Intraoral Hymenoptera sting.
Four days before a routine dental examination, the patient had been stung on the left side of the soft palate by a yellow jacket. The lesion was well demarcated, with a prominent area of deep red erythema approximately 1.5 cm in diameter. inside of which was a coral pink ring approximately 0.5 cm in diameter. The patient was not experiencing discomfort at the time of examination. Reactions to Hymenoptera stings usually include pain, erythema, and swelling, but, in more severe instances, extensive swelling and systemic reactions in the form of anaphylaxis or delayed allergic responses may be seen. The patient should be referred immediately to a physician or medical treatment facility for observation and treatment if necessary. If the stinger is located either periorally or intraorally, it should be carefully removed by flicking so that additional venom from the sac is not injected into the patient.


Detection of minimal residual disease in acute myeloid leukemia.
The distinction of clonogenic leukemic cells (CFU-L) and normal myeloid progenitors (GM-CFU) is a problem because both types of cells respond to the same growth factors and their clones resemble each other morphologically in culture. We investigated by means of an indirect enzyme-immunoassay the expression of "early" and "late" differentiation markers on bone marrow cell suspensions, as well as on agar clones in 18 cases of newly diagnosed acute myeloid leukemia (AML) as compared with 13 normal controls. Uncultured AML cells carried only low amounts of "late" myeloid differentiation antigen (CD15) but expressed nearly normal levels when cultured in agar with colony-stimulating factor (CSF). In contrast to normal bone marrow, AML cells were strongly reactive with "early" differentiation markers (CD10, CD20, CD34) and remained so during culture. Normal and leukemic agar clones could be specifically distinguished by CD20- and CD34 antibodies. By means of a double marker technique, it could be shown that "late" myeloid differentiation markers (CD15) and "early" markers (CD10, CD20, CD34) were coexpressed on the same cells only in AML but not in normal bone marrow. Leukemic clones were identified by phenotyping of agar clones in 17 of 19 cases investigated during complete clinical remission (CR) of the disease. A formal proof of the leukemic origin of CD20/CD34 positive clones grown in CR was made possible in four cases either by Southern blot analysis or by a cytogenetic marker. These results demonstrate that AML cells can partially differentiate in vitro in the presence of CSF. A distinction of AML from normal clones, however, is possible by their reactivity with "early" differentiation markers, because this is maintained under the differentiating influence of CSF. The technique described here identifies residual leukemic clones in the majority of AML in CR, which persist at a constant rate and increase 6 months before cytological relapse.


Coproporphyrin excretion in healthy newborn babies.
The urinary and fecal coproporphyrins (CP) undergo significant changes in cholestatic diseases of both adults and infants and their determination may provide a diagnostic tool. Little is known about CP excretion in the first days of life. The authors have studied the daily urinary and fecal excretion of CP as well as the I and III isomer distribution in 10 healthy newborn babies from 1 to 10 days old. CP were determined by the solvent partition method and the isomer distribution by thin-layer chromatographic technique. Preliminary studies on urinary porphyrin pattern were performed using a personal high-performance liquid chromatographic method. CP excretion was almost 10 times higher on the 1st day than on the 10th, when expressed by adult standards. The isomer I accounted for almost 80% of the total amount on the first days, whereas at the end of the study, both the CP total amount and isomer distribution overlapped the infant and adult pattern. The authors propose a personal interpretation based on a possible transient enzymatic defect in the metabolic chain of heme synthesis.


Maternal postpartum deworming and infant milk intake: Secondary outcomes from a trial.
The World Health Organization recommends deworming to reduce soil-transmitted helminth (STH)-attributable morbidity in women of reproductive age, including pregnant and lactating women, to reduce blood loss, iron deficiency anaemia and nutrient malabsorption. This study assessed the impact of maternal postpartum deworming with albendazole approximately 1 day after delivery on infant milk intake among a subset of 216 randomly selected mother-infant pairs recruited into a large trial in Peru. Infant milk intake was measured using the deuterium-oxide method at 1- and 6-month postpartum. Maternal STH infection was measured at 6-month postpartum. At 1-month postpartum, mean intake was 756 ± 16 and 774 ± 18 mL day-1 in the albendazole and placebo groups, respectively (mean difference: -18 mL day-1 ; 95% CI: -65, 30). At 6-month postpartum, mean intake was 903 ± 16 and 908 ± 18 mL day-1 in the albendazole and placebo groups, respectively (mean difference: -5 mL day-1 ; 95% CI: -52, 43). There was no statistically significant difference in milk intake between groups at either time point. At 6-month postpartum, mothers infected with Trichuris trichiura had infants with higher milk intakes (adjusted mean difference: 70 mL day-1 ; 95% CI: 20, 120) compared with uninfected mothers. However, there was no statistically significant difference in infant milk intake between mothers who had moderate-and-heavy intensity infection compared with the comparison group (mothers with no and light intensity infection). A lower prevalence and intensity of infection, and inclusion of uninfected mothers in both arms of the trial, resulting in effect dilution, may explain the null findings.


Impedance Pumping and Resonance in a Multi-Vessel System.
Impedance pumping is a mechanism that generates flow in a compliant vessel by repeatedly actuating the vessel asymmetrically, without employing any internal valves, blades, or other mechanisms. The net flow is obtained by establishing a constructive wave pattern. Elaborate studies of impedance pumping in a single vessel have shown that the flow rate strongly depends on the actuation frequency, as well as on other parameters, such as actuator location and amplitude, and that it operates best in the resonance mode. The present study extends these principles to a network of multiple compliant vessels, representing a cardiovascular system. The flow is modeled numerically by the one-dimensional approximation of the Navier-Stokes equations. Two configurations were examined, systems consisting of three and five compliant vessels. First, the natural frequencies of these configurations were identified. Then, the dependence of the net flow rate (NFR) on the actuating frequency was explored, showing that impedance pumping operates best in the resonance mode in the case of a network of vessels as well. The impact of other parameters were studied as well, such as the location of one or two actuators, actuation amplitude, actuator width, the duty cycle, and the phase lag between the actuators. The results show that impedance pumps can generate significant NFR and the obtained NFR can be manipulated by properly setting up one or more of the governing parameters. These findings indicate that impedance pumping principles may be applied to flow control of the cardiovascular system.


Oral chromium picolinate improves carbohydrate and lipid metabolism and enhances skeletal muscle Glut-4 translocation in obese, hyperinsulinemic (JCR-LA corpulent) rats.
Human studies suggest that chromium picolinate (CrPic) decreases insulin levels and improves glucose disposal in obese and type 2 diabetic populations. To evaluate whether CrPic may aid in treatment of the insulin resistance syndrome, we assessed its effects in JCR:LA-corpulent rats, a model of this syndrome. Male lean and obese hyperinsulinemic rats were randomly assigned to receive oral CrPic [80 microg/(kg. d); n = 5 or 6, respectively) in water or to control conditions (water, n = 5). After 3 mo, a 120-min intraperitoneal glucose tolerance test (IPGTT) and a 30-min insulin tolerance test were performed. Obese rats administered CrPic had significantly lower fasting insulin levels (1848 +/- 102 vs. 2688 +/- 234 pmol/L; P < 0.001; mean +/- SEM) and significantly improved glucose disappearance (P < 0.001) compared with obese controls. Glucose and insulin areas under the curve for IPGTT were significantly less for obese CrPic-treated rats than in obese controls (P < 0.001). Obese CrPic-treated rats had lower plasma total cholesterol (3.57 +/- 0.28 vs. 4.11 +/- 0.47 mmol/L, P < 0.05) and higher HDL cholesterol levels (1.92 +/- 0.09 vs. 1.37 +/- 0.36 mmol/L, P < 0.01) than obese controls. CrPic did not alter plasma glucose or cholesterol levels in lean rats. Total skeletal muscle glucose transporter (Glut)-4 did not differ among groups; however, CrPic significantly enhanced membrane-associated Glut-4 in obese rats after insulin stimulation. Thus, CrPic supplementation enhances insulin sensitivity and glucose disappearance, and improves lipids in male obese hyperinsulinemic JCR:LA-corpulent rats.


Human osteoblast-like cells contain specific, saturable, high-affinity glucocorticoid, androgen, estrogen, and 1 alpha,25-dihydroxycholecalciferol receptors.
Glucocorticoids, androgens, estrogens and 1 alpha,25-dihydroxycholecalciferol (1 alpha,25-(OH)2D3) exert a variety of effects on bone homeostasis. We have measured the receptors for these hormones in cultured human osteoblast-like cells. Specific binding was found with each of the four steroids tested, namely maximum binding capacities, Bmax, of 2,581 (1,368-4,223), 146 (101-237), 176 (20-552), and 387 (290-620) fmol.mg DNA-1 (mean, range) for [3H]dexamethasone, [3H]5 alpha-dihydrotestosterone, [3H]17 beta-estradiol ([3H]E2), and [3H]1 alpha,25-(OH)2D3, respectively. The corresponding apparent dissociation constants were 13.3 (9.2-22.2), 0.43 (0.23-0.94), 0.45 (0.17-0.88), and 0.020 (0.008-0.030) nM, respectively. Both high-affinity, low-capacity and low-affinity, high-capacity specific [3H]E2 binding were demonstrable. In conclusion, we could demonstrate that human osteoblast-like cells contain specific glucocorticoid receptors. In addition specific androgen, estrogen, and 1 alpha,25-(OH)2D3 binding was demonstrated. These cells contain several times more binding sites for dexamethasone than for dihydrotestosterone, estradiol, and 1 alpha,25-(OH)2D3, a feature that might contribute to the marked sensitivity of human bone to glucocorticoids.


Association between Fundus Tessellation and Contrast Sensitivity in Myopic Eyes.
To assess the association of fundus tessellation with contrast sensitivity, Quality of Vision questionnaire, and other factors at five years postcorneal refractive surgery. This is a cross-sectional study. Both eyes of 98 subjects (196 eyes) who received femtosecond laser in situ keratomileusis (FS-LASIK) or small incision lenticular extraction (SMILE) five years prior were enrolled in this study. Fundus tessellation was imaged using wide-angle fundus photographs and graded into four categories with the assistance of the ETDRS grid. Photopic and mesopic contrast sensitivity were measured under the best correction. The Quality of Vision (QoV) questionnaire was used to assess visual symptoms. Fundus tessellation was classified as follows: 19 eyes were grade 0 (9.7%), 28 eyes were grade 1 (14.3%), 59 eyes were grade 2 (30.1%), and 90 eyes were grade 3 (45.9%). Higher degrees of fundus tessellation were associated with lower photopic contrast sensitivity, a significant difference was observed at spatial frequencies of 6cpd (p = 0.030, grade 1 >grade 3 p = 0.011). Higher degrees of fundus tessellation were also associated with lower mesopic contrast sensitivity, a significant difference was observed at spatial frequencies of 18cpd (p = 0.011, grade 0 >grade 3 p = 0.012). The preoperative degree of myopia was positively associated with fundus tessellation grade (p < 0.001). However, in linear mixed-effect model analysis, no significant influence of parameters (contrast sensitivity, preoperative myopia, and QoV scores) upon different tessellation grades was found (p > 0.05). Patients with moderate and high myopia were more likely to have higher grades of fundus tessellation. Higher degree of fundus tessellation associates with lower contrast sensitivity. Patients with moderate and high myopia should be concerned with retinal-choroidal changes. Contrast sensitivity could be a clinical sign for progression of tessellation and used to screen for early retinal-choroidal changes to prevent pathologic myopia.


On-the-Fly Machine Learning of Atomic Potential in Density Functional Theory Structure Optimization.
Machine learning (ML) is used to derive local stability information for density functional theory calculations of systems in relation to the recently discovered SnO_{2}(110)-(4×1) reconstruction. The ML model is trained on (structure, total energy) relations collected during global minimum energy search runs with an evolutionary algorithm (EA). While being built, the ML model is used to guide the EA, thereby speeding up the overall rate by which the EA succeeds. Inspection of the local atomic potentials emerging from the model further shows chemically intuitive patterns.


Ocular Adnexal Reconstruction for Cutaneous Periocular Malignancies.
Although the majority of lesions present in the periocular region are benign, periocular cutaneous malignancies are certainly not uncommon and must be considered. The management of nonmelanoma cutaneous malignancies is predominately surgical with Mohs micrographic surgery or excision with frozen sections. The approach to reconstruction of the resulting defects depends on the defect location and size. When able, it is preferable to close lesions directly or with the recruitment of adjacent tissue in an effort to preserve the inherent anatomy. The eyelid's dynamic function is thus maintained, which is essential for optimal ocular surface protection. However, larger and more extensive defects will require complex reconstructions that are able to restore the necessary structural integrity to the eyelids. The authors review the various reconstruction approaches for defects of all sizes involving the periocular area including nonmarginal defects and defects of the lower and upper eyelids, as well as those of the medial canthal region.


Pentoxifylline for the prevention of bronchopulmonary dysplasia in preterm infants.
Bronchopulmonary dysplasia (BPD) is a common complication in preterm infants. BPD is associated with poor long-term respiratory and neurodevelopmental outcome and increased mortality. The prophylactic use of agents that modulate inflammation such as pentoxifylline, a synthetic methylxanthine and phosphodiesterase inhibitor, may reduce the incidence of BPD. The primary objective of this review was to determine the effect of pentoxifylline on the incidence of BPD, death prior to 36 weeks postmenstrual age (PMA), and BPD or death prior to 36 weeks PMA in preterm neonates. We searched the Cochrane Neonatal Review Group Specialized Register, CENTRAL (The Cochrane Library Issue 9, 2012), EMBASE (January 1974 to September 2012), PubMed (January 1966 to September 2012), and CINAHL (January 1982 to September 2012) in September 2012. We checked references and cross-references from identified studies. We handsearched abstracts from the proceedings of the Pediatric Academic Societies Meetings (from January 1990 to September 2012). We placed no restrictions on language. Randomised or quasi-randomised clinical trials of systemic or nebulised pentoxifylline in preterm neonates less than 32 weeks gestational age or less than 1500 g birth weight, reporting on at least one outcome of interest, were eligible for inclusion in the review. We used the standard methods of the Cochrane Neonatal Review Group and The Cochrane Collaboration. Two review authors (SMS and SK) independently searched the literature as described above and selected studies. Any disagreements were resolved by discussion involving all review authors. We identified one randomised clinical trial eligible for inclusion in this review. This study compared the use of nebulised pentoxifylline versus placebo for prevention of BPD in 100 preterm infants and was at high risk of bias due to lack of blinding of intervention and outcome assessors, and incomplete outcome data. There was no statistically significant effect of nebulised pentoxifylline versus placebo on individual outcomes of BPD at 36 weeks PMA or on death prior to 36 weeks PMA. There was no significant effect of nebulised pentoxifylline on intraventricular haemorrhage, periventricular leukomalacia, sepsis, or patent ductus arteriosus (PDA) requiring ligation. The study did not report any of the other secondary outcomes considered for this review. Reporting of adverse events was very limited and did not allow for reliable judgement on the incidence of such events. No long-term outcomes were reported. There is insufficient evidence to determine the safety and efficacy of pentoxifylline for prevention of BPD in preterm neonates. We encourage researchers to conduct clinical trials to confirm or refute the role of pentoxifylline for prevention of BPD in preterm neonates. These trials should report on clinically important outcomes and, ideally, on long-term neurodevelopmental outcome.


Supramolecular bimetallic assemblies for photocatalytic hydrogen generation from water.
A series of supramolecular assemblies of the type [Ru(L-L)2(L'-L)MX2)](n+) are reported where L-L is 2,2'-bipyridine (bipy), 4,4'-di-tetra-butyl-bipyridine (tbbipy) or 4,4'-diethoxycarbonyl-2,2'-bipyridine (dceb), L-L' is tetrapyrido[3,2-a:2',3'-c:3'',2''-h:2''',3'''-j]phenazine (tpphz), 2,2':5',2''-terpyridine (2,5-bpp), 2,2':6',2''-terpyridine, (2,6-bpp), 2,5-di(pyridine-2-yl)pyrazine (2,5-dpp) or 2,3-di(pyridine-2-yl)pyrazine (2,3-dpp), and MX2 is PdCl2, PtCl2 or PtI2. The photocatalytic behaviour with respect to hydrogen generation of these compounds and their ultrafast photophysical properties are discussed as a function of the nature of the peripheral ligands, the bridging ligands and the catalytic centre. The results obtained show how differences in the chemical composition of the photocatalysts can affect intramolecular photoinduced electron transfer processes and the overall photocatalytic efficiency.


Effect of Boiling and roasting on lipid quality, proximate composition, and mineral content of walnut seeds (Tetracarpidium conophorum) produced and commercialized in Kumba, South-West Region Cameroon.
The effect of boiling and roasting on the lipid quality, proximate composition, and mineral content of African walnut seeds (Tetracarpidium conophorum) was assessed. Results indicated that the quality of walnut oil significantly (p < .05) reduces with the treatments. Oils extracted from DBWN 60 min (Dried and boiled walnuts 60 min) and FBWN 60 min (Boiled fresh walnuts 60 min) were the most altered. The proximate composition and mineral content of walnut seeds was also significantly affected (p < .05) by the treatments. This study reveals that, thermal processing has significant effects on the nutrients and quality of lipids of walnut oil. DTRWN 60 min (Dried and traditionally roasted walnuts 60 min), DORWN 60 min (Dried and oven roasted walnuts 60 min), and TRFWN 30 min (traditionally roasted fresh nuts 30 min) are the best methods for cooking walnut because they preserve the quality of its lipids and some of the nutrients.


Memory prerequisites of mismatch negativity in the auditory event-related potential (ERP).
The mismatch negativity (MMN) is a component of the auditory event-related brain potential that occurs in response to infrequent changes in the physical properties of homogeneous series of sounds, even when subjects are instructed to ignore the auditory channel of stimulation. It has been proposed (e.g., Näätänen, 1990) that the MMN is generated by an automatic process in which a difference between the deviant sound and the previous, standard sound is detected by the brain. However, it is unclear how the form of memory involved is related to the rest of the memory system. The present study indicates that, for an MMN to be elicited in response to a change in tone frequency, the representation of the standard tone must be both (a) well-established as a standard in memory, and (b) in a currently active state. The relation between physiological and psychological aspects of memory representation is discussed.


Mechanistic Impact of Zinc Deficiency in Human Development.
Zinc (Zn) deficiency in humans is an emerging global health issue affecting approximately two billion people across the globe. The situation prevails due to the intake of Zn deficient grains and vegetables worldwide. Clinical identification of Zn deficiency in humans remains problematic because the symptoms do not appear until impair the vital organs, such as the gastrointestinal track, central nervous system, immune system, skeletal, and nervous system. Lower Zn body levels are also responsible for multiple physiological disorders, such as apoptosis, organs destruction, DNA injuries, and oxidative damage to the cellular components through reactive oxygen species (ROS). The oxidative damage causes chronic inflammation lead toward several chronic diseases, such as heart diseases, cancers, alcohol-related malady, muscular contraction, and neuro-pathogenesis. The present review focused on the physiological and growth-related changes in humans under Zn deficient conditions, mechanisms adopted by the human body under Zn deficiency for the proper functioning of the body systems, and the importance of nutritional and nutraceutical approaches to overcome Zn deficiency in humans and concluded that the biofortified food is the best source of Zn as compared to the chemical supplementation to avoid their negative impacts on human.


Choriocarcinoma syndrome: A rare presentation of testicular germ cell tumour.
Germ cell tumours (GCT) are the most common malignancy in men between the ages of 15 and 35 years. Pure choriocarcinoma is a very rare entity of non- seminomatous germ cell tumour and comprises only 1% -3% of all the testicular tumours. Choriocarcinoma syndrome is a clinical condition in which haemorrhage occurs from the metastatic sites with elevated level of the Beta-Human Chorionic gonadotropin (Beta -HCG). A 15-year-old adolescent boy presented in with left sided testicular swelling along with dark coloured cutaneous lesions of the scalp, chest and chin for the last one month. He underwent left sided orchiectomy, and the histopathology report showed Pure Choriocarcinoma. Unfortunately, he died after the beginning of chemotherapy due to alveolar haemorrhage.


A convenient chemo-enzymatic synthesis and 18F-labelling of both enantiomers of trans-1-toluenesulfonyloxymethyl-2-fluoromethyl-cyclopropane.
The present report is concerned with a stereoselective, reliable route to trans-1,2-disubstituted cyclopropanes and in particular to (S,S)-1-tosyloxymethyl-2-fluoromethyl-cyclopropane (1) and (R,R)-1-tosyloxymethyl-2-fluoromethyl-cyclopropane (ent-1) as conformationally restricted, terminally fluorinated C4-building blocks for medicinal chemistry. The enzymatic kinetic resolution based synthesis of 1 and ent-1 utilises inexpensive, commercially available starting materials. It is based on enantiomeric resolution of rac-cyclopropane carboxylic esters using esterase from Streptomyces diastatochromogenes. Both enantiomers of 1 were prepared selectively in high overall yield over nine steps, starting from ethyl acrylate. The successful radiosynthesis of [18F]-1 and [18F]-ent-1 is also reported.


Epicuticular wax chemicals of Lablab purpureus subsp. bengalensis influence short-range attraction and oviposition responses in Aphis craccivora and Aphis gossypii.
Lablab purpureus subsp. bengalensis (Jacq.) Verdc. is an important legume of India and Africa. Both aphids, Aphis craccivora Koch and A. gossypii Glover (Hemiptera: Aphididae), are important herbivorous pests of this legume crop. These viviparous females lay nymphs on the leaf surface of this legume plant. Therefore, it is of considerable interest to study whether leaf surface wax chemicals (long-chain alkanes and free fatty acids) of this legume plant served as short-range attractants and oviposition stimulants in both females to lay nymphs. Twenty-one n-alkanes from n-C12 to n-C35 and 11 free fatty acids from C12:0 to C22:0 were identified in leaf surface waxes. Nonacosane and nonadecanoic acid were the most abundant among n-alkanes and free fatty acids, respectively. Both females were attracted towards one leaf equivalent surface wax against the control solvent (petroleum ether) in short Y-tube olfactometer bioassays. A synthetic blend of tetradecane, pentadecane, tetracosane, tridecanoic acid, tetradecanoic acid, and heneicosanoic acid comparable to one leaf equivalent surface wax served as short-range attractants and oviposition stimulants in A. craccivora; whereas a synthetic blend of tetradecane, hexadecane, docosane, nonadecanoic acid, and arachidic acid comparable to one leaf equivalent surface wax acted as short-range attractants and oviposition stimulants in A. gossypii. These results can provide the basis for efficient pest management strategies of A. craccivora and A. gossypii against L. purpureus subsp. bengalensis using host plant leaf surface wax compounds. Further, SEM studies of antennae and forelegs of both aphids were conducted to observe sensilla structures, which help in chemoreception.


Radiation protectants: current status and future prospects.
In today's heightened nuclear/biological/chemical threat environment, there is an increased need to have safe and effective means to protect not only special high-risk service groups, but also the general population at large, from the health hazards of unintended ionizing radiation exposures. An unfulfilled dream has been to have a globally effective pharmacologic that could be easily taken orally without any undue side effects prior to a suspected or impending nuclear/radiological event; such an ideal radioprotective agent has yet to be identified, let alone fully developed and approved for human use. No one would argue against the fact that this is problematic and needs to be corrected, but where might the ultimate solution to this difficult problem be found? Without question, representative species of the aminothiol family [e.g., Amifostine (MedImmune, Gaithersburg, Maryland)] have proven to be potent cytoprotectants for normal tissues subjected to irradiation or to radiomimetic chemicals. Although Amifostine is currently used clinically, drug toxicity, limited times of protection, and unfavorable routes of administration, all serve to limit the drug's utility in nonclinical settings. A full range of research and development strategies is being employed currently in the hunt for new safe and effective radioprotectants. These include: (1) large scale screening of new chemical classes or natural products; (2) restructuring/reformulating older protectants with proven efficacies but unwanted toxicities; (3) using nutraceuticals that are only moderately protective but are essentially nontoxic; (4) using low dose combinations of potentially toxic but efficacious agents that protect through different routes to foster radioprotective synergy; and (5) accepting a lower level of drug efficacy in lieu of reduced toxicity, banking on the premise that the protection afforded can be leveraged by post-exposure therapies. Although it is difficult to predict which of these strategies will ultimately prove to be successful, it is certain that the probability of a useful protectant being fielded is increased significantly. This is due to the resurgence of interest in radiation protection, increased resources being expended by federal agencies, and by the Food and Drug Administration's willingness to innovate relative to new approval guidance.


Effect of RNA secondary structure and modified bases on the inhibition of trypanosomatid protein synthesis in cell free extracts by antisense oligodeoxynucleotides.
Every messenger RNA from leishmanias and trypanosomes has at its 5' end a conserved region termed the mini-exon sequence which, however, varies from species to species. In a systematic study mRNAs from Trypanosoma brucei, Trypanosoma vivax, and Leishmania enriettii were translated in cell-free extracts in the presence of oligodeoxynucleotides complementary to part of the mini-exon sequence. The affinity of the same oligonucleotides for target and non-target mRNAs was determined by thermal elution of filter-bound complexes showing that the critical temperature of half-dissociation of the complexes was linearly related to log (l + x), where l is the length of the oligomer and x its G + C content. A few oligomers exhibited a lower Tc value than expected which was ascribed to the presence of modified RNA bases or to the existence of a hairpin structure in the L. enriettii mini-exon. In most cases the efficiency of translation inhibition by the oligonucleotides was clearly correlated to their affinity for the target RNA. The modified bases weakened the inhibition of protein synthesis by oligonucleotides complementary to these regions.


Phyto-mediated biosynthesis of silver nanoparticles using the rind extract of watermelon (Citrullus lanatus) under photo-catalyzed condition and investigation of its antibacterial, anticandidal and antioxidant efficacy.
The biological synthesis of nanoparticles has gained tremendous interest, and plants and plant extracts are preferred over other biological sources for this process because of their rich content of bioactive metabolites. In this study, silver nanoparticles (AgNPs) were produced utilizing the aqueous extract of watermelon rind (WRA), an agricultural waste material under photo exposed condition at room temperature, and tested for their antibacterial, anticandidal and antioxidant activities. The synthesized AgNPs showed surface plasmon resonance at 425nm with an average size of 109.97nm. The morphology and elemental composition was confirmed by scanning electron microscopy (SEM) and energy dispersive X-ray analysis (EDX). The Fourier transform infrared spectroscopy (FT-IR) and thermogravimetric and differential thermogravimetric analysis (TG/DTG) confirmed that the bioactive compounds from the WRA extract were involved in the synthesis and capping of AgNPs. X-ray diffraction (XRD) revealed the crystallite nature of the AgNPs. The AgNPs exhibited strong broad spectrum antibacterial activity against five different foodborne bacteria with zones of inhibition 9.12-14.54mm in diameter. When AgNPs were mixed with kanamycin and rifampicin the mixture exhibited strong antibacterial synergistic activity. The AgNPs also exerted strong synergistic anticandidal activity when they were combined with amphotericin b. The AgNPs had high antioxidant activity and reducing power. Overall, the results confirmed the bio-potentials of the synthesized AgNPs using WRA, which could have applications in the biomedical, cosmetic, pharmaceutical, food preservation and packaging industries.


Reward processing and psychopathic traits in children.
Growing evidence has suggested that the mechanisms underlying the 3 dimensions of psychopathic traits, including grandiose-manipulative, callous-unemotional, and daring-impulsive, are different. As yet, the neurobiological correlates of each dimension have not been fully understood. In this study, we examined if reward processing deficits were differentially associated with these traits, and whether social adversity moderated these relationships. Pre-ejection period (PEP) was assessed in children between 8 and 10 years of age from the community (N = 340, Mage = 9.06, SD = .60; 48.2% boys) while they were completing a reward task, and the caregivers rated children's psychopathic traits. Results indicated that (a) high callous-unemotional traits were associated with less PEP shortening, reflecting reward hyporesponsivity, at low levels of social adversity, and more PEP shortening, indicating hyperresponsivity, at high levels of social adversity, (b) high daring-impulsive traits were associated with hyperresponsivity at low levels of adversity only, and (c) grandiose-manipulative traits were not linked to reward processing deficits. Findings provide further evidence that different etiologies may underlie various dimensions of psychopathic traits and highlight the important role of psychosocial factors in understanding the neurobiological mechanism of youth psychopathy. (PsycInfo Database Record (c) 2021 APA, all rights reserved).


Mile high on heroin: Lessons on the opioid epidemic from the Mile High City.
This commentary discusses the novelty of the preclinical opioid choice model published in Heinsbroek et al., Nat Commun, 2021, and the potential influence of altitude on the reported findings. The studies were performed in the Mile High City of Denver, Colorado, where a unique subpopulation of heroin-choosing rats were noted.


Phosphatidylinositol 3-kinase regulates macrophage responses to double-stranded RNA and encephalomyocarditis virus.
Virus infection of macrophages stimulates the expression of proinflammatory and antiviral genes interleukin-1 (IL-1), inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). In this study, we show that phosphatidylinositol 3-kinase (PI3K) is required for the inflammatory response of macrophages to virus infection. When macrophages are infected with encephalomyocarditis virus (EMCV) there is a rapid and transient activation of PI3K and phosphorylation of its downstream target Akt. Inhibitors of PI3K attenuate EMCV- and double-stranded RNA-induced iNOS, COX-2 and IL-1 beta expression in RAW264.7 cells and mouse peritoneal macrophages. The attenuation of inflammatory gene expression in response to PI3K inhibition correlates with the induction of macrophage apoptosis. The morphology of macrophages shifts from activation in response to EMCV infection to apoptosis in the cells treated with PI3K inhibitors and EMCV. These morphological changes are accompanied by the activation of caspase-3. These findings suggest that PI3K plays a central role in the regulation of macrophage responses to EMCV infection. When PI3K is activated, it participates in the regulation of inflammatory gene expression; however, if PI3K is inhibited macrophages are unable to mount an inflammatory antiviral response and die by apoptosis.


Curcumin Acetate Nanocrystals for sustained Pulmonary Delivery: Preparation, Characterization and In Vivo Evaluation.
The main objective of this study was to test the hypothesis that inhaled nanocrystals of a highly lipophilic drug could be used as a novel approach for producing sustained pulmonary delivery. Curcumin acetate, an ester prodrug of curcumin, was utilized as a highly lipophilic model drug. Curcumin acetate was subjected to wet ball milling to produce different particle sizes of nanocrystals and microparticles, and the milled curcumin acetate was spray-dried to yield similar inhalable microparticles. Following intrapulmonary administration in rats, pharmacokinetic experiments indicated that curcumin acetate significantly extended the pulmonary absorption time by 7.2-fold compared to curcumin, possibly due to the high lipophilicity of the former. The biodistribution data showed that aerosolized curcumin acetate nanocrystals 123.7 nm in size not only prolonged pulmonary retention, with the AUC value of curcumin acetate being 7.62-fold higher than that of the microparticles 1120 nm in size, but also increased the local in vivo release rate by 3.3-fold and the local availability of converted curcumin by 25.1-fold. In addition, the improved local availability resulted in better pharmacological efficacy in a monocrotaline-induced rat model of pulmonary arterial hypertension. This study was the first to demonstrate that inhalable nanocrystals are a feasible means for the sustained pulmonary delivery of highly lipophilic drugs.


High-Pressure-Sintering-Induced Microstructural Engineering for an Ultimate Phonon Scattering of Thermoelectric Half-Heusler Compounds.
Thermal management is of vital importance in various modern technologies such as portable electronics, photovoltaics, and thermoelectric devices. Impeding phonon transport remains one of the most challenging tasks for improving the thermoelectric performance of certain materials such as half-Heusler compounds. Herein, a significant reduction of lattice thermal conductivity (κL ) is achieved by applying a pressure of ≈1 GPa to sinter a broad range of half-Heusler compounds. Contrasting with the common sintering pressure of less than 100 MPa, the gigapascal-level pressure enables densification at a lower temperature, thus greatly modifying the structural characteristics for an intensified phonon scattering. A maximum κL reduction of ≈83% is realized for HfCoSb from 14 to 2.5 W m-1 K-1 at 300 K with more than 95% relative density. The realized low κL originates from a remarkable grain-size refinement to below 100 nm together with the abundant in-grain defects, as determined by microscopy investigations. This work uncovers the phonon transport properties of half-Heusler compounds under unconventional microstructures, thus showing the potential of high-pressure compaction in advancing the performance of thermoelectric materials.


Consequentialism and the Synthetic Biology Problem.
This article analyzes the ethics of synthetic biology (synbio) from a consequentialist perspective, examining potential effects on food and agriculture, and on medicine, fuel, and the advancement of science. The issues of biosafety and biosecurity are also examined. A consequentialist analysis offers an essential road map to policymakers and regulators as to how to deal with synbio. Additionally, the article discusses the limitations of consequentialism as a tool for analysing synbioethics. Is it possible to predict, with any degree of plausibility, what the consequences of synthetic biology will be in 50 years, or in 100, or in 500? Synbio may take humanity to a place of radical departure from what is known or knowable.


Perspectives on the use of new diagnostic tools in the treatment of chronic lymphocytic leukemia.
Recently, considerable progress has been made in the identification of molecular and cellular markers that may predict the tendency for disease progression in patients with chronic lymphocytic leukemia (CLL) or detect minimal residual disease after therapy. These developments have created uncertainty for clinicians who hope to incorporate the use of these markers and new disease-assessment tools into standard clinical practice. However, clinical trials are required to determine whether poor-prognosis leukemia-cell markers, such as expression of unmutated immunoglobulin genes or the zeta-associated protein of 70 kDa (ZAP-70), can be used as the basis for determining the time or type of therapy. Pending the outcome of such trials, treatment decisions outside the context of a clinical trial still should be based on guidelines established by the most recent National Cancer Institute-sponsored Working Group.


The relationship between charge and molecular dynamics in viscous acid hydrates.
Oscillatory shear rheology has been employed to access the structural rearrangements of deeply supercooled sulfuric acid tetrahydrate (SA4H) and phosphoric acid monohydrate, the latter in protonated (PA1H) and deuterated (PA1D) forms. Their viscoelastic responses are analyzed in relation to their previously investigated electric conductivity. The comparison of the also presently reported dielectric response of deuterated sulfuric acid tetrahydrate (SA4D) and that of its protonated analog SA4H reveals an absence of isotope effects for the charge transport in this hydrate. This finding clearly contrasts with the situation known for PA1H and PA1D. Our analyses also demonstrate that the conductivity relaxation profiles of acid hydrides closely resemble those exhibited by classical ionic electrolytes, even though the charge transport in phosphoric acid hydrates is dominated by proton transfer processes. At variance with this dielectric simplicity, the viscoelastic responses of these materials depend on their structural compositions. While SA4H displays a "simple liquid"-like viscoelastic behavior, the mechanical responses of PA1H and PA1D are more complex, revealing relaxation modes, which are faster than their ubiquitous structural rearrangements. Interestingly, the characteristic rates of these fast mechanical relaxations agree well with the characteristic frequencies of the charge rearrangements probed in the dielectric investigations, suggesting appearance of a proton transfer in mechanical relaxation of phosphoric acid hydrates. These findings open the exciting perspective of exploiting shear rheology to access not only the dynamics of the matrix but also that of the charge carriers in highly viscous decoupled conductors.


Exceptionally Strong Electron-Donating Ability of Bora-Ylide Substituent vis-à-vis Silylene and Silylium Ion.
Electropositive boron-based substituent (phosphonium bora-ylide) with an exceptionally strong π- and σ-electron donating character dramatically increases the stability of a new type of N-heterocyclic silylene 2 featuring amino- and bora-ylide-substituents. Moreover, the related silylium ion 4 and transition-metal-silylene complexes, with trigonal-planar geometries around the silicon center, are also well stabilized. Therefore, the N,B-heterocyclic silylene 2 can be used as a strongly electron-donating innocent ligand in coordination chemistry similarly to N-heterocyclic carbenes.


Detailed Structural Characterization of the Lipooligosaccharide from the Extracellular Membrane Vesicles of Shewanella vesiculosa HM13.
Bacterial extracellular membrane vesicles (EMVs) are membrane-bound particles released during cell growth by a variety of microorganisms, among which are cold-adapted bacteria. Shewanella vesiculosa HM13, a cold-adapted Gram-negative bacterium isolated from the intestine of a horse mackerel, is able to produce a large amount of EMVs. S. vesiculosa HM13 has been found to include a cargo protein, P49, in the EMVs, but the entire mechanism in which P49 is preferentially included in the vesicles has still not been completely deciphered. Given these premises, and since the structural study of the components of the EMVs is crucial for deciphering the P49 transport mechanism, in this study the complete characterization of the lipooligosaccharide (LOS) isolated from the cells and from the EMVs of S. vesiculosa HM13 grown at 18 °C is reported. Both lipid A and core oligosaccharide have been characterized by chemical and spectroscopic methods.


Coeliac disease and multiple immunodeficiencies: case report of a diagnostic dilemma.
Coeliac disease (CD) often coexists with other autoimmune and primary immunodeficiency diseases (PID), creating a problem in timely diagnosis and management. An unusual case of coeliac disease that was difficult to diagnose and manage because of its unusual clinical presentation. Initially diagnosed as celiac disease but showed poor response to standard therapy is reported. Frequent attacks of opportunistic infections led to immunodeficiency work-up that revealed natural killer cell (NK) deficiency with low serum IgA and IgG2 levels. The patient eventually succumbed to recurrent infections. The co-existence of PID is unusual in a patient with CD. This case report highlights the importance of investigating PID in patients with autoimmunity.


Differential Effects of Erythropoietin Administration and Overexpression on Venous Thrombosis in Mice.
Deep vein thrombosis (DVT) is a common condition associated with significant mortality due to pulmonary embolism. Despite advanced prevention and anticoagulation therapy, the incidence of venous thromboembolism remains unchanged. Individuals with elevated hematocrit and/or excessively high erythropoietin (EPO) serum levels are particularly susceptible to DVT formation. We investigated the influence of short-term EPO administration compared to chronic EPO overproduction on DVT development. Additionally, we examined the role of the spleen in this context and assessed its impact on thrombus composition. We induced ligation of the caudal vena cava (VCC) in EPO-overproducing Tg(EPO) mice as well as wildtype mice treated with EPO for two weeks, both with and without splenectomy. The effect on platelet circulation time was evaluated through FACS analysis, and thrombus composition was analyzed using immunohistology. We present evidence for an elevated thrombogenic phenotype resulting from chronic EPO overproduction, achieved by combining an EPO-overexpressing mouse model with experimental DVT induction. This increased thrombotic state is largely independent of traditional contributors to DVT, such as neutrophils and platelets. Notably, the pronounced prothrombotic effect of red blood cells (RBCs) only manifests during chronic EPO overproduction and is not influenced by splenic RBC clearance, as demonstrated by splenectomy. In contrast, short-term EPO treatment does not induce thrombogenesis in mice. Consequently, our findings support the existence of a differential thrombogenic effect between chronic enhanced erythropoiesis and exogenous EPO administration. Chronic EPO overproduction significantly increases the risk of DVT, while short-term EPO treatment does not. These findings underscore the importance of considering EPO-related factors in DVT risk assessment and potential therapeutic strategies.


An evaluation of Thiomicrospira, Hydrogenovibrio and Thioalkalimicrobium: reclassification of four species of Thiomicrospira to each Thiomicrorhabdus gen. nov. and Hydrogenovibrio, and reclassification of all four species of Thioalkalimicrobium to Thiomicrospira.
Thiomicrospira(Tms) species are small sulfur-oxidizing chemolithoautotrophic members of the Gammaproteobacteria. Whilst the type species Tms. pelophila and closely related Tms. thyasirae exhibit canonical spiral morphology under sub-optimal growth conditions, most species are vibrios or rods. The 16S rRNA gene diversity is vast, with identities as low as 91.6 % for Tms. pelophila versus Tms. frisia, for example. Thiomicrospira was examined with closely related genera Hydrogenovibrio and Thioalkalimicrobium and, to rationalize organisms on the basis of the 16S rRNA gene phylogeny, physiology and morphology, we reclassify Tms. kuenenii, Tms. crunogena, Tms. thermophila and Tms. halophila to Hydrogenovibrio kuenenii comb. nov., H. crunogenus corrig. comb. nov., H. thermophilus corrig. comb. nov. and H. halophilus corrig. comb. nov. We reclassify Tms. frisia, Tms. arctica, Tms. psychrophila and Tms. chilensis to Thiomicrorhabdus (Tmr) gen. nov., as Tmr. frisia comb. nov., Tmr. arctica comb. nov., Tmr. psychrophila comb. nov. and Tmr. chilensis comb. nov. - the type species of Thiomicrorhabdus is Tmr. frisia. We demonstrate that Thioalkalimicrobium species fall within the genus Thiomicrospira sensu stricto, thus reclassifying them as Tms. aerophila corrig. comb. nov., Tms. microaerophila corrig. comb. nov., Tms. cyclica corrig. comb. nov. and Tms. sibirica corrig. comb. nov. We provide emended descriptions of the genera Thiomicrospira and Hydrogenovibrio and of Tms. thyasirae.


Effect of neuromuscular stimulation and individualized rehabilitation on muscle strength in Intensive Care Unit survivors: A randomized trial.
Intensive Care Unit (ICU) survivors experience muscle weakness leading to restrictions in functional ability. Neuromuscular electrical stimulation (NMES) has been an alternative to exercise in critically ill patients. The aim of our study was to investigate its effects along with individualized rehabilitation on muscle strength of ICU survivors. Following ICU discharge, 128 patients (age: 53±16years) were randomly assigned to daily NMES sessions and individualized rehabilitation (NMES group) or to control group. Muscle strength was assessed by the Medical Research Council (MRC) score and hand grip at hospital discharge. Secondary outcomes were functional ability and hospital length of stay. MRC, handgrip, functional status and hospital length of stay did not differ at hospital discharge between groups (p>0.05). ΔMRC% one and two weeks after ICU discharge tended to be higher in NMES group, while it was significant higher in NMES group of patients with ICU-acquired weakness at two weeks (p=0.05). NMES and personalized physiotherapy in ICU survivors did not result in greater improvement of muscle strength and functional status at hospital discharge. However, in patients with ICU-aw NMES may be effective. The potential benefits of rehabilitation strategies should be explored in larger number of patients in future studies. www.Clinicaltrials.gov: NCT01717833.


The yin and yang of B cells in a constant state of battle: intestinal inflammation and inflammatory bowel disease.
Inflammatory bowel disease (IBD) is a chronic inflammatory disease of the gastrointestinal tract, defined by a clinical relapse-remitting course. Affecting people worldwide, the origin of IBD is still undefined, arising as a consequence of the interaction between genes, environment, and microbiota. Although the root cause is difficult to identify, data clearly indicate that dysbiosis and pathogenic microbial taxa are connected with the establishment and clinical course of IBD. The composition of the microbiota is shaped by plasma cell IgA secretion and binding, while cytokines such as IL10 or IFN-γ are important fine-tuners of the immune response in the gastrointestinal environment. B cells may also influence the course of inflammation by promoting either an anti-inflammatory or a pro-inflammatory milieu. Here, we discuss IgA-producing B regulatory cells as an anti-inflammatory factor in intestinal inflammation. Moreover, we specify the context of IgA and IgG as players that can potentially participate in mucosal inflammation. Finally, we discuss the role of B cells in mouse infection models where IL10, IgA, or IgG contribute to the outcome of the infection.


Combined evaluation of interaural time and intensity differences: psychoacoustic results and computer modeling.
The physical and the psychophysical relationships between interaural time and intensity differences were studied for 24 frequency bands of critical bandwidth covering the full audio range. For the physical investigations a catalogue of outer ear impulse responses for 122 directions of the upper hemisphere was analyzed according to the combinations of interaural time and level differences found in each critical band. From these data curves of "natural combinations" of the interaural parameter differences were determined by the minimum square error method. In a psychoacoustical study it is shown that signals containing "natural" parameter combinations produce response patterns that differ from those produced when signals with contradictory interaural properties have been used. Finally an extension to the powerful binaural model of Lindemann [J. Acoust. Soc. Am. 80, 1608-1622 (1986)] is introduced, taking into account the results of the previous investigations.


Statins, ventricular arrhythmias and heart rate variability in patients with implantable cardioverter defibrillators and coronary heart disease.
The aim of this study was to evaluate whether the incidence of ventricular arrhythmias and heart rate variability were influenced by statin treatment and lipid levels in patients treated with an implantable cardioverter defibrillator (ICD). Heart rate variability measurements were performed in 86 patients with coronary heart disease and an ICD implant. The number of events with ventricular fibrillation and ventricular tachycardia were recorded during a 12-month period. This study lends little support for an antiarrhythmic effect of statins or any relation between plasma lipids and lipoproteins and malignant ventricular arrhythmias in patients with an ICD.


The stability of choline ascorbate.
The stability of choline ascorbate was studied considering concentration, temperature, and pH of the drug solution. Our results revealed that choline ascorbate is almost fully stable with respect to these parameters. Practically no loss was observed when 3 x l0(-1) (50%) drug solution is preserved in the refrigerator, at ambient temperature, or at 37 degrees C for one year, a finding that favors the high stability of this compound. Choline ascorbate was also found to be more stable in comparison to vitamin C and crystalline ascorbic acid. Its dilution within a vitamin B solution did not modify the amount of ascorbic acid within 120 min at ambient temperature. We conclude that the choline ascorbate form of ascorbic acid appears to be more reliable and promising when the quality of therapy with this agent is concerned.


Prognostic impact of tumor lymphocytic infiltrates in patients with breast cancer undergoing neoadjuvant chemotherapy.
The presence of a pronounced tumor lymphocytic infiltrate (TLI) is deemed to reflect the presence of an immunoinflammatory response against the tumor and may thus have prognostic significance. We investigated the prognostic value of TLI detected in pathological specimens collected following neoadjuvant chemotherapy (NACT) in patients with breast cancer. 100 consecutive patients with breast cancer (mean age 47.8±11.4 years) who were scheduled to undergo anthracycline-and/or taxane-containing NACT were enrolled. Specimens collected after NACT were scored with the 4-point Klintrup scoring criteria for the presence of TLI. 60 patients had low-grade TLI and 40 high-grade TLI. Comparison of the patient population according to low-grade vs high-grade TLI revealed statistically significant difference both in terms of disease-free survival (DFS) (log rank-4.28, p<0.05) and overall survival (OS) (log rank=3.96, p<0.05), with high-grade TLI patients showing a better prognosis. Multivariate Cox regression analysis identified postoperative tumor size and low-grade TLI as the two main independent adverse prognostic factors. High-grade TLI may interfer with tumor growth and can represent a favorable prognostic factor in women with breast cancer undergoing NACT.


IFN-α-2b Inhibits the Proliferation and Migration of Fibroblasts via the TGFβ/Smad Signaling Pathway to Reduce Postoperative Epidural Fibrosis.
Epidural fibrosis after lumbar laminectomy refers to a serious complication, and excessive proliferation of fibroblasts is considered the major factor. Interferon-alpha-2b (IFN-α-2b) can exert antiviral and antiproliferative effects, which has been suggested to effectively prevent several fibrotic diseases. However, the effect of IFN-α-2b on the prevention of epidural fibrosis (EF) and its possible mechanism remain unclear. In this study, in vitro and in vivo experiments were performed to examine the possible mechanism of IFN-α-2b for preventing EF. Cell counting kit-8 (CCK-8), cell cycle test, Edu incorporation, wound healing assay, transwell test, and Western blotting assay were performed to investigate the inhibitory effect of IFN-α-2b on the proliferation and migration of fibroblasts in vitro. As indicated from the results, IFN-α-2b was capable of inhibiting proliferation and migration of fibroblasts and inhibiting the activity of the transforming growth factor β (TGFβ)/Smad signaling pathway. In vivo, the effect of IFN-α-2b on the reduction of EF was determined by performing histological macroscopic evaluation and histological and immunohistochemical staining. As suggested from the results, IFN-α-2b significantly inhibited EF after laminectomy. As revealed from the mentioned results, IFN-α-2b may have a promising application for preventing EF in the future.


Perfusion cultures require optimum respiratory ATP supply to maximize cell-specific and volumetric productivities.
Perfusion processes are an emerging alternative to common fed-batch processes in the growing biopharmaceutical industry. However, the challenge of maintaining high cell-specific productivities remains. In this study, glucose limitation was applied to two perfusion steady states and compared with a third steady state without any detectable limitation. The metabolic phenotype was enhanced under glucose limitation with a decrease of 30% in glucose uptake and 75% in lactate formation. Cell-specific productivities were substantially improved by 50%. Remarkably, the productivities showed a strong correlation to respiratory adenosine triphosphate (ATP) supply. As less reduced nicotinamide adenine dinucleotide (NADH) remained in the cytosol, the ATP generation from oxidative phosphorylation was increased by almost 30%. Consequently, the efficiency of carbon metabolism and the resulting respiratory ATP supply was crucial for maintaining the highly productive cellular state. This study highlights that glucose limitation can be used for process intensification in perfusion cultures as ATP generation via respiration is significantly increased, leading to elevated productivities.


Tumor exome sequencing and copy number alterations reveal potential predictors of intrinsic resistance to multi-targeted tyrosine kinase inhibitors.
Multi-targeted tyrosine kinase inhibitors (TKIs) have broad efficacy and similar FDA-approved indications, suggesting shared molecular drug targets across cancer types. Irrespective of tumor type, 20-30% of patients treated with multi-targeted TKIs demonstrate intrinsic resistance, with progressive disease as a best response. We conducted a retrospective cohort study to identify tumor (somatic) point mutations, insertion/deletions, and copy number alterations (CNA) associated with intrinsic resistance to multi-targeted TKIs. Using a candidate gene approach (n=243), tumor next-generation sequencing and CNA data was associated with resistant and non-resistant outcomes. Resistant individuals (n=11) more commonly harbored somatic point mutations in NTRK1, KDR, TGFBR2, and PTPN11 and CNA in CDK4, CDKN2B, and ERBB2 compared to non-resistant (n=26, p<0.01). Using a random forest classification model for variable reduction and a decision tree classification model, we were able to differentiate intrinsically resistant from non-resistant patients. CNA in CDK4 and CDKN2B were the most important analytical features, implicating the cyclin D pathway as a potentially important factor in resistance to multi-targeted TKIs. Replication of these results in a larger, independent patient cohort has potential to inform personalized prescribing of these widely utilized agents.


Diagnostic Approaches to Pediatric Cardiomyopathy of Metabolic Genetic Etiologies and Their Relation to Therapy.
Inborn errors of metabolism (IEM) account for only 5% of all pediatric cardiomyopathy and 15% of those with known causes, but they are of particular interest to clinicians because many have disease-specific treatments. More than 40 different IEM involving cardiomyopathy exist, including fatty acid oxidation defects, organic acidemias, amino acidopathies, glycogen storage diseases, and congenital disorders of glycosylation as well as peroxisomal, mitochondrial, and lysosomal storage disorders. Most IEM present in infancy or early childhood with signs and symptoms of multi-organ system dysfunction. Except for mitochondrial disorders, each IEM is generally associated with one functional type of cardiomyopathy by echocardiography. Disease pathophysiology may include infiltration of cardiac myocytes with stored substrate, impaired energy production, and/or production of toxic intermediary metabolites. Although the diagnosis of an IEM often is evident from certain key clinical, laboratory, and biopsy findings, underdiagnosis is likely because of the lack of a systematic clinical approach to diagnosis and inadequate diagnostic testing. Dietary modification, avoidance of fasting, and anticipatory management during times of stress are the mainstays of treatment for most "small molecule" diseases, whereas treatment options for mitochondrial diseases remain limited and primarily involve vitamin supplements. Several lysosomal storage disorders are now treatable by enzyme replacement therapy and/or bone marrow transplantation. Newborn screening using tandem mass-spectrometry offers the potential for presymptomatic diagnosis and early treatment for a growing number of IEM, which will likely change their prevalence and natural history of cardiomyopathy.


Attempt to eliminate health inequalities in Poland arising at the time of political and economic transformation: Polish 400 Cities Project.
Epidemiological data show that citizens of small towns and villages have presented worse trends in cardiovascular mortality during the political, social and economic transformation in Poland during past 15 years than citizens of large towns. To try to eliminate these inequalities the Polish 400 Cities Project (P400CP), a large educational and interventional project, was prepared. The project consists of two arms: medical and social interventions. The main aim of the medical screening intervention in P400CP is to increase detection and control of cardiovascular risk factors in inhabitants of 418 small cities (<8000 inhabitants) and surrounding villages, particularly in men and people of lower education. In 2003 and 2004 the P400CP covered 123 cities. All together, 36 696 subjects aged between 18 and 98 years were examined. In all participants, blood pressure (BP), anthropometric measurements, laboratory tests and questionnaire interviews were performed. The social arm of P400CP is one of multi-level educational intervention. Modern techniques of social psychology and marketing were involved to increase participation in interventions. Only 12.5% of all subjects had normal BP, cholesterol (<190 mg/dl) and glucose (<100 mg/dl in whole capillary blood) levels. During the first screening visit 65.5% of all examined subjects had BP>/=140 mmHg or >/=90 mmHg. The fasting glucose level was increased in 19% of women and 26% of men. Almost two-third of all subjects had a total cholesterol level above the norm. The prevalence of cardiovascular risk factors in participants of the screening programme P400CP in small towns in Poland was very high. High prevalence and low control of risk factors in participants of the P400CP confirm the decision to target this programme at citizens of small towns and villages.


Arabidopsis as a model for wood formation.
Wood (secondary xylem) is one of the most important sustainable energy sources for humans. Arabidopsis, despite its herbaceous nature, has become an excellent model to study wood formation. Recent progress has shown that conserved molecular mechanisms may exist in herbaceous plants and trees during vascular development and wood formation. Several transcription factor families and plant hormone species as well as other factors contribute to the regulation of xylem development in both Arabidopsis and woody plants. In this review, we highlight how information gained from the analysis of vascular development in Arabidopsis has improved our understanding of wood formation in trees.


Changing profile of diabetic ketosis.
Forty-three cases of diabetic ketosis were analysed to determine the mode of presentation, treatment modalities and outcome. Among these cases 62.8% were non-insulin dependent diabetes mellitus (NIDDM) patients and 37.2% belonged to the insulin dependent diabetes mellitus (IDDM) group. Six patients had blood glucose levels of more than 250 mg/dl but less than 300 mg/dl who were grouped separately for analysis under the term "euglycaemic diabetic ketoacidosis (EGDK)". Infection was the commonest precipitating factor in diabetic ketosis in all groups. Abdominal pain and vomiting occurred with NIDDM and EGDK cases. Drowsiness was common and coma was rare. Acute myocardial infarction (MI) and pulmonary oedema occurred with NIDDM cases. Shock, acidosis, acquired respiratory distress syndrome (ARDS) and mucor mycosis were seen with IDDM cases. Mortality was 7 out of 43(16.3%). Saline requirement was lower in NIDDM and EGDK cases. Intensive insulin therapy with hourly intravenous doses were needed for IDDM cases while majority of NIDDM cases could be managed with 6 hourly doses of insulin given subcutaneously or intramuscularly.


Acceptability and understanding of the Ages & Stages Questionnaires®, Third Edition, as part of the Healthy Child Programme 2-year health and development review in England: Parent and professional perspectives.
The Healthy Child Programme is the universal public health system in England to assess and monitor child health from 0 to 19. Following a review of measures for closer monitoring at age 2 years, the Department of Health for England implemented the Ages & Stages Questionnaires®, Third Edition (ASQ-3™; Hereon, ASQ-3). The aim of this study was to evaluate the acceptability and understanding of the ASQ-3 in England by health professionals and parents. A mixed-methods approach was used. This paper reports on the qualitative data drawn from interviews with 40 parents and 12 focus groups with 85 health professionals. The data were analysed using applied thematic analysis. Overall, parents and health professionals found the ASQ-3 acceptable and understandable and could use it as a measure at age 2 years. The ability to work in partnership was valued. Some limitations included potential to cause anxiety, concerns around the safety of some of the items, and use of Americanized language. Health professional's training in the use the ASQ-3 was inconsistent. The ASQ-3 is an acceptable and understandable measure to use as part of the 2-year assessment with some adaptations to the English context and some standardized training for health professionals.


Sleep disruption in chronic rhinosinusitis.
Chronic rhinosinusitis (CRS) is a common disease of the upper airways and paranasal sinuses with a marked decline in quality of life (QOL). CRS patients suffer from sleep disruption at a significantly higher proportion (60 to 75%) than in the general population (8-18 %). Sleep disruption in CRS causes decreased QOL and is linked to poor functional outcomes such as impaired cognitive function and depression. Areas covered: A systematic PubMed/Medline search was done to assess the results of studies that have investigated sleep and sleep disturbances in CRS. Expert commentary: These studies reported sleep disruption in most CRS patients. The main risk factors for sleep disruption in CRS include allergic rhinitis, smoking, and high SNOT-22 total scores. The literature is inconsistent with regard to the prevalence of sleep-related disordered breathing (e.g. obstructive sleep apnea) in CRS patients. Although nasal obstruction is linked to sleep disruption, the extent of sleep disruption in CRS seems to expand beyond that expected from physical blockage of the upper airways alone. Despite the high prevalence of sleep disruption in CRS, and its detrimental effects on QOL, the literature contains a paucity of studies that have investigated the mechanisms underlying this major problem in CRS.


Human basophil releasability. VI. Changes in basophil releasability in patients with allergic rhinitis or bronchial asthma.
We evaluated basophil releasability in two groups of allergic patients with positive skin tests to Dermatophagoides pteronyssinus major allergen (Der p l) (29 adults with bronchial asthma and 17 with allergic rhinitis) and in 31 age-matched normal donors. Both basophil reactivity (maximal percent histamine release) and basophil sensitivity (the concentration that causes 50% of maximal percent histamine release: HC50) to Der p l in patients with asthma were similar to those in patients with allergic rhinitis. On the contrary, basophil reactivity to anti-IgE was significantly higher in patients with asthma (58.0 +/- 3.6%) than in patients with allergic rhinitis (46.3 +/- 5.2%; p less than 0.05). Both groups of patients showed an increased releasability compared to control subjects (27.3 +/- 4.6%; p less than 0.001), whereas there were no significant differences in basophil sensitivity to anti-IgE among the three groups of donors. Differences were also found with respect to basophil reactivity and sensitivity to f-met peptide, whereas no differences appeared when basophils from the three groups of donors were challenged with the Ca2+ ionophore A23187. There was a significant correlation between basophil reactivity and sensitivity to Der p l and to anti-IgE in both asthmatic and allergic rhinitis patients. A significant correlation was found between basophil reactivity and sensitivity to anti-IgE and serum IgE level only in patients with bronchial asthma, whereas no correlations were found in patients with allergic rhinitis. There was no correlation between in vivo mast cell releasability and in vitro basophil releasability in response to Der p l in either group of allergic patients.(ABSTRACT TRUNCATED AT 250 WORDS)


A case of necrotizing fasciitis due to Streptococcus agalactiae, Arcanobacterium haemolyticum, and Finegoldia magna in a dog-bitten patient with diabetes.
We report a case of necrotizing fasciitis involving Streptococcus agalactiae, Arcanobacterium haemolyticum, and Finegoldia magna in a 36-yr-old female diabetic patient, which started after a minor dog bite to the toe of the patient. This case suggested that a trivial infection after a minor dog bite in an immunocompromised patient such as diabetes patient could result in a significant complication such as necrotizing fasciitis. The life-threatening infection was cured by timely above-the-knee amputation, as well as penicillin G and clindamycin therapy.


Molecular Dynamics of Double Stranded Xylo-Nucleic Acid.
Xylo-nucleic acid (XyloNA) is a synthetic analogue of ribo-nucleic acid (RNA), where the ribose sugar has been replaced by xylose. We present a molecular dynamics study of the conformational evolution of XyloNA double strand oligomers derived from A-RNA through the substitution of β-d-ribofuranose by β-d-xylofuranose and having lengths of 8, 16, and 29 base pairs, using a set of independent all-atom simulations performed at various time scales ranging from 55 to 100 ns, with one long 500 ns simulation of the 29-mer. In order to validate the robustness of XyloNA conformation, a set of simulations using various cutoff distances and solvation box dimensions has also been performed. These independent simulations reveal the uncoiling or elongation of the initial conformation to form an open ladder type transient state conformation and the subsequent formation of a highly flexible duplex with a tendency to coil in a left-handed fashion. The observed open ladder conformation is in line with recently obtained NMR data on the XyloNA 8-mer derived using 5'-d(GUGUACAC)-3'. The observed negative interbase pair twist leads to the observed highly flexible left-handed duplex, which is significantly less rigid than the stable left-handed dXyloNA duplex having a strong negative twist. A comparison between the xylo-analogues of DNA and RNA shows a clear distinction between the helical parameters, with implications for the pairing mechanism.


Association between physical and echographic fat thickness assessments and a lipodystrophy grading scale in lipodystrophic HIV patients: practical implications.
A simple diagnostic method for detecting in clinical routine HAART-associated lipodystrophy in HIV-infected patients is lacking. We studied the relationships between the scores obtained with a subjective lipodystrophy severity grading scale (LSGS) and standard anthropometric and echographic measurements of the subcutaneous and visceral fat thickness of 74 HIV-infected patients. Patients were divided into four groups according to their LSGS score (0, 1-7, 8-14, 15-21). Significant correlations between the LSGS and the anthropometric and echographic measurements of fat thickness, mainly the limb circumferences (brachial: r= -0.43, p < 0.001; thigh: r= -0.41, p < 0.001), and, especially, the echographically assessed perirenal fat diameters either adjusted (r= 0.46, p < 0.001) or nonadjusted to the body mass index (r= 0.35, p < 0.001) were observed. Significant differences in most of these anthropometric parameters between either the lowest (score 0) and the highest (score 15-21) score groups and the remaining groups were found, but not between the two intermediate groups (scores 1-7 vs. 8-14). This suggests that lipodystrophy should be clinically categorized as absent, mild, or marked, and that even minor changes in physical aspect should be considered as indicative of this disorder. The combination of these subjective and objective parameters could be helpful in the early detection of lipodystrophy in clinical practice.


Some futuristic possibilities for resuscitation.
Future possibilities for resuscitation must take into account our still limited understanding of the reperfusion syndrome. Clinical resuscitation research must incorporate the use of prolonged life-support techniques. These may depend on the use of cardiopulmonary bypass to provide improved reperfusion of vital organs and to permit the time necessary to evaluate and treat the mediators and modifiers of the reperfusion syndrome. It is likely that some patients who require prolonged life support will need replacement organs or, should their brains fail to survive resuscitation, become organ donors. Physicians involved in resuscitation and transplantation must come to grips with the logistic problems of techniques for prolonged resuscitation.


Sleep disturbances and dementia.
Sleep is a complex behavioural state, the ultimate functions of which remain poorly understood. It becomes more fragmented as we age, with more night-time awakenings and greater tendency for daytime sleep. The magnitude of disordered sleep among individuals affected by dementia has been clearly demonstrated, and disturbed sleep is a major clinical problem in dementia. Comorbid insomnia and other sleep disturbances are common in patients with neurodegenerative disorders, such Alzheimer's disease and other dementing disorders. How and when sleep problems manifest themselves can depend on the type of dementia involved as well as the stage of the dementia. However, differences in sleep pattern presentation show more variation during the initial stages of dementias than they do during the later stages. Effective, pragmatic interventions are largely anecdotal and untested.


Description of a new species of Gracixalus (Amphibia: Anura: Rhacophoridae) from Guangdong Province, southeastern China.
A new species of tree frog, G. guangdongensis sp nov., is described based on a series of specimens collected from Dawuling Forest Station, Mount Nankun and Nanling Nature Reserve of Guangdong Province, southeastern China. The new species is distinguished from all known congeners by a significant genetic divergence at the mitochondrial 16S rRNA gene fragment examined (p-distance ≥ 4.6%) and the following combination of morphological characters: relatively small body size (SVL 26.1-34.7 mm in adult males, 34.9-35.4 mm in adult females); upper eyelid and dorsum lacking spines; supratympanic fold and tympanum distinct; dorsal and lateral surface rough, sparsely scattered with tubercles; ventral skin granular; tibiotarsal projection absent; toe-webbing moderately developed, finger webbing rudimentary; heels slightly overlapping when flexed hindlimbs are held at right angles to the body axis; brown to beige above, with an inverse Y-shaped dark brown marking extendeing from the interorbital region to the centre of the dorsum; males with a single subgular vocal sac and protruding nuptial pads with minute granules on the dorsal surface of the base of first finger. The discovery and description of Gracixalus guangdongensis sp. nov. represents the 14th species known in this genus.


Antidepressant Discontinuation: In Need of Scientific Evidence.
The topic of patients' discontinuing use of antidepressants has received increasing attention. Patients and physicians can encounter challenges regarding the three major questions in the field of antidepressant discontinuation: who can discontinue, what is the best time to discontinue; and what is the best method to discontinue. This commentary summarizes the current state of the evidence related to antidepressant discontinuation. There is limited evidence underlying the extremely relevant clinical topic of antidepressant discontinuation. It is poorly understood which patients, after response to antidepressants, benefit (most) from discontinuation. Moreover, established and validated markers of an individual's risk of relapse after antidepressant cessation are lacking, and non-sponsored discontinuation studies are rare. Many discontinuation studies do not distinguish between relapse and antidepressant discontinuation symptoms, and very few studies compared different discontinuation strategies, with none of the compared strategies exceeding 2 weeks of tapering. Finally, blinding of discontinuation strategies is often insufficient to properly address placebo and nocebo aspects, whereas the pharmacological characteristics of different antidepressants in relation to discontinuation have hardly been studied. Antidepressant discontinuation is a clinically relevant topic. There is a strong need for more robust evidence to indicate who can discontinue antidepressants, when and in which manner (how). Blinded randomized controlled trials are pivotal to optimally advise physicians, patients and policy-makers. This scientific knowledge can guide evidence-based decision making in clinical practice.


Disorders of communication: investigating the development of language of mentally retarded children.
Research conducted at the Waisman Center on Mental Retardation and Human Development over the past 10 years documents the multidimensional nature of the development of children's language in retarded and nonretarded populations. Recent advances in research methodology now available for investigating language comprehension and production will allow large-scale indepth studies of the lexical, semantic, syntactic, and pragmatic aspects of the language performance of a variety of retarded populations.


Regulation of peripherin in mouse neuroblastoma and rat PC 12 pheochromocytoma cell lines.
Peripherin (Formerly the Y protein) is found in the peripheral nervous system. This Triton-insoluble protein is characterized by its isoelectric point (5.6), its apparent molecular weight (56,000 daltons) and its peptide map. Peripherin was also observed in a mouse neuroblastoma cell line, NIE 115, where its expression appeared regulated by the presence of an inducer of morphological differentiation. In order to analyze more precisely this control, the presence of peripherin was investigated in several neuroblastoma cell lines which exhibit different morphological patterns of differentiation and in the rat pheochromocytoma PC 12 cell line. Differentiation of these cells was induced with 1-methylcyclohexane carboxylic acid (CCA) and nerve growth factor (NGF), respectively. Peripherin was found in these different cell lines. Moreover, the cellular amount of peripherin appraised by [35S]-methionine incorporation was significatively increased in differentiated cells. In contrast, other cytoskeletal components did not undergo a similar raise. The level at which the control of the peripherin content takes place was studied in a cell-free translation system. Poly(A)-rich RNAs extracted from growing or differentiated NIE 115 cells directed the synthesis of similar amounts of peripherin in a reticulocyte lysate. In contrast, polysomes prepared from differentiated cells and the corresponding polysomal RNA programmed in vitro the synthesis of twice more peripherin than polysomes or polysomal RNA from growth-phase cells. Since peripherin synthesis is enhanced 5 times in living cells, it seems probable that the cellular amount of peripherin is controlled partly at the translational level and partly at the turn-over level.


How finger tapping practice enhances efficiency of motor control.
Maximum-speed movements have been suggested to put maximum neural control demands on the primary motor cortex; hence, we are asking how primary motor cortex function changes to enable enhanced maximum movement rates induced by long-lasting practice. Cortical function was assessed by recording task-related spectral electroencephalogram alpha-power. Low-resolution brain electromagnetic tomography was used to localize intracortical neuronal sources. The main result is a decrease in neural activity in the left hemisphere (ipsilateral to trained hand) from pretraining to posttraining, whereas right hemispheric activity remained constant across training. This likely reflects the initially limited capacity of the right hemisphere to control demanding left-hand movements, but also highlights its ability to become more efficient with training, indicated by reduced involvement of the left primary motor cortex after training.


Forty Years After Hearing Lips and Seeing Voices: the McGurk Effect Revisited.
Since its discovery 40 years ago, the McGurk illusion has been usually cited as a prototypical paradigmatic case of multisensory binding in humans, and has been extensively used in speech perception studies as a proxy measure for audiovisual integration mechanisms. Despite the well-established practice of using the McGurk illusion as a tool for studying the mechanisms underlying audiovisual speech integration, the magnitude of the illusion varies enormously across studies. Furthermore, the processing of McGurk stimuli differs from congruent audiovisual processing at both phenomenological and neural levels. This questions the suitability of this illusion as a tool to quantify the necessary and sufficient conditions under which audiovisual integration occurs in natural conditions. In this paper, we review some of the practical and theoretical issues related to the use of the McGurk illusion as an experimental paradigm. We believe that, without a richer understanding of the mechanisms involved in the processing of the McGurk effect, experimenters should be really cautious when generalizing data generated by McGurk stimuli to matching audiovisual speech events.


Legionella Pneumophilla Infection Masquerading as Acute Cholecystitis.
Legionella pneumophilla represents a relatively common cause of community acquired pneumonia with high mortality related burden if not promptly diagnosed and treated with appropriate antibiotics. Clinical characteristics of Legionella infection are often non-specific making accurate diagnosis challenging. We report a case of a middle aged immunocompetent woman referred to our department via her gene ral practitioner with a history of fever and abdominal pain located in the right upper abdominal quadrant. Initial diagnostic work up disclosed a moderate elevation of inflammation markers and chololithiasis. The paucity of respiratory symptoms led initially to an altered presumed diagnosis of acute cholecystitis. Development of pulmonary symptoms during hospitalization raised the suspicion of Legionella community acquired pneumonia. The diagnosis was later confirmed by serology.


[Blood levels of trace elements in urban children with diffuse non-toxic goiter].
The blood concentrations of cadmium, cobalt, lead, manganese, copper, and zinc were studied in Vladivostok schoolchildren with diffuse non-toxic goiter followed up by an endocrinologist for 2-5years. It was established that the content of cadmium, cobalt, lead, and manganese significantly exceeded the relevant values in healthy adolescents and that of copper was lower. Zinc levels did not differ from those in healthy individuals.


The influence of tissue microenvironment (stroma and extracellular matrix) on the development and function of mammary epithelium.
The morphogenesis and functional differentiation of mammary epithelium depends on signalling from systemic hormones and on cues from the local tissue microenvironment. With regard to the latter, regulatory cues are mainly provided by two subcompartments of the mesenchyme/stroma [fibroblastic and adipocyte] and the subjacent basement membrane. During embryogenesis, fibroblastic mesenchyme determines the sexual phenotype of the gland while adipocyte mesenchyme controls mammary-specific ductal morphogenesis. In the juvenile animal, adipocyte stroma continues to support ductal expansion while fibroblasts negatively regulate ductal outgrowth via interactions with the epithelium possibly involving TGF-beta mediated deposition of collagen I and chondroitin sulphate. In the adult, evidence from culture studies show that the signals required for the induction of tissue-specific differentiation during pregnancy and maintenance of function during lactation arise primarily from basement membrane. Beta-casein synthesis is induced in single mammary epithelial cells embedded within a basement membrane matrix via an integrin-dependent pathway. Further support for a critical role for basement membrane in the functional differentiation of the gland comes from studies in involution where degradative loss of basement membranes correlates with loss of functional activity in the epithelium. Thus the extracellular matrix in conjunction with certain cytokines plays a central role in coordinating mammary epithelial development. The findings discussed give further credence to a modal where mammary epithelium, together with certain elements of the subjacent microenvironment, form a dynamic and reciprocally interactive functional unit that regulates tissue specific gene expression in the mammary gland.


Effect of follicle-stimulating hormone on different cell sub-populations in the ovary of newly hatched chicks treated during embryonic development.
1. Cell sub-populations of the ovary of newly-hatched chicks were assessed following follicle stimulating hormone (FSH) treatment during embryonic development. Changes in cell number and the amount of oestradiol in serum were determined. 2. White Leghorn chick embryos received 1 microgram FSH applied to the chorioallantoic membrane at 13, 15, and 17 d of incubation. Within 24 h after hatching, animals were killed and blood was collected. The left ovary was immediately removed then weighed and processed by an enzymatic-mechanical dissociation method for total cell count. An air-drying method was also used for meiotic preparations to study the germinal cells. 3. The pre-follicular ovary is able to respond to FSH by inducing an increase both in the serum oestradiol concentration and in the number of steroidogenic cells and of poorly differentiated cells of the ovarian medulla. 4. FSH increases the number of oogonia, which are responsible for a sharp increase in the total population of germ cells in the FSH-treated ovary. 5. It is possible that FSH acts to increase the proliferation of oogonia and a delay in the meiotic prophase through a change in the microenvironment rather than by a direct effect on germ cells.


Analysis of circulating miRNAs 21 and 375 as potential biomarkers for early diagnosis of prostate cancer.
To investigate the diagnostic potential of plasma miR-21 and miR-375 by comparing their levels in prostate cancer (PCa) patients to subjects without cancer in a Chinese population. The study population included 57 PCa patients and 28 benign prostatic hyperplasia (BPH) patients. The plasma levels of miR-21 and miR-375 were quantitated with Taqman based quantitative real-time polymerase chain reaction. In the BPH group, the median relative expression levels of miR-21 and miR-375 were 0.07 and 0.55, respectively; In the PCa group, the median values of miR-21 and miR-375 were 1.32 and 1.74, respectively. Both miR-21 (p=0.014) and miR-375 (p=0.005) plasma levels were significantly higher in PCa group than in BPH group. Using ROC analysis the AUC of miR-21 was 0.799, 95% CI between 0.690 and 0.908 (p=8×10-6); for miR-375, the AUC was 0.757, 95% CI between 0.640-0.874 (p=0.000126). The largest AUC (0.881) was obtained when the data of miR-21, miR-375 and PSA were combined, with a sensitivity of 87.7% and a specificity of 75%. The results of this study showed that circulating miR-21 and miR-375 can discriminate PCa patients from BPH controls at early stages. Combinations of the studied miRNAs and PSA remarkably increased specificity compared with PSA alone. The combination method has the potential to be used as a noninvasive diagnostic cocktail for PCa screening.


Structural characteristics of tenecin 3, an insect antifungal protein.
Tenecin 3, an antifungal protein, previously isolated from the insect Tenebrio molitor, inhibits growth of the fungus Candida albicans. However, the antifungal mechanism and functions of tenecin 3 remain unknown. As an initial step to study the mechanism and functions, physical and structural properties of tenecin 3 were examined by circular dichroism (CD) analysis and 2D nuclear overhauser effect spectroscopy. These analyses suggest that tenecin 3 has a propensity of random structure with very loose turn-like elements. The CD results also indicate that this random structural propensity is not significantly affected by temperature, pH, and by the presence of organic solvents or sodium dodecyl sulfate (SDS) micelles. However, the hydrodynamic studies suggest that tenecin 3 is not in extended form in spite of its random structural feature.


Higher-order aberrations due to the posterior corneal surface in patients with keratoconus.
This study was designed to investigate higher-order aberrations (HOAs) due to the posterior corneal surface in keratoconic eyes compared with normal eyes. We studied 24 normal and 28 keratoconic eyes. The anterior/posterior corneal heights and pachymetric data were obtained with a rotating Scheimpflug camera. HOAs for 6 mm pupils were calculated from the differences between the height data and the best-fit sphere, using an original program for each corneal surface. The reference axes of the measurements were aligned with the primary line of sight. The HOAs were expanded with normalized Zernike polynomials. For each pair of standard Zernike terms for trefoil, coma, tetrafoil, and secondary astigmatism, one value for the magnitude and axis was calculated by Zernike vector analysis. The mean total corneal HOAs (root mean square [microm]) from the anterior/posterior surfaces were significantly (P < 0.001) higher in keratoconic (4.34/1.09, respectively) than in control eyes (0.46/0.15). The mean magnitude of each Zernike vector terms for trefoil, coma, and spherical aberration from the anterior/posterior surfaces was significantly (P < 0.001) higher in keratoconic (0.77/0.19, 3.57/0.87, -0.44/0.17) than control eyes (0.09/0.04, 0.33/0.07, 0.25/-0.07), respectively. The mean axes by vector calculation for coma due to the anterior (63.6 degrees ) and posterior surfaces (241.9 degrees ) were in opposite directions. Corneal HOAs on both corneal surfaces in keratoconic eyes were higher than in control eyes. Coma from the posterior surface compensated partly for that from the anterior surface. Residual irregular astigmatism in patients with keratoconus wearing rigid gas permeable contact lenses can be estimated by measuring the HOA from the posterior corneal surface.


The big picture: effects of surround on immersion and size perception.
Despite the fear of the entertainment industry that illegal downloads of films might ruin their business, going to the movies continues to be a popular leisure activity. One reason why people prefer to watch movies in cinemas may be the surround of the movie screen or its physically huge size. To disentangle the factors that might contribute to the size impression, we tested several measures of subjective size and immersion in different viewing environments. For this purpose we built a model cinema that provided visual angle information comparable with that of a real cinema. Subjects watched identical movie clips in a real cinema, a model cinema, and on a display monitor in isolation. Whereas the isolated display monitor was inferior, the addition of a contextual model improved the viewing immersion to the extent that it was comparable with the movie theater experience, provided the viewing angle remained the same. In a further study we built an identical but even smaller model cinema to unconfound visual angle and viewing distance. Both model cinemas produced similar results. There was a trend for the larger screen to be more immersive; however, viewing angle did not play a role in how the movie was evaluated.


Three-dimensional culture and chondrogenic differentiation of mesenchymal stem cells in interconnected collagen scaffolds.
Interconnected scaffolds are useful for promoting the chondrogenic differentiation of stem cells. Collagen scaffolds with interconnected pore structures were fabricated with poly(lactic acid-co-glycolic acid) (PLGA) sponge templates. The PLGA-templated collagen scaffolds were used to culture human bone marrow-derived mesenchymal stem cells (hMSCs) to investigate their promotive effect on the chondrogenic differentiation of hMSCs. The cells adhered to the scaffolds with a homogeneous distribution and proliferated with culture time. The expression of chondrogenesis-related genes was upregulated, and abundant cartilaginous matrices were detected. After subcutaneous implantation, the PLGA-templated collagen scaffolds further enhanced the production of cartilaginous matrices and the mechanical properties of the implants. The good interconnectivity of the PLGA-templated collagen scaffolds promoted chondrogenic differentiation. In particular, the collagen scaffolds prepared with large pore-bearing PLGA sponge templates showed the highest promotive effect.


Traumatic dislocation of the hip in a child caused by trivial force for age.
Traumatic hip dislocation in children has a relatively rare occurrence. There are some residual complications, such as avascular necrosis of the femoral head, growth disturbance caused by premature fusion, neurological injury, recurrent dislocation, and posttraumatic arthritis. There is no consensus in the literature about the period of non-weight bearing after reduction. A rare case of a 13-year-old boy of hip dislocation caused by trivial force for age is reported followed by review of the pediatric literatures with treatment recommendation.


Predicting Flavonoid UGT Regioselectivity.
MACHINE LEARNING WAS APPLIED TO A CHALLENGING AND BIOLOGICALLY SIGNIFICANT PROTEIN CLASSIFICATION PROBLEM: the prediction of avonoid UGT acceptor regioselectivity from primary sequence. Novel indices characterizing graphical models of residues were proposed and found to be widely distributed among existing amino acid indices and to cluster residues appropriately. UGT subsequences biochemically linked to regioselectivity were modeled as sets of index sequences. Several learning techniques incorporating these UGT models were compared with classifications based on standard sequence alignment scores. These techniques included an application of time series distance functions to protein classification. Time series distances defined on the index sequences were used in nearest neighbor and support vector machine classifiers. Additionally, Bayesian neural network classifiers were applied to the index sequences. The experiments identified improvements over the nearest neighbor and support vector machine classifications relying on standard alignment similarity scores, as well as strong correlations between specific subsequences and regioselectivities.


Removal of carbamazepine and clofibric acid from water using double templates-molecularly imprinted polymers.
A novel double templates-molecularly imprinted polymer (MIP) was prepared by precipitation polymerization using carbamazepine (CBZ) and clofibric acid (CA) as the double templates molecular and 2-vinylpyridine as functional monomer. The equilibrium data of MIP was well described by the Freundlich isotherm model. Two kinetic models were adopted to describe the experimental data, and the pseudo second-order model well-described adsorption of CBZ and CA on the MIP. Adsorption experimental results showed that the MIP had good selectivity and adsorption capacity for CBZ and CA in the presence of competitive compounds compared with non-imprinted polymer, commercial powdered activated carbon, and C18 adsorbents. The feasibility of removing CBZ and CA from water by the MIP was demonstrated using tap water, lake water, and river water.


Shiftwork locus of control effects in police officers.
Personality and experientially-based differences are suggested to moderate the negative effects of shiftworking. This investigation was one of a series of studies aimed at examining the relationship between internal locus of control (internality) and commonly reported outcomes of exposure to shiftworking. The study concentrated on whether or not shiftwork-specific internality appeared to be associated with better experiences for two groups of shiftworkers on different shift rotas. The Shiftwork Locus of Control (SHLOC) scale was completed by each group along with a range of outcome measures (including: sleep disturbance, alertness on shift, psychological well-being, disturbance of social and family life, and fatigue). The analyses controlled for for age, shiftwork experience and years of service effects. The results showed that for the majority of outcome variables, the higher internality was associated with significantly lower levels of shiftwork problems, especially when compared to the low internality group. The findings of this study further support the use of shiftwork-specific locus of control in shiftwork research as an indicator of potentially better tolerance, and possibly as part of an occupational health monitoring process to aid the targeting of interventions.