Emotion regulation and tic disorders in children.

Tic disorders (TD) are developmental neuropsychiatric conditions often accompanied by comorbid conditions, and psychosocial hardships for child and family. The etiology of tics is unknown, and is complex and multifactorial. Stress is known to aggravate tic expression as well as associated comorbidities. Consequently, this study focused on possible connections between stress, emotion regulation, tic expression, and related psychopathology. Sixty consecutive admissions were assessed for perceived stress, emotional dysregulation, severity of obsessions and compulsions, anxiety, depression, attention deficit disorder, and tic expression at a TD clinic, in a university affiliated pediatric hospital. The results indicated that stress and emotion dysregulation were significantly related to both tic expression and severity of comorbidities. We discuss the role of emotion regulation dimensions regarding TD and related psychopathology as well as the mediating role of emotion regulation, and how they may contribute to the development of improved therapies for children with TD.

Role of Mechanotransduction in Periodontal Homeostasis and Disease.

Novel findings broaden the concept of mechanotransduction (MT) in biophysically stimulated tissues such as the periodontium by considering nuclear MT, convergence of intracellular MT pathways, and mechanoresponsive cotranscription factors such as Yes-associated protein 1 (YAP1). Regarding periodontal disease, recent studies have elucidated the role of bacterial gingipain proteases in disturbing the barrier function of cadherins, thereby promoting periodontal inflammation. This leads to dysregulation of extracellular matrix homeostasis via proteases and changes the cell's biophysical environment, which leads to alterations in MT-induced cell behavior and loss of periodontal integrity. Newest experimental evidence from periodontal ligament cells suggests that the Hippo signaling protein YAP1, in addition to integrin-FAK (focal adhesion kinase) mechanosignaling, also regulates cell stemness. By addressing mechanosignaling-dependent transcription factors, YAP1 is involved in osteogenic and myofibroblast differentiation and influences core steps of autophagy. Recent in vivo evidence elucidates the decisive role of YAP1 in epithelial homeostasis and underlines its impact on oral pathologies, such as periodontitis-linked oral squamous cell carcinogenesis. Here, new insights reveal that YAP1 contributes to carcinogenesis via overexpression rather than mutation; promotes processes such as apoptosis resistance, epithelial-mesenchymal transition, or metastasis; and correlates with poor prognosis in oral squamous cell carcinoma. Furthermore, YAP1 has been shown to contribute to periodontitis-induced bone loss. Mechanistically, molecules identified to regulate YAP1-related periodontal homeostasis and disease include cellular key players such as MAPK (mitogen-activated protein kinase), JNK (c-Jun N-terminal kinase), Rho (Ras homologue) and ROCK (Rho kinase), Bcl-2 (B-cell lymphoma 2), AP-1 (activator protein 1), and c-myc (cellular myelocytomatosis). These findings qualify YAP1 as a master regulator of mechanobiology and cell behavior in human periodontal tissues. This review summarizes the most recent developments in MT-related periodontal research, thereby offering insights into outstanding research questions and potential applications of molecular or biophysical strategies aiming at periodontal disease mitigation or prevention.

Internal fixation of proximal fractures of the 2nd and 4th metacarpal and metatarsal bones using bioabsorbable screws.

OBJECTIVE: Fractures involving the proximal one-third of the splint bone are relatively rare and are challenging to treat. A variety of management techniques have been reported in the literature. The aim of this retrospective case series was to describe the clinical presentation and evaluate the efficacy of bioabsorbable polylactic acid screws in internal fixation of proximal fractures of the 2nd and 4th metacarpal and metatarsal bones in horses. METHODS: The medical records, diagnostic images and outcome of all horses diagnosed with a proximal fracture of the splint bones and treated with partial resection and internal fixation of the proximal stump using bioabsorbable polylactic acid screws between 2014 and 2015 were reviewed. RESULTS: Eight horses met the inclusion criteria. The results showed that there were no complications encountered during screw placement or postoperatively. Six horses returned to full work 3 months after the operation and two horses remained mildly lame. On follow-up radiographs 12 months postoperatively (n = 2) the screws were not completely absorbed. The screws resulted in a cone-shaped radiolucency, which was progressively replaced from the outer margins by bone sclerosis. CONCLUSION: The use of bioabsorbable screws for fixation of proximal fractures of the splint bone appears to be a safe and feasible technique and may offer several advantages over the use of traditional metallic implants.

The effects of various mixing solutions on the biocompatibility of mineral trioxide aggregate.

AIM: To evaluate the effects of various mixing solutions on the biocompatibility of mineral trioxide aggregate (MTA). METHODOLOGY: Human alveolar osteoblasts (hOAs) were incubated with eluates of 24 h-set cement discs of MTA mixed with sterile H2 O, 3% sodium hypochlorite (NaOCl), 4% articaine (Ultracain(®) D-S), 0.9% NaCl, Ringer's solution or citrated blood, respectively. The cell proliferation in the presence of eluates was assessed by real-time cell analysis, and the expression of genes associated with proliferation (histone H3, HistH3), inflammation (interleukin-6, IL-6, matrix metalloproteinases 1 and 3, MMP1, MMP3) or apoptosis (caspase 3, Casp3) was analysed by qPCR after 24 and 72 h. The ultrastructure of cells grown on cement discs was visualized by scanning electron microscopy (SEM), whilst actin cytoskeleton was monitored by fluorescence staining in the presence of eluates after 7 and 14 days. A repeated-measure analysis was performed, and P-values were adjusted by Tukey. RESULTS: Whilst articaine-MTA sustained hOA proliferation patterns similar to H2 O-MTA, NaOCl-MTA reduced hOA proliferation and significantly increased the expression of MMP1 and MMP3. The addition of H2 O and articaine modulated the gene expression of Casp3 or Hist3H3. The use of NaCl, Ringer and blood induced mRNA levels comparable to matched controls. With the exception of NaOCl-MTA, SEM and FM revealed regular hOA morphology for all mixing solutions. CONCLUSIONS: NaOCl was highly cytotoxic for hOAs whilst all other mixing solutions can be considered as convenient biocompatible mixing solutions as alternatives to H2 O for clinical use.

Effect of ultraviolet photofunctionalisation on the cell attractiveness of zirconia implant materials.

Ultraviolet (UV) light treatment of implant surfaces has been demonstrated to enhance their bioactivity significantly. This study examined the effect of UV treatment of different zirconia surfaces on the response of primary human alveolar bone-derived osteoblasts (PhABO). Disks of two zirconia-based materials with two different surface topographies (smooth, roughened) were exposed to UV light. Qualitative and quantitative assessment of PhABO on zirconia surfaces, by means of immunofluorescence, scanning electron microscopy and DNA quantification at 4 and 24 h revealed a higher number of initially attached osteoblasts on UV-treated surfaces. Cell area and perimeter were significantly larger on all UV-treated surfaces (p<0.05). The proliferation activity was significantly higher on both roughened UV-treated surfaces than on untreated samples at day 3 of culture (p<0.05). The expression levels of collagen I, osteopontin and osteocalcin at day 14 and alkaline phosphatase activity at day 7 and 14 of culture period were similar among UV-treated and untreated surfaces. Alizarin-Red-Staining at day 21 demonstrated significantly more mineralised nodules on UV-treated samples than on untreated samples. Contact angle measurements and X-ray photoelectron spectroscopy showed that UV light transformed zirconia surfaces from hydrophobic to (super-) hydrophilic (p<0.05) and significantly reduced the atomic percentage of surface carbon. The results showed that UV light pre-treatment of zirconia surfaces changes their physicochemical properties and improves their attractiveness against PhABO, primarily demonstrated by an augmented cell attachment and spreading. This may result in faster healing and better bone-to-implant contact of zirconia implants in vivo following such a pre-treatment.

Disturbances of basic self and prodromal symptoms among non-psychotic help-seeking adolescents.

BACKGROUND: The goal of this study was to explore the notion that anomalies of self-experience (ASE) are a core, 'not-yet-psychotic' clinical phenotype of emerging schizophrenia and its spectrum. Method To accomplish this goal, we examined the relationship between ASE and commonly accepted risk markers in a sample of 87 help-seeking, non-psychotic adolescents (aged 14-18 years). ASE were assessed with the Examination of Anomalous Self-Experience (EASE), subclinical psychotic symptoms were assessed with the Prodromal Questionnaire and the Structured Interview for Prodromal Syndromes, deterioration in psychosocial functioning was assessed with the Social and Role Functioning Scales, and level of distress with the Mood and Anxiety Symptoms Questionnaire. RESULTS: About 82 participants completed the entire EASE interview. The number of participants who reported ASE at a clinically meaningful level (n = 18, 22%) was smaller than that who met diagnostic criteria for a prodromal syndrome (n = 28, 34%). The degree of overlap between the two conditions was moderate but statistically significant (χ2 (1) = 7.01, p = 0.008). An exploratory factor analysis revealed that ASE load on a different factor than prodromal symptoms and deterioration in functioning, but that there is a moderate correlation between the three factors. CONCLUSIONS: These results suggest that ASE are prevalent among non-psychotic help-seeking adolescents, yet at a considerably lower rate than prodromal symptoms. In addition, they suggest that ASE and prodromal symptoms constitute distinct but moderately related dimensions of potential risk. Taken together, they provide preliminary support for the clinical usefulness of supplementing and refining the methods of early detection of risk with assessment of ASE.

Environmental biomechanics substantiated by defined pillar micropatterns govern behavior of human mesenchymal stem cells.

While evidence on the impact of the biomechanical environment elasticity on human mesenchymal stem cell (hMSC) behavior is growing, the aspect of micropatterning is still poorly understood. Thus, the present study aimed at investigating the influence of defined environmental micropatterning on hMSC behavior. Following characterization, hMSCs were grown on defined pillar micropatterns of 5, 7, 9, and 11 µm. With respect to cell behavior, primary hMSC adhesion was detected by indirect immunofluorescence (iIF) for paxillin, vinculin, integrin αV, and actin, while proliferation was visualized by histone H3. Morphogenesis was monitored by scanning electron microscopy and the expression of stem cell-specific biomarkers by real-time PCR. Favoritism of primary adhesion of hMSCs on pillar tops occurred at smaller pillar micropatterns, concomitant with cell flattening. While vinculin, integrin αV, and paxillin appeared initially more cytoplasmic, high pillar micropatterns favored a progressive redistribution with polarization to cell tension sites and at cell borders. Accomplishment of morphogenesis at day 3 revealed establishment of fully rotund cell somata at 5 µm, while hMSCs appeared progressively elongated at rising micropatterns. The hMSC proliferation capacity was influenced by pillar micropatterns and gene expression analysis of stem cell- and differentiation-associated biomarkers disclosed clear modulation by distinct pillar micropatterns. In response to environmental biomechanics, our results show that hMSC behavior is governed by pillar micropatterning. In turn, these findings may form the basis to prospectively direct lineage specificity of hMSCs in a customized fashion.

Canine status epilepticus due to acute intoxication.

OBJECTIVES: The purpose of this study was to describe the type of toxin ingested, clinical presentation and outcome of dogs with status epilepticus (SE) due to acute poisoning presented to a large referral veterinary hospital. MATERIALS AND METHODS: Retrospective case series. Medical records of all dogs suffering from SE were reviewed (Jan 1, 2002 to April 30, 2009). RESULTS: Fourteen dogs with SE due to acute intoxication were identified. Toxicological analyses (qualitative analysis with gas chromatography/mass spectrometry; n=11) detected poisonings with carbofuran, crimidine, paraoxone, metaldehyde, strychnine and diazinon. In the other three cases the uptake of a known poison was observed (zink phosphide, metaldehyde). None of the dogs showed evidence of neurological disease up to the day of presentation. The dogs were hospitalised for 2-10 days (median 5 days). The survival rate was 85.7%. None of the dogs experienced any more seizures after discharge (median observation period 2.6 years). CONCLUSION AND CLINICAL RELEVANCE: Ancillary to the acute clinical presentation, preliminary reports (possible uptake of poisonous material) and an inconspicuous medical history may suggest a tentative diagnosis. Managed adequately, these patients can have a high survival rate. Clinicians should also keep uncommon intoxications in mind.

Liver transplantation for primary biliary cirrhosis: results of aggressive corticosteroid withdrawal.

INTRODUCTION: A subset of patients with primary biliary cirrhosis (PBC) may require long-term corticosteroid (CS) therapy following liver transplantation (OLT) due to concern over the possibility of recurrence. Our center has attempted to minimize CS use in all of our OLT recipients. In this study, we review our experience in this cohort to determine (1) patient outcome including PBC recurrence following transplantation and (2) the long-term requirement for CS use in PBC patients. METHODS: From 1988 to 2006, 1102 OLTs were performed in 1032 adults at the University of Colorado, of which 70 patients (6.8%) with PBC received 74 allografts. Bivariate and multivariate analyses were used to evaluate predictors of CS withdrawal. Thirteen potential predictors of CS discontinuation were considered: age, gender, body mass index (BMI), race, type of graft (cadaveric or living donor [LD]), recurrence of PBC, warm ischemia time, and immunosuppressant. RESULTS: Overall survival at 5 years was 85%. The 1-, 5-, and 10-year recurrence-free survivals were 90%, 72%, and 54%, respectively. PBC recurred in 18 patients (25.7%). Of these, none received a second transplant due to disease recurrence. At the time of last follow-up, 73% of recipients were steroid free. Independent predictors of CS discontinuation are age (>54; P = .0059) and LD graft type (P = .0008). Conversely, cyclosporine (P = .0007), female gender (P = .0216), and BMI > 31 (P = .0306) were negatively associated with CS withdraw. Importantly, steroid discontinuation did not influence PBC recurrence. CONCLUSIONS: While long-term outcomes in PBC patients are favorable, disease recurrence can generally be managed medically without the need for a second transplant. Using an aggressive CS minimization approach, nearly three-quarters of the patients were CS free at the time of last follow-up. Increasing age and LD grafts were associated with successful CS withdraw. Conversely, cyclosporine use, female gender, and increasing BMI were associated with unsuccessful steroid discontinuation.

Unilateral and bilateral congenital sensorineural deafness in client-owned pure-breed white cats.

BACKGROUND: Congenital sensorineural deafness has been reported frequently in experimental mixed-breed white cats but there is a paucity of data on occurrence of deafness in client-owned pure-breed white cats. OBJECTIVE: To describe hearing status in client-owned pure-breed white cats. ANIMALS: Eighty-four pure-breed client-owned cats with white coat color of 10 registered breeds presented for routine hearing evaluation before breeding (1995-2008). METHODS: Hearing was assessed by click-evoked brainstem auditory evoked response. RESULTS: Overall deafness prevalence was 20.2%; 9 cats (10.7%) were bilaterally deaf and 8 cats (9.5%) were unilaterally deaf. There was no association between sex and deafness status (P= .85). Deafness status was associated with iris color (P= .04). CONCLUSIONS AND CLINICAL IMPORTANCE: Congenital sensorineural deafness frequently occurs in pure-breed cats with white coat color. Unilateral sensorineural deafness was as common as bilateral deafness.

Disseminated angiostrongylosis with fatal cerebral haemorrhages in two dogs in Germany: a clinical case study.

Canine angiostrongylosis is a nematode infection in domestic dogs and wild carnivores. Few single case reports describing the occurrence of this disease in Germany exist and until recently angiostrongylosis has not been considered endemic in this country. The present report focuses on clinical, pathological and parasitological findings in two cases of fatal disseminated canine angiostrongylosis associated with multifocal haemorrhages in the central nervous system. Both animals, which lived in Germany, presented with rapidly progressive neurological signs including depression, ataxia, unilateral central blindness and epileptic seizures. Blood work revealed grossly elevated D-dimers and mild thrombocytopenia. Both animals were subsequently euthanised due to progressive clinical aggravation. Necropsy showed cerebral and lung haemorrhages in both animals. Multiple sections of nematode larvae consistent with Angiostrongylus vasorum were identified on histopathological sections of the brain, heart, kidney and lung in both animals and a predominantly granulomatous inflammation with the occurrence of multinucleated giant cells was observed. Adult nematodes were found in the larger lung arteries of one dog and Angiostrongylus infection was subsequently confirmed by PCR-analysis and sequencing in both dogs. A. vasorum larvae were not detected by faecal Baermann examination performed in one of the dogs. It was concluded that canine angiostrongylosis should be considered as differential diagnosis in dogs in Germany, even if faecal examination is negative. There is currently still a lack of studies investigating the occurrence of angiostrongylosis in dogs and intermediate hosts in Germany which would be necessary to survey the endemic realities of this disease.

Elevation of collagen type I in fibroblast-keratinocyte cocultures emphasizes the decisive role of fibroblasts in the manifestation of the phenotype of cyclosporin A-induced gingival overgrowth.

BACKGROUND AND OBJECTIVE: Collagen type I elevation in cyclosporin A-induced gingival overgrowth supports evidence that gingival fibroblasts play a decisive role in the manifestation of the phenotype. To analyze the role of gingival fibroblasts under more in vivo-like conditions, we evaluated the effect of cyclosporin A on collagen type I gene and protein expression in gingival overgrowth-derived gingival fibroblasts established as cocultures with gingival keratinocytes as well as in matched gingival fibroblast monolayers. MATERIAL AND METHODS: Monolayers and cocultures of primary gingival fibroblasts were treated with cyclosporin A for 6 and 72 h. The expression of collagen type I mRNA was analyzed by quantitative real time polymerase chain reaction, while expression and secretion of collagen type I protein was analyzed by indirect immunofluorescence and western blotting. RESULTS: Compared with controls, significant elevation of collagen type I mRNA was restricted to cocultures after 6 and 72 h of treatment with cyclosporin A. In keratinocytes, collagen type I remained undetectable. In monolayers and cocultures, indirect immunofluorescence showed a slightly higher level of collagen type I protein in gingival fibroblasts in response to stimulation with cyclosporin A. Semiquantitative detection of collagen type I by western blotting demonstrated a nonsignificant increase for cell extracts in monolayers and cocultures. For secreted collagen type I, western blot analysis of the supernatants revealed elevated protein levels in cultures stimulated with cyclosporin A. Compared with the corresponding monolayers, the stimulatory effect of cyclosporin A on protein secretion was significant only in coculture. CONCLUSION: Our results indicate that collagen type I is a target of cyclosporin A and that gingival fibroblasts are decisive for the manifestation of the gingival overgrowth-phenotype. Furthermore, the results suggest that cocultures of gingival overgrowth-derived gingival fibroblasts and gingival keratinocytes permit analysis of cyclosporin A-induced effects under more in vivo-like conditions.

Absence of Pneumocystis jiroveci pneumonia in liver transplantation recipients receiving short-term (3-month) prophylaxis.

UNLABELLED: Pneumocystis jiroveci (formerly known as Pneumocystis carinii) is a fungal pathogen that causes pneumonia (PCP) in liver transplant recipients. Consequently, prophylaxis with trimethoprim-sulfamethoxazole (TMP/SMZ) is typically administered for at least 1 year at most liver transplant programs. At our center we have utilized a short-term (3-month) prophylactic regimen with TMP/SMZ for the past decade and report our experience and speculate on the potential widespread application of this approach. METHODS: For patients transplanted at our center between January 1997 and January 2007, we recorded all documented PCP infections by review of our liver transplant database and hospital-based electronic medical records system, both of which record all infections and culture results. RESULTS: We recorded no cases of PCP in any of the liver transplant recipients at our center during the study period. CONCLUSIONS: We report the absence of PCP in a large cohort of liver transplant recipients receiving a short-term (3-month) prophylaxis with TMP/SMZ. These findings provide a rational basis to consider short-term (3-month) PCP prophylaxis or avoidance of prophylaxis altogether in selected low-risk patients.

Cognition, psychosocial adjustment and coping in familial cases of velocardiofacial syndrome.

Velocardiofacial syndrome (VCFS) is characterized by both physical manifestations and neuropsychiatric disabilities. About 6-28% of cases are familial. The aim of the present study was to compare the clinical characteristics of subjects with familial and nonfamilial VCFS, with a special focus on cognitive and psychiatric disabilities. In addition, the complexities of coping with the disease in families in which both a parent and children are affected were highlighted in case vignettes. Sixteen patients from six families with VCFS were compared to 63 subjects with nonfamilial VCFS for physical parameters, IQ, and rate of major psychiatric disorders. After controlling for the effect of age, IQ was significantly lower in the familial compared to the nonfamilial group of VCFS patients. Rate of psychiatric disorders was similarly high in both groups. The familial group had fewer cardiac and palate anomalies. A significant negative correlation was found between IQ and age. Most of the adults with familial VCFS were neuropsychiatrically disabled. Thus, although familial VCFS seems to be associated with a milder physical phenotype than nonfamilial VCFS, the neuropsychiatric deficits are significant in both types, at all ages.

Imaging diagnosis--intracranial epidermoid cyst in a Doberman Pinscher.

A 4-year-old Doberman Pinscher was evaluated for chronic progressive central vestibular disease and aggressiveness. A cyst-like lesion was identified in the region of the left cerebellopontine angle. The lesion was hypointense on T1-weighted and hyperintense on T2-weighted images. Differentials included an epidermoid or dermoid cyst, cystic neoplasm, and brain abscess. Hyperintensity on subsequent fluid-attenuated inversion recovery images excluded an arachnoid cyst. The histopathologic diagnosis was epidermoid cyst within the fourth ventricle.

Analysis of interleukin-1beta-modulated mRNA gene transcription in human gingival keratinocytes by epithelia-specific cDNA microarrays.

BACKGROUND/OBJECTIVES: Proinflammatory cytokines such as interleukin-1beta are known to be synthesized in oral gingivitis and periodontitis and lead to the activation of the transcription factor nuclear factor-kappaB (NF-kappaB). Although numerous effects of interleukin-1beta on mesenchymal cells are known, e.g. up-regulation of intercellular adhesion molecule-1 in endothelial cells, little is known of the effects of interleukin-1beta on oral keratinocytes. The purpose of the present study was to seek interleukin-1beta-mediated alterations in mRNA gene transcription and a putative activation of NF-kappaB in oral gingival keratinocytes. METHODS: As an in vitro model for gingivitis and periodontitis, immortalized human gingival keratinocytes (IHGK) were stimulated with the proinflammatory cytokine interleukin-1beta. An epithelia-specific cDNA microarray was used to analyze mRNA expression profiles from IHGK cells treated with 200 units interleukin-1beta/ml for 3, 6, 9, 12, and 24 h. Indirect immunofluorescence was carried out to detect NF-kappaB in IHGK following interleukin-1beta treatment. RESULTS: Detailed analysis revealed distinct patterns of time-dependent changes, including genes induced or repressed early (3-6 h) or late (12-24 h) after interleukin-1beta treatment. Differentially expressed genes were involved in (i) cell stress, (ii) DNA repair, (iii) cell cycle and proliferation, (iv) anti-pathogen response, (v) extracellular matrix turnover, and (vi) angiogenesis. A large number of genes were responsive to NF-kappaB and induction was concomitant with nuclear translocation of the p65 RelA subunit of NF-kappaB. Interestingly, many of these genes contain multiple NF-kappaB binding sites in their promoters. CONCLUSION: Analysis of altered gene expression allows identification of gene networks associated with inflammatory responses. In addition to a number of well-known genes involved in gingivitis and periodontitis, we identified novel candidates that might be associated with the onset and maintenance of an inflammatory disease.

Association with ZO-1 correlates with plasma membrane partitioning in truncated connexin45 mutants.

Zonula occludens-1 (ZO-1), the most abundant known connexin-interacting protein in osteoblastic cells, associates with the carboxyl termini of both Cx43 and Cx45. To learn more about the role of the cormexin-ZO-1 interaction, we analyzed connexin trafficking and function in ROS 17/2.8 cells that were stably transfected either with full length Cx45 or with Cx45 lacking 34 or 37 amino acids on the carboxyl terminus (Cx45t34 or Cx45t37). All three proteins were transported to appositional membranes in the transfected cells: Cx45 and Cx45t34 displayed a punctate appositional membrane-staining pattern, while Cx45t37 staining at appositional membranes was more linear. Expression of Cx45 decreased gap junction communication as assayed by dye transfer, while expression of Cx45t34 or Cx45t37 increased the amount of dye transfer seen in these cells. We found that Cx43, Cx45 and Cx45t34 co-precipitated with ZO-1 in these cells, while Cx45t37 did not. We also found that Cx45t37 was much more soluble in 1% Triton X-100 than the other connexins examined. In addition, Cx45t37 migrated to a fraction of lighter buoyant density on sucrose flotation gradients than Cx43, Cx45, ZO-1 and Cx45t34. As ZO-1 is an actin-binding protein, this suggested that the differences in Cx45t37 solubility might be due to a difference between the interaction of gap junctions and the actin cytoskeleton in the ROS/Cx45t37 and in the other transfected ROS cells. To examine this possibility, the transfected ROS cells were stained with fluorescently labeled phalloidin and demonstrated that there was a notable loss of actin stress fibers in the ROS/Cx45t37 cells. These findings suggest that association with ZO-1 alters the plasma membrane localization of Cx45 by removing it from a lipid raft compartment and rendering it Triton-insoluble, presumably by promoting an interaction with the actin cytoskeleton; they also suggest that Cx45 has a complex binding interaction with ZO-1 that involves either an extended carboxyl terminal domain or two distinct binding sites.

Comparison of beam characteristics of a gold x-ray target and a tungsten replacement target.

A new W-Cu target was designed to replace the existing Au target on a linear accelerator model in common use in radiotherapy. This work shows that targets of different material composition can be designed to produce beams with the same dosimetric character over a wide range of beam energies without adjusting the beam energy. The target design objective was to improve mechanical robustness, replacing water in the beam path with a Cu heat sink, without altering the beam properties for the nominal clinical energy range of 4-25 MV. The W-Cu could then be installed in place of the Au target without recommissioning. The effect of the target swap was measured in the test cells for 11 different beams ranging in nominal energy from 4 to 25 MV, with focus on open field dose distributions, including diagonal profiles taken for the largest (40x40 cm) field, measured at 4 different gantry angles. Depth dose curves agreed to 0.4% or better, profiles to 1.2% or better. Monte Carlo simulations of the treatment head were done for representative energies of 6 and 18 MV. Calculated and measured dose distributions generally matched within 1%, although dose measured in the build-up region of large fields was significantly more than in the simulations. Calculated spectral distributions on the central axis and angular distributions of energy fluence matched for the two targets, whereas angular distributions of fluence were significantly different. Matching energy fluence gave a more favorable match of dose profiles than matching fluence. The target was further tested on several machines operating in a radiotherapy clinic. Measurements were made for a wide range of open field sizes and with selected wedges and blocks. Dose distributions for the two targets agreed to 1.4% or better, including the dose in wedged fields. Wedge factors changed by no more than 0.5%, transmission through a 4.4 HVL block no more than 1.5%. The response of the monitor chamber was found to change, generally by 1%-2%. Therefore, when the W-Cu target was used to replace the Au target, the output of the machine was measured and adjusted appropriately, but there was no requirement for recommissioning.

Low incidence of cytomegalovirus disease in liver transplant recipients receiving sirolimus primary immunosuppression with 3-day corticosteroid taper.

BACKGROUND: Cytomegalovirus (CMV) disease is the most common infection following liver transplantation, occurring in approximately 20% of recipients. In liver transplant recipients, CMV is associated with a higher cost following transplantation, subsequent infections, and recurrent hepatitis C. Since we have initiated a prednisone-free immunosuppressive regimen in January 2000, we have noted an extremely low incidence of CMV disease in our cohort of liver transplant recipients. We report our findings here. METHODS: All 150 patients transplanted between January 2000 and December 2002 with tacrolimus (or cyclosporin A) and sirolimus, and 3-day corticosteroid taper were retrospectively analyzed. Recipients who were CMV IgG negative with a CMV IgG-positive donor ("CMV mismatch") received conventional prophylactic therapy with intravenous and oral ganciclovir. The incidence of CMV disease (defined as positive tissue culture or positive immunohistochemical stain of affected tissue or CMV-DNA >3000 associated with clinical symptoms) was recorded for each patient. RESULTS: The proportion of "CMV mismatches" (donor CMV IgG positive, recipient CMV IgG negative) was 15%. The mean total number of days of ganciclovir prophylaxis (intravenous and/or oral) administered to "CMV mismatch" patients was 45.6 days. The incidence of CMV disease in patients receiving sirolimus primary immunosuppression was 2%. The mean time to diagnosis of CMV disease was 139 days. CONCLUSIONS: (1) The incidence of CMV disease is very low using a prednisone-free, sirolimus immunosuppressive regimen. (2) Two possible explanations for this finding include appropriate prophylaxis with ganciclovir and low levels of immunosuppression including the absence of prednisone.