Role of adipokines signaling in the modulation of T cells function.
The field that links immunity and metabolism is rapidly expanding. Apparently non-immunological disorders such as obesity and type 2 diabetes have been linked to immune dysregulation, suggesting that metabolic alterations can be induced by or be consequence of an altered self-immune tolerance. In this context, adipose tissue produces and releases a variety of pro-inflammatory and anti-inflammatory factors, termed "adipokines," which can be considered as the bridge between obesity-related exogenous factors, such as nutrition and lifestyle, and the molecular events leading to metabolic syndrome, inflammatory, and/or autoimmune conditions. In obesity, increased production of most adipokines impacts on multiple functions such as appetite and energy balance, modulation of immune responses, insulin sensitivity, angiogenesis, blood pressure, lipid metabolism, and so on. This report aims to discuss some of the recent topics of adipocytokine research and their related signaling pathways, that may be of particular importance as could lead to effective therapeutic strategies for obesity-associated diseases.


CREB antisense oligodeoxynucleotide administration into the dorsal hippocampal CA3 region impairs long- but not short-term spatial memory in mice.
The transcription factor cAMP response-element binding protein (CREB) has a pivotal role in hippocampal synaptic plasticity and hippocampus-dependent long-term memory. We recently demonstrated that the dorsal hippocampal CA3 region is involved in memory consolidation of spatial information tested on a Morris water maze in mice. To test whether activation of CREB in the CA3 region is required for memory consolidation of spatial information, bilaterally cannulated mice were infused 18 h before the beginning of the behavioral training with antisense or control sense CREB oligodeoxynucleotides (ODNs) or buffer. Mice were then subjected to massed training in a spatial version of the water maze and tested for retention 0 or 24 h after the last training session. We showed that CREB antisense ODN-infusion in the CA3 region impaired long-term memory when tested 24 h later but had no effect on spatial acquisition or short-term memory tested immediately after behavioral training. These findings provide evidence that the regionally restricted activation of CREB in the dorsal hippocampal CA3 region is critical for the long-term memory consolidation phase of spatial learning but not for short-term memory.


Survival of B lineage leukemic cells: signals from the bone marrow microenvironment.
Stromal cells are an essential component of the bone marrow microenvironment that regulate development of immature hematopoietic progenitor cells. Through production of soluble cytokines, and signaling through adhesion molecule interactions, stromal cells impact survival, proliferation, and differentiation of hematopoietic progenitor cells. Similarities between normal pro-B and pre-B cells and B lineage acute lymphoblastic leukemic (ALL) progenitors have been well characterized which provide a model for investigation of the mechanisms by which ALL cells respond to bone marrow microenvironment signals. In addition to providing survival signals to B lineage ALL during initiation of disease, the bone marrow has long been recognized as a "sanctuary site" for leukemic cells during traditional chemotherapy. In the current review, mechanisms by which stromal cells contribute to leukemic cell survival, and the potential impact on treatment efficacy, are discussed. A growing appreciation of the significance of the bone marrow microenvironment in the progression of ALL, and further investigation of the signaling between leukemic progenitors and stromal cells, may contribute to novel treatment strategies aimed at enhancing sensitivity of ALL cells to currently available chemotherapeutic agents.


Metabolism of antisense oligonucleotides in rat liver homogenates.
Phosphorothioate antisense oligodeoxynucleotides are novel therapeutic agents designed to selectively and specifically inhibit production of various disease-related gene products. In vivo pharmacokinetic experiments indicate that these molecules are widely distributed in many species, with the majority of oligomers accumulating within liver and kidney. To better understand the metabolism of these agents, we studied the stability of several phosphorothioate oligodeoxynucleotides, their congeners, and second generation oligomer chemistries in rat liver homogenates. To examine metabolism, background nuclease activity was characterized in whole liver homogenates by using ISIS 1049, a 21-mer phosphodiester oligodeoxynucleotide. Nuclease activity could readily be detected in liver homogenates. Under optimized conditions, the predominant enzymatic activity was 3'-exonucleolytic and could be influenced by pH and ionic conditions. However, in addition to 3' exonucleases, 5' exo- and endonuclease activities were also observed. Our data indicate that metabolism of phosphorothioate oligodeoxynucleotides was more complex than that of phosphodiesters for many reasons, including phosphorothioate oligodeoxynucleotide inhibition of nucleases and the presence of R(p) and S(p) stereoisomers. The rate of phosphorothioate metabolism also appeared to be influenced by sequence, with pyrimidine-rich compounds being metabolized to a greater extent than purine-rich oligomers. Other factors affecting stability included oligomer chemistry and length. Concomitant experiments performed in rats dosed systemically with the same compounds mimic the activities seen in vitro and suggest that this liver homogenate system is a valuable model with which to study the mechanism of metabolism of antisense oligonucleotides.


Systemic Mycobacterium kansasii infection and regulation of the alloantigenic response.
Specific-pathogen-free B6D2 F1 hybrid mice were infected intravenously with 10(7) to 10(8) viable Mycobacterium kansasii cells. The growth of the five test strains in vivo was correlated with the level of delayed hypersensitivity to a cytoplasmic protein antigen injected into the footpad. M. kansasii TMC no. 1201 and 1203 gave rise to persisting systemic infections with an early delayed hypersensitivity response (day 7) followed by a profound anergy to the cytoplasmic protein antigen injections. Strains 1204, 1214, and 1217 declined in viability relatively rapidly and failed to induce detectable levels of delayed hypersensitivity. Spleens harvested from mice infected 20 to 30 days earlier with 10(8) M. kansasii 1203 cells contained a T-cell subpopulation capable of suppressing mixed lymphocyte reactions between normal B6D2 and C3H(He) cells. On the other hand, splenic T-cells taken from M. kansasii 1214-infected mice enhanced, rather than suppressed, the indicator mixed lymphocyte reactions. The kinetics of stimulator-suppressor T-cell production within the spleens of the heavily infected mice differed as the two contrasting M. kansasii infections progressed. Such cellular interactions could well be responsible for the observed persistence of the systemic M. kansasii 1203 infection.


Susceptibilities of Neisseria gonorrhoeae to the glycylcyclines.
To assess the activities of two glycylcyclines, N,N-dimethylglycylamido (DMG) derivatives of minocycline (MINO) and 6-demethyl-6-deoxytetracycline (DMDOT), 203 gonococcal isolates recovered at six sexually transmitted disease clinics in the western United States were evaluated. Antimicrobial susceptibilities to tetracycline HCl, doxycycline, MINO, DMG-DMDOT, and DMG-MINO were determined by agar dilution tests. DMG-DMDOT and DMG-MINO were more active than tetracycline HCl, doxycycline, or MINO regardless of the presence of Tet M or of chromosomal mutations mediating tetracycline resistance (P < 0.001).


Donepezil: tolerability and safety in Alzheimer's disease.
The tolerability and safety of donepezil HCI in patients with mild to moderate Alzheimer's disease (AD) were examined in an integrated analysis of phase II/III placebo-controlled trials. Patients with mild to moderately severe AD (n=1,920) were randomised to receive donepezil (n=1,291) or placebo (n=629). Adverse events, physical examinations and clinical laboratory tests were assessed. A high completion rate (79%) was achieved in these trials. Of the 1,291 patients receiving donepezil only, 142 (11%) withdrew because of an adverse event compared with 43 of the 629 (7%) placebo patients. The most common adverse events included nausea, diarrhoea, headache, insomnia, dizziness, rhinitis, vomiting, asthenia/fatigue and anorexia. Donepezil had no clinically significant effect on any laboratory evaluations and was not associated with hepatotoxicity. These results demonstrate that donepezil is well tolerated and has a favourable safety profile at clinically effective, once-daily doses of 5 mg and 10 mg.


Protective effect of maternal prenatal melatonin administration on rat pups born to mothers submitted to constant light during gestation.
We studied the effects of adverse conditions such as constant light (LL) on the circadian rhythm of malate (MDH, EC 126.96.36.199) and lactate (LDH, EC 188.8.131.52) dehydrogenase activities of the testes of male Wistar rats on postnatal day 28 (PN28), anxiety-like behavior (elevated plus-maze test) at PN60 and sexual behavior at PN120. The rats were assigned to mother groups on day 10 of pregnancy: control (12-h light/dark), LL (light from day 10 to 21 of pregnancy), and LL+Mel (LL and sc injection to the mothers of a daily dose of melatonin, 1 mg/kg body weight at circadian time 12, from day 17 to 21 of pregnancy). LL offspring did not show circadian rhythms of MDH (N = 62) and LDH (N = 63) activities (cosinor and ANOVA-LSD Fisher). They presented a 44.7% decrease in open-arm entries and a 67.9% decrease in time (plus-maze test, N = 15, P < 0.001, Mann-Whitney U-test and Kruskal-Wallis test), an increase in mounting (94.4%), intromission (94.5%) and ejaculation (56.6%) latencies (N = 12, P < 0.01, Mann-Whitney U-test and Kruskal-Wallis test) and lower numbers of these events (61, 59 and 73%, respectively; P < 0.01, N = 12) compared to controls. The offspring of the LL+Mel group presented MDH and LDH circadian rhythms (P < 0.05, N = 50, cosinor and ANOVA-LSD Fisher), anxiety-like and sexual behaviors similar to control. These findings supported the importance of the melatonin signal and provide evidence for the protective effects of hormones on maternal programming during gestation. This protective action of melatonin is probably related to its entrainment capacity, favoring internal coupling of the fetal multioscillatory system.


[The effect of antifreeze glycoproteins on survival and quality of fish spermatozoa under the conditions of long-term storage at +4 degree C].
It was already shown that antifreeze glycoproteins isolated from the blood of fish occurring in circumpolar regions inhibited the growth of ice crystals both in vitro and in vivo. When the spermatozoa were frozen to liquid nitrogen temperature, addition of antifreeze glycoproteins to cryoconserving media made it possible to decrease twofold the concentration of the synthetic cryoprotector dimethylsulfoxide without the loss and even with a certain increase in the number of viable spermatozoa. This effect was observed in the case of combined, rather than separate, addition of the fraction of weakly active (low molecular weight) and active (high molecular weight) antifreeze glycoproteins. Here, we studied the effect of antifreeze glycoproteins on the survival of carp spermatozoa under storage at +4 degrees C for varying periods of time. In the presence of total fraction of low and high molecular weight antifreeze glycoproteins (2 and 10 mg/ml) added in a physiological proportion (3:1), the survival of spermatozoa increase but this increase did not depend linearly on the medium concentration of protein. Low and high molecular weight antifreeze glycoproteins added separately (10 mg/ml) either did not affect or slightly affected the preservation of cells. The hypothermic effect of antifreeze glycoproteins in water was significantly higher than in a medium with salt activator.


Developing a successful recruitment/retention plan for hospital pharmacy personnel.
Due to various external factors, recruitment through traditional methods, such as newspaper ads, failed to produce the pool of applicants for hospital pharmacy staff positions it had in the past. As a result of this and other factors specific to University Hospital, the number of staff pharmacists decreased from 11 to four full-time equivalents (FTEs). The number of technicians dropped to the point where per diem nurses had to be hired to help make IV admixtures. Through some short-term measures (salary increases, intensive recruitment efforts, etc), the number of pharmacist and technician vacancies was reduced by 60%. However, a long-range recruitment/retention plan was needed to achieve full staffing and to prevent such drastic staffing shortages in the future. The four components of the plan that was developed included: commitment to provide for full-time human resources management, improved forecasting of personnel turnover, supply, and demand, design and implementation of retention strategies, and design and implementation of innovative recruitment programs. Seven months after initiation of much of the plan, there was no pharmacist turnover and minimal technician turnover. In fact, one pharmacist stays on staff despite relocation 90 miles away. Almost all positions are filled, despite a large number of openings at other institutions in the area.


Hypocalcemia and osteopathy in mice with kidney-specific megalin gene defect.
Megalin is an endocytic receptor highly expressed in the proximal tubules of the kidney. Recently, we demonstrated that this receptor is essential for the renal uptake and conversion of 25-OH vitamin D3 to 1,25-(OH)2 vitamin D3, a central step in vitamin D and bone metabolism. Unfortunately, the perinatal lethality of the conventional megalin knockout mouse model precluded the detailed analysis of the significance of megalin for calcium homeostasis and bone turnover in vivo. Here, we have generated a new mouse model with conditional inactivation of the megalin gene in the kidney by using Cre recombinase. Animals with a renal-specific receptor gene defect were viable and fertile. However, lack of receptor expression in the kidney results in plasma vitamin D deficiency, in hypocalcemia and in severe bone disease, characterized by a decrease in bone mineral content, an increase in osteoid surfaces, and a lack of mineralizing activity. These features are consistent with osteomalacia (softening of the bones) as a consequence of hypovitaminosis D and demonstrate the crucial importance of the megalin pathway for systemic calcium homeostasis and bone metabolism.


Losartan reduces cigarette smoke-induced airway inflammation and mucus hypersecretion.
The aim was to determine whether losartan reduces cigarette smoke (CS)-induced airway inflammation and mucus hypersecretion in an in vitro model and a small clinical trial. Primary human bronchial epithelial cells (HBECs) were differentiated at the air-liquid interface (ALI) and exposed to CS. Expression of transforming growth factor (TGF)-β1 and the mucin MUC5AC, and expression or activity of matrix metalloproteinase (MMP)-9 were measured after CS exposure. Parameters of mucociliary clearance were evaluated by measuring airway surface liquid volumes, mucus concentrations, and conductance of cystic fibrosis transmembrane conductance regulator (CFTR) and large conductance, Ca2+-activated and voltage-dependent potassium (BK) channels. Nasal cells were collected from study participants and expression of MUC5AC, TGF-β1, and MMP-9 mRNAs was measured before and after losartan treatment. In vitro, CS exposure of HBECs caused a significant increase in mRNA expression of MUC5AC and TGF-β1 and MMP-9 activity and decreased CFTR and BK channel activities, thereby reducing airway surface liquid volumes and increasing mucus concentrations. Treatment of HBECs with losartan rescued CS-induced CFTR and BK dysfunction and caused a significant decrease in MUC5AC expression and mucus concentrations, partially by inhibiting TGF-β signalling. In a prospective clinical study, cigarette smokers showed significantly reduced mRNA expression levels of MUC5AC, TGF-β1, and MMP-9 in the upper airways after 2 months of losartan treatment. Our findings suggest that losartan may be an effective therapy to reduce inflammation and mucus hypersecretion in CS-induced chronic airway diseases.


Neuroanatomical distribution and functions of brain-derived neurotrophic factor in zebrafish (Danio rerio) brain.
Brain-derived neurotrophic factor (BDNF) is an extensively studied protein that is evolutionarily conserved and widely distributed in the brain of vertebrates. It acts via its cognate receptors TrkB and p75NTR and plays a central role in the developmental neurogenesis, neuronal survival, proliferation, differentiation, synaptic plasticity, learning and memory, adult hippocampal neurogenesis, and brain regeneration. BDNF has also been implicated in a plethora of neurological disorders. Hence, understanding the processes that are controlled by BDNF and their regulating mechanisms is important. Although, BDNF has been thoroughly studied in the mammalian models, contradictory effects of its functions have been reported on several occasions. These contradictory effects may be attributed to the sheer complexity of the mammalian brain. The study of BDNF and its associated functions in a simpler vertebrate model may provide some clarity about the effects of BDNF on the neurophysiology of the brain. Keeping that in mind, this review aims at summarizing the current knowledge about the distribution of BDNF and its associated functions in the zebrafish brain. The main focus of the review is to give a comparative overview of BDNF distribution and function in zebrafish and mammals with respect to distinct life stages. We have also reviewed the regulation of bdnf gene in zebrafish and discussed its role in developmental and adult neurogenesis.


Anaphylaxis to Ciprofloxacin Requiring Emergent Surgical Cricothyrotomy.
Although allergies to antibiotics are commonly stated, anaphylactic reactions are uncommonly reported. This is especially the case with reactions to fluoroquinolone antibiotics. Furthermore, airway emergencies are rare. We present a case of ciprofloxacin-induced acute airway obstruction and anaphylaxis, necessitating emergent surgical cricothyrotomy following respiratory distress. Anaphylactic reactions to fluoroquinolone antibiotics are extremely rare.There are currently no standardized diagnostic tests, making the diagnosis of anaphylaxis challenging and largely based on history alone.Treating clinicians should be aware of this rare, but potentially rapidly fatal adverse drug reaction.


Tonsillectomy as Prevention of Tonsil and Base of Tongue Cancer: Systematic Review and Meta-analysis on the Immuno-Oncological Effect of One Among the Most Common Surgeries in the World.
Otorhinolaryngology tradition is that tonsillectomy (TE) is conducted among children and adolescents for obstructive sleep apnea secondary to adenotonsillar hypertrophy and in adults for chronic disease of the tonsils and adenoids (recurrent tonsillitis). Nevertheless, over the last 50 years, we have observed a decline in TE worldwide. As a result, there is an emerging concern of a correlated possible increased risk of tonsil cancer (TC) and other subtypes of oropharyngeal squamous cell carcinoma. Since the available data on such topics are limited and controversial, our aim was to elucidate the impact of TE on the incidence mainly of TC through a systematic review of the literature and a meta-analysis of the studies. After a thorough search, 7 retrospective studies were considered eligible for review and meta-analysis (MA). At MA, patients with a history of TE seem to show a reduced risk of TC but a higher predisposition for base of tongue (BOT) cancer (p<0.001): however, the elevated heterogeneity of the studies hampers drawing firm and convincing conclusions (statistical inconsistency >95%). In future, randomized control trials will be welcome to elucidate the prophylactic role of TE against TC and its real impact on BOT cancer.


Application of HPTLC with Densitometry for Evaluation of the Impact of External Factors on Contents of Diphenhydramine in Its Solutions.
The subject of durability of drugs is a very important problem investigated by researches. The method of accelerated aging is very often used for stability testing. It involves the influence of temperature, humidity, and light exposure. The aim of this work is estimation of contents of diphenhydramine in its standard solutions undergoing the impact of external factors, that is, temperature and UV light. The standard solutions of diphenhydramine were prepared in distilled water. The analysis of contents of compound investigated was carried out by use of HPTLC. Adsorption thin layer chromatography was performed on aluminum HPTLC plates precoated with silica gel 60F254 using mixture of ammonia, methanol, and ethyl acetate as mobile phase. The solutions investigated were exposed to UV light as well as being heated in 40°C. The contents of diphenhydramine were measured in initial solution and during experiment. The additional peaks on densitograms as well as changes in color of solution were observed as a result of exposure to UV light which can give information about new substances, degradation products of diphenhydramine, which were created during experiment.


Endogenous, hyperactive Rac3 controls proliferation of breast cancer cells by a p21-activated kinase-dependent pathway.
Uncontrolled cell proliferation is a major feature of cancer. Experimental cellular models have implicated some members of the Rho GTPase family in this process. However, direct evidence for active Rho GTPases in tumors or cancer cell lines has never been provided. In this paper, we show that endogenous, hyperactive Rac3 is present in highly proliferative human breast cancer-derived cell lines and tumor tissues. Rac3 activity results from both its distinct subcellular localization at the membrane and altered regulatory factors affecting the guanine nucleotide state of Rac3. Associated with active Rac3 was deregulated, persistent kinase activity of two isoforms of the Rac effector p21-activated kinase (Pak) and of c-Jun N-terminal kinase (JNK). Introducing dominant-negative Rac3 and Pak1 fragments into a breast cancer cell line revealed that active Rac3 drives Pak and JNK kinase activities by two separate pathways. Only the Rac3-Pak pathway was critical for DNA synthesis, independently of JNK. These findings identify Rac3 as a consistently active Rho GTPase in human cancer cells and suggest an important role for Rac3 and Pak in tumor growth.


Adult valvular heart disease: a practical approach.
The diagnosis and management of valvular heart disease is an important element of primary care practice. This article reviews the essential elements of four common valvular disorders, including signs and symptoms. The disorders reviewed are aortic stenosis, aortic regurgitation, mitral stenosis, and mitral regurgitation. The article places an emphasis on practical aspects of care.


Identification of chromosome regions associated with seedling vigor in rice.
Seedling vigor is important for optimum stand establishment in rice cropping. In this paper,a set of 264 F12 recombinant inbred lines (RILs) derived by single seed descent from a cross between Lemont (japonica) and Teqing (indica) was phenotyped for three seedling vigor related traits, including seed germination rate (GR), seedling shoot length and dry weight by the rolled paper towel tests. The phenotype data and a linkage map consisting of 198 DNA markers were combined to map quantitative trait loci (QTL) for seedling vigor by using a computer program QTLMapper1.0. A total of 13 putative main-effect QTL were detected. All of these QTL had much smaller effects on the traits with a mean R2 of 6.2%, ranging from 2.9% to 12.7%. As for digenic interaction, 18 pairs of epistatic loci with R2 > or = 5% were resolved with a mean R2 of 6.9% ,ranging from 5.1% to 11.8%, which was slightly larger than that of the main-effect QTL identified for the traits. The majority of the main-effect and epistatic loci detected for seedling vigor related traits were clustered in a few chromosome regions. Together, seven such chromosome regions (CRs), each with three or more seedling vigor main-effect and epistatic loci, were found to be highly associated with seedling vigor. These CRs can be classified into three types, i.e. M-CRs, E-CRs and ME-CRs. For some CRs just like CR(SV-6), the QTL within one CR were found to interact simultaneously with QTL within more than one other CRs to affect different seedling vigor related traits. The above results revealed that seedling vigor in rice is controlled by many loci, most of which have relatively small effects. Comparatively, epistasis as a genetic factor would be more important than main-effects of QTL for seedling vigor in rice. Nevertheless, the effects of the QTL are still large enough to be detected and in fact several chromosome regions were found to be highly associated with seedling vigor in very different populations as compared with previous studies. Molecular tagging of favorable alleles and marker-aided selection strategy may, therefore, be a promising approach to the improvement of rice seedling vigor.


Serotonin-immunoreactive varicosities in the cell body region and neural sheath of the snail, Helix pomatia, ganglia: an electron microscopic immunocytochemical study.
The distribution and connections of serotonin-immunoreactive fibers in the cell body region and neural sheath of the central ganglia of the snail, Helix pomatia, have been examined. The cell body region of the ganglia is supplied by an extremely dense network of varicose serotonin-immunoreactive fibers which surround neuronal perikarya in the ganglia. Immunoreactive processes also run to the neural sheath of both the ganglia and the peripheral nerve roots, forming a dense network. Electron microscopy revealed five different connections of serotonin-immunoreactive varicosities, according to their target: (i) non-specialized contacts with neuronal perikarya; (ii) non-specialized contacts with axon processes on the surface of the peripheral nerve roots; (iii) non-specialized neuromuscular connections with smooth muscle fibers in the neural sheath; (iv) varicosities engulfed by glial processes in both the cell body region and neural sheath; (v) varicosities embedded in the connective tissue elements of the sheath either partly or completely free of glial processes. In all cases of appositions no membrane specializations could be observed on either site of the contacts. These observations provide morphological evidence for non-synaptic regulatory actions of serotonin-containing neurons in Helix central nervous system: (i) modulation of the activity of neuronal perikarya; (ii) involvement in neuromuscular regulation; (iii) neurohormonal modulation of peripheral processes by release through the neural sheath.


Increased ventral striatal functional connectivity in patients with schizophrenia during reward anticipation.
Growing evidence points towards dysfunction of the ventral striatum as a neural substrate of motivational impairments in schizophrenia. Ventral striatal activity during reward anticipation is generally reduced in patients with schizophrenia and specifically correlates with apathy. However, little is known about the cortico-striatal functional connectivity in patients with schizophrenia during reward anticipation and its relation to negative symptoms. The aim of this study was to identify categorical group differences in ventral striatal functional connectivity during reward anticipation between patients with schizophrenia and healthy controls, and dimensional associations between cortico-striatal functional connectivity and negative symptom severity. A total of 40 patients with schizophrenia (10 females) and 33 healthy controls (8 females) were included from two previously published studies. All participants performed a variant of the Monetary Incentive Delay Task while undergoing event-related fMRI. Functional connectivity was assessed using psychophysical interactions (PPI) with the left and right ventral striatum as seeds and the contrast [High Reward Anticipation - No Reward Anticipation]. Negative symptoms were assessed using the Brief Negative Symptom Scale. Compared to controls, patients with schizophrenia showed increased functional connectivity between the left ventral striatum and the left precuneus and right parahippocampal gyrus, two hubs of the default mode network (cluster-level threshold: FWE, p < .05). In addition, we found a negative association between apathy scores on the BNSS and increased functional connectivity between the left ventral striatum and the left ventral anterior insula / putamen and the left inferior frontal gyrus / dorsal anterior insula (cluster-level threshold: FWE, p < .05). Our results indicate that the patterns of increased functional connectivity between the ventral striatum and the dorsal default mode network during reward anticipation could act as a compensatory mechanism to regulate the activity of the ventral striatum. Our results also showed that functional connectivity patterns from the ventral striatum, much like its local activity, is specifically related to apathy, and not diminished expression.


Human papillomavirus in paired normal and abnormal cervical biopsies--implications for treatment.
A total of 143 consecutive patients with abnormal cervical cytology was examined at a large colposcopy clinic in Glasgow. Each patient had paired biopsies from normal and abnormal cervical epithelium examined both histologically and by immunoperoxidase staining for human papillomavirus (HPV) infection. More than 71% of the abnormal biopsies and 39% of the normal paired biopsies had histological evidence of HPV infection. Cytological evidence of HPV infection was seen in 38.5% of cervical smears. Immunocytochemistry revealed HPV antigen in 22% of the abnormal biopsies and in 4.2% of the 'normal' biopsies. The presence of HPV infection in colposcopically normal cervical tissue both inside and outside the transformation zone may help to explain why current methods for treatment of cervical HPV infection are often unsuccessful.


[Clinical study of rhIL-11 for prevention and treatment of chemotherapy-induced thrombocytopenia].
Cancer chemotherapy can induce thrombocytopenia. It is necessory to develop drugs that can prevent and treat thrombocytopenia. The current study was designed to evaluate the efficacy and toxicity of rhIL-11 in prevention and treatment of chemotherapy-induced thrombocytopenia. A total of 109 cancer patients were involved randomly into AB or BA group and every patient received 2 cycles of chemotherapy. IL-11 was administered subcutaneously(50 micrograms/kg/d), beginning 24 hours after completion of chemotherapy for 14 consecutive days or continuing until platelet count was > 400 x 10(9)/L during cycle A. Patients did not received IL-11 during cycle B. Another 41 cases of cancer patients whose platelet were less than 50 x 10(9)/L after chemotherapy entered into open study group. IL-11 administration was the same as above. Efficacy can be evaluated in 107 cases in controlled study group. Mean platelet count of cycle A was (246.49 +/- 88.64) x 10(9)/L and cycle B was (180.24 +/- 83.34) x 10(9)/L(P = 0.000). Grade III/IV thrombocytopenia in cycle A and cycle B were 7/107(6.5%) and 15/107(14%), respectively (P = 0.04). The minimum platelet counts were (136.46 +/- 74.64) x 10(9)/L and (107.77 +/- 61.33) x 10(9)/L, respectively (P = 0.000). The maximum platelet counts were (381.28 +/- 150.39) x 10(9)/L and (207.44 +/- 113.32) x 10(9)/L, respectively (P = 0.000). For open study group, 32 patients could be evaluated. The platelet count increased from(30.1875 +/- 12.13) x 10(9)/L to (226.25 +/- 163.91) x 10(9)/L after IL-11 administration. Major adverse effects were edema, dizziness, palpitation, etc. rhIL-11 can reduce thrombocytopenia induced by chemotherapy and is a safe and effective drug for treatment of thrombocytopenia.


Effect of coliform bacteria, feed deprivation, and pH on ruminal D-lactic acid production by steer or continuous-culture microbial populations changed from forage to concentrates.
Fecal coliform bacteria were isolated from three herbivores (cattle, horse, and red panda) and shown to produce primarily the D-form of lactate, plus acetate and ethanol when grown anaerobically in 1.0% glucose broth. To evaluate coliform contribution to D-lactate acidosis in cattle, experiments involving a forage-adapted steer (fasted or normally fed) and four 500-ml fermentors were compared during 3 d of grain overload. In both systems, coliforms and D- and L-lactic acid production were greater from fasted than from normally fed steer inoculum. With fasted inoculum, coliform counts peaked (3 x 10(7)/ml at 7 h after initial engorgement) and receded to 10(3)/ml by the time D-lactate concentration peaked, indicating that bacteria other than coliform were responsible for the delayed peaking of D- (48 h) compared with L-lactate (24 h). Increases in lactobacilli more closely mimicked D-lactate increases than did changes in coliforms. The comparisons between the steer and fermentors showed many similar shifts in end-products and groups of bacteria, more so with the experiment initiated with fasted than with normal inoculum. With normal inoculum, VFA content and moles of butyrate/100 mol of VFA were greater in vitro than in vivo; VFA content presumably was larger because of VFA absorption in vivo. In a separate experiment, cultures initiated with identical inoculum and given the same amount of feed accumulated more lactate when pH was permitted to decrease to 5.0 than when pH was maintained at 5.5 for 6.0 or above, indicating the role buffers can have in controlling acidosis during diet change to concentrates.


Monoclonal antibodies to three separate domains on 124 kilodalton phytochrome from Avena.
Forty-six monoclonal antibodies have been prepared against 124 kilodalton phytochrome from Avena sativa cv Garry. Clones grown in mice have yielded ascites fluids with antibodies which bind to three distinct regions of the molecule, as visualized by immunoblot analysis of proteolytically produced peptides of the protein. One antibody group (type 1) recognizes an antigenic domain(s) that lies within 6 kilodaltons of the amino terminus of the molecule, a region critical to correct protein-chromophore interaction. The second group (type 2) binds to an antigenic site(s) present within the chromophore-containing half of the molecule that is adjacent to the domain recognized by the type 1 antibodies. The third group (type 3) recognizes an antigenic site(s) that resides in the nonchromophoric, carboxy terminal end of the molecule between 88 and 97 kilodaltons from the amino terminus. One of the type 1 antibodies cross-reacts with apparently undegraded 120 kilodalton phytochrome from zucchini, and therefore may be useful for identifying conserved domains which are essential to the regulatory role of the photoreceptor.


Clinical statistics analysis on the characteristics of pneumoconiosis of Chinese miner population.
Pneumoconiosis is one of the most common occupational diseases, which shows the progressive and irreversible pathological changes. It ultimately can induce pulmonary failure and lead to death. To date, these patients have no curative treatment option under the current standard of care, so it is especially important to delay the onset of the disease and slow down its progression. Therefore, understanding of clinical features of pneumoconiosis is particularly critical for medical intervention. We collected the clinical data from 118 pneumoconiosis cases of miners admitted in hospital and processed the statistics analysis by using the Chi-square test and the risk assessment. Compared to other types of miners, gold miners are liable to cause Broncho-pulmonary co-infection with Chi-square value 18.748 and the P value <0.001. However, unexpectedly, the smoking miners displayed a better Activities of Daily Living (ADLs) compared to non-smokers, which showed 19.318 of Chi-square score and less than 0.001 of P value. And this connection was associated with the dust exposure time (P<0.05), showing the increasing risk of non-smoking miners occurred as the increasing time exposed to dust. In addition, our analysis indicated that the probability of smoking miners suffered from Broncho-pulmonary co-infection was less than non-smoking miners with Chi-square value 8.044 and P<0.01, which was also associated with the dust exposure time tendentiously, though P>0.05. Moreover, smoking history exhibited a deteriorating effect to the overall survival (OS) with 9.546 of Chi-square value and P<0.05, in accordance with smoking reducing life time. Interestingly, pneumoconiosis drugs could extend the smokers' OS, but not non-smokers'. Our studies suggest that the history of smoking and exposure time of dust play important roles in the development of pneumoconiosis and smoking could be a factor that determines the treatment options depending on patients' smoking history.


Drugs, alcohol and pregnant women--changing characteristics of women engaging with a specialist perinatal outreach addictions service.
Pregnant substance misusers present an increased risk to themselves and the unborn child. The aim of this study was to investigate changes in the characteristics of women referred to a specialist perinatal addictions outreach service (1989-1991 versus 2002-2005). A cross-sectional audit of health records was conducted. Information was gathered for each woman who contacted the service (2002-2005). Data were compared to an earlier study in the same locality (1989-1991). A total of 167 pregnant substance-using women were referred between 2002 and 2005, of whom 126 made contact. The mean age was 30.2 years at 20.8 weeks' fetal gestation, with 76% not in addictions treatment, 32% from black or minority ethnic (BME) communities, 49% polysubstance users and 29% homeless. The primary substance used was illicit heroin (38%), followed by cocaine (24%). Compared to 1989-1991, there were significantly more pregnant women presenting at an older age, later gestation, with increased polysubstance use and a higher percentage of women from BME communities. This service was able to access vulnerable substance-abusing women with an altered pattern of substance use compared to over 10 years previously. However, improvements are needed for engaging all referred women and accessing women at an earlier gestation.


Stereospecificity of the glucose carrier in sugar beet suspension cells.
The stereospecificity of the binding site on the glucose carrier system in sugar beet suspension culture cells was determined using a series of aldo and keto hexose sugars and sugar alcohols. Specificity was determined as competition with [(14)C]glucose transport and glucose/proton symport.The binding site of the glucose carrier system was specific for the stereo orientation of the three equatorial OH groups on the three carbons opposite the oxygen and for the CH(2)OH group. Hexopyranose isomers with the same orientation at the three OH groups (carbons 2, 3, and 4 of C-1 d-glucose), but not with the CH(2)OH group, have only little (1-C d-glucose) or no effect (1-C d-idose and myoinositol) on d-glucose uptake. The C-1 l-sorbose molecule matches the C-1 d-glucose at many points including the stereo configuration of the CH(2)OH group, but it had no effect on d-glucose uptake perhaps because of an interference of the OH group adjacent to the CH(2)OH substituent. The d-glucose analogs, 3-O-methylglucose and glucosamine, were the most effective in binding to the glucose carrier. The isomers d-fructose, d-galactose, and d-mannose have separate distinctive proton cotransport systems. However, in starved cells they compete with d-glucose uptake, but the competition is for the available energy and not the carrier binding site.


Efficacy of Induced Sputum for the Diagnosis of Pulmonary Tuberculosis in Adults Unable to Expectorate Sputum.
Induced sputum (IS) has been used to collect airway secretions in subjects who have inadequate sputum production. The aim of this study was to investigate the efficacy of IS for the diagnosis of pulmonary tuberculosis (PTB) in adults unable to expectorate sputum. Medical records of 39 PTB patients who underwent IS due to absence of spontaneous sputum production between January 2011 and March 2014 at a tertiary hospital in South Korea were reviewed. Results of acid fast bacilli smear, Mycobacterium tuberculosis culture and polymerase chain reaction assay for M. tuberculosis (TB-PCR) of IS specimens from these patients were analyzed. Clinical and high-resolution computed tomography (HRCT) characteristics were also analyzed to find characteristics associated with IS culture positivity. Of the 39 IS specimens from PTB patients, 7 (17.9%) were smear positive and 31 (79.5%) were culture positive. Twenty-four IS specimens were tested for TB-PCR and 13 (54.2%) were positive on TB-PCR. Multivariate analysis showed that younger age (p=0.04) and presence of tree-in-bud appearance on HRCT (p=0.03) were independent predictors of IS culture positivity. IS is useful for the diagnosis of PTB in adults unable to expectorate sputum. Younger age and tree-in-bud appearance on HRCT were associated with IS culture positivity in these patients.


Mandibular osteoradionecrosis: reconstructive surgery.
Osteoradionecrosis of the mandible is a serious complication following radiotherapy of head and neck cancers. A retrospective study of 20 reconstructions of mandibular defects due to osteoradionecrosis was performed. Various osseocutaneous free flaps were used: upper lateral arm (n = 5), radial forearm (n = 1), iliac crest (n = 4) and fibula (n = 7). Four grafts had a condylar prosthesis, and for seven grafts fixation was accomplished with a reconstruction plate. In three patients the mandibular defect was reconstructed using a bridging plate only. We defined a successful reconstruction as a graft or plate that did not need removal. Success was noted in 15 out of 20 patients, giving an overall success rate of 75%. For the free grafts alone (n = 17), successful reconstruction was achieved in 15 patients (88%). Two fibular grafts were lost owing to exposure and infection, as well as all three alloplastic reconstructions. Minor postoperative complications were observed in 11 patients (58%).


Acquisition of basic ear surgery skills: a randomized comparison between endoscopic and microscopic techniques.
Endoscopic ear surgery is gaining increasing popularity and has an important impact on teaching middle ear anatomy and basic surgical skills among residents and fellows. Due to the wide-angled views offered, the approach significantly differs from the established microscopic technique. This randomized study compares the acquisition of basic ear-surgery skills using the endoscopic and microscopic technique under standardized conditions. We aim to investigate the required surgical times, attempts and accidental damages to surrounding structures (errors) in surgeons with different training levels. Final-year medical students (n = 9), residents (n = 14) and consultants (n = 10) from the Department of Otorhinolaryngology, Head and Neck Surgery at the University Hospital of Bern, Switzerland were enrolled in the present study. After randomization every participant had to complete a standard set of grasping and dissecting surgical tasks in a temporal bone model. After the first session the participants were crossed over to the other technique. Time required for completion of the surgical tasks was similar for both techniques, but highly dependent on the training status. A significant increase in the number of damages to the ossicular chain was observed with the microscopic as compared to the endoscopic technique (p < 0.001). Moreover, students beginning with the endoscopic technique showed an overall significantly lower amount of time to complete the tasks (p = 0.04). From the subjective feedback a preference towards the endoscopic technique mainly in medical students was observed. The endoscopic approach is useful and beneficial for teaching basic surgical skills, mainly by providing a reduction of damage to surrounding tissues with similar operating times for both techniques. Moreover, medical students performed significantly faster, when first taught in the endoscopic technique. Especially for young surgeons without previous training in ear surgery, the endoscope should be considered to improve surgical skills in the middle ear.


Oleuropein-Rich Diet Attenuates Hyperglycemia and Impaired Glucose Tolerance in Type 2 Diabetes Model Mouse.
Oleuropein, a phenolic compound found in abundance in olive leaves, has beneficial effects on various diseases. However, it is unknown whether an oleuropein-rich diet is efficacious against type 2 diabetic phenotypes. In this study, we investigated the effects of the oleuropein-containing supplement OPIACE, whose oleuropein content exceeds 35% (w/w), on the diabetic phenotypes in type 2 diabetes model Tsumura Suzuki Obese Diabetes (TSOD) mouse. TSOD mice were fed OPIACE at 4 weeks of age, i.e., before the TSOD mice exhibited diabetic phenotypes. We revealed that OPIACE attenuated hyperglycemia and impaired glucose tolerance in TSOD mice over the long-term (from 10 to 24 weeks of age) but had no effect on obesity. Furthermore, we demonstrated that OPIACE mildly reduced oxidative stress in TSOD mice by 26.2% and attenuated anxiety-like behavioral abnormality in aged TSOD mice. The results suggest that oleuropein suppresses the progression of type 2 diabetes and diabetes-related behavioral abnormality over the long-term.


(2n × 1) Reconstructions of TiO2(011) Revealed by Noncontact Atomic Force Microscopy and Scanning Tunneling Microscopy.
We have used noncontact atomic force microscopy (NC-AFM) and scanning tunneling microscopy (STM) to study the rutile TiO2(011) surface. A series of (2n × 1) reconstructions were observed, including two types of (4 × 1) reconstruction. High-resolution NC-AFM and STM images indicate that the (4 × 1)-α phase has the same structural elements as the more widely reported (2 × 1) reconstruction. An array of analogous higher-order (2n × 1) reconstructions were also observed where n = 3-5. On the other hand, the (4 × 1)-β reconstruction seems to be a unique structure without higher-order analogues. A model is proposed for this structure that is also based on the (2 × 1) reconstruction but with additional microfacets of {111} character.


Dietary n-3 PUFAs augment caspase 8 activation in Staphylococcal aureus enterotoxin B stimulated T-cells.
Epidemiological studies have linked consumption of n-3 PUFAs with a variety of beneficial health benefits, particularly with respect to putative anti-inflammatory effects. Unfortunately, many of these results remain somewhat controversial because in most instances there has not been a linkage to specific molecular mechanisms. For instance, dietary exposure to low levels of mercury has been shown to be damaging to neural development, but concomitant ingestion of n-3 PUFAs as occurs during consumption of fish, has been shown to counteract the detrimental effects. As the mechanisms mediating the neurotoxicity of environmental mercury are not fully delineated, it is difficult to conceptualize a testable molecular mechanism explaining how n-3 PUFAs negate its neurotoxic effects. However, environmental exposure to mercury also has been linked to increased autoimmunity. By way of a molecular understanding of this immuno-toxic association, disruption of CD95 signaling is well established as a triggering factor for autoimmunity, and we have previously shown that environmentally relevant in vitro and dietary exposures to mercury interfere with CD95 signaling. In particular we have shown that activation of caspase 8, as well as downstream activation of caspase 3, in response to CD95 agonist stimulation is depressed by mercury. More recently we have shown in vitro that the n-3 PUFA docosahexaenoic acid counteracts the negative effect of mercury on CD95 signaling by restoring caspase activity. We hypothesized that concomitant ingestion of n-3 PUFAs with mercury might be protective from the immuno-toxic effects of mercury, as it is with mercury's neuro-toxic effects, and in the case of immuno-toxicity this would be related to restoration of CD95 signal strength. We now show that dietary ingestion of n-3 PUFAs generally promotes CD95 signaling by upregulating caspase 8 activation. Apart from accounting for the ability of n-3 PUFAs to specifically counteract autoimmune sequelae of mercury exposure, this novel finding for the first time suggests a testable molecular mechanism explaining the overall anti-inflammatory properties of n-3 PUFAs.


Targeting osteomyelitis with complete [99mTc]besilesomab and fragmented [99mTc]sulesomab antibodies: kinetic evaluations.
The aim of this retrospective study was to compare the targeting of "pure" osteomyelitis (i.e., without surrounding soft tissue infection) by directly 99mTc-labelled complete immunoglobulin G (IgG) monoclonal antibody (MAb) ([99mTc]besilesomab) and by directly 99mTc-labelled fragment antigen-binding (FAb) MAb ([99mTc]sulesomab) in relation to their kinetic fate. A total of 73 patients with "pure" osteomyelitis were examined with [99mTc]besilesomab, (Scintimun®, IBA/CIS bio international, Saclay, France; N.=38) and [99mTc]sulesomab (LeukoScan®, Immunomedics Inc., Morris Plains, NJ, USA; N.=35). Kinetic data were deduced from whole-body and single-photon emission computed tomographic scans, performed 10 minutes to 24 hour p.i. (region-of-interest technique [ROI]). In targeting "pure" osteomyelitis, sensitivities at 1-4 hours were found to be higher for [99mTc]sulesomab (44% and 80% for [99mTc]besilesomab and [99mTc]sulesomab, respectively) but at significantly lower target/background (T/B) ratios than with [99mTc]besilesomab (1.8±0.3 versus 1.4±0.5 for [99mTc]besilesomab and [99mTc]sulesomab respectively; P<0.01). With [99mTc]besilesomab, there was a continuous osteomyelitis uptake over 24 hours, whereas with [99mTc]sulesomab, the maximal uptake occurred mostly within 1-4 hours, with subsequent clearance being slower for antigen-bound activity than for nonspecific background. Hence, diagnosis was possible mostly after 4h with [99mTc]sulesomab but often not before 24 hours with [99mTc]besilesomab, the later increasing significantly (P<0.01) in sensitivity (87% and 84% for [99mTc]besilesomab and [99mTc]sulesomab, respectively). These results show that the higher sensitivity of [99mTc]sulesomab in osteomyelitis targeting at earlier p.i. times does not rely on an increased antibody uptake but on a more rapid clearance of nonspecific background activity due to faster metabolism and excretion. Intact [99mTc]besilesomab show a slow, continuous uptake, leading to higher T/B at later p.i. times, often beyond the imaging possibilities of 99mTc.


Characterization of a Brg1 hypomorphic allele demonstrates that genetic and biochemical activity are tightly correlated.
Mammalian SWI/SNF-related complexes are recruited to the promoters of numerous target genes, and the BRG1 catalytic subunit confers ATPase activity necessary to slide or evict nucleosomes and to regulate transcription. Based on gene-targeting experiments in mice, BRG1 is essential for early embryonic development. However, Brg1 null mutants have provided limited insight into gene-dosage considerations and structure-function relationships. To extend our knowledge of BRG1 function, we describe the genetic and biochemical characteristics of an ENU-induced hypomorphic mutation that encodes a protein with a single amino-acid substitution (E1083G) within the bilobal ATPase/chromatin-remodeling domain. Brg1(ENU1/ENU1) mice have ~50% genetic activity and survive embryogenesis but exhibit a postnatal developmental phenotype associated with runting and incompletely penetrant lethality. The E1083G mutant protein is stable, and experiments with recombinant FLAG-tagged BRG1 proteins demonstrated that it retains full ATPase activity. Yet the biochemical activity of the mutant protein is diminished to ~50% of normal in chromatin-remodeling assays. Consistent with these findings, the E1083G substitution is predicted to disrupt a structurally conserved α-helix within the lobe that participates in DNA translocation but does not contain the ATPase catalytic site. We propose that this α-helix participates in the DNA translocation cycle by mechanistically linking DNA interaction surfaces at the DNA entry/anchor point to those within the Helicase C domain of lobe 2 of the bilobal ATPase motor. Taken together, these results demonstrate that BRG1 genetic and biochemical activities are tightly correlated. They also indicate that BRG1 ATPase activity is necessary but not sufficient for chromatin remodeling.


Focal sclerosing glomerulonephritis: a kinetic evaluation of hemostasis and the effect of anticoagulant therapy: a controlled study.
Seventeen children, 12 boys and 5 girls with histopathologic confirmation of focal sclerosing glomerulonephritis (FSG) presented with nephrosis (100%), hypertension (64.7%), intermittent hematuria (58.8%) and associated infection (82.3%). The coagulation-profile study in these patients revealed a hypercoagulable state characterized by significant elevation of fibrinogen and factor V concentrations and platelet count (P less than .002--.02). Increased blood viscosity (13.64 +/- 3.3 cp) was also noted in the patients (controls 10.8 +/- 0.9 cp). Determination of platelet half-life and fibrinogen half-life demonstrated that these were both shortened (P less than .001). Predominant shortening of platelet half-life was observed in 3 of the 4 patients during heparin therapy but this reverted to normal during therapy with the antiplatelet agent (Persantin). These findings signify the presence of a low-grade intravascular coagulation which perhaps occurs in the glomerular capillaries. Significant increments in creatinine clearance (CCr) and renal blood flow (RBF) were observed with treatment in the 9 anticoagulant-treated patients but not in the 8 control patients treated with prednisone and cyclophosphamide.


Understanding the essential components and experiences of youth with autism spectrum disorders in peer mentorship programmes during the transition to adulthood: A qualitative meta-ethnography.
Youth with an autism spectrum disorder (ASD) often require additional supports during the period of transition to from high school to post-secondary education or career paths. Peer mentorship (PM) programmes create opportunities to support youth with ASD in identifying their personal, academic and career goals after graduating from high school; however, there is limited insight about the components of these programmes that are valued by both participants and peer mentors and that are perceived to contribute to the overall success of a programme in achieving their goals. Our objective was to identify, describe and synthesize the components of PM programmes valued by youth with ASD and their peer mentors, as well as to document their experiences in these transitional support services. A meta-ethnography was conducted to synthesize qualitative and mixed methods studies of PM programmes for youth with ASD. A systematic search of seven databases yielded 142 nonduplicate articles. Data analysis and synthesis involved (1) extraction of raw data; (2) extraction of study authors' interpretations, followed by inductive coding; (3) synthesis of key themes and (4) schematic diagram development to illustrate the relationship of themes. Ten studies of PM programmes from Canada (2), United States (4), Australia (3) and United Kingdom (1) were included. Extracted data reflected experiences of 131 mentees and 82 mentors. The essential programme components identified were (1) mentorship, (2) skill building, (3) peer group and (4) facilitating transition. PM characterized by clear communication and connection between mentors and mentees was valuable to the success of the programme. Peer mentors played an essential role to facilitate the positive experiences that mentees had with programme components, including interactions with peer groups. Successful PM programmes created a safe environment for mentees to practice skills and helped mentees gain confidence to expand their roles to take leadership in their learning.


Natural Products Targeting Liver X Receptors or Farnesoid X Receptor.
Nuclear receptors (NRs) are a superfamily of transcription factors induced by ligands and also function as integrators of hormonal and nutritional signals. Among NRs, the liver X receptors (LXRs) and farnesoid X receptor (FXR) have been of significance as targets for the treatment of metabolic syndrome-related diseases. In recent years, natural products targeting LXRs and FXR have received remarkable interests as a valuable source of novel ligands encompassing diverse chemical structures and bioactive properties. This review aims to survey natural products, originating from terrestrial plants and microorganisms, marine organisms, and marine-derived microorganisms, which could influence LXRs and FXR. In the recent two decades (2000-2020), 261 natural products were discovered from natural resources such as LXRs/FXR modulators, 109 agonists and 38 antagonists targeting LXRs, and 72 agonists and 55 antagonists targeting FXR. The docking evaluation of desired natural products targeted LXRs/FXR is finally discussed. This comprehensive overview will provide a reference for future study of novel LXRs and FXR agonists and antagonists to target human diseases, and attract an increasing number of professional scholars majoring in pharmacy and biology with more in-depth discussion.


Eukaryotic protein disulfide isomerase complements Escherichia coli dsbA mutants and increases the yield of a heterologous secreted protein with disulfide bonds.
Eukaryotic protein disulfide isomerase (PDI) is a 55-kDa enzyme with cysteine oxidoreductase, chaperone, and antichaperone activities that catalyzes disulfide formation and rearrangement in the eukaryotic endoplasmic reticulum. In Gram-negative bacteria, the formation of disulfide bonds in the periplasm is mediated by DsbA, a strong cysteine oxidase but an inefficient catalyst of disulfide bond isomerization with no known chaperone activity. We show that rat PDI (rPDI) secreted in the periplasmic space of Escherichia coli can catalyze the formation of disulfide bonds and complement several of the phenotypes of dsbA mutants. The function of rPDI was dependent on the dsbB gene, suggesting that the reoxidation of this eukaryotic enzyme involves direct interactions with bacterial redox proteins. Co-expression of rPDI increased the yield of bovine pancreatic trypsin inhibitor (BPTI) severalfold, an effect that was enhanced when reduced glutathione was added to the growth medium. Whereas PDI is thought to function primarily as an isomerase in the eukaryotic endoplasmic reticulum, rPDI failed to decrease the accumulation of two-disulfide folding intermediates of BPTI and thus did not appear to appreciably catalyze the rate-limiting step in the oxidative folding pathway of BPTI. These results demonstrate that expression of eukaryotic foldases in E. coli can be exploited to better understand their function in vivo and also to increase the yield of biotechnologically valuable proteins.


[Analysis of the clinical characteristics of severe tsutsugamushi disease in Yunnan Province from 2017 to 2018].
To analyze the clinical characteristics of severe tsutsugamushi disease, and to improve the ability of clinicians to recognize severe cases. The clinical data of patients with tsutsugamushi disease from January 1st, 2017 to December 31st, 2018 in hospitals of Yunnan Province were retrospectively collected by the Case Report Form (CRF). The age, gender, clinical symptoms at admission; white blood cell (WBC), eosinophil count (EO), red blood cell (RBC), platelet count (PLT), hemoglobin (Hb), hematocrit (HCT), albumin (ALB), alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBil), lactate dehydrogenase (LDH), blood urea nitrogen (BUN), serum creatinine (SCr), uric acid (UA) on the first day of admission; and clinical outcomes were recorded. The patients were divided into the non-critical group and the critical group according to the diagnostic criteria, the data of clinical manifestation, laboratory examination, imaging examination and prognosis were compared between the two groups. Multivariate Logistic regression analysis was performed on the variables with statistical significance. The receiver operating characteristic (ROC) curve of LDH and UA for differential diagnosis of severe tsutsugamushi disease were drawn. From January 1st, 2017 to December 31st, 2018, 408 patients with tsutsugamushi disease were enrolled in 37 hospitals in 15 prefectures and municipalities of Yunnan Province. 385 cases were clinically diagnosed and 23 cases were laboratory diagnosed. There were 265 cases in non-critical group and 143 cases in critical group. A total of 8 cases died and the remaining 400 cases were discharged from hospital. (1) Compared with the non-critical group, age of the critical group was older, the incidence of dizziness, cough, expectoration, general soreness, dyspnea, palpitation, abdominal pain, diarrhea, bulbar conjunctival congestion, pleural effusion, peritoneal effusion, pericardial effusion, hepatomegaly, splenomegaly, and the levels of WBC, ALT, AST, LDH, TBil, BUN, SCr, UA were significantly increased, the incidence of lymph node enlargement and the levels of EO, PLT and ALB were significantly decreased, and there was no significant difference in other indicators between the two groups. (2) Multivariate Logistic regression analysis showed that age, dyspnea, palpitations, LDH, UA, ALB were risk factors for severe tsutsugamushi disease, β value was 0.040, -2.147, -1.414, 0.002, 0.005 and -0.132 respectively, and the odds ratio (OR) was 1.041, 0.117, 0.243, 1.002, 1.005 and 0.877 respectively (all P < 0.01). (3) ROC curve analysis showed that UA and LDH had better accuracy in differential diagnosis of severe tsutsugamushi disease (both P < 0.01), and the area under ROC curve (AUC) was 0.693 [95% confidence interval (95%CI) = 0.633-0.754], 0.819 (95%CI = 0.776-0.862), respectively. When the cut-off of UA was 306.2 μmol/L, the sensitivity was 60.8%, and the specificity was 77.4%. When the cut-off of LDH was 485.5 U/L, the sensitivity was 74.8%, and the specificity was 74.7%. The diagnostic value of UA combined with LDH was higher, AUC was 0.832, the sensitivity was 69.9%, and the specificity was 85.3%. Severe tsutsugamushi disease can be diagnosed at an early stage according to age, respiratory distress, palpitations, hypoalbuminemia, UA > 306.2 μmol/L, and LDH > 485.5 U/L.


Immune mechanisms in chlamydial eye infection. Development of T suppressor cells.
In vitro proliferation assays of whole peripheral blood mononuclear leukocytes (PBML) and PBML depleted of suppressor T cells were performed in cynomolgus monkeys after they had received one, two, or repeated ocular inoculations with Chlamydia trachomatis. Whole PBML responded only weakly to chlamydial antigen, and responses to concanavalin A were depressed for 12 wk following ocular infection. Depletion of the suppressor T cell population did not result in increased chlamydia-specific proliferation until 14-20 wk after initial antigen contact, suggesting that circulating suppressor T cells are not responsible for the initiation of the chronic state.


The systemic movement of a tobamovirus is inhibited by a cadmium-ion-induced glycine-rich protein.
Systemic movement is central to plant viral infection. Exposure of tobacco plants to low levels of cadmium ions blocks the systemic spread of turnip vein-clearing tobamovirus (TVCV). We identified a tobacco glycine-rich protein, cdiGRP, specifically induced by low concentrations of cadmium and expressed in the cell walls of plant vascular tissues. Constitutive cdiGRP expression inhibited systemic transport of TVCV, whereas suppression of cdiGRP production allowed TVCV movement in the presence of cadmium. cdiGRP exerted its inhibitory effect on TVCV transport by enhancing callose deposits in the vasculature. So cdiGRP may function to control plant viral systemic movement.


Relationships between maximum tongue pressure and second formant transition in speakers with different types of dysarthria.
The effects of muscle weakness on speech are currently not fully known. We investigated the relationships between maximum tongue pressure and second formant transition in adults with different types of dysarthria. It focused on the slope in the second formant transition because it reflects the tongue velocity during articulation. Sixty-three Japanese speakers with dysarthria (median age, 68 years; interquartile range, 58-77 years; 44 men and 19 women) admitted to acute and convalescent hospitals were included. Thirty neurologically normal speakers aged 19-85 years (median age, 22 years; interquartile range, 21.0-23.8 years; 14 men and 16 women) were also included. The relationship between the maximum tongue pressure and speech function was evaluated using correlation analysis in the dysarthria group. Speech intelligibility, the oral diadochokinesis rate, and the second formant slope were based on the impaired speech index. More than half of the speakers had mild to moderate dysarthria. Speakers with dysarthria showed significantly lower maximum tongue pressure, speech intelligibility, oral diadochokinesis rate, and second formant slope than neurologically normal speakers. Only the second formant slope was significantly correlated with the maximum tongue pressure (r = 0.368, p = 0.003). The relationship between the second formant slope and maximum tongue pressure showed a similar correlation in the analysis of subgroups divided by sex. The oral diadochokinesis rate, which is related to the speed of articulation, is affected by voice on/off, mandibular opening/closing, and range of motion. In contrast, the second formant slope was less affected by these factors. These results suggest that the maximum isometric tongue strength is associated with tongue movement speed during articulation.


Preparation and Characterization of Highly Porous Polyacrylonitrile Electrospun Nanofibers Using Lignin as Soft Template via Selective Chemical Dissolution Technique.
In this study, polyacrylonitrile (PAN) was mixed with a renewable polymer, lignin, to produce electrospun nanofibers by using an electrospinning technique. Lignin was utilized as a soft template that was removed from the nanofibers by using a selective dissolution technique to create porous PAN nanofibers. These nanofibers were characterized with Fourier transform infrared (FTIR), field emission scanning electron microscopy (FESEM), thermogravimetry analysis (TGA), X-ray diffraction (XRD), and Brunauer-Emmett-Teller (BET) to study their properties and morphology. The results showed that lignin can be homogeneously mixed into the PAN solution and successfully electrospun into nanofibers. FESEM results showed a strong relationship between the PAN: lignin ratio and the diameter of the electrospun fibers. Lignin was successfully removed from electrospun nanofibers by a selective chemical dissolution technique, which resulted in roughness and porousness on the surface of the nanofibers. Based on the BET result, the specific surface area of the PAN/lignin nanofibers was more than doubled following the removal of lignin compared to PAN nanofibers. The highest specific surface area of nanofibers after selective chemical dissolution was found at an 8:2 ratio of PAN/lignin, which was 32.42 m2g-1 with an average pore diameter of 5.02 nm. The diameter of electrospun nanofibers was also slightly reduced after selective chemical dissolution. Porous PAN nanofibers can be seen as the precursors to the production of highly porous carbon nanofibers.


Ultrasensitive detection of serum hepatitis B virus by coupling ultrafiltration DNA extraction with real-time PCR.
A simple and reliable DNA extraction of hepatitis B virus (HBV) is critical in developing an ultrasensitive detection method for HBV infection. Current commercially available serum Hepatitis B Virus (HBV) DNA extraction methods are time-consuming, expensive and/or require specialized equipment, which hinders wide adoption of clinical laboratories. This study offers a report on an ultrasensitive HBV DNA detection method by coupling serum HBV DNA extraction by ultrafiltration (UF) with real-time PCR (qPCR) detection. Serum proteins were precipitated by phenol to release HBV DNA in the supernatant which was then transferred to the UF devices. The resultant DNA concentrate was eluted and released into qPCR pre-mixture. The UF-qPCR assay performance, including recovery rate, linearity, detection sensitivity, precision and diagnostic accuracy that compared to the CAP-CTM V2.0 assay by analyzing batched low viral load clinical samples was evaluated. The recovery rate of the UF-based HBV DNA extraction method was above 80%. The assay linearity was demonstrated with a slope of 0.95 and R2 values of 0.99. Limit-of-detection (LOD) of the UF-qPCR assay was determined to be 12.1IU/ml. The coefficient of variation (CV) of HBV quantitation for high, low and limit titer samples was 2.28%, 5.77% and 25.59%, respectively. Accuracy of the UF-qPCR assay was confirmed with the reference panel, and there was a strong correlation between these two methods (R2 = 0.55, p < 0.01). The UF-qPCR assay is reliable, highly sensitive, affordable and time-saving, and the method can be used for ultrasensitive detection of serum HBV.


Resting-State Networks Associated with Behavioral and Self-Reported Measures of Persecutory Ideation in Psychosis.
Persecutory ideations are self-referential delusions of being the target of malevolence despite a lack of evidence. Wisner et al. (2021) found that reduced connectivity between the left frontoparietal (lFP) network and parts of the orbitofrontal cortex (OFC) correlated with increased persecutory behaviors among psychotic patients performing in an economic social decision-making task that can measure the anticipation of a partner's spiteful behavior. If this pattern could be observed in the resting state, it would suggest a functional-structural prior predisposing individuals to persecutory ideation. Forty-four patients in the early course of a psychotic disorder provided data for resting-state functional connectivity magnetic resonance imaging across nine brain networks that included the FP network and a similar OFC region. As predicted, we found a significant and negative correlation between the lFP-OFC at rest and the level of suspicious mistrust on the decision-making task using a within-group correlational design. Additionally, self-reported persecutory ideation correlated significantly with the connectivity between the right frontoparietal (rFP) network and the OFC. We extended the previous finding of reduced connectivity between the lFP network and the OFC in psychosis patients to the resting state, and observed a possible hemispheric difference, such that greater rFP-OFC connectivity predicted elevated self-reported persecutory ideation, suggesting potential differences between the lFP and rFP roles in persecutory social interactions.


Association of advanced hypodontia and craniofacial morphology in Japanese orthodontic patients.
The purpose of this study was to examine the effects of advanced hypodontia on craniofacial morphology in Japanese patients. We defined advanced hypodontia as a congenital absence of four or more permanent teeth, excluding the third molars. Lateral cephalometric radiographs of 20 female orthodontic patients (age range, 8.5 to 19 years; mean age, 13.9 years) were examined. Twenty-eight angular and 37 linear measurements were taken from each cephalogram, and these cephalometric data were statistically analyzed and compared with the Japanese cephalometric standards. The most frequently missing teeth were the mandibular and maxillary second premolars, followed by the maxillary first premolars and the maxillary first molars, in that order. Compared with the Japanese standards, a smaller cranial base length and angle, a shorter maxillary length, a slightly prognathic and upward-rotated mandible, and retroclination of the upper and lower incisors were found in the patients studied. These craniofacial anomalies should be taken into consideration in treatment planning and mechanotherapy.


Early change of plasma and cerebrospinal fluid arginine vasopressin in traumatic subarachnoid hemorrhage.
To investigate the changes and effects of arginine vasopressin (AVP) in patients with acute traumatic subarachnoid hemorrhage (tSAH). The plasma and cerebrospinal fluid (CSF) level of AVP, and intracranial pressure (ICP) were measured in a total of 21 patients within 24 hours after tSAH. The neurological status of the patients was evaluated by Glasgow Coma Scale (GCS). Correlation between AVP and ICP, GCS was analyzed respectively. Meanwhile, 18 healthy volunteers were recruited as control group. Compared with control group, the levels (pg/ml) of AVP in plasma and CSF (x+/-s) in tSAH group were significantly increased within 24 hours (38.72+/-24.71 vs 4.54+/-1.38 and 34.61+/-21.43 vs 4.13+/-.26, P less than 0.01), and was remarkably higher in GCS less than or equal to 8 group than GCS larger than 8 group (50.96+/-36.81 vs 25.26+/-12.87 and 44.68+/-31.72 vs 23.53+/-10.94, P less than 0.05). The CSF AVP level was correlated with ICP (r eqaul to 0.46, P less than 0.05), but no statistically significant correlation was found between plasma AVP, CSF AVP and initial GCS (r equal to -0.29, P larger than 0.05 and r equal to -0.32, P larger than 0.05, respectively). The ICP (mm Hg) in tSAH patients was elevated and higher in GCS less than or equal to 8 group than in GCS larger than 8 group (25.9+/-9.7 vs 17.6+/-5.2, P less than 0.05). Our research suggests that AVP is correlated with the severity of tSAH, and may be involved in the pathophysiological process of brain damage in the early stage after tSAH. It seems that compared with the plasma AVP concentration, CSF AVP is more related to the severity of tSAH.


Highly stable polymer coated nano-clustered silver plates: a multimodal optical contrast agent for biomedical imaging.
Here, we present a new optical contrast agent based on silver nanoplate clusters embedded inside of a polymer nano matrix. Unlike nanosphere clusters, which have been well studied, nanoplate clusters have unique properties due to the different possible orientations of interaction between the individual plates, resulting in a significant broadening of the absorption spectra. These nanoclusters were immobilized inside of a polymer cladding so as to maintain their stability and optical properties under in vivo conditions. The polymer-coated silver nanoplate clusters show a lower toxicity compared to the uncoated nanoparticles. At high nanoparticle concentrations, cell death occurs mostly due to apoptosis. These nanoparticles were used for targeted fluorescence imaging in a rat glioma cell line by incorporating a fluorescent dye into the matrix, followed by conjugation of a tumor targeting an F3 peptide. We further used these nanoparticles as photoacoustic contrast agents in vivo to enhance the contrast of the vasculature structures in a rat ear model. We observed a contrast enhancement of over 90% following the nanoparticle injection. It is also shown that these NPs can serve as efficient contrast agents, with specific targeting abilities for broadband multimodal imaging that are usable for diagnostic applications and that extend into use as therapeutic agents as well.


Model studies on the photosensitized isomerization of bixin.
The photosensitized isomerization reaction of the natural cis carotenoid bixin (methyl hydrogen 9'-cis-6, 6'-diapocarotene-6, 6'-dioate) with rose bengal or methylene blue as the sensitizer in acetonitrile/methanol (1:1) solution was studied using UV-vis spectroscopy, high-performance liquid chromatography (HPLC), and time-resolved spectroscopic techniques, such as laser-flash photolysis and singlet oxygen phosphorescence detection. In both N(2)- and air-saturated solutions, the main product formed was all-trans-bixin. The observed isomerization rate constants, k(obs), decreased in the presence of air or with increase in the bixin concentration, suggesting the participation of the excited triplet state of bixin, (3)Bix, as precursor of the cis--> trans process. On the other hand, bixin solutions in the absence of sensitizer and/or light did not degrade, indicating that the ground state of bixin is stable to thermal isomerization at room temperature. Time-resolved spectroscopic experiments confirmed the formation of the excited triplet state of bixin and its deactivation by ground state bixin and molecular oxygen quenching processes. The primary isomerization products only degraded in the presence of air and under prolonged illumination conditions, probably due to the formation of oxidation products by reaction with singlet molecular oxygen. An energy-transfer mechanism was used to explain the observed results for the bixin transformations, and the consequences for food color are discussed.


Impact of management of abdominal aortic dissection following the successful operation of annulo-aortic ectasia in Marfan's syndrome--a case report.
A 21-year-old female patient with Marfan's syndrome suffering from chronic ascending aortic dissection and aortic insufficiency was treated with total aortic root replacement by Cabrol technique (or procedure). The post-operative course was smooth and the patient recovered satisfactorily with very stable hemodynamic condition and good appetite. Unfortunately she complained of sudden severe abdominal pain followed by complete anuria on the fifth post-operative day. The MRI demonstrated abdominal aortic dissection with malperfusion of all the abdominal organs. Rapid increase of aminotransferases (SGOT and SGPT), severe acidosis and rapid deterioration of vital signs within 10 hours discouraged us from trying surgical intervention. The puzzle of management in those cases will be discussed.


[Investigations of the development of immunity in the course of experimental murine toxocariasis].
Mice were infected with Toxocara canis by an oral administration of embryonated eggs of the parasite, then they were killed between 1st and 8th week after infection to obtain sera and splenic lymphocytes. The lymphocytes were kept in culture medium for 3 to 6 days with either concanavalin A or excretory-secretory antigen of T. canis and assayed for proliferative responses. The obtained sera were examined for the presence of specific IgG and IgM antibodies. It was found that cell-mediated immunity was depressed for 3 weeks after infection and the first signs of the developing immunity were detected only at the 4th week of infection. Subsequently, the blastogenic responses increased reaching a level significantly higher when compared with those of the control cultures at 8th week of infection. Specific toxocaral IgG and IgM antibodies were first detected in the samples collected at the 4th week.


Structure of the cro repressor from bacteriophage lambda and its interaction with DNA.
The three-dimensional structure of the 66-amino acid cro repressor protein of bacteriophage lambda suggests how it binds to its operator DNA. We propose that a dimer of cro protein is bound to the B-form of DNA with the 2-fold axis of the dimer coincident with the 2-fold axis of DNA. A pair of 2-fold-related alpha-helices of the repressor, lying within successive major grooves of the DNA, seem to be a major determinant in recognition and binding. In addition, the C-terminal residues of the protein, some of which are disordered in the absence of DNA, appear to contribute to the binding.


Surgical treatment of coronary artery anomalies: report of a 37 1/2-year experience at the Texas Heart Institute.
The surgical treatment of coronary artery anomalies continues to evolve. The most common coronary artery anomalies requiring surgical intervention include coronary artery fistulae, anomalous pulmonary origins of the coronary arteries, and anomalous aortic origins of the coronary arteries. The choice of surgical intervention for each type of coronary anomaly depends on several anatomic, physiologic, and patient-dependent variables. As surgical techniques have progressed, outcomes have continued to improve, however, controversy still exists about many aspects of the proper management of patients who have these coronary artery anomalies. We reviewed the surgical treatment of 178 patients who underwent surgery for the above-mentioned types of coronary artery anomalies at the Texas Heart Institute from December 1963 through June 2001. On the basis of this experience, we discuss historical aspects of the early treatment of these anomalies and describe their present-day management.


LAITOR--Literature Assistant for Identification of Terms co-Occurrences and Relationships.
Biological knowledge is represented in scientific literature that often describes the function of genes/proteins (bioentities) in terms of their interactions (biointeractions). Such bioentities are often related to biological concepts of interest that are specific of a determined research field. Therefore, the study of the current literature about a selected topic deposited in public databases, facilitates the generation of novel hypotheses associating a set of bioentities to a common context. We created a text mining system (LAITOR: Literature Assistant for Identification of Terms co-Occurrences and Relationships) that analyses co-occurrences of bioentities, biointeractions, and other biological terms in MEDLINE abstracts. The method accounts for the position of the co-occurring terms within sentences or abstracts. The system detected abstracts mentioning protein-protein interactions in a standard test (BioCreative II IAS test data) with a precision of 0.82-0.89 and a recall of 0.48-0.70. We illustrate the application of LAITOR to the detection of plant response genes in a dataset of 1000 abstracts relevant to the topic. Text mining tools combining the extraction of interacting bioentities and biological concepts with network displays can be helpful in developing reasonable hypotheses in different scientific backgrounds.


Downregulation of long noncoding RNA ZMAT1 transcript variant 2 predicts a poor prognosis in patients with gastric cancer.
Gastric cancer is the second most common cause of cancer-related death partially because of its aggressive metastasis and the fact that it is often diagnosed at an advanced stage. Recent studies have shown that long noncoding RNAs (lncRNAs) play critical roles in multiple biological processes including oncogenesis. In the present study, we found for the first time that the lncRNA ZMAT1 transcript variant 2 is downregulated in gastric cancer tissues compared with adjacent normal tissues (P<0.001). The expression of ZMAT1 transcript variant 2 was inversely correlated with lymph node metastasis (P<0.05), depth of tumor invasion and tumor node metastasis stage (P<0.05). Univariate and multivariate analyses showed that ZMAT1 transcript variant 2 expression was an independent predictor for overall survival (P<0.05). Our study suggests that ZMAT1 transcript variant 2 is a potential diagnostic factor in patients with gastric cancer.


A plant signal sequence enhances the secretion of bacterial ChiA in transgenic tobacco.
When the secreted bacterial protein ChiA is expressed in transgenic tobacco, a fraction of the protein is glycosylated and secreted from the plant cells; however most of the protein remains inside the cells. We tested whether the efficiency of secretion could be improved by replacing the bacterial signal sequence with a plant signal sequence. We found the signal sequence and the first two amino acids of the PR1b protein attached to the ChiA mature protein directs complete glycosylation and secretion of the ChiA from plant cells. Glycosylation of this protein is not required for its efficient secretion from plant cells.


Education of pediatric surgery residents over time: Examining 15 years of case logs.
Surgical indications and techniques have changed over the last 15 years. The number of Pediatric Surgery training programs has also increased. We sought to examine the effect of these changes on resident education by examining case log data. Accreditation Council for Graduate Medical Education (ACGME) case logs for graduating Pediatric Surgery residents were examined from 2004 to 2018. Using the summary statistics provided, linear regression analysis was conducted on each case log code and category. In 2004, there were 24 Pediatric Surgery training programs and 24 Pediatric Surgery residents graduating with an average of 979.8 total cases logged. In 2018, there were 36 programs with 38 residents graduating with an average of 1260.2 total cases logged. Total case volume of graduating residents significantly increased over the last 15 years (p < 0.001). Significant increases were demonstrated in skin/soft tissue/musculoskeletal (p < 0.01), abdominal (p < 0.001), hernia repair (p < 0.001), genitourinary (p < 0.01), and endoscopy (p < 0.001). No significant changes were seen in the head and neck, thoracic, cardiovascular, liver/biliary, and non-operative trauma categories. No categories significantly decreased over the time period. No significant changes were seen in the number of multiple index congenital cases, including tracheoesophageal fistula/esophageal atresia repair, omphalocele, gastroschisis, choledochal cyst excision, perineal procedure for imperforate anus, and major hepatic resections for tumors. Pertinent increases in specific procedures include diaphragmatic hernia repair (p < 0.01), ECMO cannulation/decannulation(p < 0.05), thyroidectomy (p < 0.001), parathyroidectomy (p < 0.001), biliary atresia (p < 0.001), and circumcision (p < 0.001) as well as most laparoscopic abdominal procedures. Specific procedure codes with significant decreases include tracheostomy (p < 0.05), minimally invasive decortication/pleurectomy/blebectomy (p < 0.001), laparoscopic splenectomy (p < 0.001), as well as most open abdominal procedures. Despite increasing numbers of Pediatric Surgery residents and training programs, the number of cases performed by each graduating resident has increased. This increase is primarily fueled by increase in abdominal, skin/soft tissue/musculoskeletal, hernia repair, genitourinary, and endoscopic cases. Level II.


Study on Foaming Quality and Impact Property of Foamed Polypropylene Composites.
In the present work, foamed polypropylene (PP) composites were prepared by chemical foaming technology, and the foaming quality and impact property of the foamed PP composites were studied. The results showed that the foaming quality was significantly improved after the introduction of thermoplastic rubber (TPR) and polyolefin elastomer (POE). Meanwhile, it was found that the impact property depended on the intrinsic toughness and contribution of foams (cells) to the PP composites. Furthermore, the data regarding impact property in low temperature showed that when the temperature was between -80 and -20 °C, the impact properties of the foamed PP composites were higher than that of the unfoamed sample, which was due to the impact property being completely contributed by cells under this condition. Meanwhile, when the temperature ranged from -20 to 20 °C, the impact property of the unfoamed sample was higher, which was due to the PP matrix contributing more to the impact property under this temperature. This work significantly improved the foaming quality of foamed PP composites and provided reliable evidence for the improvement of impact property.


[Morphology, immunohistochemistry and differential diagnosis of 70 cases of adenocarcinoma of uterine cervix].
Seventy cases of cervical adenocarcinoma were classified into five types, namely: mucinous adenocarcinoma, endometrioid adenocarcinoma, mixed adenosquamous carcinoma, papillary adenocarcinoma and clear cell carcinoma. According to the morphological features, the results of mucin and immunohistochemical stainings, the histogenesis of cervical endometrioid adenocarcinoma and the differential diagnosis between cervical adenocarcinoma and endometrioid adenocarcinoma are discussed. The significance of vimentin staining for the differential diagnosis is also evaluated.


Predictors of clinical virulence in community-onset methicillin-resistant Staphylococcus aureus infections: the importance of USA300 and pneumonia.
Though USA300 community-onset methicillin-resistant Staphylococcus aureus (CO-MRSA) has emerged as a major public health concern in the United States, its relative virulence is unknown. We sought to evaluate if the USA300 strain of CO-MRSA causes more severe infections than other MRSA (ie, USA100, -500, -800, and others) strains. An epidemiologic study was conducted from 2000 to 2007 to measure rates of severe infection. A matched case-control study was conducted from 2004 to 2006 to assess the relationship of strain type, syndrome, and severity of infection. Severe illness was defined as CO-MRSA infections with medical intensive care unit (MICU) admission or death within 1 week of admission. Controls were those with CO-MRSA infection without MICU admission. We found an incidence of 75 cases per 100000 people of CO-MRSA infection in 2000, which increased to a rate of 396 per 100000 in 2007 (relative risk [RR], 5.3; 95% confidence interval [CI], 4.47-6.27). The incidence of severe infections increased from 5 cases per 100000 in 2000 to 17 per 100000 in 2007 (RR, 3.4; 95% CI; 1.67-6.43). USA300 strains were negatively associated with severe clinical courses or death as compared with other MRSA strain types. The highest risk of severe infection was found in those with pulmonary embolic infiltrates and bacteremia in the setting of USA300 infection (odds ratio, 31.41; 95% CI, 6.40-154.23). Our findings suggest that USA300 infections are negatively associated with severe clinical courses, suggesting less virulence than other MRSA strains, except in the setting of pneumonia with septic pulmonary emboli.


Bursal peptide BP-IV as a novel immunoadjuvant enhances the protective efficacy of an epitope peptide vaccine containing T and B cell epitopes of the H9N2 avian influenza virus.
Short peptide antigens covering conserved T or B cell epitopes have been investigated in influenza vaccines. Bursal pentapeptide V (BPP-V) and bursal peptide IV (BP-IV) are small molecular peptides that were isolated and identified from the bursa of Fabricius (BF) and induce a strong immune response at both the humoural and cellular levels. To explore the molecular adjuvant potential of BPP-V and BP-IV with an epitope vaccine, an epitope peptide (HA284-298, GNCVVQCQTERGGLN) rich in T and B cell epitopes for the H9N2 avian influenza virus (AIV) haemagglutinin (HA) protein was selected. BPP-V and BP-IV were coupled with the epitope peptide sequence to form BPP-V and BP-IV-epitope vaccines, respectively. The immunoefficacy of BPP-V and BP-IV-epitope peptide vaccines was evaluated. The results showed that the epitope peptide had weak immunogenicity. The BPP-V-epitope peptide vaccine promoted only the secretion of anti-HA IgG and IgG1 antibodies. The BP-IV-epitope peptide vaccine not only promoted the production of anti-HA IgG and IgG1 antibodies but also significantly induced the production of the IgG2a antibody. The BP-IV-epitope peptide vaccine significantly promoted the production of interleukin (IL-4) and interferon-γ (IFN-γ) (the BPP-V epitope peptide vaccine promoted only the production of IL-4), enhanced the cytotoxic T lymphocyte (CTL) response, and increased the proportion of CD3+ T lymphocytes. Moreover, the BP-IV-epitope peptide vaccine promoted a cell-mediated immune response similar to that of the AIV vaccine group. Furthermore, BPP-V and BP-IV-epitope peptide vaccines could also accelerate the clearance of pulmonary virus and reduce pathological damage after the challenge with H9N2 AIV. This study demonstrates the potential of BP-IV as an effective adjuvant for the epitope peptide vaccine for the H9N2 AIV.


Molecular mechanisms of analgesia induced by opioids and ethanol: is the GIRK channel one of the keys?
Opioids and ethanol have been used since ancient times for pain relief. Opioid signaling is mediated by various effectors, including G protein-activated inwardly rectifying potassium (GIRK) channels, adenylyl cyclases, voltage-dependent calcium channels, phospholipase Cbeta(PLCbeta), and mitogen-activated protein kinases, although it has been unclear which effector mediates the analgesic effects of opioids. Ethanol induces a variety of physiological phenomena via various proteins, including GIRK channels rather than via membrane lipids. GIRK channel activation by either G proteins or ethanol is impaired in weaver mutant mice. The mutant mice may therefore serve as a useful animal model for studying the role of GIRK channels in vivo. Reduced analgesia by using either opioids or ethanol in weaver mutant mice suggests that GIRK channels are important effectors in both opioid- and ethanol-induced analgesia. This hypothesis is supported by similar findings in GIRK2 knockout mice. Among the various effectors coupled with opioid receptors and various targets of ethanol, GIRK channels are the only molecules whose involvement in opioid- and ethanol-induced analgesia has been demonstrated in vivo. The GIRK channel is potentially one of the key molecules in furthering the understanding of the pain control system and in developing advanced analgesics with fewer adverse effects.


Well-differentiated mesenteric liposarcoma: report of two cases.
Liposarcoma is a rare tumor that can be treated by surgery in the absence of distant metastases. Management of liposarcoma, including diagnosis and therapy, is challenging because it has no characteristic symptoms and no established effective treatment. Here, we report two rare cases of primary mesenteric liposarcoma. In the first case, the tumor caused small bowel obstruction, and the patient presented with abdominal distention and severe abdominal pain. The second case is an occasional finding that occurred during laparoscopic surgery for incisional hernia. Both patients underwent successful resection of the tumor. Histopathology found a well-differentiated liposarcoma in both cases.


Melanocytoma of the left optic nerve head and right retrobulbar optic neuropathy compressed by a tuberculum sellae meningioma.
A 40-year-old woman had a highly pigmented, slightly elevated tumor on the left optic disc. She had no visual disturbance in the left eye. The tumor was stationary for 5 years. At age 45 years, she complained of decreased visual acuity in the right eye. Magnetic resonance imaging showed a right-shifted homogeneous lesion at the tuberculum sellae. Histopathologic study of the excised lesion revealed interlacing bundles of spindle-shaped fibroblast-like cells with whorl formation. We believe that a relationship between melanocytoma of the optic nerve head and a tuberculum sellae meningioma may exist rather than a chance occurrence, as previously suggested by others.


In vivo evaluation of phosphorous-containing derivatives of dodecahydro-closo-dodecaborate for boron neutron capture therapy of gliomas and sarcomas.
The in vivo uptake of dodecahydro-closo-dodecaborate derivatives substituted with phosphate- and bisphosphonate groups was evaluated in two different experimental tumor model systems and compared to other boronated and non-boronated compounds. These phosphorous-containing boron clusters may have potential for use in boron neutron capture therapy, a chemoradiotherapeutic form of cancer treatment. Using the F98 rat glioma as a brain tumor model in syngeneic Fischer rats, there was selective tumor uptake of the phosphate derivative with 21.5 micrograms boron/g tumor versus 5.2 micrograms/g normal brain and a tumor:blood ratio of 2.7. However, this compound was toxic to test animals and lethal at relatively low doses. The uptake of the bisphosphonate by the murine K8 osteosarcoma was approximately 18 micrograms boron/g tumor with a T:Bl ratio of 7.6 and a tumor:bone ratio of 1.5. This compound was non toxic to the test animals. The results indicate that phosphate- and bisphosphonate derivatives of dodecahydro-closo-dodecaborate may have potential for BNCT of gliomas and osteosarcomas, respectively.


Case report of prenatal diagnosis of Stüve-Wiedemann Syndrome in a woman with another child affected too.
Stüve-Wiedemann Syndrome (SWS; MIM 601 559) is an autosomal-recessive syndrome characterized by myotonia with mask-like face, skeletal dysplasia and intrauterine growth restriction. Other clinical findings are pursed mouth, hypoplastic midface, congenital contractures and muscular hypotonia. We discuss about the importance of prenatal diagnosis in SWS and the possibility of survival after the first year of life in patients suffering from this disease. we report a case of Stüve-Wiedemann Syndrome detected by morphological examination in our Operative Unit. Prenatal presumptive diagnosis was given with two-dimensional and 3-D probe, during the second trimester of pregnancy. Caesarean section was performed at 38(th) week of gestation. Then diagnosis was genetically performed. at birth, clinical examination was concordant with the ultrasound findings. Genetic analysis also confirmed the presumptive diagnosis. Episodes of respiratory distress and hyperthermia decreased until it disappeared altogether at 1 year of age. we underline the usefulness of ultrasound study of fetal skeleton in the prenatal diagnosis. It allowed us to do an early detection of birth defects and their appropriate management.