7 T MRI of the Cervical Neuroforamen: Assessment of Nerve Root Compression and Dorsal Root Ganglia in Patients With Radiculopathy.
The aim of this study was to assess the diagnostic value of 3-dimensional dual-echo steady-state (DESS) magnetic resonance imaging (MRI) of the cervical spine at 7 T compared with 3 T in patients with cervical radiculopathy. Patients diagnosed with cervical radiculopathy were prospectively recruited between March 2020 and January 2023 before undergoing surgical decompression and received 3-dimensional DESS imaging at 3 T and 7 T MRI. Cervical nerve root compression and the dimensions of the dorsal root ganglia were assessed by 2 radiologists independently. Signal intensity, visibility of nerve anatomy, diagnostic confidence, and image artifacts were evaluated with Likert scales. The degree of neuroforaminal stenosis was assessed on standard clinical 3 T scans. Statistics included the analysis of the diagnostic accuracy and interreader reliability. The Wilcoxon signed rank test was used to assess differences between the groups. Forty-eight patients (mean age, 57 ± 12 years; 22 women) were included in the study with the highest prevalence of severe neuroforaminal stenosis observed at C6 (n = 68) followed by C7 (n = 43). Direct evaluation of nerve root compression showed significantly higher diagnostic confidence and visibility of cervical nerve rootlets, roots, and dorsal root ganglia on 7 T DESS than on 3 T DESS (diagnostic confidence: P = 0.01, visibility: P < 0.01). Assessment of nerve root compression using 7 T DESS allowed more sensitive grading than standard clinical MRI (P < 0.01) and improved the performance in predicting sensory or motor dysfunction (area under the curve combined: 0.87). 7 T DESS imaging allows direct assessment of cervical nerve root compression in patients with radiculopathy, with a better prediction of sensory or motor dysfunction than standard clinical MRI. Diagnostic confidence and image quality of 7 T DESS were superior to 3 T DESS.


A Case Report of Bowel Perforation in a Gravid COVID-19 Patient.
Bowel perforation in a pregnant patient with COVID-19 infection is a rarely reported complication. With the uncovering of the different treatment modalities and complications of this disease, this case highlights diagnostic and therapeutic dilemmas and limitations in a special population. Clinical Presentation. A 35-year-old female, Gravida 2 Para 1 at 31 weeks age of gestation (AOG) who underwent cesarean section for nonreassuring fetal status in 2019, was admitted for severe COVID-19 infection presenting with dyspnea. During her hospitalization, she developed progressive dyspnea from worsening of COVID-19 infection. Patient was eventually intubated and was given a total of two doses of tocilizumab, adequate antibiotic treatment, remdesivir, and dexamethasone. An emergency repeat cesarean section was performed due to maternal deterioration and poor variability of the fetus. She delivered to a live preterm baby girl, with an Apgar score of 1 and 7 on the 1st and 5th minute of life respectively. During the postoperative days, patient remained intubated and sedated. Increasing residuals were noted per nasogastric tube (NGT). Serial scout film of the abdomen (SFA) and medical management were performed. Upon weaning from sedation, patient complained of right lower quadrant pain. A whole abdominal computed tomography (CT) scan with contrast was requested which revealed large bowel obstruction. Patient was referred to surgery service. Upon assessment, abdomen was noted to be rigid with guarding during palpation. A scout film of the abdomen was requested and revealed extensive amount of pneumoperitoneum with scanty to absent colonic gas suggestive of bowel perforation. Patient underwent emergency exploratory laparotomy. Upon opening the peritoneum, free air was evacuated. Approximately 1.4 liters of fecaloid peritoneal fluid was suctioned and adhesive band was noted at the pelvic area. A 2 cm full thickness perforation at the cecum with 17 cm serosal tear from the cecum to ascending colon was noted. Bowel loops proximal to the perforation were dilated. Nasogastric tube was inserted for bowel decompression. Right hemicolectomy was performed. Specimen was sent for histopathology. Acute inflammatory cells infiltrating the blood vessels and possible microthrombi and beginning thrombus formation were noted in the subserosa. Patient eventually expired on the 14th hospital day from sepsis. This case highlights a rarely reported complication of COVID-19 infection. Confluence of factors that predisposed the patient include pregnancy, COVID-19 infection, use of tocilizumab, and recent surgery. High index of suspicion is vital in the management and improvement of outcomes.


Clinical and bioethical implications of health care interruption during the COVID-19 pandemic: A cross-sectional study in outpatients with rheumatic diseases.
To determine the impact of health care interruption (HCI), on clinical status of the patients reincorporated to an outpatient clinic for rheumatic diseases (OCDIR), from a tertiary care level center who was temporally switched to a dedicated COVID-19 hospital, and to provide a bioethical analysis. From March to June 2020, the OCDIR was closed; since June, it is limited to evaluate 25% of the ongoing outpatients. This cross-sectional study surveyed 670 consecutive rheumatic outpatients between June 24th and October 31th, concomitant to the assessment of the rheumatic disease clinical status by the attendant rheumatologist, according to disease activity level, clinical deterioration and adequate/inadequate control. Multiple logistic regression analysis identified factors associated to HCI and to clinical deterioration. Patients were middle-aged females (86.7%), with median disease duration of 10 years, comorbidity (38.5%) and 138 patients (20.6%) had discontinued treatment. Primary diagnoses were SLE and RA, in 285 (42.5%) and 223 (33.3%) patients, respectively. There were 344 patients (51.3%) with HCI. Non-RA diagnosis (OR: 2.21, 95%CI: 1.5-3.13), comorbidity (OR: 1.7, 95%CI: 1.22-2.37), patient's need for rheumatic care during HCI (OR: 3.2, 95%CI: 2.06-4.97) and adequate control of the rheumatic disease (OR: 0.64, 95%CI: 0.45-0.9) were independently associated to HCI. There were 160 patients (23.8%) with clinical deterioration and associated factors were disease duration, substantial disease activity previous HCI, patients need for rheumatic care and treatment discontinuation. HCI during COVID-19 pandemic impacted course of rheumatic diseases and need to be considered in the bioethical analysis of virus containment measures.


Malaria Infection and Gametocyte Carriage Rates in Preparation for Transmission Blocking Vaccine Trials in Bancoumana, Mali.
The epidemiological characterization of transmission reservoirs is a critical step in preparation for interventional trials for malaria elimination/eradication. Using cluster sampling and households/compounds as units of sampling, we recruited and followed monthly, from June 2011 to June 2012, 250 volunteers 3 months to 50 years of age in Bancoumana, Mali. In July 2012, only participants 5-35 years of age (N = 121) were reenrolled and followed for an additional year. Malaria infection prevalence was highest in October in both 2011 (21.5%, 50/233) and 2012 (38.2%, 26/68). During both years, malaria infection prevalence was highest in children 5-14 years of age (P = 0.01 and P = 0.02, respectively). The gametocyte carriage prevalence was highest in November 2011 (7.6%, 17/225) and in October 2012 (16.2%, 11/68). Gametocyte carriage rates by age did not significantly differ in 2011 and 2012. In Bancoumana, the asexual and sexual parasite carriage rates are relatively high and highly seasonal. Seasonal variation and age differences in parasite and gametocyte carriage provide essential knowledge for the design of transmission blocking assay and vaccine studies in the field.


Neutron-proton asymmetry dependence of spectroscopic factors in ar isotopes.
Spectroscopic factors have been extracted for proton-rich 34Ar and neutron-rich 46Ar using the (p, d) neutron transfer reaction. The experimental results show little reduction of the ground state neutron spectroscopic factor of the proton-rich nucleus 34Ar compared to that of 46Ar. The results suggest that correlations, which generally reduce such spectroscopic factors, do not depend strongly on the neutron-proton asymmetry of the nucleus in this isotopic region as was reported in knockout reactions. The present results are consistent with results from systematic studies of transfer reactions but inconsistent with the trends observed in knockout reaction measurements.


IL-12 transiently induces IFN-gamma transcription and protein synthesis in human CD4+ allergen-specific Th2 T cell clones.
IL-12 is a cytokine produced by monocytes and Epstein-Barr virus-transformed B cells which initiates Th1 responses by inducing the development of CD4+, IFN-gamma producing Th1 T cells in mouse and human. We have previously reported that allergen-specific CD4+ Th2 T cell clones produce IFN-gamma, following activation by phorbol ester (TPA) and calcium ionophore, indicating that these cells still have the ability to produce IFN-gamma. This observation, together with the capacity of IL-12 to induce IFN-gamma, prompted us to examine the effects of rIL-12 on the cytokine production profiles of a panel of cloned allergen-specific Th2 cell lines, and compare these to the effects of rIL-12 on the cytokine production by Th0 and Th1 T cell clones. Activation with antigen or TPA/anti-CD3 mAb of Th2 T cell clones that had been preincubated with rIL-12 and rIL-2 for 5 days induced or enhanced the expression of IFN-gamma transcripts, as well as the production of IFN-gamma by these cells. Furthermore, in a different set of experiments, it was found that the presence of rIL-12 during a 12 h stimulation of Th2 T cell clones induced or enhanced the expression of IFN-gamma transcripts, as well as the production of IFN-gamma by these cells. rIL-12 also enhanced IFN-gamma production by Th0 and Th1 T cells, but, in contrast, rIL-12 had no effect on the production of IL-4, nor on the frequency of IL-4 producing cells, as judged by analysis of intracellularly produced cytokines.(ABSTRACT TRUNCATED AT 250 WORDS)


Absorption, transport and distribution of copper.
This paper deals with the way animals regulate the supply of copper to sites within the body where the metal exercises its functions. Homeostasis is maintained by the control of both absorption and excretion of the metal, although the efficiency with which this balanced is achieved varies between species. These processes are influenced by dietary intake of copper and they also depend on genetic factors, age, dietary composition and the physiological state of the animal. Some of these effects are described, with emphasis on the possible mechanism of absorption of the metal. The distribution of copper after its absorption from the intestine and, in particular, its uptake by the liver and kidneys are also discussed. Much of the copper removed by these organs is incorporated into, and may induce synthesis of, metallothionein. The precise role of this protein in copper metabolism is still, however, a matter of conjecture. The subsequent binding of hepatic copper to metalloenzymes, its excretion in bile and its incorporation into lysosomes during copper overload are also considered.


On the size and the role of a free cytosolic pool of acidic ribosomal proteins in yeast Saccharomyces cerevisiae.
A small but distinct amount of yeast acidic ribosomal proteins A1/A2 was detected in cytosol by immunoblotting on a two-dimensional gel electrophoretogram, while 38 kDa acidic protein A0 was not detected. The free forms of A1/A2 in the cytosol were eluted in gel filtration at the molecular mass of about 30 kDa under non-denaturation conditions, suggesting that they exist as a dimer or timer without association with A0. The amount of free A1/A2 was determined by immunoblotting to be 0.3% of the ribosome-bound A1/A2 in yeast. The time course of incorporation of radioactive amino acid showed that the cytosolic free A1/A2 are labeled more rapidly with high specific radioactivity than the ribosome-bound A1/A2. This result suggested that some of the cytosolic A1/A2, if not all, are newly-synthesized proteins which are ready for incorporation into cytoplasmic ribosomes.


A comparison of ropivacaine and lidocaine with epinephrine for intraligamentary anesthesia.
The purpose of this study was to compare the efficacy of 2 different concentrations of ropivacaine with lidocaine containing epinephrine for intraligamentary anesthesia. Ethical approval was obtained and a randomized, double-blind, cross-over volunteer investigation was conducted. Twenty-four volunteers had intraligamentary injections of 2% lidocaine with 1:80,000 epinephrine, 0.75% ropivacaine, or 1% ropivacaine at the upper lateral incisor and lower first bicuspid teeth. The response of the test teeth to electrical pulp testing and the reaction of the gingiva to sharp probing were assessed up to 29 minutes after injection. Injection discomfort and side effects were also recorded. Data were analyzed by using the chi-square test and analysis of variance. Lidocaine with epinephrine was more successful than the ropivacaine solutions in obtaining pulpal anesthesia (chi-square = 12; P <.002) and produced longer-lasting pulpal (F = 21; P <.001) and soft tissue (F = 16; P <.001) anesthesia. Injection discomfort and incidence of side effects were similar between solutions, and none produced serious adverse effects. Lidocaine with epinephrine is more effective than ropivacaine as an intraligamentary anesthetic.


Clinicopathological aspects of V-Raf murine sarcoma viral oncogene homolog B1 (BRAF) mutated non-small cell lung carcinoma in an Indian cohort: is there a difference?
Activating mutations in the BRAF gene have been reported in 0.8%-8% cases of NSCLC. Traditionally, diagnostics have mainly focused on detection of V600E and modalities like mutation specific IHC, allele specific real-time PCR have been utilized. This may underestimate true prevalence of the non-V600E variants. Broader panel NGS testing offers a one stop solution and may identify newer potentially targetable variants. This is a retrospective single center experience of patients with BRAF mutated NSCLC characterizing the molecular spectrum and clinicopathologic characteristics. 260 patients underwent panel based NGS testing at our center, between 2017-2020. 13 BRAF mutant cases, were detected and were clinically reviewed. Thirteen cases of BRAF alterations were seen in out of 260 (5%) patients. Median age of the cohort was 62 years (range: 39-86 years) with a female predilection). Canonical BRAF V600E mutation was seen in 6 (46.2%) patients and 7 (53.8%) harbored a non-V600E alteration. Spectrum of non V600E alterations included G466E, G469A, N581I, V600_K601delins, D594G, L597Q, G649V and were commonly female (P>0.01) with a higher trend for liver metastases (P=0.09). Median PFS was 4.8 months on chemotherapy (P=0.8). All patients (13/13, 100%) were never smokers with an adenocarcinoma histology. This is a single center experience from an Indian NSCLC cohort and shows higher prevalence of non-V600E than V600E mutation reported in literature. This may be attributed to increased use of NGS testing revealing otherwise missed alterations on sequential single gene testing.


Changes in proteinase/proteinase inhibitor levels in rat skeletal muscle tissue during diabetes and fasting.
The skeletal muscle content of three rat proteinase inhibitors, a 1-proteinase inhibitor, contrapsin and a 1-cysteine proteinase inhibitor was measured by immunochemical techniques following streptozotocin-induced diabetes. When compared with normal rats, a 1-cysteine proteinase inhibitor and a 1-proteinase inhibitor levels remained essentially unchanged, whereas the content of rat contrapsin was reduced by nearly 80% after the onset of diabetes. Similarly, fasting of rats for three days resulted in a lowering of the levels of contrapsin in skeletal muscles. Under these conditions, levels of chymotrypsin-like activity (chymase) were increased by 150%, whereas the content of the trypsin-like, neutral proteinase was unchanged. Kinetic studies in vitro with Tosyl-Gly-Pro-Arg-4-nitroanilide as substrate showed no inhibition of the trypsin-like proteinase by a 1-proteinase inhibitor, while contrapsin inhibited the enzyme with a Ki value of 40nM. The changing pattern of these proteinases and their potential inhibitors (chymase/a 1-proteinase inhibitor and trypsin-like proteinase/contrapsin) may be a factor contributing to muscle wasting as observed in diabetes and fasting.


[HCH soil pollution (hexachlorocyclohexane) in Twente, public health aspects].
A large waste heap consisting of HCH isomers was stored near the factory. In the seventies the spread of this waste was found to give rise to severe pollution of the soil resulting in unacceptable contamination of foods. Regulations on the basis of the Meat Inspection Act are recommended, under which slaughtered cattle from polluted areas may be traced according to Meat Inspection regulations.


An unusual case of talonavicular dislocation with associated ipsilateral foot fractures.
We describe a previously unreported form of a talonavicular dislocation complicated by navicular, talar neck and open calcaneal fractures. Prompt recognition and rapid reduction of fractures and dislocations gives the best possible outcome. The presence of serious distracting injuries can alter priorities, however the "lesser" injuries often lead to long term morbidity after recovery from the life-threatening injuries.


Chronic bee paralysis as a serious emerging threat to honey bees.
Chronic bee paralysis is a well-defined viral disease of honey bees with a global distribution that until recently caused rare but severe symptomatology including colony loss. Anecdotal evidence indicates a recent increase in virus incidence in several countries, but no mention of concomitant disease. We use government honey bee health inspection records from England and Wales to test whether chronic bee paralysis is an emerging infectious disease and investigate the spatiotemporal patterns of disease. The number of chronic bee paralysis cases increased exponentially between 2007 and 2017, demonstrating chronic bee paralysis as an emergent disease. Disease is highly clustered spatially within most years, suggesting local spread, but not between years, suggesting disease burnt out with periodic reintroduction. Apiary and county level risk factors are confirmed to include scale of beekeeping operation and the history of honey bee imports. Our findings offer epidemiological insight into this damaging emerging disease.


Functional characterization of serotonin receptors in rat isolated aorta.
Interactions of serotonin (5-HT) with different specific 5-HT receptors that can coexist in the same blood vessel sometimes generate opposite effects. The aim of this study was to characterize the functional role of previously described mRNAs for 5-HT receptors in the rat aorta (5-HT(2A), 5-HT(2B), 5-HT(1B), 5-HT(7)) as well as to study the known 5-HT(2A) receptor-mediated constrictor response and investigate the influences of endothelium and preconstriction on the tissue in that response. A slight endothelium- and concentration-dependent relaxant effect was observed for 5-HT in aorta precontracted with either 5 microM phenylephrine (PE) or 1 microM prostaglandin F2alpha (PGF2alpha) in the presence of 0.3 microM ketanserin. EC50 values for 5-HT and alpha-methyl-5-HT relaxant responses after PE were 43.10 +/- 4.00 and 57.11 +/- 8.01 nM, respectively. pK(B) values for antagonists cyproheptadine and rauwolscine were 8.92 +/- 0.22 and 7.15 +/- 0.12, respectively. In nonprecontracted tissues, the contractile potency of 5-HT was higher in the absence of endothelium (EC50, degreesM): 2.60 +/- 0.28 and 4.12 +/- 0.21 in the absence and in the presence of endothelium, respectively. The differences were statistically significant (p<0.05). In precontracted tissues, the differences in EC50 values (2.22 +/- 0.40 and 4.65 +/- 0.60 microM without and with endothelium, respectively) were also statistically significant (p<0.05). pK(B) values for the 5-HT(2A) antagonist ketanserin were similar under all conditions tested. In conclusion, under our experimental conditions there are two functional 5-HT receptors in rat aorta: 5-HT(2A) contractile receptor in smooth muscle and a high-affinity relaxant receptor that mediates a very slight response and the pharmacology of which could be compatible with an endothelial 5-HT(2B) receptor.


Genome-Wide Differential Expression Profiling of Pulmonary circRNAs Associated With Immune Reaction to Pasteurella multocida in Goats.
Pasteurella multocida is a highly versatile pathogen that infects a wide range of animals, including goats, causing pneumonia and hemorrhagic septicemia. Circular RNA (circRNA) is a type of non-coding RNA that plays an important role in regulating cellular metabolism. However, whether and how circRNA is involved in regulating immune responses in the goat lung has not been reported. Thus, this study was designed to examine the function of circRNA in goats infected with Pasteurella multocida. Goats were assigned into one of two groups: an uninfected control group (CK) and an infected group challenged with P. multocida. Compared with the CK group, which remained healthy, the infected goats showed clinical signs of infection, including depression, cough, nasal discharge, and dyspnea, along with elevated body temperature and lesions in the lung. Whole-transcriptome sequencing and small RNA sequencing were then performed using lung samples from goats from each group. A total of 138 circRNA, 56 microRNAs (miRNA), and 2,673 messenger RNA (mRNA) molecules were significantly differentially expressed in the P. multocida-infected group compared with the CK group. Randomly selected differentially expressed circRNA, miRNA, and mRNA molecules (n = 5 per group) were then validated by quantitative reverse-transcriptase polymerase chain reaction analysis. Gene ontology (GO) analysis of the source genes indicated that six immune-related terms were enriched among the differentially expressed cirRNA molecules, including inflammatory response, immune effector process, cell activation involved in immune response, cytokine-mediated signaling pathway, response to endogenous stimulus, and immune response. The corresponding circRNA molecules were then selected for construction of a competitive endogenous RNA network to identify networks that may be involved in the immune response to P. multocida infection. The results indicated that P. multocida HN01 may cause pneumonia and stimulate an immune response in goats via regulation of circRNA expression. This study presents the first comprehensive circRNA profile in response to P. multocida infection in goats, thus, providing a basis for understanding the function of circRNA in the host immune response to P. multocida infection.


The cell cycle positions influence DNA migration as measured with the alkaline comet assay in stimulated human lymphocytes.
Virtually any eukaryotic cell can be processed for analysis of DNA damage using the comet assay. The most commonly examined human cells are lymphocyte populations. However, many parameters can affect the response of lymphocytes to the assay in terms of the ability to detect damage. The response of cultivated lymphocytes in the comet assay indicated cycle-dependent differences. The cell cycle position has been shown to affect the results obtained using both the alkaline and neutral assays. This is primarily a reflection of the complications of including S-phase DNA. In the alkaline assay, replicating structures are interpreted as strand breaks when denatured, increasing the level of detectable damage. We performed the alkaline comet assay to detect differences in the extent of DNA in stimulated human lymphocytes collected at different sample times after mitogen stimulation. Our results clearly indicate that proliferating lymphocytes have a greater migration of DNA (measured with the comet assay as DNA damage) than quiescent lymphocytes. The lymphocytes collected at 36, 42, and 48 h after mitogen stimulation showed a significantly increased extent of DNA migration in comparison to the lymphocytes collected at 0 and 24 h after stimulation. It, probably, can be explained by the higher frequency of the S phase cells in lymphocyte populations collected at 36, 42, and 48 h. Sites of active DNA replication during the S phase behave like single-strand breaks when denatured in alkali, and their presence may result in a significant increase of the tail moments in S phase cells.


Principles and analysis of hematopoietic stem cell transplantation outcomes: the physician's perspective.
Hematopoietic stem cell transplantation (HSCT) is used widely for the treatment of malignant and non-malignant diseases. Advances in transplantation strategies such as modifications to existing transplant-conditioning regimens to lower morbidity and mortality, use of alternative donors and grafts, supportive care including graft-versus-host disease prophylaxis and antimicrobial therapy have led to increasing numbers of HSCT being performed. The procedure is now available to children, young and older adults with an ever increasing number of survivors from this procedure. Analysis of outcomes after HSCT giving consideration to existing strategies warrants using appropriate statistical methodology. This is critical not only in documenting the current success of HSCT but to plan future strategies to optimize accessibility to HSCT, donor and graft choices, patient selection, counsel potential HSCT candidates and long-term survivors and plan intervention trials for these persons. We describe concepts and principles of HSCT to better understand the complexities associated with outcome analysis.


Development of a videotape on adverse drug reactions.
A pharmacy department's development and evaluation of a 20-minute videotape on adverse drug reaction (ADR) reporting is described. At the University of Mississippi Medical Center Hospital, a 545-bed hospital, it was determined that inadequate education of staff was a major contributing factor to the failure of ADR-reporting programs. Since no videotape educational program on ADRs was available, the pharmacy department developed its own at a cost of approximately $400. The videotape demonstrates a variety of ADRs that occur in adult inpatients and provides instructions on how to report ADRs. The description of each ADR includes manifestations of the reaction, drugs associated with the reaction, and implications for the patient. During a three-month evaluation period on four patient-care units, nine ADRs were reported by nurses who were shown the videotape, while no ADRs were reported by nurses who were provided with only an oral presentation on ADR reporting. The videotape is now used hospitalwide, primarily with nurses and new pharmacy personnel. The videotape developed by the pharmacy department proved to be an effective means for demonstrating clinical manifestations of ADRs and explaining procedures for voluntary reporting.


Well-differentiated liposarcoma of the breast arising in a background of malignant phyllodes tumor in a pregnant woman: A rare case report and review of literature.
Pure mesenchymal sarcomas and phyllodes tumor with sarcomatous differentiation of the breast are rare tumors. Primary breast sarcomas are a heterogenous group of neoplasms which include malignant fibrous histiocytoma, fibrosarcoma, angiosarcoma, leiomyosarcoma, osteosarcoma, rhabdomyosarcoma, and liposarcoma. Sarcomatous differentiation in phyllodes tumor is seen in the form of angiosarcoma, chondrosarcoma, leiomyosarcoma, osteosarcoma, rhabdomyosarcoma, and liposarcoma. Here, we report a case of a 28-year-old pregnant woman with a breast lump during her second trimester which drastically increased in size in the postpartum period. Wide local excision revealed a malignant phyllodes tumor with liposarcomatous differentiation. Later, the patient underwent completion mastectomy which showed residual tumor.


[Spatial pattern and regeneration characteristics of main woody species in natural secondary forest in Maoershan, Northeast China.]
Based on the survey data from a 1 hm2 plot of the second forest in Maoershan, we divided the stand into four size degrees, including seedlings (tree height H<30 cm), saplings (H 30-130 cm or H>130 cm meanwhile DBH< 5 cm), medium trees (DBH 5-10 cm) and big trees (DBH≥10 cm). The spatial pattern and spatial association of all woody plants and three dominant tree species in four size degrees, as well as the basic forest regeneration, were chosen as study objects, to explore the renewal trend and provide theoretical basis for the sustainable forest management. The O-ring point pattern analysis method was used to analyze the spatial distribution and spatial association. The dominant trees were planted Pinus koraiensis and three common broadleaved tree species (Fraxinus mandshurica, Juglans mandshurica, Phellodendron amurense), and Ulmus pumila. The results showed that the regeneration of the stand was quite common, with 2894 seedlings·hm-2 and 3337 saplings·hm-2 . For the whole forest, the seedlings in the stand were positively associated with large trees and medium trees and saplings respectively at the scales of 0-25 m, 0-15 m and 0-40 m, and negatively associated at the subsequent scales. The saplings were positively associated with large trees and medium trees at 0-15 m, 0-25 m respectively, and had no significant association at the subsequent scales. Medium trees showed no significant association with big trees at all the scales. For the dominant trees, the saplings and seedlings of Pinus koraiensis showed negative association at the scale of 0-40 m, while the saplings and seedlings of the three common broadleaved tree species or Ulmus pumila were mainly non-associated. There was a negative association between the saplings of Pinus koraiensis and each size degree of the three common broadleaved tree species or Ulmus pumila at most scale, whereas saplings of the three common broadleaved tree species and Ulmus pumila showed a negative association with non-conspecies only at 0-20 m scale. In the medium and large size degrees, there was no significant association between each two of the three dominant tree species at the scale above 20 m. The secondary forest in Maoershan is still under the process of succession. During the process of forest resource management, measures should be taken to promote the renewal, and the unreasonable spatial pattern should be adjusted in time.


Why Is Research on Amyloid-β Failing to Give New Drugs for Alzheimer's Disease?
The two hallmarks of Alzheimer's disease (AD) are the presence of neurofibrillary tangles (NFT) made of aggregates of the hyperphosphorylated tau protein and of amyloid plaques composed of amyloid-β (Aβ) peptides, primarily Aβ1-40 and Aβ1-42. Targeting the production, aggregation, and toxicity of Aβ with small molecule drugs or antibodies is an active area of AD research due to the general acceptance of the amyloid cascade hypothesis, but thus far all drugs targeting Aβ have failed. From a review of the recent literature and our own experience based on in vitro, in silico, and in vivo studies, we present some reasons to explain this repetitive failure.


Analysis of flagellar bending in hyperactivated hamster and mouse spermatozoa.
Flagellar bending was analysed using photographs of hyperactivated hamster and mouse spermatozoa. The flagellar waveform consists of several bends; the centre of each bend was therefore located on the flagellum, and the angle of the bend measured. The direction of the bend was determined by using the asymmetry of hook-shaped head to assess the asymmetry of flagellar waveform. The bend that occurred in the same direction as the curve of head was defined as the reverse bend and the bend in the opposite direction as the principal bend. In hamster spermatozoa, flagellar bending was asymmetric to the direction of the reverse bend after incubation for 5 min. After incubation for 4 h the asymmetry had increased, as the angles of the reverse bends had increased in all regions of the flagellum but the principal bend had not. In mouse spermatozoa incubated for 5 min, flagellar bending was relatively symmetric. In the hyperactivated mouse spermatozoa incubated for 3 h, the angle of the principal bend increased in the distal region and those of the reverse bends increased in almost all regions of the flagellum. Since the increase in the reverse bend was relatively high, flagellar bending became asymmetric to the direction of the reverse bend as in hamster spermatozoa. These increases in asymmetry were also evident in the measurement of the total changes in angular direction between the proximal and distal end of flagella in both species. The increase in asymmetry could provide an explanation for the changes in the motility patterns seen in spermatozoa after the onset of hyperactivation.(ABSTRACT TRUNCATED AT 250 WORDS)


Pattern of growth of dominant follicles during the oestrous cycle of heifers.
Ovarian follicular development was studied in 13 heifers by daily ultrasound examination during 2 complete and consecutive natural oestrous cycles. In 21 cycles (81%) 3 dominant follicles were identified, in 4 cycles (15%) 2 and in the remaining cycle 1 (4%). Consistently, the first dominant follicle was detected on average on Day 4, reached a maximum size on Day 6, went through a period of relative stability between Days 6 and 10, then began to decrease in size and was undetectable by Day 15. The second dominant follicle was detected by Day 12, reached maximum size on Day 16 (or 19 in the 4 cycles in which the 2nd dominant follicle was the ovulatory follicle) and was undetectable by Day 19. The 3rd (ovulatory) follicle was identified on average by Day 16 (range Days 10 to 19) and maximum size was reached on Day 21. The ovulatory follicles were larger (P less than 0.05) than the previous ones and the stage of the cycle at which maximum size was reached was significantly different for each dominant follicle (P less than 0.05). The analysis of the rates of growth and atresia suggest that the rate of growth is slowest during mid-cycle. The number of dominant follicles that developed in the ovary ipsilateral to the corpus luteum was greater (P less than 0.05) than in the contralateral ovary.


Correlations among general stress, family environment, psychological distress, and pain experience.
For 15 subjects with chronic low back pain and 15 matched healthy controls analysis of scores on Life Experiences Survey (general stress), Family Environment Scale (family relationships), Beck Depression Inventory (psychological distress), and McGill Pain Questionnaire (pain experience) indicated that the scores on environmental stressors, general stress, and psychological distress were higher for the group with pain. They experienced more negative life events and were more depressed. Certain family characteristics (decreased scores on Cohesion, Independence, Organization, and increased scores on Conflict) were unique to that group. Finally, certain family variables which did not differentiate between the groups were associated with the pain experience.


Patient compliance with tenoxicam in family practice.
This study evaluated factors that may influence patient compliance and also confirmed tolerability and efficacy of tenoxicam in routine clinical practice. Compliance in 1809 patients was evaluated over a 4-week period by physician pill-counts, patient assessment cards, and, for a subpopulation, by electronically monitored pill vials. In addition, physicians documented patient improvement and side effects after 2 weeks and after 4 weeks of therapy; patients reported satisfaction with therapy and side effects on a weekly basis. A total of 399 physicians provided data on 1809 patients, of whom 84.3% had osteoarthritis, 12.6% had rheumatoid arthritis, and 3.2% had ankylosing spondylitis. The typical patient was a woman (64.9%), white (91.2%), in her 50s (mean age, 57.9 years), with a duration of osteoarthritis of at least 1 year (72.3%). High and similar compliance rates were achieved by patients regardless of age, gender, or diagnostic category. Patient and disease characteristics were similar between compliant and noncompliant patients. Most patients (81.1%) experienced improvement of symptoms after 4 weeks of treatment. A low incidence of side effects (12.6%) was reported, with no significant differences observed among patients with respect to age, gender, or diagnostic category. Product characteristics, such as tolerability, efficacy, and dosing regimen, are more significant factors of compliance than patient or disease characteristics. Tenoxicam's tolerability and clinical effectiveness were confirmed in patients with arthritis in routine clinical practice settings.


[Effects of gastrodin injection on blood pressure and vasoactive substances in treatment of old patients with refractory hypertension: a randomized controlled trial].
To examine and determine the contents of endothelin (ET) and nitric oxide (NO) in plasma, and to observe the effects of gastrodin injection on blood pressure, ET and NO levels in old patients with refractory hypertension. A total of 63 old patients with refractory hypertension, 30 patients with common hypertension and 30 healthy people were included. The contents of ET and NO in plasma of patients in different groups and healthy people were examined and analyzed. The old patients with refractory hypertension were randomly divided into two groups: gastrodin-treated and routine treatment groups. Besides conventional hypotensive drugs, intravenous drip infusion of 1 000 mg gastrodin was administered to the patients in gastrodin-treated group for two courses (4 weeks), while the patients in routine treatment group were treated only with conventional hypotensive drugs. The changes of blood pressure, ET and NO levels before and after treatment in different groups were measured. The plasma level of ET in refractory hypertension group was higher than that in common hypertension group (t=3.27, P=0.008), while the level of NO was lower (t=-3.81, P=0.002). The systolic pressure and pulse pressure difference in gastrodin-treated group were decreased significantly after one course of treatment (t=1.85, P=0.03; t=1.74, P=0.04). The level of ET in gastrodin-treated group decreased gradually after treatment, but there were no significant difference between before treatment and two courses of treatment, while the level of NO in gastrodin-treated group was increased after treatment (t=-2.70; P=0.04). Gastrodin injection is beneficial to old patients with refractory hypertension, and can improve the balance of ET and NO levels in plasma.


A role in DNA binding for the linker sequences of the first three zinc fingers of TFIIIA.
Zinc fingers of the TFIIIA type are connected by short linker sequences between the structural units. Structural investigations by 2D NMR in solution and by X-ray crystallographic analyses of complexes with DNA point to a passive role for the linkers. We have therefore investigated the influence of the linker sequence on DNA binding using as a model the first three fingers of the protein TFIIIA. Insertion of certain heterologous linkers abolishes binding, and replacement of individual amino acids can reduce binding by factors of up to twenty-four.


Protein gene product 9.5 (PGP 9.5) is not a specific marker of neural and nerve sheath tumors: an immunohistochemical study of 95 mesenchymal neoplasms.
In non-neoplastic tissues, the expression of protein gene product 9.5 (PGP 9.5), a member of the ubiquitin hydrolase family of proteins, is confined to neural and neuroendocrine cells. Although it has been claimed that PGP 9.5 is a specific marker of neural and/or nerve sheath differentiation in human tumors, careful review of the literature suggests that relatively few nonneural or nerve sheath tumors have been studied. Prompted by our recent observation of a PGP 9.5-positive malignant fibrous histiocytoma, we undertook a study of PGP 9.5 expression in a large group of well-characterized mesenchymal neoplasms. Sections from 95 mesenchymal tumors were retrieved from our archives and immunostained for PGP 9.5 using standard avidin-biotin complex technique and heat-induced epitope retrieval. Scoring was as follows: negative, 1+ (<10-25% of cells), 2+ (25-50% of cells), and 3+ (>50% of cells). Normal nerves and fibrous tissue were internal positive and negative controls, respectively. Positive immunostaining was seen in 80/95 (84%) of cases. Positive results by tumor subtype were as follows: (1) nerve sheath tumors: malignant peripheral nerve sheath tumor (7/10), neurofibromas (10/10), and perineuriomas (3/3); (2) (Myo) fibroblastic tumors: malignant fibrous histiocytoma (18/20), low-grade fibromyxoid sarcomas (8/9), fibromatoses (7/7), and desmoplastic fibroblastomas (2/2); (3) vascular tumors: angiosarcomas (4/4), hemangioendotheliomas (3/5), and hemangiomas (3/4); and (4) other non-nerve sheath tumors: pleomorphic liposarcoma (4/4), dermatofibrosarcoma protuberans (2/5), rhabdomyosarcomas (2/2), synovial sarcomas (8/8), melanomas (1/2). All positive cases were 2-3+ except 6 malignant peripheral nerve sheath tumor, 1 neurofibroma, 3 malignant fibrous histiocytoma, 2 low-grade fibromyxoid sarcoma, and 1 dermatofibrosarcoma protuberans. Positive staining was seen in normal smooth muscle and germinal centers in addition to nerves. We conclude that in this, the largest study to date of PGP 9.5 expression in mesenchymal neoplasms, we have found strong (2-3+) expression in the vast majority of nonneural or nerve sheath neoplasms studied. Although PGP 9.5 is a sensitive neural/nerve sheath marker, it is essentially totally nonspecific for diagnostic purposes. It is possible that our findings reflect cross-reactivity of the 13C4 clone with epitopes present on other ubiquitin hydrolases. Alternatively, PGP 9.5 expression may be aberrantly up-regulated in a variety of mesenchymal neoplasms.


Self adjusting stent in the management of malignant tracheo-oesophageal fistula.
The development of a malignant oesophago-respiratory fistula is a distressing situation which often leads to an early death. Dissatisfaction with the high levels of mortality and morbidity associated with the surgical bypass procedures, coupled with the failure of many of the oesophageal tubes, to completely occlude the fistula, has led to the development of a new cuffed tube (Wilson Cooke tube). This tube has the potential to not only relieve dysphagia but also to occlude the fistula without risk of pressure necrosis.


Pattern dynamics of the reaction-diffusion immune system.
In this paper, we will investigate the effect of diffusion, which is ubiquitous in nature, on the immune system using a reaction-diffusion model in order to understand the dynamical behavior of complex patterns and control the dynamics of different patterns. Through control theory and linear stability analysis of local equilibrium, we obtain the optimal condition under which the system loses stability and a Turing pattern occurs. By combining mathematical analysis and numerical simulation, we show the possible patterns and how these patterns evolve. In addition, we establish a bridge between the complex patterns and the biological mechanism using the results from a previous study in Nature Cell Biology. The results in this paper can help us better understand the biological significance of the immune system.


Comparing two diagnostic tests against the same "gold standard" in the same sample.
Methods are proposed for comparing two diagnostic tests for the same data where a threshold for positive for each test is specified. One method contrasts the diagnostic tests' estimated risks. A second method compares the two tests' kappa coefficients. When thresholds for positive test results are specified a priori, maximum likelihood estimators and their asymptotic variances are derived and test statistics are presented for both case-control and naturalistic methods of sampling. The bootstrap is proposed as a method to assess differences in risk estimators when thresholds for positive test results are chosen by scanning the data. Examples are given to illustrate the methods.


[A case of pneumocystis carinii pneumonia associated with low dose methotrexate treatment for rheumatoid arthritis and trimethoprim-sulphamethoxazole induced pancytopenia].
A 64-year-old man was admitted to our hospital complaining of dyspnea and fever. He had been treated with low-dose methotrexate for rheumatoid arthritis. Chest radiography showed diffuse ground-glass attenuation in both lung fields, and hypoxia was detected. Pneumosystis carinii pneumonia was demonstrated on transbronchial lung biopsy, and the serum beta-D glucan level was high. We started treatment with trimethoprim-sulphamethoxazole, but respiratory failure worsened, and drug-induced pancytopenia occurred. Although trimethoprim-sulphamethoxazole was stopped, pancytopenia persisted and the patient required ventilatory support. After we changed the medication from trimethoprim-sulphamethoxazole to pentamidine, respiratory failure improved. It was thought that pneumocystis carinii pneumonia was associated with low-dose methotrexate and that trimethoprim-sulphamethoxazole interacted with methotrexate to induce severe pancytopenia.


Facial and scalp burns from hair activator products.
Review of 1,008 admissions over the past two years to the Detroit Medical Center Burn Unit revealed 227 patients with facial or scalp burns. Of these, 12 patients sustained burns directly as a result of accidentally igniting a hair activator product called "Jheri-Curl." Eleven patients sustained superficial partial-thickness burns and were adequately treated with Dermaide. One had deeper burns requiring split-thickness skin grafting.


Comparing Open Radical Cystectomy and Robot-assisted Laparoscopic Radical Cystectomy: A Randomized Clinical Trial.
Open radical cystectomy (ORC) and urinary diversion in patients with bladder cancer (BCa) are associated with significant perioperative complication risk. To compare perioperative complications between robot-assisted radical cystectomy (RARC) and ORC techniques. A prospective randomized controlled trial was conducted during 2010 and 2013 in BCa patients scheduled for definitive treatment by radical cystectomy (RC), pelvic lymph node dissection (PLND), and urinary diversion. Patients were randomized to ORC/PLND or RARC/PLND, both with open urinary diversion. Patients were followed for 90 d postoperatively. Standard ORC or RARC with PLND; all urinary diversions were performed via an open approach. Primary outcomes were overall 90-d grade 2-5 complications defined by a modified Clavien system. Secondary outcomes included comparison of high-grade complications, estimated blood loss, operative time, pathologic outcomes, 3- and 6-mo patient-reported quality-of-life (QOL) outcomes, and total operative room and inpatient costs. Differences in binary outcomes were assessed with the chi-square test, with differences in continuous outcomes assessed by analysis of covariance with randomization group as covariate and, for QOL end points, baseline score. The trial enrolled 124 patients, of whom 118 were randomized and underwent RC/PLND. Sixty were randomized to RARC and 58 to ORC. At 90 d, grade 2-5 complications were observed in 62% and 66% of RARC and ORC patients, respectively (95% confidence interval for difference, -21% to -13%; p=0.7). The similar rates of grade 2-5 complications at our mandated interim analysis met futility criteria; thus, early closure of the trial occurred. The RARC group had lower mean intraoperative blood loss (p=0.027) but significantly longer operative time than the ORC group (p<0.001). Pathologic variables including positive surgical margins and lymph node yields were similar. Mean hospital stay was 8 d in both arms (standard deviation, 3 and 5 d, respectively; p=0.5). Three- and 6-mo QOL outcomes were similar between arms. Cost analysis demonstrated an advantage to ORC compared with RARC. A limitation is the setting at a single high-volume, referral center; our findings may not be generalizable to all settings. This trial failed to identify a large advantage for robot-assisted techniques over standard open surgery for patients undergoing RC/PLND and urinary diversion. Similar 90-d complication rates, hospital stay, pathologic outcomes, and 3- and 6-mo QOL outcomes were observed regardless of surgical technique. Of 118 patients with bladder cancer who underwent radical cystectomy, pelvic lymph node dissection, and urinary diversion, half were randomized to open surgery and half to robot-assisted laparoscopic surgery. We compared the rate of complications within 90 d after surgery for the open group versus the robotic group and found no significant difference between the two groups. ClinicalTrials.gov identifier NCT01076387, www.clinicaltrials.gov.


An integrated process for the recovery of high added-value compounds from olive oil using solid support free liquid-liquid extraction and chromatography techniques.
An integrated extraction and purification process for the direct recovery of high added value compounds from extra virgin olive oil (EVOO) is proposed by using solid support free liquid-liquid extraction and chromatography techniques. Two different extraction methods were developed on a laboratory-scale Centrifugal Partition Extractor (CPE): a sequential strategy consisting of several "extraction-recovery" cycles and a continuous strategy based on stationary phase co-current elution. In both cases, EVOO was used as mobile phase diluted in food grade n-hexane (feed mobile phase) and the required biphasic system was obtained by adding ethanol and water as polar solvents. For the sequential process, 17.5L of feed EVOO containing organic phase (i.e. 7L of EVOO treated) were extracted yielding 9.5g of total phenolic fraction corresponding to a productivity of 5.8g/h/L of CPE column. Regarding the second approach, the co-current process, 2L of the feed oil phase (containing to 0.8L of EVOO) were treated at 100mL/min yielding 1.03g of total phenolic fraction corresponding to a productivity of 8.9g/h/L of CPE column. The total phenolic fraction was then fractionated by using stepwise gradient elution Centrifugal Partition Chromatography (CPC). The biphasic solvent systems were composed of n-hexane, ethyl acetate, ethanol and water in different proportions (X/Y/2/3, v/v). In a single run of 4h on a column with a capacity of 1L, 910mg of oleocanthal, 882mg of oleacein, 104mg of hydroxytyrosol were successfully recovered from 5g of phenolic extract with purities of 85%, 92% and 90%, respectively. CPC fractions were then submitted to orthogonal chromatographic steps (adsorption on silica gel or size exclusion chromatography) leading to the isolation of additional eleven compounds belonging to triterpens, phenolic compounds and secoiridoids. Among them, elenolic acid ethylester was found to be new compound. Thin Layer Chromatography (TLC), Nuclear magnetic Resonance (NMR) and High Performance Liquid Chromatography - Diode Array Detector (HPLC-DAD) were used for monitoring and evaluation purposes throughout the entire procedure.


Pseudophakia for traumatic cataracts in children.
The purpose of this prospective study is to evaluate the postoperative visual acuity, refractive error, intraocular pressure, and status of the posterior capsule in children with traumatic cataracts who undergo extracapsular cataract extraction and insertion of a posterior chamber lens. Extracapsular cataract extraction and primary endocapsular fixation of a posterior chamber lens implant were performed in eight children (age range, 4-17 years) with unilateral traumatic cataracts. There were no intraoperative complications, and seven of eight eyes achieved 20/40 or greater spectacle visual acuity during an average follow-up interval of 10 months (range, 5-20 months). The average postoperative spherical equivalent refractive error was +0.33 diopter (D) (range, -2.25 to +2.12 D); the average postoperative anisometropia was approximately 1 D (range, 0-2.25 D). In one patient, a coagulase-negative staphylococcal endophthalmitis developed 10 days after surgery. In three eyes that had opacified posterior capsules, YAG laser capsulotomy was performed. These preliminary results suggest that intraocular lens (IOL) implantation may be a safe and effective method of optical correction for children with traumatic cataracts.


Vitreous substitute. Experimental studies and review.
We studied a synthetic hydrogel, PHEA [poly(2-hydroxyethyl acrylate)], experimentally. The material is transparent, autoclavable , highly viscous, nonabsorbable, easily injectable, cohesive, and does not fragment on passage through small-gauge needles. Results in animal studies revealed that injection of PHEA into the vitreous cavity promoted inflammatory changes such as vitreous haziness , membrane formation, and chorioretinal atrophy. Histopathologic studies showed extensive retinal disorganization, chorioretinal scarring, and vitritis . We reviewed the literature and concluded that an ideal vitreous substitute for long-term use in complex cases of retinal detachment is not available at this time.


Direct synthesis of 2,4,5-trisubstituted imidazoles from primary alcohols by diruthenium(ii) catalysts under aerobic conditions.
Herein we report a straightforward synthetic approach to 2,4,5-trisubstituted imidazoles from readily available primary alcohols using arene diruthenium(ii) catalysts. Dinuclear arene ruthenium complexes have been synthesized and structurally characterized with the aid of analytical and spectral techniques. A library of 2,4,5-trisubstituted imidazoles was achieved with a yield up to 95% by loading 0.25 mol% of the catalyst. The present protocol is environmentally benign, which is performed under aerobic conditions and liberates water as the sole by-product.


Comparison of felodipine and hydrochlorothiazide for the treatment of mild to moderate hypertension in black Africans.
A double-blind, parallel-group study was performed to assess the antihypertensive effects and tolerability of felodipine and hydrochlorothiazide (HCT) in black patients with mild to moderate uncomplicated hypertension [entry supine diastolic blood pressure (DBP) of 96-116 mm Hg]. The medicines were given as monotherapy and the additional effect of metoprolol was assessed in patients unresponsive to felodipine or HCT alone. After a 4-week placebo period, 45 patients were randomly allocated to treatment with felodipine (21) or HCT (24). Initial doses of felodipine 2.5 mg or HCT 12.5 mg twice daily were doubled after 1 week and doubled again after week 4 in cases with supine DBP above 90 mm Hg. At week 8, metoprolol 100 mg twice daily was added to the regimen of uncontrolled patients (supine DBP greater than 90 mm Hg) and maintained for the remaining 4-week trial period. Felodipine significantly reduced supine and erect systolic BP (SBP) and DBP after 4, 8, and 12 weeks of treatment. Responses to HCT were similar although standing diastolic BP at week 4 and standing SBP at week 8 were not significantly reduced. After 4 weeks, the mean fall in supine DBP was significantly greater for the felodipine than the HCT group. Eight patients on felodipine and 14 in the HCT group required additional metoprolol to achieve BP control. A significantly greater number of adverse effects were associated with HCT than felodipine treatment. Monotherapy with felodipine produced a more rapid control of hypertension, was more frequently effective, and was associated with a lower incidence of side effects than HCT.


Retrospective comparison of clinical and angiographic outcomes after primary stenting using sirolimus-eluting and bare-metal stents in nonrandomized consecutive 568 patients with first ST-segment elevated myocardial infarctions.
The long-term safety and efficacy of primary stenting using drug-eluting stents (DES) in patients with ST-segment elevation myocardial infarction (STEMI) are not fully understood in Japan. Therefore, we retrospectively examined the midterm clinical and angiographic outcomes in STEMI patients after primary stenting using sirolimus-eluting stents (SES) in a clinical setting through a historical comparison with those of bare-metal stents (BMS). The study design was a retrospective, nonrandomized, and single-center study. The clinical outcomes for 568 consecutive patients who presented within 12 h of their first STEMI and who were treated with BMS (n = 198; 184 STEMIs from June 2003 to August 2004 and 14 STEMIs from September 2004 to May 2007) or SES (n = 370; from August 2004 to May 2007) at our medical center in Japan were retrospectively investigated in February 2010. The incidence of post-discharge events (comprising cardiac death and nonfatal recurrent MI) after SES placement (3.9%) was not significantly different from that after BMS placement (6.7%). SES was not related to the risk of post-discharge events (mean follow-up for SES, 1327 ± 415 days; BMS, 1818 ± 681 days) (hazard ratio of 0.369 at 95% CI, 0.119-1.147, p = 0.085). The incidence of definite stent thromboses after SES placement (0.54%) was not significantly higher than that after BMS placement (0%). The incidence of binary in-stent restenosis (% diameter stenosis of more than 50% at secondary angiography) after SES placement (8.3%) was significantly lower than that after BMS placement (25.7%; p < 0.001). From the present historical comparison of SES and BMS, we conclude that primary stenting using SES in a clinical setting has favorable clinical and angiographic outcomes in Japanese STEMI patients.


[Perioperative Management of a Patient with Severe Parkinson's Disease with Intravenous Levodopa Administration].
A 70-year-old man with severe Parkinson's disease was scheduled for thoracic aortic aneurysm resection and aortic valve replacement. We administered levodopa intravenously during the perioperative period to avoid the malignant syndrome which is reported to arise with abrupt cessation of anti-Parkinson's drugs. The dose of intravenous administration was tapered with the resumption of oral intake. No manifestation of malignant syndrome was observed. We measured blood concentrations of levodopa several times during the perioperative period. The concentration of levodopa during the surgery was relatively high; however no adverse events of overdose (e.g. dyskinesis) occurred. In the postoperative period, administration of levodopa was changed to the oral route and serum levels of levodopa showed a notable decrease, the cause of which may be poor absorption through the digestive system during the perioperative period. Therefore, in the peri- and post-operative periods, it is necessary to take great care when reducing the infusion dose.


A new role for IQ motif proteins in regulating calmodulin function.
IQ motifs are found in diverse families of calmodulin (CaM)-binding proteins. Some of these, like PEP-19 and RC3, are highly abundant in neuronal tissues, but being devoid of catalytic activity, their biological roles are not understood. We hypothesized that these IQ motif proteins might have unique effects on the Ca2+ binding properties of CaM, since they bind to CaM in the presence or absence of Ca2+. Here we show that PEP-19 accelerates by 40 to 50-fold both the slow association and dissociation of Ca2+ from the C-domain of free CaM, and we identify the sites of interaction between CaM and PEP-19 using NMR. Importantly, we demonstrate that PEP-19 can also increase the rate of dissociation of Ca2+ from CaM when bound to intact CaM-dependent protein kinase II. Thus, PEP-19, and presumably similar members of the IQ family of proteins, has the potential to alter the Ca2+-binding dynamics of free CaM and CaM that is bound to other target proteins. Since Ca2+ binding to the C-domain of CaM is the rate-limiting step for activation of CaM-dependent enzymes, the data reveal a new concept of importance in understanding the temporal dynamics of Ca2+-dependent cell signaling.


Commentary: Diagnostic and Treatment Issues in Psychosis.
The 3 cases presented in this issue highlight challenges in evaluating and treating patients with psychotic symptoms. The first case involved the rare but debilitating condition of periodic catatonia, the second case involved the use of intranasal oxytocin to augment an antipsychotic for a patient with worsening psychotic symptoms (and a prior diagnosis of schizophrenia) in the postpartum period, and the third case involved auto-enucleation (often referred to as "Oedipism"), a violent form of self-mutilation, in a patient presenting with first-episode schizophrenia. These case reports reinforce the need to consider a wide differential diagnosis before initiating treatment. Understanding the broad spectrum with which psychotic symptoms can present, or rare presentations of more common conditions, can help clarify the diagnosis and guide treatment, and hopefully help prevent or reduce future self-harm or violence, psychotic episodes, and hospitalizations.


Posterior capsulotomy and retinal detachment following extracapsular lens surgery.
A retrospective analysis of the results of extracapsular cataract surgery with and without implant is presented. Surgery was performed by a group of consultants and registrars from 1975 to 1982, and minimum patient follow-up was 12 months (mean 26.2 months). The incidence of postoperative capsulotomy was 14.3%, but the need for this procedure declines, becoming negligible after 3.5 years. Of 242 eligible eyes, aphakic retinal detachment occurred in only one.


Transient P-cadherin expression in radiation proctitis; a model of mucosal injury and repair.
Morphology at both cellular and glandular levels in the colon is dependent to an extent on cell-cell adhesion mediated by cadherin-catenin complexes. Alterations in the expression of E-cadherin, the cadherin normally present in colon, have been shown to be implicated in tissue remodelling within the gastrointestinal tract. Furthermore, it has previously been shown that P-cadherin, normally present only in stratified epithelia and placenta, is expressed in colitis and during neoplastic change in the colon. The morphological features of mucosal injury induced by pre-operative radiotherapy in the non-neoplastic rectal mucosa were studied in patients with rectal adenocarcinoma. Three characteristic phases of radiation proctitis were defined on histological grounds (acute injury, and early and late regenerative phases) essentially correlating with the time interval between radiotherapy and surgery; such features were mirrored by alterations in cadherin-catenin expression and localization in rectal crypts. On immunohistochemistry and western blotting, P-cadherin was highly expressed in the acute injury and early regenerative phases, with a decreased level of expression during late regeneration. E-cadherin and associated catenins were translocated from membrane to cytoplasm in degenerating crypts, with return of normal membranous expression in regenerating crypts. In conclusion, radiation-induced proctitis represents an in vivo model of mucosal injury and regeneration and provides a valid model in which to study events during epithelial injury and repair. Altered cadherin expression, in particular transient aberrant P-cadherin expression, is intimately associated with these processes.


Identification of rare alternative splicing events in MS/MS data reveals a significant fraction of alternative translation initiation sites.
Integration of transcriptome data is a crucial step for the identification of rare protein variants in mass-spectrometry (MS) data with important consequences for all branches of biotechnology research. Here, we used Splooce, a database of splicing variants recently developed by us, to search MS data derived from a variety of human tumor cell lines. More than 800 new protein variants were identified whose corresponding MS spectra were specific to protein entries from Splooce. Although the types of splicing variants (exon skipping, alternative splice sites and intron retention) were found at the same frequency as in the transcriptome, we observed a large variety of modifications at the protein level induced by alternative splicing events. Surprisingly, we found that 40% of all protein modifications induced by alternative splicing led to the use of alternative translation initiation sites. Other modifications include frameshifts in the open reading frame and inclusion or deletion of peptide sequences. To make the dataset generated here available to the community in a more effective form, the Splooce portal (http://www.bioinformatics-brazil.org/splooce) was modified to report the alternative splicing events supported by MS data.


Nutrient metabolism by gut tissues.
The gut uses a disproportionate amount of energy (about 25% of total oxygen consumption) for the size of the tissue (about 6% of body weight). Therefore, knowledge of metabolites used in gut tissues is important to assess nutrient needs. The VFA produced intraruminally are used to varying degrees by rumen epithelial tissue. A review of net portal absorption data essentially confirms earlier studies that show acetate, propionate, and butyrate metabolism by stomach tissue to be 30, 50, and 90%, respectively, of ruminant production. Glucose also is used by rumen epithelial tissue; however, glutamine appears to be a poor substrate for energy production. Tissue of the small intestine uses glutamine, glucose, and ketones but does not use VFA very well for energy. Cecal and colonic tissues can use glucose and glutamine for energy, but butyrate is the preferred substrate in both tissues.


[Eccrine syringofibroadenoma. Report of a case].
Eccrine syringofibroadenoma is an uncommon benign adnexal tumor (about thirty reported cases). Its clinical presentation is variable and non specific. The diagnostic is never evident before histological exam. Histologically it is an epithelial proliferation organized in thin cords appended to the epidermis with cuticular differentiation. Eccrine poroma and fibroepithelial tumor of Pinkus are the main histological diagnostic problems. The authors report two new cases in two women of 35 and 69 years which had been clinically considered as histiocytofibroma and molluscum pendulum.


Microreactor of Pd nanoparticles immobilized hollow microspheres for catalytic hydrodechlorination of chlorophenols in water.
A microreactor of Pd nanoparticles immobilized shell-corona hollow microspheres of poly[styrene-co-2-(acetoacetoxy) ethyl methacrylate-co-acrylamide] has been designed for catalytic hydrodechlorination (HDC) of chlorophenols in the sole solvent of water. The strategy of the combined use of the shell-corona hollow microspheres as microcapsule and catalyst scaffold endues the microreactor several advantages. First, the microreactor can be dispersed in the sole solvent of water and acts as a quasi-homogeneous catalyst for catalytic HDC of chlorophenols. Second, the reactant of chlorophenols can be highly concentrated within the hollow microspheres of the microreactor in the sole solvent of water. Third, the resultant product of phenol can be favorably excreted off the microreactor into water because of the polar difference between the reactant of chlorophenols and the product of phenol. Ascribed to the combined advantages, catalytic HDC of chlorophenols can be performed efficiently within the microreactor in the sole solvent of water at room temperature under atmosphere pressure.


Self-assembly of ball-shaped molecular complexes in water.
We present a simple and versatile access to spheroidal molecular assemblies with pronounced stability in highly polar solvents. These complexes are composed of doubly and triply charged complementary building blocks based on ammonium or amidinium cations and phosphonate anions. Their high thermodynamic stability is best explained by the formation of a cyclic array of alternating positive and negative charges interconnected by a regular network of hydrogen bonds. Association constants reach 10(6) M(-1) in methanol and often surpass 10(3) M(-1) in water. The broad range of binding energies correlates well with the varying degree of preorganization of both complex partners. As a byproduct of these investigations, new recognition motifs for histidine and arginine esters and the unsubstituted guanidinium ion are proposed. The additional introduction of methyl groups in the 2-, 4-, and 6-positions of the central benzene ring in either cations or anions causes a marked drop in the corresponding K(a) values of 1 order of magnitude; the related rotational barriers were estimated at 0.3-2.1 kcal/mol. Spontaneous formation of defined 2:1 complexes from three components has also been observed.


Production of N-sulfated polysaccharides using yeast-expressed N-deacetylase/N-sulfotransferase-1 (NDST-1).
Heparan sulfate/heparin N-deacetylase/N-sulfotransferase-1 (NDST-1) is a critical enzyme involved in heparan sulfate/heparin biosynthesis. This dual-function enzyme modifies the GlcNAc-GlcA disaccharide repeating sugar backbone to make N-sulfated heparosan. N-sulfation is an absolute requirement for the subsequent epimerization and O-sulfation steps in heparan sulfate/heparin biosynthesis. We have expressed rat liver (r) NDST-1 in Saccharomyces cerevisiae as a soluble protein. The yeast-expressed enzyme has both N-deacetylase and N-sulfotransferase activities. N-acetyl heparosan, isolated from Escherichia coli K5 polysaccharide, de-N-sulfated heparin (DNSH) and completely desulfated N-acetylated heparan sulfate (CDSNAcHS) are all good substrates for the rNDST-1. However, N-desulfated, N-acetylated heparin (NDSNAcH) is a poor substrate. The rNDST-1 was partially purified on heparin Sepharose CL-6B. Purified rNDST-1 requires Mn(2+) for its enzymatic activity, can utilize PAPS regenerated in vitro by the PAPS cycle (PAP plus para-nitrophenylsulfate in the presence of arylsulfotransferase IV), and with the addition of exogenous PAPS is capable of producing 60-65% N-sulfated heparosan from E. coli K5 polysaccharide or Pasteurella multocida polysaccharide.


Overexpressing a putative aquaporin gene from wheat, TaNIP, enhances salt tolerance in transgenic Arabidopsis.
High soil salinity is a major abiotic stress in plant agriculture worldwide. Here, we report the characterization of a novel aquaporin gene TaNIP (Triticum asetivum L. nodulin 26-like intrinsic protein), which was involved in salt tolerance pathways in plants. TaNIP was identified and cloned through the gene chip expression analysis of a salt-tolerant wheat mutant RH8706-49 under salt stress. Quantitative reverse transcription-PCR (Q-RT-PCR) was used to detect TaNIP expression under salt, drought, cold and ABA treatment. The overexpression of TaNIP in transgenic Arabidopsis produced higher salt tolerance than wild-type plants. Localization analysis showed that TaNIP proteins tagged with green fluorescent protein (GFP) were localized to the cell plasma membrane. Under salt stress treatment, TaNIP-overexpressing Arabidopsis accumulated higher K(+), Ca(2+) and proline contents and lower Na(+) level than the wild-type plants. The overexpression of TaNIP in transgenic Arabidopsis also up-regulated the expression of a number of stress-associated genes. Our results suggest that TaNIP plays an important role in salt tolerance in Arabidopsis and can also enhance plants' tolerance to other abiotic stresses.


Variation in the morphology of spinous processes in the cervical spine - An objective and parametric assessment based on CT study.
Typically, cervical vertebrae display bifid spinous processes. Nevertheless, this feature may vary both between subjects and even within the vertebrae of the same individual. Although such variation can be important in archaeological research, anthropological studies and forensic medicine, it has not so far been the subject of any detailed studies. An analysis of 200 cervical spine CT examinations was performed. The morphology of the spinous process was evaluated, and new anthropometric parameters were selected to allow a more precise quantitative analysis of the degree of bifidity. The spinous process base (i.e. the part of the spinous process which was not bifid) was significantly longer in CII and CVII than in the other vertebrae. The spinous process branches (bifid elements) were significantly longer in CVI and CVII than in the other vertebrae. The angle between the branches was significantly sharper in CII and CVII than in CIII-CVI, on the right side, and CIII-CV, on the left side. On the right side, the branching coefficient (degree of branch development) was significantly higher for CII and significantly lower for CVI-CVII than for the other vertebrae. On the left side, the coefficient was significantly higher for CII and CIV, and significantly lower for CVI-CVII, compared to the other vertebrae. Our findings highlight new objective parameters of morphological variability in the spinous processes of the cervical spine. They can form the basis of a new detailed differentiation of vertebrae and can represent an independent determinant of anatomical variability in the cervical spine.


Psychosocial Functioning of Children with and without Dyslexia: A Follow-up Study from Ages Four to Nine.
This longitudinal study compares developmental changes in psychosocial functioning during the transition into school of children with and without dyslexia. In addition, it examines the effects of gender and family risk for dyslexia in terms of the associations between dyslexia and psychosocial functioning. Children's psychosocial functioning (social skills, inattention and externalizing and internalizing problems) was evaluated by their parents at ages 4, 6 and 9, and diagnosis for dyslexia was made at age 8 (in grade 2). The findings indicated that children with dyslexia were already rated as having poorer social skills and being more inattentive than were typical readers before their entry into school. Significant interactions of gender and diagnosis of dyslexia emerged for social skills and inattention. The social skills of boys with dyslexia improved after school entry as compared to the level of girls without dyslexia, whereas the social skills of girls with dyslexia did not improve. Boys with dyslexia were rated as showing a high level of inattention both prior to and after school entry, whereas, for girls with dyslexia, inattention ratings increased after school entry, eventually matching the boys' levels.


Sudden deafness and cerebellar tumour.
We report the case of a female patient who presented with sudden deafness as the first symptom of a cerebellar tumour which was not localized strictly in the cerebellopontine angle and did not show direct compression on the extrabulbar portion of the VIIIth cranial nerve. The clinical picture contained a number of signs and symptoms typical of cerebellar involvement. Surgical intervention restored the hearing and caused the symptoms to disappear. We also review the association between tumours and sudden deafness in the literature.


Molecular beacons as probes of RNA unfolding under native conditions.
Hybridization of fluorescent molecular beacons provides real-time detection of RNA secondary structure with high specificity. We used molecular beacons to measure folding and unfolding rates of the Tetrahymena group I ribozyme under native conditions. A molecular beacon targeted against 15 nt in the 5' strand of the P3 helix specifically hybridized with misfolded forms of the ribozyme, without invading the native tertiary structure. The beacon associated with the misfolded ribozyme 300 times more slowly than with an unstructured oligonucleotide containing the same target sequence, suggesting that the misfolded ribozyme core remains structured in the absence of Mg2+. The rate of beacon hybridization under native conditions revealed a linear relationship between the free energy of unfolding and Mg2+ concentration. A small fraction of the RNA population unfolded very rapidly, suggesting parallel unfolding in one step or through misfolded intermediates.


Condensation of 2-naphthol and naphthalenediols with o-dichlorobenzene in the presence of aluminum halides.
It is known that 1-naphthol, as a result of superelectrophilic (dicationic) activation in superacid media, is able to react with such deactivated aromatic compound as o-dichlorobenzene to give 4-(3,4-dichlorophenyl)-1-tetralone (2), which is a highly valuable intermediate in the synthesis of the antidepressant, sertraline (1) and other useful derivatives. However, the analogous reactivity of 2-naphthol and a variety of naphthalenediols towards o-dichlorobenzene has not been investigated thus far, although the corresponding tetralones, bearing dichlorophenyl moiety, could be of great pharmacochemical interest. In present work, we disclose that 1,5-, 1,6-, and 1,7- naphthalenediols (6a-c) react smoothly with o-dichlorobenzene in the presence of an excess of aluminum chloride or aluminum bromide to give the pairs of isomeric 4-(3,4-dichlorophenyl)- and 4-(2,3-dichlorophenyl)- 5-, 6-, and 7-hydroxy-1-tetralones (10a-c and 11a-c) in high overall yields. 2-Naphthol and 2,7-naphthalenediol (6d) exhibited comparatively lower reactivity, which however was sufficient to obtain the corresponding dichlorophenyl-2-tetralones in moderate yields. The mechanism of these reactions involving superelectrophilic dicationic or even tricationic intermediates, is discussed.


Effector-dependent conformational changes in protein kinase C gamma through epitope mapping with inhibitory monoclonal antibodies.
Three monoclonal antibodies (mAb) directed against the regulatory domain of the protein kinase C gamma (PKC gamma); 15G4, 5A2 and 36G9, were shown to display distinct properties with respect to PKC gamma kinase activity [Cazaubon, S., Marais, R., Parker, P. & Strosberg, A.D. (1989) Eur. J. Biochem. 182, 401-406]. The mAb 5A2 and 36G9, which act as potent inhibitors of the cofactor-dependent kinase activity, can no longer bind PKC gamma in the presence of phosphatidylserine and phosphatidylserine/phorbol ester, respectively; 15G4 binding is not influenced by effectors. Due to this functional relationship between the inhibitory mAb- and cofactor-binding sites, we sought to localize the mAb epitopes with respect to the functional sites of PKC gamma. For this purpose, several deletions were introduced at the 5' end of the PKC gamma cDNA and the mutant proteins were expressed in Escherichia coli. The determination of the immunoreactivity of the deleted PKC gamma proteins shows that the amino acid residues essential to the binding of 5A2 and 36G9 are directly adjacent to the second cysteine-rich motif: these are contained in the sequences at positions 151-163 and 164-197, respectively. In addition, various deletions around the C1 region of the regulatory domain allowed the identification of the second cysteine-rich motif as a functional binding site for phorbol dibutyrate. These deletion studies thus demonstrate that the epitopes recognized by the inhibitory mAbs 5A2 and 36G9 are distinct from the cofactor-binding sites. This suggests that the binding of phosphatidylserine and phorbol ester induce conformational changes in the regulatory domain of PKC, which are thus responsible for the loss of the 5A2 and 36G9 immunoreactivity of the native protein. In this conformational state, PKC gamma conserves its ability to interact with the non-inhibitory mAb 15G4. By using synthetic peptides, the 15G4 epitope was localized to the sequence 297-310 in the V3 variable region. This indicates that the flexibility of the V3 region, which delimits the C-terminus of the regulatory domain, may not be necessary for the allosteric activation of PKC. In view of these results, we propose that PKC activation by its cofactors results in intramolecular changes which allow the enzyme to bind exogenous substrates.


Checkpoint and physiological apoptosis in germ cells proceeds normally in spaceflown Caenorhabditis elegans.
It is important for human life in space to study the effects of environmental factors during spaceflight on a number of physiological phenomena. Apoptosis plays important roles in development and tissue homeostasis in metazoans. In this study, we have analyzed apoptotic activity in germ cells of the nematode C. elegans, following spaceflight. Comparison of the number of cell corpses in wild type or ced-1 mutants, grown under either ground or spaceflight conditions, showed that both pachytene-checkpoint apoptosis and physiological apoptosis in germ cells occurred normally under spaceflight conditions. In addition, the expression levels of the checkpoint and apoptosis related genes are comparable between spaceflight and ground conditions. This is the first report documenting the occurrence of checkpoint apoptosis in the space environment and suggests that metazoans, including humans, would be able to eliminate cells that have failed to repair DNA lesions introduced by cosmic radiation during spaceflight.


Proteomic profiling of RAW264.7 macrophage cells exposed to graphene oxide: insights into acute cellular responses.
Although the toxicity and molecular mechanisms of graphene oxide (GO) have been reported for several cell types, no proteomic study of GO has yet been conducted on macrophage cells. In this study, we used proteomics based on stable isotope labeling with amino acids in cell culture (SILAC) to quantify the proteomic changes in macrophage RAW 264.7 cells following GO treatment. We found 73 proteins that were significantly dysregulated after GO treatment. The down-regulated proteins included many ribosomal subunit proteins, indicating that GO affected cell growth. The most elevated proteins were lipoprotein lipase (LPL) and lysozyme 1 (LYZ1) which have not been reported before, and both can be used as candidate markers for GO exposure. Further enrichment analysis of the up-regulated proteins indicated these proteins are associated with the integrin complex and membrane rafts, as well as with two signal pathways: the phagosome and steroid biosynthesis pathways. We confirmed a GO concentration-dependent increase in membrane rafts and the production of phagosomes. GO exposure also induced necrotic cell death and an inflammation response in RAW 264.7 cells. We also observed an increase in the oxidative stress response (ROS) and autophagy, and the results suggest that ROS induced autophagy by the ROS-NRF2-P62 pathway.


Simultaneous Use of Both Bilateral Intralaminar and Pedicle Screws for C2 Stabilization.
Four patients underwent stabilization surgery using both bilateral C2 pedicle screw (PS) and intralaminar screw (LS). Neural and vascular injury resulting from incorrect screw placement was assessed using computed tomography (CT). The evaluation of bone union was assessed by lateral flexion-extension X-ray films and CT. The symptoms were improved in all patients. There were no intraoperative complications. Furthermore, there were no cases of neurological worsening or vascular injury from incorrect screw placement. Failure of instrumentation or screw loosening during the follow-up period did not occur in any of the patients. All cases had accomplished bone union at the final follow-up. Theoretically, the stabilization technique using both bilateral C2 PS and LS at the same time can provide more stability than any other single technique. Simultaneous use of both bilateral C2 PS and LS is potentially a good choice for surgical repair.


17,18-Epoxyeicosatetraenoic Acid Inhibits TNF-α-Induced Inflammation in Cultured Human Airway Epithelium and LPS-Induced Murine Airway Inflammation.
17,18-Epoxyeicosatetraenoic acid (17,18-EpETE), an eicosapentaenoic acid metabolite, is generated from dietary oil in the gut, and antiinflammatory activity of 17,18-EpETE was recently reported. To evaluate the inhibitory effects of 17,18-EpETE in airway inflammation, we examined in vitro and in vivo effects on mucus production, neutrophil infiltration, and cytokine/chemokine production in airway epithelium. Nasal tissue localization of G protein-coupled receptor 40 (GPR40), a receptor of 17,18-EpETE, was determined by immunohistochemical staining. Expression of GPR40 mRNA in nasal mucosa of chronic rhinosinusitis (CRS) patients and control subjects was determined by reverse transcription-polymerase chain reaction (RT-PCR). The in vitro effects on airway epithelial cells were examined using normal human bronchial epithelial cells and NCI-H292 cells. To examine the in vivo effects of 17,18-EpETE on airway inflammation, we induced goblet cell metaplasia, mucus production, and neutrophil infiltration in mouse nasal epithelium by intranasal lipopolysaccharide (LPS) instillation. GPR40 is mainly expressed in human nasal epithelial cells and submucosal gland cells. RT-PCR analysis revealed that the expression of GPR40 mRNA was increased in nasal tissues from CRS patients compared with those from control subjects. 17,18-EpETE significantly inhibited tumor necrosis factor (TNF)-α-induced production of interleukin (IL)-6 , IL-8, and mucin from cultured human airway epithelial cells dose dependently, and these antiinflammatory effects on cytokine production were abolished by GW1100, a selective GPR40 antagonist. Intraperitoneal injection or intranasal instillation of 17,18-EpETE significantly attenuated LPS-induced mucus production and neutrophil infiltration in mouse nasal epithelium. Inflammatory cytokine/chemokine production in lung tissues and bronchoalveolar lavage fluids was also inhibited. These results indicate that 17,18-EpETE plays a regulatory role in mucus hypersecretion and neutrophil infiltration in nasal inflammation. Local or systemic administration may provide a new therapeutic approach for the treatment of intractable airway disease such as CRS.


[Arterial thrombosis in the course of nephrotic syndrome. Report of three cases].
Vascular thrombosis remains severe complication in patients with nephrotic syndrome. Both venous and arterial thrombosis are observed. We report three new cases of arterial thrombosis in patients with nephrotic syndrome. The role of acquired hemostasis disorders, inducing hypercoagulability, is predominant. Extramembranous glomerulonephritis remains the most frequent cause of nephrotic syndrome, complicated by vascular thrombosis. Treatment is based on anticoagulation and corticosteroid therapy. Search for proteinuria should be part of the etiology work-up in all patients with vascular thrombosis of undetermined origin.


Functional and diffusion tensor magnetic resonance imaging of the sheep brain.
An ovine model can cast great insight in translational neuroscientific research due to its large brain volume and distinct regional neuroanatomical structures. The present study examined the applicability of brain functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) to sheep using a clinical MR scanner (3 tesla) with a head coil. The blood-oxygenation-level-dependent (BOLD) fMRI was performed on anesthetized sheep during the block-based presentation of external tactile and visual stimuli using gradient echo-planar-imaging (EPI) sequence. The individual as well as group-based data processing subsequently showed activation in the eloquent sensorimotor and visual areas. DTI was acquired using 26 differential magnetic gradient directions to derive directional fractional anisotropy (FA) and apparent diffusion coefficient (ADC) values from the brain. White matter tractography was also applied to reveal the macrostructure of the corticospinal tracts and optic radiations. Utilization of fMRI and DTI along with anatomical MRI in the sheep brain could shed light on a broader use of an ovine model in the field of translational neuroscientific research targeting the brain.


Rabbit myocardial 82Rb kinetics and a compartmental model for blood flow estimation.
Quantification of regional myocardial blood flow (MBF) with rubidium-82 (82Rb) and positron emission tomography (PET) requires the validation of a tracer kinetic model that adequately describes the kinetics of 82Rb in tissue. We performed 134 82Rb kinetic experiments in 24 isolated, arterially perfused rabbit interventricular septa at different flow rates (0.5-4.5 ml.min-1.g-1) and under the following conditions: varied concentrations of glucose (2.8-11 mM), insulin (0-5 mU/ml), and potassium (5-8 mM); varied pH (7.2-7.8); varied workload; and the addition of acetylstrophanthidin (1.0 microM). The measured 82Rb tissue time-activity curves consisted of two exponential components, with half times inversely related to MBF. The size of the slow component decreased as MBF increased (from 70% at 0.3 ml.min-1.g-1 to 30% at 2.0 ml. min-1.g-1). The kinetics were not strongly dependent on the conditions studied and were consistent with a compartmental model containing two communicating compartments. The volume of the fast exchangeable compartment and the transport rate constant from the fast to the slow compartment were found to be independent of MBF. Values of MBF were estimated with the compartmental model from 82Rb kinetics, and they correlated well with the directly measured MBF (r = 0.91; slope = 1.03).


Prevalence and distribution of different diarrhoeagenic Escherichia coli virulotypes in major water bodies in Bangladesh.
Escherichia coli, a prominent waterborne pathogen, causes a variety of gastrointestinal and extraintestinal infections that depend on virulence determinants. To monitor natural aquatic systems for virulence-associated genes of E. coli, multiplex PCR was used in a survey covering 46 major natural water bodies in Bangladesh. DNA was extracted directly from water samples as well as from pre-enriched and enriched cultures during three successive seasons and assessed for E. coli virulotype distribution. From the five virulotypes, genes from the enterotoxigenic (ETEC), enteropathogenic (EPEC), and enterohaemorrhagic (EHEC) virulotypes were detected consistently, but genes from the enteroinvasive (EIEC) and enteroaggregative (EAEC) virulotypes were traced only occasionally. ETEC was the most prevalent virulotype, followed by EPEC. However, EIEC and EAEC virulotypes could not be detected in winter or the rainy season, respectively. Specific regional distribution patterns of different E. coli virulotypes and their temporal fluctuations were identified. These observations may assist with assessing seasonal risk and identifying vulnerable areas of the country prone to E. coli-associated outbreaks.


Ventrolateral medulla: an important site of action for the hypotensive effect of drugs that activate serotonin-1A receptors.
The purpose of our study was to test the hypothesis that drugs that activate the 5-HT1A receptor lower arterial pressure by interacting with 5-HT1A receptors located in the ventrolateral medulla. For this purpose, cats were anesthetized with alpha-chloralose while arterial pressure, heart rate, and several indices of respiratory activity were being monitored during either topical application or microinjection of 5-HT1A receptor agonist and antagonist drugs in the region of the intermediate area of the ventrolateral medulla. Topical application of drugs that activate 5-HT1A receptors (e.g., 8-OH-DPAT and urapidil) produced decreases in arterial pressure, heart rate, and tidal volume but an increase in respiratory rate. These effects were prevented by prior topical application of the 5-HT1A antagonist drug, spiperone. Intravenous administration of 5-HT1A receptor agonist drugs produced similar cardiorespiratory effects, and these effects were counteracted by topical application of spiperone to the intermediate area of the ventrolateral medulla. Microinjection of 8-OH-DPAT into two sites associated with the intermediate area, namely the subretrofacial nucleus and the bicuculline-sensitive hypotensive site, also resulted in decreases in arterial pressure (-40 +/- 10 mm Hg, n = 5; and -21 +/- 4 mm Hg, n = 3, respectively). These data indicate that hypotension produced by drugs that activate 5-HT1A receptors occurs, at least in part, from an action in the ventrolateral medulla, presumably in the subretrofacial nucleus and/or the bicuculline-sensitive hypotensive site.


Mental efficacy and physical efficacy at the team level: inputs and outcomes among newly formed action teams.
The authors demarcated mental efficacy and physical efficacy at the team level, and they explored these 2 factors as outcomes of 4 potential inputs and as predictors of 3 outcomes among 110 newly formed action teams in a military setting. Both types of team efficacy benefited from greater team size and an initial experience of enactive mastery, but they were not influenced by teams' female representation or knowledge pool. In terms of predictive contributions, both mental and physical efficacy facilitated internal social cohesion, yet only mental efficacy promoted problem solving and observed teamwork effectiveness.


Chitosan-coated nanoparticles enhanced lung pharmacokinetic profile of voriconazole upon pulmonary delivery in mice.
Chitosan-coated polylactic-co-glycolic acid nanoparticles of voriconazole (VChNP) were developed to increase residence time and provide sustained drug release locally to treat recurrent lung-fungal infection. VChNP has been developed using a simple, unique technique and characterized. Pharmacokinetics, lung deposition with time and gamma imaging were conducted with optimized formulations. The deposition of fluorescein isothiocyanate-labeled VChNP in lung was confirmed by confocal microscopy. Gamma-scintigraphic images showed that Tc-99m-labeled VChNP had better pulmonary retention for longer period than that of noncoated formulation. Drastic improvement in pharmacokinetic profile of VChNP than noncoated formulation was observed. Thus, VChNP may be useful for effective pulmonary delivery with improved bioavailability. Such chitosan-coated nanoparticles may open up a new avenue for efficacious treatment of lung-fungal infection.


Sodium butyrate protects against severe burn-induced remote acute lung injury in rats.
High-mobility group box 1 protein (HMGB1), a ubiquitous nuclear protein, drives proinflammatory responses when released extracellularly. It plays a key role as a distal mediator in the development of acute lung injury (ALI). Sodium butyrate, an inhibitor of histone deacetylase, has been demonstrated to inhibit HMGB1 expression. This study investigates the effect of sodium butyrate on burn-induced lung injury. Sprague-Dawley rats were divided into three groups: 1) sham group, sham burn treatment; 2) burn group, third-degree burns over 30% total body surface area (TBSA) with lactated Ringer's solution for resuscitation; 3) burn plus sodium butyrate group, third-degree burns over 30% TBSA with lactated Ringer's solution containing sodium butyrate for resuscitation. The burned animals were sacrificed at 12, 24, and 48 h after burn injury. Lung injury was assessed in terms of histologic changes and wet weight to dry weight (W/D) ratio. Tumor necrosis factor (TNF)-α and interleukin (IL)-8 protein concentrations in bronchoalveolar lavage fluid (BALF) and serum were measured by enzyme-linked immunosorbent assay, and HMGB1 expression in the lung was determined by Western blot analysis. Pulmonary myeloperoxidase (MPO) activity and malondialdehyde (MDA) concentration were measured to reflect neutrophil infiltration and oxidative stress in the lung, respectively. As a result, sodium butyrate significantly inhibited the HMGB1 expressions in the lungs, reduced the lung W/D ratio, and improved the pulmonary histologic changes induced by burn trauma. Furthermore, sodium butyrate administration decreased the TNF-α and IL-8 concentrations in BALF and serum, suppressed MPO activity, and reduced the MDA content in the lungs after severe burn. These results suggest that sodium butyrate attenuates inflammatory responses, neutrophil infiltration, and oxidative stress in the lungs, and protects against remote ALI induced by severe burn, which is associated with inhibiting HMGB1 expression.


Palladium-Decorated Silicon Nanomesh Fabricated by Nanosphere Lithography for High Performance, Room Temperature Hydrogen Sensing.
A hydrogen (H2 ) gas sensor based on a silicon (Si) nanomesh structure decorated with palladium (Pd) nanoparticles is fabricated via polystyrene nanosphere lithography and top-down fabrication processes. The gas sensor shows dramatically improved H2 gas sensitivity compared with an Si thin film sensor without nanopatterns. Furthermore, a buffered oxide etchant treatment of the Si nanomesh structure results in an additional performance improvement. The final sensor device shows fast H2 response and high selectivity to H2 gas among other gases. The sensing performance is stable and shows repeatable responses in both dry and high humidity ambient environments. The sensor also shows high stability without noticeable performance degradation after one month. This approach allows the facile fabrication of high performance H2 sensors via a cost-effective, complementary metal-oxide-semiconductor (CMOS) compatible, and scalable nanopatterning method.


"Silent" β-thalassemia mutation (promoter nt-101 C > T) with increased hemoglobin A2.
One of the most common silent β-thalassemia mutations is the C > T substitution at position -101 within the distal CACCC box, which leads to a mild reduction in the expression level of the β-globin gene. Carriers of this mutation have a normal hematologic picture without microcytosis and borderline hemoglobin A2 values, and may be missed during screening. Co-occurrence of this mutation with one of the classical β-thalassemia mutations leads to β-thalassemia intermedia, and this is important for Mediterranean populations where β-thalassemia is frequent. Awareness of this mutation, which may have a heterogeneous clinical presentation, is required. We herein present the unusual hematologic findings of a Turkish family carrying this mutation.