Randomized, controlled trial of telcagepant over four migraine attacks.
This study evaluated the calcitonin gene-related peptide (CGRP) receptor antagonist telcagepant (tablet formulation) for treatment of a migraine attack and across four attacks. Adults with migraine were randomized, double-blind, to telcagepant 140 mg, telcagepant 280 mg, or control treatment sequences to treat four moderate-to-severe migraine attacks. Control patients received placebo for three attacks and telcagepant 140 mg for one attack. Efficacy for the first attack (Attack 1) and consistency of efficacy over multiple attacks were assessed. For an individual patient, consistent efficacy was defined as ≥ 3 successes, and lack of consistent efficacy was defined as ≥ 2 failures, in treatment response. A total of 1677 patients treated ≥ 1 attack and 1263 treated all four attacks. Based on Attack 1 data, telcagepant 140 mg and 280 mg were significantly (p < .001) more effective than placebo for 2-hour pain freedom, 2-hour pain relief, 2-hour absence of migraine-associated symptoms (phonophobia, photophobia, nausea), and 2-24 hours sustained pain freedom. The percentage of patients with 2-hour pain freedom consistency and 2-hour pain relief consistency was significantly (p < .001) higher for both telcagepant treatment sequences versus control. Adverse events within 48 hours for telcagepant with an incidence ≥ 2% and twice that of placebo were somnolence (placebo = 2.3%, 140 mg = 5.9%, 280 mg = 5.7%) and vomiting (placebo = 1.4%, 140 mg = 1.0%, 280 mg = 2.9%). Telcagepant 140 mg and 280 mg were effective for treatment of a migraine attack and were more consistently effective than control for intermittent treatment of up to four migraine attacks. Telcagepant was generally well tolerated. (Clinicaltrials.gov; NCT00483704).


Rapid odor processing by layer 2 subcircuits in lateral entorhinal cortex.
Olfactory information is encoded in lateral entorhinal cortex (LEC) by two classes of layer 2 (L2) principal neurons: fan and pyramidal cells. However, the functional properties of L2 cells and how they contribute to odor coding are unclear. Here, we show in awake mice that L2 cells respond to odors early during single sniffs and that LEC is essential for rapid discrimination of both odor identity and intensity. Population analyses of L2 ensembles reveal that rate coding distinguishes odor identity, but firing rates are only weakly concentration dependent and changes in spike timing can represent odor intensity. L2 principal cells differ in afferent olfactory input and connectivity with inhibitory circuits and the relative timing of pyramidal and fan cell spikes provides a temporal code for odor intensity. Downstream, intensity is encoded purely by spike timing in hippocampal CA1. Together, these results reveal the unique processing of odor information by LEC subcircuits and highlight the importance of temporal coding in higher olfactory areas.


Campylobacter pylori in Israel: prospective study of prevalence and epidemiology.
Antral biopsy samples were taken from 147 patients undergoing gastroscopy. Campylobacter pylori was cultivated from 100 of these patients. C. pylori was isolated from 76% of the specimens showing any degree of histologic gastritis, but from only 11% of specimens with completely normal histology. A questionnaire was completed on all patients and included demographic, epidemiologic and clinical information. Sephardic origin, smoking, and a bad taste in the mouth were more prevalent in the campylobacter-positive group. Previous use of antibiotics was negatively associated with the presence of C. pylori. Histologically confirmed gastritis was highly associated with the presence of C. pylori, especially in the moderate or severe grades in which 84% of biopsy specimens were positive. C. pylori was also cultivated from 50% of patients with mild gastritis, in 88% of patients with duodenal ulcer and in 71% of patients with gastric ulcer. The presence of C. pylori in 11% of normal specimens and the absence of C. pylori in 24% of specimens with gastritis further raises the question of the exact role played by C. pylori in the etiology of gastritis.


Update on the inherited platelet disorders.
The inherited platelet disorders have witnessed a surge in our understanding of molecular mechanisms of disease in the past few years due in large to part to the introduction of next-generation sequencing for discovery of novel genes. The purpose of this review is to update the reader on the novel discoveries with regard to the inherited platelet disorders, with a particular focus on describing the novel disorders described most recently. The description of novel mechanisms of disease including mutations in PRKACG, in a family with severe macrothrombocytopenia, RUNX1 and FLI1 mutations in patients with inherited mild platelet function disorders and CalDAG-GEFI resulting in a severe platelet bleeding phenotype show that there is still much to be learned from studying families and molecular sequencing of patients with well phenotyped platelet disorders. The implications for clinical practice of the continually growing list of genes described in small numbers of families makes whole exome/genome tempting as an option for evaluation of patients, but use outside of the research setting still needs to be done with extreme caution as interpretation of variants is likely to require additional studies.


Heterozygosity of mitogen-activated protein kinase organizer 1 ameliorates diabetic nephropathy and suppresses epithelial-to-mesenchymal transition-like changes in db/db mice.
Progressive diabetic nephropathy (DN) is characterized by tubulointerstitial fibrosis that is caused by accumulation of extracellular matrix. Induced by several factors, matrix-producing myofibroblasts may to some extent originate from tubular cells by epithelial-to-mesenchymal transition (EMT). Although previous data document that activation of hypoxia-inducible factor (HIF) signalling can be renoprotective in acute kidney disease, this issue remains controversial in chronic kidney injury. Here, we studied whether DN and EMT-like changes are ameliorated in a mouse model of type 2 diabetes mellitus with increased stability and activity of the HIF. We used db/db mice that were crossed with transgenic mice expressing reduced levels of mitogen-activated protein kinase organizer 1 (MORG1), a scaffold protein interacting with prolyl hydroxylase domain 3 (PHD3), because of deletion of one MORG1 allele. We found significantly reduced nephropathy in diabetic MORG1+/- heterozygous mice compared with the diabetic wild-types (db/dbXMORG1+/+). Furthermore, we demonstrated that EMT-like changes in the tubulointerstitium of diabetic wild-type MORG1+/+ mice are present, whereas diabetic mice with reduced expression of MORG1 showed significantly fewer EMT-like changes. These findings reveal that a deletion of one MORG1 allele inhibits the development of DN in db/db mice. The data suggest that the diminished interstitial fibrosis in these mice is a likely consequence of suppressed EMT-like changes.


Wheat lines monogenic for resistance to stem rust from the wheat cultivar 'Waldron'.
The Triticum aestivum L. cultivar 'Waldron' has long lasting resistance to most North American stem rust (Puccinia graminis Pers.:Pers. f. sp. tritici Eriks. and E. Henn.) isolates. The objective of this research was to develop wheat lines monogenic for resistance to stem rust from 'Waldron' using allelism tests and tests for reaction to a series of ten stem rust cultures having a range of virulences. Twelve lines homozygous for single resistance genes were selected as parents of a diallel cross to test for allelism among genes for resistance. We identified 6 lines or groups of lines (WDR-A1, the WDR-B1 and WDR-B2 group, the WDR-C1 and WDR-C2 group, WDR-D1, the WDR-E1, WDR-E2, WDR-E3, and WDR-E4 group, and WDR-F1) that carried different single genes for resistance from 'Waldron'. A seventh line (WDR-G1) probably has two genes for resistance, one in common with WDR-C1 and WDR-C2. The gene in the WDR-E group is probably the same as SrWld1, and the one in WDR-F1 the same as Sri11. 'Waldron' probably has two or more genes for resistance to stem rust that previous genetic studies did not detect.


Development of Photosystem II Activity in Chlamydomonas reinhardi Mutants: Insertion of Photosystem II Units into Inactive Preexisting Membranes versus Continuous Formation of New Photosynthetic Membranes.
In a previous work the development of photosystem II activity during the greening process of the y-1 mutant of Chlamydomonas reinhardi was studied (Cahen, Malkin, Shochat, Ohad. Plant Physiol 58: 257-267). Measurements of quantum yield, maximal rate of electron transfer, flash yield, and fluorescence induction indicated that photosystem II development consists of two partially overlapping phases: (a) reorganization and integration of preexisting units; and (b) addition of newly formed units to the growing membranes.In the present work an attempt was made to study these two processes independently. This was achieved using two experimental systems: (a) cells of the y-1 mutant, greened in the presence of chloramphenicol (CAP), whose activity is repaired under conditions which prevent further chlorophyll synthesis and membrane growth (dark or light with addition of cycloheximide [CHI]); (b) greening cells of a pale mutant derived from y-1 in which chloroplast membranes are formed gradually during several cell divisions.In both systems different parameters of 2,6-dichlorophenolindophenol reduction, as well as fluorescence, were measured. The results are interpreted using a kinetic model reported previously. It is concluded that during repair of photosynthetic activity in inactive membranes which were formed previously in the presence of chloramphenicol, photosystem II reaction centers are formed and integrated in preexisting membranes. In the pale green there is complete de novo synthesis of units of constant composition which are added during formation of new chloroplast membranes.


Sex Differences in Plasma MicroRNA Biomarkers of Early and Complicated Diabetes Mellitus in Israeli Arab and Jewish Patients.
MicroRNAs play functional roles in the etiology of type 2 diabetes mellitus (T2DM) and complications, and extracellular microRNAs have attracted interest as potential biomarkers of these conditions. We aimed to identify a set of plasma microRNAs, which could serve as biomarkers of T2DM and complications in a mixed Israeli Arab/Jewish patient sample. Subjects included 30 healthy volunteers, 29 early-stage T2DM patients, and 29 late-stage T2DM patients with renal and/or vascular complications. RNA was isolated from plasma, and the levels of 12 candidate microRNAs were measured by quantitative reverse transcription and polymerase chain reaction (qRT-PCR). MicroRNA levels were compared between the groups and correlated to clinical measurements, followed by stepwise regression analysis and discriminant analysis. Plasma miR-486-3p and miR-423 were respectively up- and down-regulated in T2DM patients compared to healthy controls. MiR-28-3p and miR-423 were up-regulated in patients with complicated T2DM compared to early T2DM, while miR-486-3p was down-regulated. Combined, four microRNAs (miR-146a-5p, miR-16-2-3p, miR-126-5p, and miR-30d) could distinguish early from complicated T2DM with 77% accuracy and 79% sensitivity. In male patients only, the same microRNAs, with the addition of miR-423, could distinguish early from complicated T2DM with 83.3% accuracy. Furthermore, plasma microRNA levels showed significant correlations with clinical measurements, and these differed between men and women. Additionally, miR-183-5p levels differed significantly between the ethnic groups. Our study identified a panel of specific plasma microRNAs which can serve as biomarkers of T2DM and its complications and emphasizes the importance of sex differences in their clinical application.


Early posttreatment assessment of MRI perfusion biomarkers can predict long-term response of lung cancer brain metastases to stereotactic radiosurgery.
Imaging criteria to evaluate the response of brain metastases to stereotactic radiosurgery (SRS) in the early posttreatment period remains a crucial unmet need. The aim of this study is to correlate early (within 12 wk) posttreatment perfusion MRI changes with long-term outcomes after treatment of lung cancer brain metastases with SRS. Pre- and posttreatment perfusion MRI scans were obtained in patients treated with SRS for intact non-small cell lung cancer brain metastases. Time-dependent leakage (Ktrans), blood plasma volume (Vp), and extracellular extravascular volume (Ve) were calculated for each lesion. Patients were followed longitudinally with serial MRI until death, progression, or intervention (whole brain radiation or surgery). We included 53 lesions treated with SRS from 41 total patients. Median follow-up after treatment was 11 months. Actuarial local control at one year was 85%. Univariate analysis demonstrated a significant difference (P = 0.032) in posttreatment Ktrans SD between patients with progressive disease (mean = 0.0317) and without progressive disease (mean = 0.0219). A posttreatment Ktrans SD cutoff value of 0.017 was highly sensitive (89%) for predicting progressive disease and no progressive disease. Early posttreatment volume change was not associated with outcome (P = 0.941). Posttreatment Ktrans SD may be used as an early posttreatment imaging biomarker to help predict long-term response of lung cancer brain metastases to SRS. This can help identify patients who will ultimately fail SRS and allow for timelier adjustment in treatment approach. These data should be prospectively validated in larger patient cohorts and other histologies.


Comparison of the pharmacokinetics of dolasetron and its major active metabolite, reduced dolasetron, in dog.
Dolasetron mesilate (Anzemet) ((2 alpha, 6 alpha, 8 alpha, 9a beta)-octahydro-3-oxo-2,6-methano-2H-quinolizin-8-yl-1 H-indole-3-carboxylate monomethane-sulfonate) is a 5-HT3 receptor antagonist, which is in development for the treatment of chemotherapy-induced emesis. The ketone moiety of dolasetron is rapidly reduced by carbonyl reductase to form an alcohol, reduced dolasetron (red-dolasetron), which is the major pharmacologically active metabolite in humans. The pharmacokinetics of dolasetron and red-dolasetron were compared in dog, after single intravenous (i.v.) (2 mg/kg) and oral (p.o.) (5 mg/kg) administration of [14C]dolasetron or [14C]red-dolasetron. Pharmacokinetic parameters of dolasetron showed a terminal elimination half-life (t1/2) of 0.1 h, total body plasma clearance (Cltot) of around 109 mL/min/kg, apparent volume of distribution (aVd beta) of 0.83 L/kg, and bioavailability (F) of 7%. Pharmacokinetic parameters of red-dolasetron, calculated after dolasetron or red-dolasetron administration, were very similar. The t1/2 was around 4.0 h, Cltot 25 mL/min/kg, aVd beta 8.5 L/kg, and F around 100%. The apparent first-order formation rate constant (ki) of red-dolasetron was 7 h-1, which was similar to the first-order elimination rate constant (kel) of dolasetron. Cmax of red-dolasetron was similar, after po administration of either compound, but the median Tmax was 0.33 h after dolasetron, compared with 1.5 h after red-dolasetron. The first-order absorption rate constants (ka) of dolasetron and red-dolasetron were 14 h-1 and 2 h-1, respectively. Dolasetron transport across Caco-2 cell monolayers was also higher than that of red-dolasetron. Thus dolasetron was more quickly absorbed than red-dolasetron, and its administration led to the more rapid appearance of red-dolasetron in plasma. There appears to be no advantage in the direct administration of the metabolite, especially as in humans oral administration of dolasetron, 30 min before chemotherapy, has been shown to be effective in preventing emesis.


Rethinking voluntary euthanasia.
Our goal in this article is to explicate the way, and the extent to which, euthanasia can be voluntary from both the perspective of the patient and the perspective of the health care providers involved in the patient's care. More significantly, we aim to challenge the way in which those engaged in ongoing philosophical debates regarding the morality of euthanasia draw distinctions between voluntary, involuntary, and nonvoluntary euthanasia on the grounds that drawing the distinctions in the traditional manner (1) fails to reflect what is important from the patient's perspective and (2) fails to reflect the significance of health care providers' interests, including their autonomy and integrity.


Cytology of prostatic carcinoma. Quantification and validation of diagnostic criteria.
The validity of diagnostic criteria for the cytologic differentiation between benign and malignant cases and between normal (hyperplastic) and inflammation-activated (prostatitis) prostatic cells was tested by means of semiautomated image analysis and cytophotometry. The following criteria were found to have significant differences between benign and malignant prostatic cells: nucleoli (number, size and size variability), regularity of nuclear arrangement, anisonucleosis, nuclear size, nuclear polymorphism and dissociation of cells. The following criteria were found to be invalid for the detection of prostatic cancer cells: nuclear-cytoplasmic ratio, hyperchromasia and anisochromasia. the cytologic diagnosis of prostatic cancer was achieved by observing a variable constellation of at least three of six pathognomically altered diagnostic criteria. No fixed pattern of diagnostic criteria was found either for prostatic cancer cells in general or for the different malignancy grades.


Long working hours and health.
This article examines associations between long working hours, depression and changes in selected health behaviours. Based on an analysis of people followed over a two-year period, the relationship between changes in work hours and changes in health behaviours is explored. The data are from the household longitudinal component of the 1994/95 and 1996/97 cycles of the National Population Health Survey, conducted by Statistics Canada. Results are based on 3,830 adult workers aged 25 to 54 (2,181 men and 1,649 women) who worked 35 hours or more per week throughout the year before their 1994/95 interview. Multivariate analyses were used to estimate associations between working hours and depression, and changes in weight, smoking, drinking and exercise, while controlling for potential socioeconomic and work-related confounders such as education, income, occupation, shift work and self-employment. Women who worked long hours had increased odds of subsequently experiencing depression. Moving from standard to long hours was associated with unhealthy weight gain for men, with an increase in smoking for both men and women, and with an increase in drinking for women. No associations were detected for physical activity.


Patch-Clamp Recordings of the KcsA K+ Channel in Unilamellar Blisters.
Patch-clamp electrophysiology is the standard technique used for the high-resolution functional measurements on ion channels. While studies using patch clamp are commonly carried out following ion channel expression in a heterologous system such as Xenopus oocytes or tissue culture cells, these studies can also be carried out using ion channels reconstituted into lipid vesicles. In this chapter, we describe the methodology for reconstituting ion channels into liposomes and the procedure for the generation of unilamellar blisters from these liposomes that are suitable for patch clamp. Here, we focus on the bacterial K+ channel KcsA, although the methodologies described in this chapter should be applicable for the functional analysis of other ion channels.


Relationship between the iron regulated outer membrane proteins and the outer membrane proteins of in vivo grown Pasteurella multocida.
The SDS-PAGE patterns of the outer membrane protein (OMP) extracts of Pasteurella multocida strain P1059, grown under iron-restricted, iron-replete and in vivo conditions, were examined. The results showed that the iron-regulated outer membrane proteins (IROMPs) with molecular masses of 76 kDa, 84 kDa, and 94 kDa were expressed by bacteria grown in iron-restricted media. They were also expressed by in vivo grown P. multocida. Convalescent-phase sera, obtained from turkeys which had survived pasteurellosis, contained antibodies that reacted intensly with th three IROMPs. This indicated that these proteins were expressed in vivo. Bacteria expressing the IROMPs showed greater binding to Congo Red when compared to cells not expressing IROMPs. Cells expressing the IROMPs or its OMP extracts grown in iron-restricted media also showed greater binding to 59Fe-pasteurella siderophore (multocidin) when compared to bacteria or its extracts not expressing IROMPs. Convalescent-phase sera, which contained antibodies against the IROMPs, blocked this specific 59Fe-multocidin binding to IROMPs. Autoradiography was used to determine which of these IROMPs functioned as a receptor for the iron-multocidin complex. The results suggested that these three IROMPs have specific epitopes for binding to the iron multocidin complex.


Poly[penta-kis-(μ-cyanido-κN:C)tris-(5-phenyl-2,2'-bipyridine-κN,N')penta-copper(I)].
The hydro-thermal reaction of Cu(acetate)(2) and K(3)[Fe(CN)(6)] with 5-phenyl-2,2'-bipyridine (5-ph-2,2'-bpy) in water yields the polymeric title complex, [Cu(5)(CN)(5)(C(16)H(12)N(2))(3)](n), which consists of ribbons along the a axis, constructed from 26-membered {Cu(10)(CN)(8)} rings. In these rings, the metal atoms are bridged by cyanide groups, except for one close Cu⋯Cu contact [2.7535 (12) Å], which can be considered as ligand-unsupported. Within the rings, one Cu atom has a distorted tetra-hedral geometry through the coordination to two N atoms from 5-ph-2,2'-bpy and two N/C atoms from two cyanide groups. Two Cu atoms have a trigonal planar environment being coordinated by three cyanide groups and two other Cu atoms have a distorted square planar geometry through coordination to two N atoms from 5-ph-2,2'-bpy and two N/C atoms from two cyanide groups.


Malignant fibrous histiocytoma of the spermatic cord: a case report.
We present a case of malignant fibrous histiocytoma of the spermatic cord. An 86-year-old man was admitted to the hospital with a right painless scrotal mass. Under the diagnosis of a testicular tumor, right radical orchiectomy was performed. Grossly, the tumor firmly adhered to the spermatic cord. The right testis and epididymis were normal. The histologic diagnosis was malignant fibrous histiocytoma. There was local recurrence 2 months after surgery. The recurrent tumor was resected with the surrounding soft tissue, but the patient died 5 months after the initial operation.


Intracortical and corticothalamic coherency of fast spontaneous oscillations.
We report that fast (mainly 30- to 40-Hz) coherent electric field oscillations appear spontaneously during brain activation, as expressed by electroencephalogram (EEG) rhythms, and they outlast the stimulation of mesopontine cholinergic nuclei in acutely prepared cats. The fast oscillations also appear during the sleep-like EEG patterns of ketamine/xylazine anesthesia, but they are selectively suppressed during the prolonged phase of the slow (<1-Hz) sleep oscillation that is associated with hyperpolarization of cortical neurons. The fast (30- to 40-Hz) rhythms are synchronized intracortically within vertical columns, among closely located cortical foci, and through reciprocal corticothalamic networks. The fast oscillations do not reverse throughout the depth of the cortex. This aspect stands in contrast with the conventional depth profile of evoked potentials and slow sleep oscillations that display opposite polarity at the surface and midlayers. Current-source-density analyses reveal that the fast oscillations are associated with alternating microsinks and microsources across the cortex, while the evoked potentials and the slow oscillation display a massive current sink in midlayers, confined by two sources in superficial and deep layers. The synchronization of fast rhythms and their high amplitudes indicate that the term "EEG desynchronization," used to designate brain-aroused states, is incorrect and should be replaced with the original term, "EEG activation" [Moruzzi, G. & Magoun, H.W. (1949) Electroencephalogr. Clin. Neurophysiol. 1, 455-473].


Lipolysis--not inflammation, cell death, or lipogenesis--is involved in adipose tissue loss in cancer cachexia.
Cancer cachexia is an important, negative prognostic marker that has been linked to systemic inflammation and cell death through unclear mechanisms. A key feature of cancer cachexia is loss of white adipose tissue (WAT) because of increased adipocyte lipolysis and possibly reduced lipid synthesis (lipogenesis). In this study, the authors investigated whether alterations in fat cell numbers, lipogenesis, or cytokine and/or leukocyte infiltration could account for some of the functional changes observed in WAT in cancer cachexia. Blood and subcutaneous WAT samples were obtained from a 10 weight-stable patients, from 13 weight losing (cachexia) patients with cancer, and from 5 patients without cancer (noncancer patients) who initially were classified with cancer. Systemic inflammation (increased circulating levels of interleukin 6 [IL-6]) and enhanced lipolysis were confirmed in the cachectic patients compared with the other patients. However, the messenger RNA expression of IL-6 and other cytokine or leukocyte markers, as well as WAT secretion of IL-6, were not altered in the patients with cachexia. Thus, the elevated serum levels of IL-6 that were observed in cachexia were not derived from WAT. Insulin-induced lipogenesis in adipocytes from patients with cachexia was the same as that in adipocytes from patients with weight-stable cancer and from noncancer patients (2.5-fold maximal stimulation; half-maximum effective concentration, approximately 0.03 nmol/L). Fat cell size was decreased but adipocyte numbers were normal in cancer patients with cachexia, suggesting that there was no major fat cell death. The current findings indicated that subcutaneous WAT does not contribute to the systemic inflammatory reaction and does not induce adipocyte insulin resistance in cancer cachexia. Moreover, increased fat cell lipolysis, not reduced lipogenesis or adipocyte cell death, appeared to be the primary cause of fat loss in this condition.


Postoperative pain control using epidural catheters after anterior spinal fusion for adolescent scoliosis.
A prospective review of patients undergoing epidural catheter placement after anterior spinal fusion and instrumentation for adolescent scoliosis was performed. Data were collected using visual analog pain scores reflecting the patients' perception of their pain control. To present the authors' technique for epidural catheter placement and dosing protocol, and to demonstrate the results from postoperative pain control after anterior spinal instrumented fusion for 10 consecutive patients. The literature regarding the benefits of epidural catheters after spinal surgery is contradictory, even with controlled studies comparing epidural catheters with intravenous morphine patient-controlled anesthesia. The authors believe that this lack of consensus stems from varied epidural dosing protocols and techniques in catheter placement, which they have witnessed anecdotally at their own institution. This prompted the authors to develop and refine a standardized dosing and catheter placement protocol for pain control after spinal surgery. Epidural catheters were placed intraoperatively before wound closure, then removed on postoperative Day 5. Dosing consisted of fentanyl (1 microg/kg) and hydromorphone (5 microg/kg) diluted in preservative-free saline (0.2 mL/kg). After surgery, dosing consisted of 0.1% ropivacaine and hydromorphone (10 microg/ml) continuously infused at 0.2 mL/kg/hour. Postoperative pain control was assessed on each postoperative day using a visual analog pain scale with choices ranging from 0 to 10. The arithmetic mean of the median pain scores after surgery was 2.1. The mean of the maximum pain scores for the 5 days was 4.1. Three patients required an epidural bolus and a 20% increase in the epidural infusion rate. One patient was judged to be excessively sleepy, so the epidural infusion rate was decreased by 20%. Pruritus requiring diphenhydramine developed in three patients. No other adverse effects related to epidural analgesia were noted. No catheters were accidentally pulled out or disconnected. By following the dosing protocol described, epidural catheters can be used safely and effectively to control postoperative pain after anterior instrumentation and spinal fusion for adolescent scoliosis.


An intra-K-complex oscillation with independent and labile frequency and topography in NREM sleep.
NREM sleep is characterized by K-complexes (KCs), over the negative phase of which we identified brief activity in the theta range. We recorded high resolution EEG of whole-night sleep from seven healthy volunteers and visually identified 2nd and 3rd stage NREM spontaneous KCs. We identified three major categories: (1) KCs without intra-KC-activity (iKCa), (2) KCs with non-oscillatory iKCa, and (3) KCs with oscillatory iKCa. The latter group of KCs with intra-KC-oscillation (iKCo), was clustered according to the duration of the iKCo. iKCa was observed in most KCs (1150/1522, 75%). iKCos with 2, 3, and 4 waves were observed in 52% (786/1522) of KCs in respective rates of 49% (386/786), 44%, and 7%. Successive waves of iKCos showed on average a shift of their maximal amplitude in the anterio-posterior axis, while the average amplitude of the slow KC showed no spatial shift in time. The iKCo spatial shift was accompanied by transient increases in instantaneous frequency from the theta band toward the alpha band, followed by decreases to upper theta. The study shows that the KC is most often concurrently accompanied by an independent brief iKCo exhibiting topographical relocation of amplitude maxima with every consecutive peak and transient increases in frequency. The iKCo features are potentially reflecting arousing processes taking place during the KC.


Dentistry's response to bioterrorism: a report of a consensus workshop.
The possibility of a significant bioterrorist attack on the civilian population of the United States has become a focus of local, state and national attention since the fall of 2001. An appropriate role for dentistry in the response to a massive bioterrorist attack has not yet been established, even though dentistry's role in other disasters has been developed and proven to be effective. To develop a consensus on a potential role for dentistry in dealing with bioterrorism, experts in bioterrorism issues and representatives of key organizations that could play a role in dentistry's response met at the American Dental Association's Workshop on the Role of Dentistry in Bioterrorism in June. In the event of a bioterrorist attack, dentists may be called on to fulfill several functions: education, risk communication, diagnosis, surveillance and notification, treatment, distribution of medications, decontamination, sample collection and forensic dentistry. Local dental societies should develop a plan for the dental response to potential bioterrorist attacks that can be integrated into each community's mass disaster response plan. Educational programs for dentists should be developed to prepare them for providing services they may be recruited to perform in an emergency. Dentistry has assets in personnel and facilities that can be of great value in responding to a major bioterrorist attack on the United States.


[Population, migration, and development].
"Rapid demographic growth in Africa has not been accompanied by economic development. It has generated important flows to the North. Family planning programs will not be sufficient to solve the problems caused by...demographic growth and they will most likely increase in the future. Controls of these [outflows] are unlikely to effective. Under these conditions, only the economic development of the South will allow the limitation of outmigration." (SUMMARY IN ENG AND SPA)


Prevalence and correlates of prolonged fatigue in a U.S. sample of adolescents.
Prolonged fatigue in adolescents has a major impact on social functioning and school attendance. In adults, prolonged fatigue substantially overlaps with mood and anxiety disorders. Extending the data to adolescents, the authors studied the prevalence and correlates of fatigue in a representative U.S. sample. The participants were 10,123 adolescents ages 13-18 years from the National Comorbidity Survey Adolescent Supplement. They were interviewed about prolonged fatigue, defined as extreme fatigue with at least one associated symptom (pains, dizziness, headache, sleep disturbance, inability to relax, irritability) that does not resolve by resting or relaxing and lasting at least 3 months. The prevalence of prolonged fatigue was 3.0% (SE=0.3), with 1.4% (SE=0.2) for prolonged fatigue only and 1.6% (SE=0.2) for prolonged fatigue concomitant with a depressive or anxiety disorder. Nearly 60% of the adolescents with prolonged fatigue only had severe or very severe disability, and their rates of poor physical and mental health were comparable to those of adolescents with mood or anxiety disorders only. Adolescents with prolonged fatigue and comorbid mood or anxiety disorders had significantly greater disability, poorer mental health, and more health service use than those with either condition alone. These findings suggest that prolonged fatigue is associated with disability and is an important clinical entity independent of mood and anxiety disorders in adolescents. Persistent fatigue with a comorbid mood or anxiety state is related to even more functional impairment, suggesting that prolonged fatigue may reflect greater severity of mood and anxiety disorders in adolescents.


Sulfated polysaccharide ascophyllan from Padina tetrastromatica enhances healing of burn wounds by ameliorating inflammatory responses and oxidative damage.
Sulfated polysaccharide ascophyllan from marine brown algae has been identified to have burn wound healing properties. Thus, we examined the effects of ascophyllan fraction (AF3) on the inflammatory response and oxidative damage in burn wounds. Full-thickness burn wounds in rats were then treated twice per day with topical AF3 ointment (5%), while control groups were treated with 10% povidone-iodine (positive control) and petroleum jelly-based ointment (negative control). The activity of cyclooxygenase-2 and myeloperoxidase and levels of C-reactive protein, nitric oxide, and proinflammatory cytokines (tumor necrosis factor-α, interleukin-6, and interleukin-1β) were observed to have significantly decreased in peripheral blood mononuclear cells, serum, and wound tissue of the group treated with AF3 ointment on day 8 after wounding. The expression of inducible nitric oxide synthase, endothelial nitric oxide synthase, and vascular endothelial growth factor at the mRNA level was determined to be upregulated in the wound tissue of the AF3 ointment-treated group. After treatment with AF3 ointment, the antioxidant enzyme activity and level of reduced glutathione were upregulated, whereas the content of thiobarbituric acid reactive substances decreased. Treatment of burn wounds using 5% AF3 ointment decreases oxidative damage associated with inflammation deceptively via inhibition of inflammatory enzymes, regulation of proinflammatory cytokines, upregulation of angiogenesis, and activity of antioxidant enzymes.


Chronic urticaria as a presenting symptom of Crohn's disease.
Clinical presentation of Crohn's disease (CD) may be variable according to the location and the intensity of the inflammation. Some patients may have atypical symptoms which could delay the diagnosis. We report the first case of chronic urticaria related to a subclinical, complicated CD. Although the pathologic mechanism of this association was unclear in our patient, this case suggests that in patients with unexplained chronic urticaria it is opportune to investigate for a possible CD, even if there are no or few specific symptoms of intestinal inflammatory disease.


A Case of Freeman-Sheldon Syndrome: Anesthetic Challenges.
Patients with Freeman-Sheldon Syndrome (FSS) often need multiple surgical procedures. We present a case of FSS and discuss the anesthetic challenges associated with the case. A 10-week-old female with FSS presented for elective Nissen fundoplication and gastrostomy tube insertion. She had a history of difficult intubation at birth. General anesthesia with inhalational anesthetic and spontaneous respirations technique was used. Fiber optic bronchoscope (FOB)-assisted nasal intubation was successful after failed attempts with a Miller blade, GlideScope, and intubation through a laryngeal mask airway (LMA). She did not exhibit any signs of malignant hyperthermia (MH) during or immediately after the procedure. Challenges to the anesthesiologist in a case with FSS include establishing IV access, intubating the trachea, risk of MH and MH-like symptoms, and postoperative pulmonary complications. Proper multidisciplinary preoperative planning is essential for optimum care of these patients, preferably in a tertiary care center.


[Coronary artery fistula between pulmonary trunk and left descending coronary artery--description of two cases].
Fistulas connecting coronary arteries with trunk of pulmonary artery are the most common congenital defects of coronary arteries. Depending on the size of fistula they cause IHD symptoms of different intensification (Coronary Steal Phenomenon). The symptoms appear very often in advanced age. In this study two patients with coronary-pulmonary artery fistula accompanied by another heart defects (VSD or stenosis of aortic valve), but with no IHD-symptoms, are presented. To find possible coronary arteries malformations, it seems to be useful to perform the catheterization of coronary arteries in all patients, who are qualified for surgical procedure because of heart's disease. It also concerns younger patients with VSD (under 35) in whom coronarography is not a routine procedure.


Effects of intramuscular fat levels on sensory characteristics of duck breast meat.
We conducted a study to evaluate the effects of intramuscular fat levels on the sensory characteristics of duck breast meat. Combining duck genotypes (Muscovy, Pekin, and their crossbreed hinny and mule ducks) and feeding levels (overfeeding between 12 and 14 wk of age vs. ad libitum feeding) enabled us to obtain a wide range of lipid levels in breast muscle. The average values were between 2.55 and 6.40 g per 100 g of muscle. Breast muscle from overfed ducks showed higher lipid and lower water levels than breast muscle from ducks fed ad libitum. Muscle from the overfed ducks was also paler in color and exhibited greater yellowness and cooking loss values. Juiciness was judged lower and flavor more pronounced in overfed ducks. Muscovy ducks exhibited higher breast weight and lower lipid levels than the other genotypes. At the other extreme, Pekin ducks exhibited the highest lipid levels and the lowest breast weights; values for these criteria were intermediate in hinny and mule ducks. Breast muscle of Muscovy ducks was paler, less red, and more yellow than that of other genotypes. Breast muscle of Pekin ducks exhibited the lowest values for lightness, yellowness, and energy necessary to shear meat, as well as the highest cooking loss values, and was judged more tender, juicy and less stringy than that of other genotypes. In contrast, scores for breast muscle of Muscovy ducks were the lowest for tenderness, juiciness, and flavor, and the highest for stringiness. Breast muscle of hinny and mule ducks scored the highest values for redness. Hinny ducks also scored the highest values for flavor. Genotype exerted a higher effect on the sensory quality of breast muscle than did feeding levels. Finally, increasing lipid levels in breast muscle increased lightness, yellowness, cooking loss, tenderness, and flavor, with correlation coefficients of 0.49, 0.47, 0.54, 0.43, and 0.28, respectively. However, breast meat color and tenderness were mainly influenced by genotype.


The neural representation of sensorimotor transformations in a human perceptual decision making network.
Humans can quickly engage a neural network to transform complex visual stimuli into a motor response. Activity from a key region within this network, the intraparietal sulcus (IPS), has been associated with evidence accumulation and motor planning, thus implicating it in sensorimotor transformations. If such transformations occur within a brain region, a key and untested prediction is that neural activity reflecting both the parametric amount of evidence available and the timing of motor planning can be independently manipulated. To investigate these ideas, we constructed a dot motion discrimination task in which information about response modality (what to use) and response mapping (how to use it) was provided independently either before or after presentation of a dot motion coherence stimulus whose strength varied across trials. Consistent with our hypothesis, activity within IPS covaried with dot motion coherence during the stimulus phase, and as information necessary for the response was delayed, the peak of IPS activity shifted to the response phase. In contrast, areas such as the motion-sensitive region MT+ and the supplementary motor area demonstrated activity limited to the stimulus and response phases of the task, respectively. These results show that activity in IPS correlates with temporally dissociable representations consistent with both evidence accumulation and motor planning, and suggest that IPS is a core component for sensorimotor transformations within the perceptual decision-making network.


Canalicular cystocele.
We report a rare case of acquired canalicular cystocele in a patient with obstructions at both the proximal and distal ends of the inferior canaliculus. Histopathologic examination revealed a dilated tubule lined with nonkeratinizing squamous epithelium that measured 19 mm long and 7 mm wide. No mucous secreting goblet cells were observed in any sections. The fibrotic, thickened wall was infiltrated with epithelioid, lymphoid, and occasional plasma cells.


Childhood eating disorders: British national surveillance study.
The incidence of eating disorders appears stable overall, but may be increasing in younger age groups. Data on incidence, clinical features and outcome of early-onset eating disorders are sparse. To identify new cases of early-onset eating disorders (<13 years) presenting to secondary care over 1 year and to describe clinical features, management and 1-year outcomes. Surveillance over 14 months through the established British Paediatric Surveillance System, and a novel child and adolescent psychiatry surveillance system set up for this purpose. Overall incidence was 3.01/100,000 (208 individuals). In total, 37% met criteria for anorexia nervosa; 1.4% for bulimia nervosa; and 43% for eating disorder not otherwise specified. Nineteen per cent showed determined food avoidance and underweight without weight/shape concerns. Rates of comorbidity were 41%; family history of psychiatric disorder 44%; and early feeding difficulties 21%. Time to presentation was >8 months. A total of 50% were admitted to hospital, typically soon after diagnosis. Outcome data were available for 76% of individuals. At 1 year, 73% were reported improved, 6% worse and 10% unchanged (11% unknown). Most were still in treatment, and seven were hospital in-patients for most of the year. Childhood eating disorders represent a significant clinical burden to paediatric and mental health services. Efforts to improve early detection are needed. These data provide a baseline to monitor changing trends in incidence.


The regulation of CD5 expression in murine T cells.
CD5 is a pan-T cell surface marker that is also present on a subset of B cells, B-1a cells. Functional and developmental subsets of T cells express characteristic CD5 levels that vary over roughly a 30-fold range. Previous investigators have cloned a 1.7 Kb fragment containing the CD5 promoter and showed that it can confer similar lymphocyte-specific expression pattern as observed for endogenous CD5 expression. We further characterize the CD5 promoter and identify minimal and regulatory regions on the CD5 promoter. Using a luciferase reporter system, we show that a 43 bp region on the CD5 promoter regulates CD5 expression in resting mouse thymoma EL4 T cells and that an Ets binding site within the 43 bp region mediates the CD5 expression. In addition, we show that Ets-1, a member of the Ets family of transcription factors, recognizes the Ets binding site in the electrophoretic mobility shift assay (EMSA). This Ets binding site is directly responsible for the increase in reporter activity when co-transfected with increasing amounts of Ets-1 expression plasmid.We also identify two additional evolutionarily-conserved regions in the CD5 promoter (CD5X and CD5Y) and demonstrate the respective roles of the each region in the regulation of CD5 transcription. Our studies define a minimal and regulatory promoter for CD5 and show that the CD5 expression level in T cells is at least partially dependent on the level of Ets-1 protein. Based on the findings in this report, we propose a model of CD5 transcriptional regulation in T cells.


Properties and bioapplications of blended cellulose and corn protein films.
A series of blend films have been prepared from cellulose and corn protein in a NaOH/urea solution by a simple, low cost, and 'green' pathway. Their structure and properties are characterized by amino acid analysis, X-ray diffraction, scanning electron microscopy, thermogravimetry, and tensile testing. The results reveal that a certain miscibility exists between cellulose and corn protein and their thermal stability and mechanical properties are improved significantly, compared with the protein materials, when the protein content is less than 18 wt.-%. The protein, which contains tyrosine and histidine, could remain in the blend films after being washed for ten days, which indicates the strong hydrogen bonding between the hydroxy groups of cellulose and the hydroxyphenyl of tyrosine and imidazolyl of histidine in the protein. Furthermore, they exhibit good biocompatibility capable of supporting cell adhesion and proliferation.


An exploratory study of the cognitive, academic, and behavioral functioning of pediatric cardiothoracic transplant recipients.
Limited information is available regarding the cognitive, academic, and behavioral outcomes of pediatric cardiothoracic transplant recipients. To examine the cognitive, behavioral, and academic functioning of a group of children who have received heart, heart/lung, or lung transplants. An exploratory cross-sectional outcomes study of surviving pediatric cardiothoracic transplant recipients at a Midwestern pediatric hospital. Transplant recipients completed measures of cognitive and academic functioning. Parents and teachers completed measures of behavioral functioning. Parents and transplant recipients also provided qualitative data regarding their main concerns after transplantation. On measures of cognitive functioning, 46% showed significant delays (> 2 SD below the normative population). Of those eligible for academic testing, 78% fell within the average range (within 1 SD of the normative population) for reading and spelling, and 57% fell within the average range for math. Twenty-seven percent of mothers, 11% of fathers, and 17% of teachers rated subjects as having significant behavioral concerns. Results highlight the need for close contact between transplant teams and school personnel to optimize outcomes. In addition, patients and families may benefit from psychological intervention after transplantation as there are ongoing concerns regarding life expectancy and quality of life.


A novel cell cycle blocker extracted from Stellera chamaejasme L. inhibits the proliferation of hepatocarcinoma cells.
Currently, liver cancer is the sixth most prevalent cancer and the third most common cause of cancer-related death. However, effective chemotherapeutic drugs with low drug resistance and few side-effects for the clinical treatment of liver cancer are lacking. Therefore, the search for novel drugs to compensate for the defects of existing drugs is urgently needed. Herein, we successfully screened an extract named from Stellera chamaejasme L. (SCL), a historically confimed antitumor plant, through a novel extraction platform. In the present study, we firstly screened the anticancer effect of ESC by the sulforhodamine B (SRB) cell proliferation assay in a wide range of malignant cell lines, including A549, NCI-H157, NCI-H460, SK-HEP-1 and HepG2. With the highest inhibitory rate in hepatocarcinoma cells, we further identified the tumor-suppressive efficacy and the safety of ESC in an H22 hepatocarcinoma xenograft model in vivo. In a mechanistic study, flow cytometry and western blot analysis were performed to evaluate the effects of ESC on the induction of cell apoptosis, intervention of cell cycle distribution and its influence on key G2/M-phase regulators. The results showed that ESC significantly inhibited the cell growth of liver cancer cell lines. Accordingly, the tumor inhibition rate was also increased following ESC administration with little systemic toxicity in H22-transplanted mice. Mechanistically, ESC caused obvious G2/M-phase arrest in both the SK-HEP-1 and HepG2 cell lines without cell apoptosis. Furthermore, cyclin B1 was downregulated, while the phosphorylation level of CDK1 was increased in response to ESC treatment. All these data confirmed that ESC possesses potent anti-proliferative efficacy for hepatocarcinoma through the induction of cyclin-mediated cell cycle arrest. Thus, ESC is a promising candidate for hepatocarcinoma treatment in the future.


Time course of changes in rat pancreatic synthesis rates and retention thresholds of four hydrolases during consumption of a low-protein followed by a balanced diet.
Synthesis rates of pancreatic amylase, trypsinogen 2 (Tg2), chymotrypsinogen 1 (Chtg1), and lipase, were measured in control rats fed a 20% protein diet for 46 days and in malnourished rats fed a 5% protein diet for 23 days (protein malnutrition) followed by refeeding a balanced diet for 23 days. In the control group, a progressive pancreatic maturation (namely an increase in hydrolase synthesis per gram of tissue) appeared with age. In the malnourished group, pancreas maturation of the four hydrolases was inhibited. Synthesis rates of the four hydrolases were reduced to a lesser extent from day 2 of protein malnutrition. With continued protein malnutrition, Tg2 synthesis rates remained steady, whereas the lipase synthesis rate continued to decrease and Chtg1 and amylase rates started to increase. As soon as refeeding was initiated, an important enhancement in synthesis was observed. The synthesis rates of Tg2, Chtg1, and amylase actually showed a rebound effect, then decreased with the refeeding time to reach control values, except for Chtg1, which remained higher than control values throughout the refeeding phase. Lipase synthesis rate rose more slowly and reached the control values only after 9 days of refeeding. The retention threshold (pancreas tissue versus pancreatic secretion) values showed that the storage levels were different from one hydrolase to the other and were variable with age in the control group, and with protein malnutrition and refeeding times in the malnourished group. In the control group, a preferential secretion of newly synthesized enzymes was observed in young rats, whereas with age, the proportion of newly synthesized hydrolases excreted decreased slowly.(ABSTRACT TRUNCATED AT 250 WORDS)


[Results of the Hughes operation].
There are several methods for the repair of large defects of the upper and lower eyelids, but we prefer the original procedure by Hughes. This operation has been used traditionally for partial and total reconstruction of lid defects after tumour resection in 7-10%. The advantage of this technique is the rebuilding of the eyelid with the lid tissue itself. We present the results of operations by the Hughes method over a 10-year-period. Between 1986 and 1996 we operated on 60 out of 600 patients with neoplastic tumours of the eyelids and 1 patient with a large traumatic defect of the upper eyelid by the original operation method of Hughes. We report on a retrospective study of 55 patients including 30 males and 25 females with a mean age of 68.6 years. The duration of the histories of the tumours ranged from 2 month to 10 years. The lower eyelids were involved in 46 patients and the upper lids in 9. In 80% (45 patients) we found basal cell carcinomas and in 17% (9 patients) squamous cell carcinomas. Therapy of tumours: 50 out of 54 tumours (92.6%) were resected in sano and 4 not. During the dissection of the lids we carried out a tissue biopsy but no further tumour tissue was found in three patients. The fourth patient needed three further operations before recovery. In six patients we recognised a new tumour, one of them suffered from Lewandowsky-Lutz-Syndrom, developed a new tumour in the orbit and required exenteration orbitae. Early complications: arterial bleeding in one case, in four cases mild dehiscence of the wound between the graft and the remaining lid, in two patients with high risk, infection of the wound, one rejection of the skin graft, one small infiltration of the cornea. Late complications: In six cases we recognised recurrence of the tumour and three patients with entropium and seven patients with heavy trichiasis needed revision. Minor complications such as mild distichiasis, partial incomplete closing of the lids, a smaller lid fissure or notching of the canthus of the lid which did not require revision. The results were quite satisfactory from a functional and aesthetic point of view. We recommend the operation method of Hughes for reconstruction of large defects of the eyelids of any reason.


Interplay between hydrido/dihydrogen and amine/amido ligands in ruthenium-catalyzed transfer hydrogenation of ketones.
This work describes the synthesis of three key intermediates of Noyori-type catalytic systems that are active precatalysts for the transfer hydrogenation of acetophenone. Isolation of the cationic chloro(dihydrogen) complex [RuCl(H(2))(H(2)NNPP)(PCy(3))][BArf(4)] provides a facile synthetic route to the corresponding cationic and neutral hydrido complexes, and the series highlights the links between hydride/dihydrogen and amine/amido ligands in neutral and cationic species.


The assessment, and glucagon-like peptide-2 modulation, of intestinal absorption and function.
The treatment of patients with short bowel syndrome is hampered by a lack of treatment and measurement methods. This article reviews our evolving understanding of the role of glucagon-like peptide 2 (GLP-2) in controlling the adaptive process. The ability of the remnant intestine to produce GLP-2 appears to be predictive of the adaptive process; exogenous GLP-2 may be a therapy to augment adaptation. Strategies for monitoring patients, including conventional means, such as anthropomorphic measurements, plasma levels of specific nutrients, and vitamins and radiological contrast studies are reviewed. Investigational methods, such as nutrient balance studies, plasma citrulline levels, and the absorption of inert sugars (3-0 methyl glucose, mannitol, and lactulose) are discussed with the evidence to support their use.


Dissecting the molecular dance: c-di-GMP, cAMP-CRP, and VfmH collaboration in pectate lyase regulation for Dickeya dadantii-unveiling the soft rot pathogen's strategy.
Bacteria respond to environmental changes and adapt to host systems. The response regulator VfmH of the Vfm quorum sensing system regulates a crucial virulence factor, pectate lyase (Pel), in Dickeya dadantii. At high c-di-GMP concentrations, VfmH binds c-di-GMP, resulting in the loss of its activation property in the Pel and virulence regulation in D. dadantii. VfmH binds to c-di-GMP via three conserved arginine residues, and mutations of these residues eliminate the c-di-GMP-related phenotypes of VfmH in Pel synthesis. Our data also show that VfmH interacts with CRP to regulate pelD transcription, thus integrating cyclic AMP and c-di-GMP signaling pathways to control virulence in D. dadantii. We propose that VfmH is an important intermediate factor incorporating quorum sensing and nucleotide signaling pathways for the collective regulation of D. dadantii pathogenesis.


Protein-losing enteropathy after the Fontan operation.
Patients were observed after the Fontan operation to determine the frequency and severity of protein-losing enteropathy. A total of 427 patients who survived for 30 days after the Fontan operation, performed between 1973 and January 1987, were analyzed and, thus far, protein-losing enteropathy has developed in 47 of 427. The cumulative risk for the development of protein-losing enteropathy by 10 years was 13.4% among 30-day survivors, and 5-year survival after the diagnosis was 46%. Hemodynamic studies done coincident with the diagnosis of protein-losing enteropathy have shown increased systemic venous pressure, decreased cardiac index, increased pulmonary vascular resistance, and increased ventricular end-diastolic pressure. Medical management of protein-losing enteropathy was only partially successful. Statistical analysis has shown that factors related to protein-losing enteropathy were ventricular anatomy, increased preoperative ventricular end-diastolic pressure, longer operative bypass time, increased length of hospital stay, and postoperative renal failure. This study suggests that scrupulous selection of cases for the Fontan operation is mandatory and that certain perioperative factors may predispose to this serious complication of the Fontan procedure.


Temperature statistics in two-dimensional stably stratified turbulence.
Using two-dimensional direct numerical simulations, the statistics of temperature differences in stably stratified turbulence are studied. Comparison with passive scalar statistics in similar flows suggests that the stably stratified case is qualitatively similar to the passive case. Probability distribution functions of temperature differences between points separated by different distances collapse using the same scalings in both passive scalar and stably stratified simulations. Some dependence on stratification strength is evident, but the qualitative similarity may be due to the dominance of the large-scale flow in determining the temperature statistics. We also explore the stratification dependence of the statistics of temperature values and gradients.


Protamine sulfate-nanodiamond hybrid nanoparticles as a vector for MiR-203 restoration in esophageal carcinoma cells.
We report an innovative approach for miRNA-203 delivery in esophageal cancer cells using protamine sulphate (PS)-nanodiamond (ND) nanoparticles. The efficient delivery of miR-203 significantly suppressed the proliferation and migration of cancer cells through targeting Ran and ΔNp63, exhibiting a great potential for PS@ND nanoparticles in miRNA-based cancer therapy.


CYP2A6 is associated with obesity: studies in human samples and a high fat diet mouse model.
CYP2A6 (CYP2A5 in mice) is mainly expressed in the liver. Hepatic CYP2A6 expression is increased in patients with non-alcoholic fatty liver disease (NAFLD). In mice, hepatic CYP2A5 is induced by high fat diet (HFD) feeding. Hepatic CYP2A5 is also increased in monosodium glutamate-induced obese mice. NAFLD is associated with obesity. In this study, we examined whether obesity is related to CYP2A6. Obesity genetic association study: The SAGE is a comprehensive genome-wide association study (GWAS) with case subjects having a lifetime history of alcohol dependence and control subjects never addicted to alcohol. We used 1030 control individuals with self-reported height and weight. A total of 12 single nucleotide polymorphisms (SNP) within the CYP2A6 gene were available. Obesity was determined as a BMI ≥30: 30-34.9 (Class I obesity) and ≥35 (Class II and III obesity). Animal experiment study: CYP2A5 knockout (cyp2a5-/-) mice and wild type (cyp2a5+/+) mice were fed HFD for 14 weeks. Body weight was measured weekly. After an overnight fast, the mice were sacrificed. Liver and blood were collected for biochemical assays. Single marker analysis showed that three SNPs (rs8192729, rs7256108, and rs7255443) were associated with class I obesity (p < 0.05). The most significant SNP for obesity was rs8192729 (odds ratio (OR) = 1.94, 95% confidence intervals = 1.21-3.10, p = 0.00582). After HFD feeding, body weight was increased in cyp2a5-/- mice to a greater extent than in cyp2a5+/+ mice, and fatty liver was more pronounced in cyp2a5-/- mice than in cyp2a5+/+ mice. PPARα deficiency in cyp2a5-/- mice developed more severe fatty liver, but body weight was not increased significantly. CYP2A6 is associated with human obesity; CYP2A5 protects against obesity and NAFLD in mice. PPARα contributes to the CYP2A5 protective effects on fatty liver but it opposes to the protective effects on obesity.


A myxoid neurothekeoma of the nose.
Neurothekeoma is a rare neoplasm assigned to the broad category of benign peripheral nerve sheath tumors. Its cell of origin is still unknown, but most ultrastructural and immunohistochemical studies have favoured the Schwann cell perineurium or fibroblast. Neurothekeoma most commonly presents in females, especially in the second and third decades of life. Typically it presents as an asymptomatic solitary, firm, flesh-coloured or hyperpigmented slow-growing papule or nodule that involves the skin and superficial subcutis. It usually involves the face, neck, arm or shoulder but can also involve extracutaneous sites. Neurothekeoma occurs in myxoid (classic), cellular and intermediate (mixed) variants. Here, we report a 45-year-old male patient presenting with a nodule on the nose that was found to be a myxoid variant of neurothekeoma. It was treated with a simple shave excision followed by removal of the lobulated deeper part by forceps. He had no recurrence after three years of follow-up. To the best of our knowledge, this is the first case of a myxoid neurothekeoma of the nose to be reported in the Middle East.


Properties of synchronous and asynchronous release during pulse train depression in cultured hippocampal neurons.
Neurotransmitter release displays at least two kinetically distinct components in response to a single action potential. The majority of release occurs synchronously with action-potential-triggered Ca(2+) influx; however, delayed release--also called asynchronous release--persists for tens of milliseconds following the peak Ca(2+) transient. In response to trains of action potentials, synchronous release eventually declines, whereas asynchronous release often progressively increases, an effect that is primarily attributed to the buildup of intracellular Ca(2+) during repetitive stimulation. The precise relationship between synchronous and asynchronous release remains unclear at central synapses. To gain better insight into the mechanisms that regulate neurotransmitter release, we systematically characterized the two components of release during repetitive stimulation at excitatory autaptic hippocampal synapses formed in culture. Manipulations that increase the Ca(2+) influx triggered by an action potential--elevation of extracellular Ca(2+) or bath application of tetraethylammonium (TEA)--accelerated the progressive decrease in synchronous release (peak excitatory postsynaptic current amplitude) and concomitantly increased asynchronous release. When intracellular Ca(2+) was buffered by extracellular application of EGTA-AM, initial depression of synchronous release was equal to or greater than control; however, it quickly reached a plateau without further depression. In contrast, asynchronous release was largely abolished in EGTA-AM. The total charge transfer following each pulse--accounting for both synchronous and asynchronous release--reached a steady-state level that was similar between control and EGTA-AM. A portion of the decreased synchronous release in control conditions therefore was matched by a higher level of asynchronous release. We also examined the relative changes in synchronous and asynchronous release during repetitive stimulation under conditions that highly favor asynchronous release by substituting extracellular Ca(2+) with Sr(2+). Initially, asynchronous release was twofold greater in Sr(2+). By the end of the train, the difference was approximately 50%; consequently, the total release per pulse during the plateau phase was slightly larger in Sr(2+) compared with Ca(2+). We thus conclude that while asynchronous release--like synchronous release--is limited by vesicle availability, it may be able to access a slightly larger subset of the readily releasable pool. Our results are consistent with the view that during repetitive stimulation, the elevation of asynchronous release depletes the vesicles immediately available for release, resulting in depression of synchronous release. This implies that both forms of release share a small pool of immediately releasable vesicles, which is being constantly depleted and refilled during repetitive stimulation.


[Collision tumor consisting in a metastatic adenocarcinoma and follicular lymphoma in the same lymph node. Report of one case].
Collision tumors are defined as the simultaneous presence of two adjacent but histologically distinct tumor types arising in the same organ or site. The occurrence of these tumors is rare. We report a 52 year-old woman with a collision tumor consisting of metastatic adenocarcinoma and follicular lymphoma present in the same lymph node, excised from the left supraclavicular space. The patient died four weeks after the diagnosis was made.


[A study on the diagnostic criteria for adult acute myeloid leukemia with morphology, immunology and cytogenetics].
This study was undertaken to establish the more reasonable criteria for diagnosis of acute myeloid leukemia (AML). 82 cases diagnosed initially or finally as AML were analyzed with morphology, immunology and cytogenetics (MIC). The results revealed that 89.0% of the pretherapy morphology conformed to MIC and 93.9% of the immunology conformed to it. 4 cases with hybrid acute leukemia (HAL), one case with acute undifferentiated leukemia (AUL) and one case with acute B-Acute lymphocytic leukemia were confirmed with MIC. The positive expression of myeloid markers on samples from 76 cases of AML was followed by CD33 > CD13 > CD65, SI6 > CD15 > CD11b > CD14, but not specific for AML subtypes. The lymphoid antigens CD2, CD7, CD10 and CD19 were positive in minority of the cases of AML, but CD2+ and CD7+ were easily found in M3 and M1 speerately. 55.4% of the patients with AML in this group showed abnormality in cytogenetics. Typical t(8;21) or its variants was found in 14/24 cases of M2 and one case of M1; t(7;11) (P15;P15) in one case of M2; t(15;17) in 4/7 cases of M3; and inv(16) in one case of M4E0. It is shown that MIC classificassion is more helpful than any signgle one of the three in diagnosis of AML, especially of HAL, AUL, Mo.


Balance Expertise Is Associated with Superior Spatial Perspective-Taking Skills.
Balance training interventions over several months have been shown to improve spatial cognitive functions and to induce structural plasticity in brain regions associated with visual-vestibular self-motion processing. In the present cross-sectional study, we tested whether long-term balance practice is associated with better spatial cognition. To this end, spatial perspective-taking abilities were compared between balance experts (n = 40) practicing sports such as gymnastics, acrobatics or slacklining for at least four hours a week for the last two years, endurance athletes (n = 38) and sedentary healthy individuals (n = 58). The balance group showed better performance in a dynamic balance task compared to both the endurance group and the sedentary group. Furthermore, the balance group outperformed the sedentary group in a spatial perspective-taking task. A regression analysis across all participants revealed a positive association between individual balance performance and spatial perspective-taking abilities. Groups did not differ in executive functions, and individual balance performance did not correlate with executive functions, suggesting a specific association between balance skills and spatial cognition. The results are in line with theories of embodied cognition, assuming that sensorimotor experience shapes cognitive functions.


Dye-Sensitized Solar Cell for Building-Integrated Photovoltaic (BIPV) Applications.
One of the important research directions in the field of photovoltaics is integration with construction. The integration of solar cell systems with a building can reduce installation costs and help optimize the used space. Among the few literature reports on photovoltaic roof tiles, solutions with silicon and thin film solar cells dominate. An interesting solution may be the application of dye-sensitized solar cells. In addition to their interesting properties, they also have aesthetic value. In the classic arrangement, they are constructed using glass with a transparent conductive layer (TCL). This article describes replacing a classic glass counter electrode with an electrode based on a ceramic tile and nickel foil. First, a continuous and homogeneous fluorine-doped tin oxide (FTO) thin film was developed so that the above-mentioned substrate could be applied. The atomization method was used for this purpose. Then, nanocolloidal platinum paste was deposited as a catalytic material using the screen printing method. The electrical parameters of the manufactured DSSCs with and without a counter electrode tile were characterized by measuring their current-voltage characteristics under standard AM 1.5 radiation. A dye-sensitized solar cell integrated with ceramic tiles and nickel foil was produced and displayed an efficiency of over 4%. This solution makes it possible to expand their construction applications. The advantage of this solution is full integration with construction, while simultaneously generating electricity. A dye-sensitized solar cell was built layer-by-layer on a ceramic tile and nickel foil.


Genetic variability and molecular epidemiology of human and simian T cell leukemia/lymphoma virus type I.
In the past few years, numerous investigators have demonstrated that human T cell leukemia/lymphoma virus type I (HTLV-I) possesses a great genetic stability, and recent data indicate that viral amplification via clonal expansion of infected cells, rather than by reverse transcription, could explain this remarkable genetic stability. In parallel, the molecular epidemiology of HTLV-I proviruses showed that the few nucleotide changes observed between isolates were specific for the geographical origin of the patients but not for the type of the associated pathologies (adult T cell leukemia/lymphoma, tropical spastic paraparesis/HTLV-I-associated myelopathy). Thus, based on sequence and/or restriction fragment length polymorphism analysis of more than 250 HTLV-I isolates originating from the main viral endemic areas, three major molecular geographical subtypes (or genotypes) emerged, strongly supported by phylogenetic analysis (high bootstrap values). Each of these genotypes (Cosmopolitan, Central African, and Melanesian) appeared to arise from ancient interspecies transmission between monkeys infected with simian T cell leukemia/lymphoma virus type I and humans. Furthermore, careful sequences analyses indicate that, within (or alongside) these three main genotypes, there are molecular subgroups defined clearly by several specific mutations but not always supported by phylogenetic analyses. Thus in Japan, there is evidence for two ancestral HTLV-I lineages: the classical Cosmopolitan genotype, representing approximately 25% of the HTLV-I present in Japan and clustering in the southern islands; and a related subgroup that we called the Japanese group. Similarly, within the Central African cluster, there are molecular subgroups defined by specific substitutions in either the env or the long terminal repeat. Furthermore, recent data from our laboratory indicate the presence of a new molecular phylogenetic group (fourth genotype) found among inhabitants of Central Africa, particularly in Pygmies. While geographical subtypes vary from 2 to 8% between themselves, HTLV-I quasi-species present within an individual appear to be much lower, with a variability of < 0.5%.


Three-dimensional cell seeding and growth in radial-flow perfusion bioreactor for in vitro tissue reconstruction.
Radial-flow perfusion bioreactor systems have been designed and evaluated to enable direct cell seeding into a three-dimensional (3-D) porous scaffold and subsequent cell culture for in vitro tissue reconstruction. However, one of the limitations of in vitro regeneration is the tissue necrosis that occurs at the central part of the 3-D scaffold. In the present study, tubular poly-L-lactic acid (PLLA) porous scaffolds with an optimized pore size and porosity were prepared by the lyophilization method, and the effect of different perfusion conditions on cell seeding and growth were compared with those of the conventional static culture. The medium flowed radially from the lumen toward the periphery of the tubular scaffolds. It was found that cell seeding under a radial-flow perfusion condition of 1.1 mL/cm2 x min was effective, and that the optimal flow rate for cell growth was 4.0 mL/cm2 x min. At this optimal rate, the increase in seeded cells in the perfusion culture over a period of 5 days was 7.3-fold greater than that by static culture over the same period. The perfusion cell seeding resulted in a uniform distribution of cells throughout the scaffold. Subsequently, the perfusion of medium and hence the provision of nutrients and oxygen permitted growth and maintenance of the tissue throughout the scaffold. The perfusion seeding/culture system was a much more effective strategy than the conventional system in which cells are seeded under a static condition and cultured in a bioreactor such as a spinner flask.


Vehicle and Person Re-Identification With Support Neighbor Loss.
One of the key tasks for an intelligent visual surveillance system is to automatically re-identify objects of interest, e.g., persons or vehicles, from nonoverlapping camera views. This demand incurs the vast investigation of person re-identification (re-ID) and vehicle re-ID techniques, especially those deep learning-based ones. While most recent algorithms focus on designing new convolutional neural networks, less attention is paid to the loss functions, which are of vital roles as well. Triplet loss and softmax loss are the two losses that are extensively used, both of which, however, have limitations. Triplet loss optimizes the model to produce features with which samples from the same class have higher similarity than those from different classes. The problem of triplet loss is that the number of triplets to be constructed grows cubically with training samples, which causes scalability issue, unstable performance, and slow convergence. Softmax loss has favorable scalable property and is widely used for large-scale classification problems. However, since Softmax loss only aims to separate well training classes, its performance for re-ID tasks is not desirable because the model is tested to measure the similarity of samples from unseen classes. We propose the support neighbor (SN) loss, which avoids the limitations of the abovementioned two losses. Unlike triplet loss that is calculated based on triplets, SN loss is derived from K -nearest neighbors (SNs) of anchor samples. The SNs of an anchor are unique, containing more valuable contextual information and neighborhood structure of the anchor, and thus contribute to more stable performance and reliable embedding from image space to feature space. Based on the SNs, a softmax-like separation term and a squeeze term are proposed, which encourage interclass separation and intraclass compactness, respectively. Experiments show that SN loss surpasses triplet and softmax losses with the same backbone network and reaches the state-of-the-art performance for both person and vehicle re-ID using a ResNet50 backbone when combined with training tricks.


Conformational stability of human skeletal tropomyosins modified by site-directed mutagenesis.
We have used human beta-tropomyosin produced in Escherichia coli and deletion mutants obtained by site-directed mutagenesis to analyse the conformational stability of this molecule under various experimental conditions. Protein engineering has allowed us to answer some questions raised by stability analysis of the wild-type tropomyosin. The complex pattern of denaturation is due neither to heterogeneity of the preparation nor to head-to-tail interactions. The N- and C-termini are not of importance for the thermal stability of the molecule. On the contrary, deletion of the 31 C-terminus amino acids leads to a dramatic decrease of the stability observed in guanidinium chloride. This lowering is interpreted as the participation of one more guanidinium chloride ions to the denaturation equilibrium. Analysis of the stability in presence of organic solvents reveals that acetonitrile and methanol induce opposite effects. Investigation of these effects by three methods (CD, fluorescence and electrophoresis that measure respectively the content in alpha-helix, the contact between the two strands and the strands exchange) leads to the conclusion that strand separation can precede the denaturation of the alpha-helix.


Effects of dehydroepiandrosterone vs androstenedione supplementation in men.
The purpose of this study was to compare the effects of short-term (12 wk) supplementation with androstenedione versus dehydroepiandrosterone (DHEA) on body composition, strength, and related hormones in middle-aged men. A randomized, placebo-controlled, double-blind design was used to study 40 healthy, trained (>1 yr weight training) male subjects (mean +/- SD: age 48.1 +/- 3.9 yr; weight 79.8 +/- 9.8 kg). Subjects were randomly assigned to one of three groups: placebo (P), DHEA (D), or androstenedione (A). Supplements (50 mg capsules) were ingested two times daily for 12 wk. All testing, including venous blood samples, body composition, and performance, was conducted at three time points: presupplementation (1 d), at 6 wk, and postsupplementation (12 wk). Despite a small increase in lean body mass (0.8 +/- 0.4 and 0.5 +/- 0.3 kg) and mean strength (6.8 +/- 2.7 and 5.7 +/- 2.4 kg) in both D and A groups respectively, these changes were not significantly different from P. In D, there was a significantly greater increase in DHEA-S levels than in P (P < 0.05). There were no adverse side effects demonstrated during D or A supplementation including significant changes in PSA, liver function, or lipid levels (P < 0.05). The results of this study suggest that supplementation with 100 mg x d(-1) of either androstenedione or DHEA does not independently elicit a statistically significant increase in lean body mass, strength, or testosterone levels in healthy adult men over a 12-wk period.


Modular Synthesis of Bioreducible Gene Vectors through Polyaddition of N,N'-Dimethylcystamine and Diglycidyl Ethers.
Bioreducible, cationic linear poly(amino ether)s (PAEs) were designed as promising gene vectors. These polymers were synthesized by the reaction of a disulfide-functional monomer, N,N'-dimethylcystamine (DMC), and several different diglycidyl ethers. The resulting PAEs displayed a substantial buffer capacity (up to 64%) in the endosomal acidification region of pH 7.4⁻5.1. The PAEs condense plasmid DNA into 80⁻200 nm sized polyplexes, and have surface charges ranging from +20 to +40 mV. The polyplexes readily release DNA upon exposure to reducing conditions (2.5 mM DTT) due to the cleavage of the disulfide groups that is present in the main chain of the polymers, as was demonstrated by agarose gel electrophoresis. Upon exposing COS-7 cells to polyplexes that were prepared at polymer/DNA w/w ratios below 48, cell viabilities between 80⁻100% were observed, even under serum-free conditions. These polyplexes show comparable or higher transfection efficiencies (up to 38%) compared to 25 kDa branched polyethylenimine (PEI) polyplexes (12% under serum-free conditions). Moreover, the PAE-based polyplexes yield transfection efficiencies as high as 32% in serum-containing medium, which makes these polymers interesting for gene delivery applications.


Serum interleukin-15 levels are associated with severity of pain in patients with knee osteoarthritis.
Inflammation plays a crucial role in the development and progression of osteoarthritis (OA). Interleukin-15 (IL-15) is a well-known proinflammatory cytokine. We aimed at evaluating the relationship between serum IL-15 levels and the severity of pain as well as radiographic progression in patients with knee OA. Two hundred and twenty-six OA patients and 106 controls were enrolled in this study. The symptomatic/radiological severity of OA was assessed by the Western Ontario McMaster University Osteoarthritis Index- (WOMAC-)pain scores/Kellgren-Lawrence (KL) grading system. Serum IL-15 levels were measured by enzyme-linked immunosorbent assay (ELISA). Serum IL-15 levels were significantly higher in OA patients compared with controls. Serum IL-15 levels were independently and positively correlated with WOMAC-pain scores but not KL grades in OA patients. We demonstrated that increased serum IL-15 levels were independently correlated with self-reported greater pain in knee OA patients. These results suggest that IL-15 might play a crucial role in the pathogenesis of OA related pain and therapeutic interventions by blocking IL-15 signaling pathways to delay the degenerative process of OA related pain which warrants further investigations.


Heat shock causes destabilization of specific mRNAs and destruction of endoplasmic reticulum in barley aleurone cells.
In response to a phytohormone, gibberellic acid, the aleurone layers of barley seeds synthesize and secrete alpha-amylases, which are coded by a set of stable mRNAs. When aleurone layers are subjected to heat shock treatment, the synthesis of alpha-amylase is suppressed while heat shock proteins are induced. The suppression of alpha-amylase synthesis is not the result of translational control as reported in several other systems. Rather, the sequences of alpha-amylase mRNA are rapidly degraded during heat shock as shown by in vitro translation and dot blot hybridization with a cDNA probe. Upon recovery from heat shock, the tissue resumes the synthesis of alpha-amylase in 2-4 hr. However, in the presence of a transcription inhibitor, cordycepin, the resumption of synthesis of alpha-amylase does not take place, indicating that new transcription of alpha-amylase genes is necessary for this recovery process. The degradation of alpha-amylase mRNAs correlates with the rapid destruction of endoplasmic reticulum as observed by electron microscopy, a phenomenon that has not been reported previously as a heat shock response. Since alpha-amylase mRNA is associated with the endoplasmic reticulum via membrane-bound polyribosomes, we suggest that the destruction of the endoplasmic reticulum during heat shock causes the destabilization and the eventual degradation of alpha-amylase mRNA.


Engineering a Cortisol Sensing Enteric Probiotic.
Chronic stress can lead to prolonged adrenal gland secretion of cortisol, resulting in human ailments such as anxiety, post-traumatic stress disorder, metabolic syndrome, diabetes, immunosuppression, and cardiomyopathy. Real time monitoring of chronic increases in cortisol and intervening therapies to minimize the physiological effects of stress would be beneficial to prevent these endocrine related illnesses. Gut microbiota have shown the ability to secrete, respond, and even regulate endocrine hormones. One such microbe, Clostridium scindens, responds transcriptionally to cortisol. We engineered these cortisol responsive genetic elements from C. scindens into an enteric probiotic, E. coli Nissle 1917, to drive the expression of a fluorescent reporter allowing for the designing, testing, and building of a robust and physiologically relevant novel cortisol probiotic sensor. This smart probiotic was further engineered to be more sensitive and to respond to elevated cortisol by expressing tryptophan decarboxylase, thereby bestowing the ability to generate tryptamine and serotonin. Here we show that upon cortisol treatment the smart probiotic produces measurable amounts of tryptamine. Accumulated levels of these neuromodulators should improve mood, anxiety, and depression and drive down cortisol levels. Importantly, this work can serve as a model for the engineering of a sense-and-respond probiotic to modulate the gut-brain axis.


The effect of six polishing systems on the surface roughness of two packable resin-based composites.
To evaluate the surface roughness of two packable composites after finishing and polishing with six different systems. Solitaire and Alert composite samples were prepared and polished with Poli I and Poli II aluminum oxide pastes, Ultralap diamond paste, Enhance finishing points, Politip rubber polishers, fine and extra fine diamond burs, and 30-blade tungsten carbide burs according to the manufacturers' instructions. The polished surfaces were then evaluated with a profilometer and a scanning electron microscope. Solitaire composite resin presented the smoothest surfaces when polished with Poli I and II aluminum oxide pastes, Ultralap diamond paste, Politip finishing points and 30-blade tungsten carbide burs. The smoothest surfaces for Alert composite were evident with the 30-blade tungsten carbide burs.


Teaching psychiatric residents about women and leadership.
The purpose of this project was to develop a seminar on women as leaders within an academic department of psychiatry and to evaluate its effectiveness. A seminar was offered as an elective to all residents within the Yale University Department of Psychiatry. Didactic presentations and open discussion were structured around the following topics: 1) exploration of leadership roles in various areas, including research, clinical practice, teaching, and administration; 2) organizational dynamics and gender; 3) negotiation skills and conflict resolution strategies; 4) role of consultation, seminars, peer support and mentoring by both men and women in the development of leadership skills; and 5) "keeping the balance: work, relationships, and personal health." The 13 participants were queried at the completion of the seminar, and a follow-up survey was performed 18 months later. The initial and follow-up evaluations were quite positive, with average ratings in the "excellent" range at both points. The 10 respondents at 18 months were unanimous that there had been a positive and lasting effect on their professional lives. A seminar on women as leaders was a successful venture within an academic department of psychiatry. The structure of the course, which incorporated specific teaching materials plus "local" expertise, could serve as a model for such seminars in other programs or could be integrated into an existing course for all residents.


Assessing effects of diet alteration on selected parameters of chronically mentally ill residents of a 24-hour Nursing Home. Part I: Effects of diet modification on carbohydrate-lipid metabolism.
The study was aimed at finding out whether, and to what extent, it is possible to introduce and maintain proper nutrition habits in chronically mentally ill residents of a24-hour Nursing Home. The study involved 52 residents of a 24-hour Nursing Home (NH) for the chronically mentally ill. The study was carried out with a prospective method using questionnaires, nutrition-related interviews, anthropometric measurements, and analysis of selected blood biochemical indicators. Diet modification, accompanied by simultaneous health-promoting nutrition-related education, involved balancing the energy and nutrient contents, with adue consideration to gender and age as well as the major ailment and the accompanying disorders. Sources of the basic nutrients, i.e., proteins, carbohydrates and lipids, were replaced by recommended and/or health-promoting ones. Both female and male patients showed a statistically significant reduction in energy uptake, resulting primarily from a significant reduction in the uptake of lipids and simple carbohydrates. Changes in nutritional habits were reflected in statistically significant increase in the uptake of vitamins, minerals and liquids (in the form of water). Diet composition modifications translated into beneficial changes in concentrations of glucose, triacylglycerols, cholesterol (total as well as HDL and LDL fractions) in numerous patients examined. The study showed chronic mental patients to be capable of adopting, with full acceptance and cooperation, proper nutritional habits. Changes in those habits were reflected in improved body functions, including carbohydrate-lipid metabolism indicators, also in schizophrenia patients treated with antipsychotics.


Inhibition of the IKK/NF-κB pathway by AAV gene transfer improves muscle regeneration in older mdx mice.
The IκB kinase (IKKα, β and the regulatory subunit IKKγ) complex regulates nuclear factor of κB (NF-κB) transcriptional activity, which is upregulated in many chronic inflammatory diseases. NF-κB signaling promotes inflammation and limits muscle regeneration in Duchenne muscular dystrophy (DMD), resulting in fibrotic and fatty tissue replacement of muscle that exacerbates the wasting process in dystrophic muscles. Here, we examined whether dominant-negative forms of IKKα (IKKα-dn) and IKKβ (IKKβ-dn) delivered by adeno-associated viral (AAV) vectors to the gastrocnemius (GAS) and tibialis anterior (TA) muscles of 1, 2 and 11-month-old mdx mice, a murine DMD model, block NF-κB activation and increase muscle regeneration. At 1 month post-treatment, the levels of nuclear NF-κB in locally treated muscle were decreased by gene transfer with either AAV-CMV-IKKα-dn or AAV-CMV-IKKβ-dn, but not by IKK wild-type controls (IKKα and β) or phosphate-buffered saline (PBS). Although treatment with AAV-IKKα-dn or AAV-IKKβ-dn vectors had no significant effect on muscle regeneration in young mdx mice treated at 1 and 2 months of age and collected 1 month later, treatment of old (11 months) mdx with AAV-CMV-IKKα-dn or AAV-CMV-IKKβ-dn significantly increased levels of muscle regeneration. In addition, there was a significant decrease in myofiber necrosis in the AAV-IKKα-dn- and AAV-IKKβ-dn-treated mdx muscle in both young and old mice. These results demonstrate that inhibition of IKKα or IKKβ in dystrophic muscle reduces the adverse effects of NF-κB signaling, resulting in a therapeutic effect. Moreover, these results clearly demonstrate the therapeutic benefits of inhibiting NF-κB activation by AAV gene transfer in dystrophic muscle to promote regeneration, particularly in older mdx mice, and block necrosis.


Foreign-body reaction to the bioabsorbable suretac device.
Arthroscopic shoulder stabilization with the bioabsorbable Suretac device (Acufex Microsurgical, Mansfield, MA) offers some technical advantages compared with other approaches. However, in 4 patients (3 men, 1 woman; between 20 and 35 years of age) with 3 SLAP lesions grades 2 and 1 post-traumatic anterior shoulder instability, breakage and early loosening of the Suretac device was observed. All patients complained about shoulder pain and loss of active and passive motion. The arthroscopic examination revealed a massive synovitis without positive cultures. Loose fragments of the Suretac device spread in the joint cavity and induced a foreign-body reaction. Histologically, there was a massive infiltration of phagocytic cells (histiocytes, multinucleated giant cells) and birefringent polymeric particles surrounded by or within histiocytes and multinucleated giant cells. All patients underwent arthroscopic synovectomy. Because of instability, 2 of them required restabilization, which was performed with suture anchors (Fastak [Arthrex, Naples, FL], Mitek [Mitek Division, Ethicon, Norderstedt, Germany]). Postoperatively all patients were pain free, progressing to full active and passive range of motion. Our patients suffered from a mechanical failure rather than from a predisposition to exaggerated inflammatory response. According to this observation, the Suretac device seems to be prone to early failure in patients with SLAP lesions because of its biodegradability.


Development of a novel diagnostic test for detection of bovine viral diarrhea persistently infected animals using hair.
The purpose of this study was to determine whether manually plucked hairs might serve as an alternative sample for a quantitative real time polymerase chain reaction (qRT-PCR) testing. Twenty three, 1~3 week old, non-bovine viral diarrhea virus (BVDV) vaccinated calves, found to be positive for BVDV by immunohistochemical staining, were selected and hairs were manually plucked from the ear. qRT-PCR was performed on samples consisting of more than 30 hairs (30~100) and whole blood. All 23 animals were positive for the virus by qRT-PCR performed on the whole blood and when samples of more than 30 hairs were assayed. Additionally, qRT-PCR was performed on groups of 10 and 20 hairs harvested from 7 out of 23 immunohistochemical staining-positive calves. When groups of 20 and 10 hairs were tested, 6 and 4 animals, respectively, were positive for the virus.


In vivo evaluation of an antibacterial coating containing halogenated furanone compound-loaded poly(l-lactic acid) nanoparticles on microarc-oxidized titanium implants.
To prevent peri-implant infection, a new antibacterial coating containing a halogenated furanone compound, (Z-)-4-bromo-5-(bromomethylene)-2(5H)-furanone-loaded poly(l-lactic acid) nanoparticles, has been fabricated. The current study was designed to evaluate the preventive effect of the antibacterial coating under a simulated environment of peri-implant infection in vivo. Microarc-oxidized titanium implants treated with minocycline hydrochloride ointment were used as positive control group, and microarc-oxidized titanium implants without any treatment were used as blank control group. Three kinds of implants were implanted in dogs' mandibles, and the peri-implant infection was simulated by silk ligation and feeding high sugar diet. After 2-month implantation, the results showed that no significant differences were detected between the experimental and positive control groups (P>0.05), but the data of clinical measurements of the blank control group were significantly higher than those of the other two groups (P<0.05), and the bone-implant contact rate and ultimate interfacial strength were significantly lower than those of the other two groups (P<0.05). Scanning electron microscope observation and histological examination showed that more new bone was formed on the surface of the experimental and positive control groups. It can be concluded that the antibacterial coating fabricated on implants has remarkable preventive effect on peri-implant infection at the early stage.


BTBD10 inhibits glioma tumorigenesis by downregulating cyclin D1 and p-Akt.
The aim of this study was to investigate the role of BTBD10 in glioma tumorigenesis. The mRNA and protein levels of BTBD10 in 52 glioma tissues and eight normal brain tissues were determined using reverse transcription polymerase chain reaction (RT-PCR) and western blot analysis, respectively. U251 human glioblastoma cells were infected with BTBD10-expressing or control lentiviruses. Cell growth was evaluated using the methyl thiazolyl tetrazolium (MTT) assay. Cell apoptosis and cell cycle distribution were analyzed using flow cytometry. Cyclin D1 and p-Akt levels were determined using western blot analysis. The results showed that BTBD10 mRNA and protein levels were significantly lower in glioma tissues than in normal brain tissues. Additionally, BTBD10 levels were significantly lower in high-grade gliomas than in low-grade tumors. Compared with control cells, U251 cells overexpressing BTBD10 exhibited decreased cell proliferation, increased cell accumulation at the G0/G1 phase, increased cell apoptosis, and decreased levels of cyclin D1 and p-Akt. These findings show that BTBD10 is downregulated in human glioma tissue and that BTBD10 expression negatively correlates with the pathological grade of the tumor. Furthermore, BTBD10 overexpression inhibits proliferation, induces G0/G1 arrest, and promotes apoptosis in human glioblastoma cells by downregulating cyclin D1- and Akt-dependent signaling pathways.


Idiopathic Retroperitoneal Hematoma with Spontaneous Resolution.
A 54-year-old man was transferred from another hospital due to a hematoma in the third portion of the duodenum on abdomen CT. He had been admitted for 2 weeks due to vomiting at another hospital. He had abdominal discomfort and nausea without abdominal pain when he visited the Gwangyang Sarang Hospital. Other than a distended abdomen and mild general abdominal tenderness, the results of physical examination were unremarkable. Abdominal CT revealed an approximately 9 cm thick walled hematoma at the anteroinferior site of the duodenal third portion. Upper endoscopy revealed stenosis of the third portion of the duodenum without mucosal lesions. The endoscope was not advanced through the narrowed duodenal lumen. A retroperitoneal hematoma was diagnosed, and his state was classified as subacute rather than acute based on the duration. The surgeon did not recommend surgical treatment. Urgent treatment was unnecessary; he was managed conservatively. The size of the hematoma decreased from 9.0 cm to 5.8 cm on the following CT. He could begin to eat food on the 26th admission day, and he was discharged on the 31st admission day. The hematoma disappeared entirely on the following CT. This paper describes a rare case of idiopathic retroperitoneal hematoma with a spontaneous resolution.