kinetic simulations. The metal plays the role of catalyst for the hydride transfer with formation of a metal hydride intermediate towards the dehydrogenation. In this process, with increasing ionic character of the metal hydride bond in the intermediate, the stability of the intermediate decreases, while the dehydrogenation process involving ionic recombination of the hydridic H with the protic H proceeds with a reduced barrier. Such correlations lead directly to a U-shaped relationship between the activation energy barrier for H(2) elimination and the ionicity of metal hydride bond. Oligomerized intermediates are formed by the chain reaction of the size-driven catalytic effects of metals, competing with the non-oligomerization pathway. The kinetic rates at low temperatures are determined by the maximum barrier height in the pathway (a Lambda-shaped relation), while those at moderately high temperatures are determined by most of multiple-barriers. This requires kinetic simulations. At the operating temperatures of proton exchange membrane fuel cells, the metal amidoboranes with lithium and sodium release H(2) along both oligomerization and non-oligomerization paths. The sodium amidoboranes show the most accelerated rates, while others release H(2) at similar rates. In addition, we predict that the novel metal amidoborane-based adducts and mixtures would release H(2) with accelerated rates as well as with enhanced reversibility. This comprehensive study is useful for further developments of active metal-based better hydrogen storage materials.


Functional connectivity in tactile object discrimination: a principal component analysis of an event related fMRI-Study.
Tactile object discrimination is an essential human skill that relies on functional connectivity between the neural substrates of motor, somatosensory and supramodal areas. From a theoretical point of view, such distributed networks elude categorical analysis because subtraction methods are univariate. Thus, the aim of this study was to identify the neural networks involved in somatosensory object discrimination using a voxel-based principal component analysis (PCA) of event-related functional magnetic resonance images. Seven healthy, right-handed subjects aged between 22 and 44 years were required to discriminate with their dominant hand the length differences between otherwise identical parallelepipeds in a two-alternative forced-choice paradigm. Of the 34 principal components retained for analysis according to the 'bootstrapped' Kaiser-Guttman criterion, t-tests applied to the subject-condition expression coefficients showed significant mean differences between the object presentation and inter-stimulus phases in PC 1, 3, 26 and 32. Specifically, PC 1 reflected object exploration or manipulation, PC 3 somatosensory and short-term memory processes. PC 26 evinced the perception that certain parallelepipeds could not be distinguished, while PC 32 emerged in those choices when they could be. Among the cerebral regions evident in the PCs are the left posterior parietal lobe and premotor cortex in PC 1, the left superior parietal lobule (SPL) and the right cuneus in PC 3, the medial frontal and orbitofrontal cortex bilaterally in PC 26, and the right intraparietal sulcus, anterior SPL and dorsolateral prefrontal cortex in PC 32. The analysis provides evidence for the concerted action of large-scale cortico-subcortical networks mediating tactile object discrimination. Parallel to activity in nodes processing object-related impulses we found activity in key cerebral regions responsible for subjective assessment and validation.


Donor site morbidity after articular cartilage repair procedures: a review.
In order to perform an Osteochondral Autologous Transplantation (OAT) or an Autologous Chondrocyte Implantation (ACI), the integrity of healthy intact articular cartilage at a second location needs to be violated. This creates the possibility for donor site morbidity. Only recently have any publications addressed this issue. The aim of this manuscript is to review the current knowledge on donor site morbidity after an OAT or an ACI. Reports were identified by searching Medline and Pubmed up to March 2010. Donor site morbidity was described mostly considering a clinical outcome, both in a qualitative (parameters in history or physical examination) and/or quantitative way (knee status reported by means of a numerical score). An increasing rate of problems is noted when using quantitative instead of qualitative parameters, and when donor site morbidity is the focus of attention, affecting up to more than half of the patients, in particular for an OAT procedure. The decision to harvest an osteochondral or cartilage biopsy to perform a repair procedure should therefore be taken with caution. This also underscores the need for further research to identify safe donor sites or to develop techniques that eliminate the need for a formal biopsy ccompletely.


[Detection of the new tumor marker MUSE 11 antigen in sera of pancreatic cancer patients: a comparison with sialyl SSEA-I antigen].
Using sera from patients with pancreatic cancer and chronic pancreatitis, we measured the level of the adenocarcinoma-associated antigen MUSE 11. A comparative study between levels of MUSE 11 and levels of sialyl SSEA-1 antigen (SLX) was also carried out. With respect to the MUSE 11 antigen, positive incidence was found in 17 out of 26 pancreatic cancer patients (65%), and in 1 out of 13 chronic pancreatitis patients (8%). Similar results were obtained from the assay of SLX levels. However, no correlation was found between the two markers. Out of 9 samples which showed MUSE 11 negative, three were positive for SLX. Out of 13 samples showing SLX negative, seven were positive for MUSE 11. Twenty out of 26 (77%) cases showed positive results for either antigen. These data suggest that the MUSE 11 antigen may be useful for the diagnosis of pancreatic cancers.


Identifying the drug seeker: the advanced practice nurse's role in managing prescription drug abuse.
To provide advanced practice nurses (APNs) with a definition of drug-seeking behaviors, to identify the common signs and symptoms of drug-seeking behaviors, to furnish tips for managing interactions with and treatment of the drug-seeking patient, and to describe prescription parameters that will help APNs avoid legal ramifications. A review of the current scientific and clinical literature regarding interaction with and treatment of patients who abuse prescription drugs. A basic understanding of drug-seeking behaviors and adherence to appropriate procedures for prescribing controlled medications are essential for APNs to maintain their safe prescribing habits; carry on with quality, effective care; and continue the advancement of their profession. As primary care providers, APNs must be aware of the potential complications resulting from interacting with patients who may be seeking prescription drugs for recreational or illicit use, rather than for legitimate reasons.


Carbonic anhydrase II gene expression in cell lines from human pancreatic adenocarcinoma.
Current evidence suggests that carbonic anhydrase II (CA II) is produced by pancreatic duct cells but not by pancreatic acinar or islet cells. The aim of this study was to determine whether CA II homologous RNA and CA II immunoreactive protein are produced by cell lines established from human pancreatic adenocarcinomas. A 1.7-Kb CA II homologous RNA was detected in poly(A+) RNA isolated from normal human pancreas, normal human liver, and to varying degrees in the cell lines examined. The CA II immunoreactivity corresponding to approximately 30 kD (consistent with the established molecular mass of CA II) was also detected by immunoblotting in normal human pancreas, normal human liver, and some of the cell lines. We also found that the levels of CA II homologous RNA increase in the pancreatic adenocarcinoma cell lines following treatment with the differentiating agent, retinoic acid.


Modifications of the human immunodeficiency virus envelope glycoprotein enhance immunogenicity for genetic immunization.
In this study, we have investigated the effect of specific mutations in human immunodeficiency virus type 1 (HIV-1) envelope (Env) on antibody production in an effort to improve humoral immune responses to this glycoprotein by DNA vaccination. Mice were injected with plasmid expression vectors encoding HIV Env with modifications in regions that might affect this response. Elimination of conserved glycosylation sites did not substantially enhance humoral or cytotoxic-T-lymphocyte (CTL) immunity. In contrast, a modified gp140 with different COOH-terminal mutations intended to mimic a fusion intermediate and stabilize trimer formation enhanced humoral immunity without reducing the efficacy of the CTL response. This mutant, with deletions in the cleavage site, fusogenic domain, and spacing of heptad repeats 1 and 2, retained native antigenic conformational determinants as defined by binding to known monoclonal antibodies or CD4, oligomer formation, and virus neutralization in vitro. Importantly, this modified Env, gp140 Delta CFI, stimulated the antibody response to native gp160 while it retained its ability to induce a CTL response, a desirable feature for an AIDS vaccine.


Inhibition of kynurenine aminotransferase II attenuates hippocampus-dependent memory deficit in adult rats treated prenatally with kynurenine.
A combination of genetic and environmental factors contributes to schizophrenia (SZ), a catastrophic psychiatric disorder with a hypothesized neurodevelopmental origin. Increases in the brain levels of the tryptophan metabolite kynurenic acid (KYNA), an endogenous antagonist of α7 nicotinic acetylcholine and NMDA receptors, have been implicated specifically in the cognitive deficits seen in persons with SZ. Here we evaluated this role of KYNA by adding the KYNA precursor kynurenine (100 mg/day) to chow fed to pregnant rat dams from embryonic day (ED) 15 to ED 22 (control: ECon; kynurenine treated: EKyn). Upon termination of the treatment, all rats received normal rodent chow until the animals were evaluated in adulthood (postnatal days 56-85). EKyn treatment resulted in increased extracellular KYNA and reduced extracellular glutamate in the hippocampus, measured by in vivo microdialysis, and caused impairments in hippocampus-dependent learning in adult rats. Acute administration of BFF816, a systemically active inhibitor of kynurenine aminotransferase II (KAT II), the major KYNA-synthesizing enzyme in the brain, normalized neurochemistry and prevented contextual memory deficits in adult EKyn animals. Collectively, these results demonstrate that acute inhibition of KYNA neosynthesis can overcome cognitive impairments that arise as a consequence of elevated brain KYNA in early brain development.


[Diagnostics of latent tuberculosis (TB) in adult vaccinated patients (BCG) in Croatia before introduction of tumor necrosis factor antagonist therapy].
Tuberculosis is now well known adverse event during anti-TNFalpha therapy and screening for TB is highly recommended before the administration of anti-TNF blockers. The purpose of screening is to asses the risk of reactivation of latent TB or new infection with mycobacterium tuberculosis. Skin test for TB with induration of 5 mm and more is considered positive. Negative skin test in immunocompromised persons does not exclude latent inefction and booster testing after 7 days is suggested. All patients with any suspicious or unclear skin testing (PPD > 5 mm on initial or booster testing) need immunologic diagnostic approach. Patients with confirmed risk for TB must take chemoprofilaxis for 6 months (isoniasid 5 mg per kilogram of body weight). Anti-TNF therapy could be started after 2 months of chemotherapy. All 3 anti-TNF biologics have the same risk of new TB infection and it seems that monoclonal antibodies have some higher risk for reactivation of latent TB. Anyhow for all biologics the same pre-therapy screening procedure is strongly recommended.


Effect of microculture on cell metabolism and biochemistry: do cells get stressed in microchannels?
Microfluidics is emerging as a promising platform for cell culture, enabling increased microenvironment control and potential for integrated analysis compared to conventional macroculture systems such as well plates and Petri dishes. To advance the use of microfluidic devices for cell culture, it is necessary to better understand how miniaturization affects cell behavior. In particular, microfluidic devices have significantly higher surface-area-to-volume ratios than conventional platforms, resulting in lower volumes of media per cell, which can lead to cell stress. We investigated cell stress under a variety of culture conditions using three cell lines: parental HEK (human embryonic kidney) cells and transfected HEK cells that stably express wild-type (WT) and mutant (G601S) human ether-a-go-go related gene (hERG) potassium channel protein. These three cell lines provide a unique model system through which to study cell-type-specific responses in microculture because mutant hERG is known to be sensitive to environmental conditions, making its expression a particularly sensitive readout through which to compare macro- and microculture. While expression of WT-hERG was similar in microchannel and well culture, the expression of mutant G601S-hERG was reduced in microchannels. Expression of the endoplasmic reticulum (ER) stress marker immunoglobulin binding protein (BiP) was upregulated in all three cell lines in microculture. Using BiP expression, glucose consumption, and lactate accumulation as readouts we developed methods for reducing ER stress including properly increasing the frequency of media replacement, reducing cell seeding density, and adjusting the serum concentration and buffering capacity of culture medium. Indeed, increasing the buffering capacity of culture medium or frequency of media replacement partially restored the expression of the G601S-hERG in microculture. This work illuminates how biochemical properties of cells differ in macro- and microculture and suggests strategies that can be used to modify cell culture protocols for future studies involving miniaturized culture platforms.


Megameatus intact prepuce hypospadias variant: application of tubularized incised plate urethroplasty.
The characteristics of the megameatus intact prepuce (MIP) hypospadias variant present a unique challenge to surgeons. Dissatisfaction with the results of conventional repair methods led to the emergence of several alternative surgical approaches, including the glanular approximation (GAP) and pyramid procedures. The application of tubularized, incised plate (TIP) urethroplasty has not been documented in this setting. Twenty-four patients (mean age 18.5 months, range 6 to 60) presented with MIP. They had all been circumcised. The meatus was glanular in 6, coronal in 15, and distal shaft in 3 patients. Glanular MIP was repaired by meatal advancement and glanuloplasty (n = 2) or the GAP technique (n = 4). Coronal MIP was repaired by the GAP (n = 7) or TIP urethroplasty (n = 8), and distal shaft MIP was repaired by TIP urethroplasty (n = 3). Stents or catheters were used only with TIP urethroplasty. The mean follow-up period was 40 months (range 8 to 80). Satisfactory cosmetic and functional results were achieved in 20 patients (83%). The other 4 patients included 1 patient who underwent GAP and meatoplasty and 3 of the 11 patients who underwent TIP urethroplasty, of whom 2 underwent meatoplasty and 1 simple local repair of a urethrocutaneous fistula without the need for urethral reconstruction. The success rates for all selected techniques were satisfactory. TIP urethroplasty can be successfully used in the more severe, proximal forms of MIP.


One-year quality-of-life outcomes of cardiac arrest survivors by initial defibrillation provider.
To assess the long-term functional and health-related quality-of-life (HRQoL) outcomes for out-of-hospital cardiac arrest (OHCA) survivors stratified by initial defibrillation provider. This retrospective study included adult non-traumatic OHCA with initial shockable rhythms between 2010 and 2019. Survivors at 12 months after arrest were invited to participate in structured telephone interviews. Outcomes were identified using the Glasgow Outcome Scale-Extended (GOS-E), EuroQol-5 Dimension (EQ-5D), 12-Item Short Form Health Survey and living and work status-related questions. 6050 patients had initial shockable rhythms, 3211 (53.1%) had a pulse on hospital arrival, while 1879 (31.1%) were discharged alive. Bystander defibrillation using the closest automated external defibrillator had the highest survival rate (52.8%), followed by dispatched first responders (36.7%) and paramedics (27.9%). 1802 (29.8%) patients survived to 12-month postarrest; of these 1520 (84.4%) were interviewed. 1088 (71.6%) were initially shocked by paramedics, 271 (17.8%) by first responders and 161 (10.6%) by bystanders. Bystander-shocked survivors reported higher rates of living at home without care (87.5%, 75.2%, 77.0%, p<0.001), upper good recovery (GOS-E=8) (41.7%, 30.4%, 30.6%, p=0.002) and EQ-5D visual analogue scale (VAS) ≥80 (64.9%, 55.9%, 52.9%, p=0.003) compared with first responder and paramedics, respectively. After adjustment, initial bystander defibrillation was associated with higher odds of EQ-5D VAS ≥80 (adjusted OR (AOR) 1.56, 95% CI 1.15-2.10; p=0.004), good functional recovery (GOS-E ≥7) (AOR 1.53, 95% CI 1.12-2.11; p=0.009), living at home without care (AOR 1.77, 95% CI 1.16-2.71; p=0.009) and returning to work (AOR 1.72, 95% CI 1.05-2.81; p=0.031) compared with paramedic defibrillation. Survivors receiving initial bystander defibrillation reported better functional and HRQoL outcomes at 12 months after arrest compared with those initially defibrillated by paramedics.


[Change of protein catabolism and immunocompetence in severely burned patients after operations and the therapeutic effect of recombinant human growth hormone].
To investigate the changes in protein catabolism and immunocompetence in severely burned patients after operations and observe the therapeutic effect of recombinant human growth hormone (rhGH) in these patients. The changes in plasma protein concentration and immune function and the clinical results of 38 severely burned patients after three operations were retrospectively analyzed. These patients were assigned to GroupI(control, n=20) and GroupII (rhGH treatment, n=18), and matched for age, total body surface area (TBSA), surgical approaches and times, perioperative bleeding volume and nutrition support etc. The patients in groupII received intramuscular injection with 0.2-0.4 U/d x kg x b.w. rhGH after the first operation, till the healing of the wounds. The concentration of retina-binding protein, transferrin, prealbumin, albumin, and IgG, the number of CD4 and CD8 cells, as well as the ratio of CD4/CD8 cells prior to the operation were below the normal levels in the two groups of patients. All these indexes in GroupII recovered to a great extent after three operations and were significantly higher than those in GroupI(P<0.05). Nutritious state and immunocompetence of patients with severe burns are severely compromised after operations, and nutrition support and rhGH treatment may produce rapid improvement of the patients' conditions.


[Regulation effects of various training modes on source-sink relation of cotton].
With the removal of vegetative branches plus the maintenance of early fruiting branches as the control, the effects of various training modes on the source-sink relation of field-grown cotton were examined in 2005 and 2006. The results showed that compared with the control, either the removal of vegetative branches plus the removal of early fruiting branches (I), the maintenance of vegetative branches plus the removal of early fruiting branches (II), or the maintenance of vegetative branches plus the maintenance of early fruiting branches (III) could increase the leaf area per plant significantly, with the average maximum LAI across the two years increased by 10.3%, 28.3%, and 9.5%, respectively, and resulting in the decreases of the load per leaf area and the ratio of sink to source. I and II alleviated the leaf senescence of cotton plants as indicated by the enhanced leaf chlorophyll content and the reduced percentage of yellow leaves and C/N ratio of functional leaves, and II also induced the late-maturing of cotton plants. III had no significant effects on senescence alleviation. I produced approximately equal seed cotton, but II and III produced 6.4%-15.6% less and 6.3% more seed cotton than the control, respectively. It was concluded that either the maintenance of vegetative branches or the removal of early fruiting branches could be an effective pathway to regulate the ratio of sink to source, C/N, and maturity performance of cotton plants.


Clergy Perceptions of Sexual Assault Victimization.
Although congregants often turn to clergy for help in dealing with personal difficulties, including marital problems, substance abuse issues, and mental illness, survivors of sexual assault do not commonly turn to clergy for support or guidance. This study utilized a mixed-methods approach, online survey, and semi-structured interviews to determine how clergy perceive sexual assault victimization. The results of this study showed that more blame was assigned to the victim as the relationship with the perpetrator became closer, with the exception of marital rape. This study also found that hostile sexism was a predictor of negative attitudes toward rape victims.


Age-dependent likelihood of in situ thrombosis in secondary pulmonary hypertension.
Pulmonary arterial thrombosis (PAT) may complicate the clinical course of pulmonary hypertension associated with congenital heart disease (so-called Eisenmenger syndrome, ES). In this study, variables were sought that could represent risk factors for the occurrence of this complication. Twenty patients aged 11 to 53 (median, 33) years were studied. The presence of PAT (spiral computed tomography angiography) was correlated with age, gender group, PAP, hematocrit, peripheral oxygen saturation (SpO(2)), and plasma levels of endothelial and coagulation dysfunction markers: von Willebrand factor antigen (vWF:Ag), tissue plasminogen activator (t-PA), and D-dimer (enzyme immunoassay). Patients were classified according to the presence (group 1, N=7), or absence (group 2, N=13) of PAT. Group 1 patients were older (42+/-8 vs. 27+/-10 years in group 2, p=0.0051), had lower SpO(2) (82+/-7% vs. 89+/-6% in group 2, p=0.0462) and increased D-dimer levels (637 vs. 149 ng/mL in group 2, median values, p=0.0235). A trend was observed toward an increase in vWF:Ag (125+/-29 vs. 103+/-18 U/dL in group 2, p=0.0789) and t-PA (15.7 vs. 9.4 ng/mL in group 2, median values, p=0.0689). Age was the main variable influencing the occurrence of PAT in multivariate analysis (p=0.0026), with odds ratio of 1.204 per year. The age of 35 years was 86% sensitive and 85% specific for occurrence of PAT. Age correlated positively with t-PA (r=0.57, p=0.0111). Thus, PAT is highly prevalent in ES as an age-dependent event, probably associated with endothelial dysfunction. Prophylactic anticoagulation should be considered before the age of 30 years, in particular in subjects with low SpO(2) and increased D-dimer levels.


A nanoscale resolution view on synaptic vesicle dynamics.
The ability of synapses to sustain neurotransmitter release during continuous activity critically relies on an efficient vesicle recycling program. Despite extensive research on synaptic function, the basic mechanisms of vesicle recycling remain poorly understood due to the relative inaccessibility of central synapses to conventional recording techniques. The extremely small size of synaptic vesicles, nearly five times below the diffraction-limited resolution of conventional light microscopy, has hampered efforts to define the mechanisms controlling their cycling. The complex sequence of dynamic processes that occur within the nerve terminals and link vesicle endocytosis and the subsequent round of release has been particularly difficult to study. The recent development of nanoscale-resolution imaging techniques has provided an opportunity to overcome these limitations and begin to reveal the mechanisms controlling vesicle recycling within individual nerve terminals. Here we summarize the recent advances in the implementation of super-resolution imaging and single-particle tracking approaches to study the dynamic steps of the vesicle recycling process within presynaptic terminals.


Population Dynamics of Xanthomonads Associated with Bacterial Spot of Tomato and Pepper during 27 Years across Taiwan.
Bacterial spot caused by Xanthomonas spp. is the second most important bacterial disease after bacterial wilt of tomato and pepper in Taiwan. To determine the species composition of the Xanthomonas population over 27 years (1989 to 2016) across the country, a large collections of strains from tomato (n = 292) and pepper (n = 198) were examined. In the 1989 to 1999 population, all strains (n = 147) from pepper and 95% strains (n = 198) from tomato were Xanthomonas euvesicatoria. The remaining 5% of strains from tomato were X. vesicatoria. In a 2000 to 2009 population from tomato (n = 36), 22% of the strains were X. perforans and the remaining 78% strains were X. euvesicatoria. In the 2010 to 2016 population, 92% of the strains (n = 50) from pepper were still X. euvesicatoria and the remaining 8% of the strains were X. perforans; however, 99% (n = 58) of the strains from tomato were X. perforans. All of the evaluated (n = 25) strains of X. euvesicatoria collected during 1990 to 2006 were tomato race T1. Four pepper races (P1, P2, P7, and P8) were identified in the X. euvesicatoria population. The strains of X. vesicatoria collected during 1989 to 1999 (n = 8) were tomato race T2 and strains of X. perforans from tomato collected during 2010 to 2016 (n = 12) were race T4 (83%) and race T3 (17%). Four strains of X. perforans from pepper were race T4. All of the strains of X. vesicatoria and X. perforans caused a hypersensitive response in all pepper differentials. Biochemical characterization of representative strains (n = 48) showed that strains of X. euvesicatoria were negative on and amylolytic test and positive on lipase and oxidative-fermentative (OF) tests. The strains of X. vesicatoria were positive on amylolytic and OF tests and were negative on the lipase test. All X. perforans strains showed positive reactions on three tests. Evaluation of the same 48 strains for the sensitivity to copper sulfate (50, 100, 200, 300, and 400 mg liter-1) revealed that the majority of X. euvesicatoria (86%) and X. perforans (94%) strains in the 2010 to 2016 population were tolerant to copper sulfate. The findings suggest that management strategies and breeding programs should consider the new X. perforans species and their new races. The increased number of copper-sulfate-tolerant strains in the 2010 to 2016 population further shows the need for alternative options to copper for managing bacterial spot of tomato and pepper.


Contribution of nitric oxide, angiotensin II and superoxide dismutase to exercise-induced attenuation of blood pressure elevation in spontaneously hypertensive rats.
Moderate chronic exercise attenuates the elevation of blood pressure in young spontaneously hypertensive rats. In order to elucidate the physiological process of the effects of exercise, we examined the involvement of nitric oxide, angiotensin II, and superoxide dismutase in this process. Rats were exercised by voluntary running in a wheel-cage for 10 weeks. Systolic blood pressure in the exercised rats (195+/-4 mmHg, n=27) was significantly (p<0.05) lower than in the post-control rats (212+/-3 mmHg, n=28). The concentration of total plasma nitrite was significantly higher in exercised rats (14.9+/-1.5 micromol l(-1)) than in the post-control rats (9.9+/-0.7 micromol l(-1), p<0.05). Superoxide dismutase activity in the exercised rats was significantly higher (p<0.05) than in the post-control rats (thoracic aorta: 4.6+/-0.3 U mg protein(-1) vs 3.6+/-0.3 U mg protein(-1), heart: 12.7+/-0.6 U mg protein(-1) vs 10.2+/-0.6 U mg protein(-1), p<0.05). The plasma angiotensin II concentration was higher in the post-control rats (74.4+/-14.0 pg mL(-1)) than in the exercised rats (45.0+/-6.4 pg mL(-1), p<0.05), and in the pre-control rats (47.2+/-6.0 pg mL(-1)). The results suggest that exercise acts to decrease the level of superoxide by increasing superoxide dismutase activity in the aorta and heart and to decrease levels of angiotensin II, both of which, in turn, increase the effective concentration of nitric oxide. We conclude that the combination of these effects with the increased NO formation resulted in the low blood pressure seen in the exercised rats.


[The diagnosis of the sinus node syndrome].
The "specific" investigations for sinus node syndrome (SNS) in 22 patients are analyzed. SNS was defined as sinusbradycardia below 40/min and sinus-standstill over 2 sec. Atropin (1 mg i.v.), exercise test and carotid pressure were of little help in establishing the diagnosis, while Holter monitoring and sinus-node recovery time were significantly abnormal in all patients investigated.


Real-time pulse measurement of nano-scale field effect transistors: cancellation of displacement current and extraction of coupling capacitance.
Real-time pulse measurements of nano-scale field effect transistors (FETs) are reported. We demonstrate the direct monitoring of the real-time current of bottom-up assembled silicon nanowire FET and top-down fabricated gate-all-around silicon nanowire FET, both with the diameter of approximately 50 nm. We demonstrate that the displacement current can be cancelled out from the measured pulse responses. On the other hand, the displacement current also can be utilized to obtain the coupling capacitance between the gate and source of the FETs.


Acute monolateral proptosis and orbital myositis in a patient with discoid lupus erythematosus: a case report.
Discoid lupus erythematosus may lead to significant orbital inflammation syndrome. Ocular manifestations related to discoid lupus erythematosus are uncommon and few cases of eye inflammation are reported. A 37-year-old Caucasian woman with 5-year history of discoid lupus erythematosus presented with exophthalmos, periorbital pain and blurred vision in her right eye. Orbital computed tomography and laboratory tests were performed. Computed tomography imaging revealed an enlargement of the right medial rectus muscle. Thyroid eye disease and orbital cellulites were excluded. Corticosteroid treatment completely resolved the symptoms. This is the first case of orbital myositis in a patient with discoid lupus erythematosus presenting with acute proptosis, diplopia and single extraocular muscle involvement.


Depression and Obsessive-Compulsive Disorders Amid the COVID-19 Pandemic in Saudi Arabia.
Coronavirus disease 2019 (COVID-19) is a global pandemic with significant morbidity and mortality. The Saudi government adopted mandatory home quarantine and curfew hours for all residents, excluding essential service workers. During the lockdown, the public's fear of infection can adversely impact mental health, causing psychological distress. The objective of this research is to assess frequency of depression and obsessive-compulsive disorder (OCD) among the general population during COVID-19 pandemic in Saudi Arabia. This was a cross-sectional study using the Patient Health Questionnaire (PHQ-9) and Obsessive-Compulsive Inventory-Revised assessment test (OCI-R) in Arabic and English languages distributed via social media platforms. Chi-square test was used with significance determined at p<0.005. We received a total of 2187 responses. Our results showed that being female, single, and unemployed had a higher frequency of suffering from depression whereas higher income levels and higher education was associated with less depression frequency. Increasing age, males, married individuals, higher income groups, higher levels of education and employed individuals were more likely to have OCD during COVID-19 pandemic. Conclusion: The COVID-19 pandemic period is associated with significant mental health risks among the Saudi population. The results can provide further scientific support to better understand the impact of quarantine on psychological distress and mental health during emergency and disaster situations.


Women's and Employers' Experiences and Views of Combining Breastfeeding with a Return to Paid Employment: A Systematic Review of Qualitative Studies.
Returning to paid employment is one of the reasons women stop breastfeeding earlier than they planned to. This systematic review aimed to provide insight into the experiences and views of women and employers on breastfeeding and returning to paid employment, with findings used to inform practice and policy. The review was guided by the Joanna Briggs Institute (JBI) methodology for systematic reviews of qualitative evidence. Medline, CINAHL, PsycINFO, and Web of Science databases were searched for studies published in English. JBI's meta-aggregative approach informed data analysis. The studies in this analysis included women who stopped breastfeeding before, and those who continued breastfeeding after, returning to paid employment and the employers, work managers, or supervisors of women who continued breastfeeding after returning to paid employment. Twenty-six articles presenting findings from 25 studies were included and critically appraised. Synthesized findings showed that women experienced physical and emotional difficulties and described gender and employment inequalities in accessing and receiving the support they needed. Women reported that the importance of their own motivation and having workplace legislation in place facilitated breastfeeding during employment. Support from employers, colleagues, and family members, as well as access to convenient child care, helped women continue breastfeeding on return to paid employment. Employers' personal experiences influenced their views on breastfeeding and working, and the need for more education and communication between employers and employers on breastfeeding in the workplace was recognized. Support from family, work colleagues, and employers was important to reduce the physical and emotional challenges women experienced when combing breastfeeding with return to paid employment. Gender inequalities, especially in low- and middle-income countries, in accessing support exacerbated the difficulties women experienced. Limited data were identified regarding employers' experiences and views, suggesting an urgent need for further research to explore employers' and work colleagues' experiences and views.


A modified Essen Stroke Risk Score for predicting recurrent ischemic stroke at one year.
Objective The Essen Stroke Risk Score (ESRS) is widely used to predict the risk of recurrent ischemic stroke but may not have sufficient discriminatory ability for predicting early recurrence. In this study, we developed a modified ESRS for predicting recurrent ischemic stroke at one year based on Chinese population. Methods Eight hundred and three consecutive patients were included in the study. We performed a univariate analysis to investigate the effect of previously identified risk factors on recurrent stroke at one year. The candidate predictors were included in a forward stepwise logistic regression model. Prediction scores were assigned based on β coefficient and a modified ESRS system was constructed. We used receiver operating characteristic (ROC) curves to compare the predictive ability of the modified and original ESRS. Results Recurrent ischemic stroke occurred in 85 (11.00%) patients and death occurred in 68 (8.80%) patients within one year. Hypertension over 15 years, diabetes over 10 years, large artery atherosclerosis cerebral infarction by TOAST criteria and a history of transient ischemic attack (TIA) or ischemic stroke (IS) were identified as independent risk factors for recurrent stroke (all P < 0.05). The areas under the ROC curves of ESRS and modified ESRS were 0.58 (P < 0.05, 95%CI: 0.51-0.64) and 0.70 (P < 0.05, 95% CI: 0.63-0.76), respectively. The modified ESRS appears to be superior to the original ESRS for predicting recurrent ischemic stroke at one year (P < 0.05). Conclusions The modified ESRS increased the ability of the original ESRS to predict recurrent stroke at one year among the Chinese population.


Combination of Chemically Characterized Pomegranate Extract and Hydrophilic Vitamins against Prolonged Fatigue: A Monocentric, Randomized, Double-Blind, Placebo-Controlled Clinical Trial.
Prolonged fatigue is associated with non-pathological causes and lacks an established therapeutic approach. The current study is aimed at assessing the efficacy of a new food supplement (Improve™) based on a chemically characterized pomegranate extract and hydro-soluble vitamins (B complex and C). UHPLC-HRMS analysis of pomegranate extract showed the presence of 59 compounds, with gallotannins and ellagitannins being the most abundant phytochemicals. For the clinical study, 58 subjects were randomized into two groups, 1 and 2 (n = 29, each), which received either the food supplement or placebo. The effects of the food supplement against fatigue were assessed via validated questionnaires, recorded at time intervals t0 (at baseline), t1 (after 28 days), t2 (56 days), and t3 (after follow-up) in combination with the analysis of biochemical markers at t0 and t2. Fatigue severity scale (FSS) questionnaire scores were significantly decreased at the t2 and t3 time intervals in subjects treated with the food supplements, while the effect of the food supplement on a 12-Item Short Form Survey (SF-12) was not considerable. Moreover, the food supplement did not significantly affect biochemical parameters associated with fatigue and stress conditions. This study shows that the food supplement tested reduces prolonged fatigue following two months of supplementation in healthy subjects with mild prolonged fatigue.


Tobacco mosaic virus as a new carrier for tumor associated carbohydrate antigens.
Tumor-associated carbohydrate antigens (TACAs) are being actively studied as targets for antitumor vaccine development. One serious challenge was the low immunogenecity of these antigens. Herein, we report the results of using the tobacco mosaic virus (TMV) capsid as a promising carrier of a weakly immunogenic TACA, the monomeric Tn antigen. The copper(I) catalyzed azide-alkyne cycloaddition reaction was highly efficient in covalently linking Tn onto the TMV capsid without resorting to a large excess of the Tn antigen. The location of Tn attachment turned out to be important. Tn introduced at the N terminus of TMV was immunosilent, while that attached to tyrosine 139 elicited strong immune responses. Both Tn specific IgG and IgM antibodies were generated as determined by enzyme-linked immunosorbent assay and a glycan microarray screening study. The production of high titers of IgG antibodies suggested that the TMV platform contained the requisite epitopes for helper T cells and was able to induce antibody isotype switching. The antibodies exhibited strong reactivities toward Tn antigen displayed in its native environment, i.e., cancer cell surface, thus highlighting the potential of TMV as a promising TACA carrier.


[Mechanisms of the stimulating action of the Rauscher leukemia virus on togavirus reproduction in the bodies of BALB/c strain mice].
Reciprocal stimulation or inhibition are observed in double infection of mice with Rauscher leukemia virus (RLV) and togaviruses Sindbis or West Nile (WN). Stimulation of togavirus infections is manifested by the enhancement of the visceral phase of pathogenesis without subsequent activation of togarivus reproduction in the CNS. This effect is accompanied by enhanced togavirus replication in splenocytes, a decrease in the number of antibody-producing cells in the spleen, a decrease of antihemagglutinins titer in the blood without any significant change in the virus-neutralizing antibody and interferon titers. RLV-induced immunosuppression is termporary and of varying intensity with regard to individual parameters of immune response and to different variants of WN virus (highly virulent, poorly virulent). It is assumed that the differentiated and temporary nature of the immunosupressive effect of RLV is conducive to selective stimulation of the visceral phase of togavirus reproduction followed by inhibition of the neural phase under the influence of restored immune mechanisms and interferon. Because of the defects of humoral and cellular immunity, however, no complete elimination of togavirus occurs and conditions for its long-term persistence are created.


Complicated appendicitis--is the laparoscopic approach appropriate? A comparative study with the open approach: outcome in a community hospital setting.
Good outcome has been reported with the laparoscopic approach in uncomplicated appendicitis, but a higher incidence of postoperative intraabdominal abscesses has been reported after laparoscopic appendectomy in complicated appendicitis. This retrospective comparative study compares outcome after laparoscopic (LA) and open appendectomy (OA) in complicated appendicitis. All patients who had LA or OA for complicated appendicitis between January 2003 and February 2006 were included in the study. Data collection included demographics, operative time, estimated blood loss, length of stay (LOS), complications, readmission, and reoperative rates. The primary end points for analysis were postoperative intraabdominal abscess and complication rates and secondary end points were LOS and operative time. All data were analyzed on an intent-to-treat basis. Of 104 patients, 43 patients underwent LA and 61 had OA. The mean age (24.8 +/- 16.5 versus 31.3 +/- 18.9, P = 0.08) in the LA group was lower than the OA group because there was a significantly higher proportion of pediatric patients (34.8% versus 14.8%, P = 0.02) who had LA. There was no significant difference in gender (female/male, 14/29 versus 27/34, P = 0.3) or American Society of Anesthesiologists class distribution (American Society of Anesthesiologists 1/2/3/4/, 35/7/1/0 versus 45/12/3/1, P = 0.68) between the two groups. The operative time (100.5 +/- 36.2 versus 81.5 +/- 29.5 minutes, P = 0.03) was significantly longer and the estimated blood loss (21 mL versus 33 mL, P = 0.01) was lower in LA when compared with OA, but there was no significant difference in the number of patients with preoperative peritonitis versus abscesses (7/36 versus 13/48, P = 0.6) in both groups. There was no difference in the median LOS (6 [interquartile range 5-9] versus 6 [interquartile range 4-8], P = 0.7) in the two groups. The conversion rate in LA was 18.6% (n = 8). There was also no significant difference in the complication (17/43 [39.5%] versus 21/61 [34.4%], P = 0.54), reoperative (3/43 [7%] versus 0/61 [0%], P = 0.07), and 30-day readmission (5/41 [11.6%] versus 3/61 [4.9%], P = 0.23) rates between the two groups. The rate of postoperative intraabdominal abscesses was significantly higher in the LA group when compared with the OA group (6/43 [14%] versus 0/61 [0%], P = 0.04) and the wound infection (1/43 [2.3%] versus 5/61 [8.2%], P = 0.4) and pulmonary complication (0/43 [0%] versus 3/61 [4.9%], P = 0.26) rate was higher in the OA group. There was no mortality in the LA group, but there was one mortality in the OA group resulting from postoperative myocardial infarction. Laparoscopic appendectomy can be performed in patients with complicated appendicitis with a comparative operative time, LOS, and complication rates but results in a significantly higher intraabdominal abscess rate and lower wound infection rate when compared with OA.


Is Arthroderma simii the perfect state of Trichophyton Quinckeanum?
Gymnothecia with asci and ascospores developed repeatedly and in abundance whenever Trichophyton quinckeanum isolates X-392 and IMI 140691 were paired with Arthroderma simii 678 A. However, repeatable fertile crosses did not occur when all of our 19 isolates of T. quinckeanum were paired with 10 other isolates of A. simii comprising A and a mating types. Additional crosses between these 19 isolates of T. quinckeanum with A. simii and with A. benhamiae revealed that 11 of the 19 isolates of T. quinckeanum produced fertile gymnothecia only when crossed with A. simii 678 A but not when crossed with another isolate of A. simii of the A mating type nor when crossed with mating type a. All 19 isolates mated with A. benhamiae mating type A; therefore, all of our T. quinckeanum isolates were of the a mating type. Study of asci and random ascospores, selected with a micromanipulator, from crosses between several isolates of T. quinckeanum and A. simii 678 A revealed irregularities in the maturation of ascospores, poor ascospore germination, and a predominance of the A. simii phenotype and mating type for those ascospores that germinated and produced mature colonies. All these reactions are characteristic of interspecific crosses. In contrast, ascus analysis of the F1 progeny of crosses between these same isolates of T. quinckeanum with A. benhamiae revealed regular maturation of ascospores, better germination, and essentially a 1:1 segregation of mating types and parental phenotypes. This study confirms the concept that T. quinckeanum is not an independent species and that it is best considered to be a variety of T. mentagrophytes, as reported by Ajello, Bostick & Cheng (1968). Furthermore, our data indicate that T. mentagrophytes var. quinckeanum appears to be more closely related to A. simii than the granular variety of T. mentagrophytes, since fertile gymnothecia resulted from crosses between T. mentagrophytes var. quinckeanum and A. simii but not between T. mentagrophytes var. mentagrophytes and A. simii. Further implications of this study suggest the importance of extensive ascospore analysis when investigating the perfect states of fungi in order to avoid creating unwarranted new species.


Calcium, magnesium, phosphorus, and parathyroid hormone interrelationships in pregnancy and newborn infants.
The ability to measure directly human parathyroid hormone (hPTH) and ionized calcium (Ca++) is of fundamental importance in understanding their interrelation in pregnancy and the newborn. hPTH and Ca++ progressively increase throughout pregnancy. Since Ca++ is the direct determinant of hPTH levels, a different "set point" appears to be operative throughout pregnancy. The newborn infant, on the other hand, has higher serum Ca++ levels than its mother, and the infant's plasma hPTH is suppressed to undetectable or low levels. Ca++, total serum Ca, magnesium, and phosphorus are all significantly elevated in the serum of the mother at delivery. An active transport mechanism of all these minerals appears to be operative and lowers the maternal serum levels at the termination of labor in relation to serum levels in the third trimester of pregnancy.