Influence of concomitant injuries on post-concussion symptoms after a mild traumatic brain injury - a prospective multicentre cohort study.

Objectives: To compare post-concussion symptoms (PCS) and return to normal activities between mild Traumatic Brain Injury (mTBI) patients with or without concomitant injuries at 7-and 90 days post-mTBI.Methods: Design: Sub-analysis of a multicentre prospective cohort study. PARTICIPANTS AND SETTING: patients with mTBI from 7 Canadian Emergency Departments. PROCEDURE: Research assistants conducted telephone follow-ups using the Rivermead Postconcussion Symptoms Questionnaire (RPQ) at 7-, 30- and 90 days post-mTBI. MAIN OUTCOME: Presence of PCS (RPQ: ≥3 symptoms) at 90 days. SECONDARY OUTCOMES: RPQ score ≥21, prevalence of individual RPQ symptoms and patients' return to normal activities, at 7- and 90-days. Adjusted risk ratios (RR) were calculated.Results: 1725 mTBI patients were included and 1055 (61.1%) had concomitant injuries. Patients with concomitant injuries were at higher risk of having ≥3 symptoms on the RPQ (RR:1.26 [95% CI 1.01-1.58]) at 90 days. They were also at higher risk of experiencing specific symptoms (dizziness, fatigue, headaches and taking longer to think) and of non-return to their normal activities (RR:2.11 [95% CI 1.30-3.45]).Conclusion: Patients with concomitant injuries have slightly more PCS and seemed to be at higher risk of non-return to their normal activities 90 days, compared to patients without concomitant injuries.

[Relation between grip strength of independent elders and functional decline following an emergency department visit : a pan-Canadian study]. / Capacité de prédiction de la force de préhension et de la peur de tomber des personnes âgées autonomes quant au déclin fonctionnel suite à une consultation aux urgences. Une étude pancanadienne.

OBJECTIVE: To determine whether grip strength and fear of falling are associated with functional decline at 3 or 6 months after a minor trauma assessed in the emergency department. METHOD: Prospective multicenter cohort study of patient's aged 65 years and older, independent for activities of daily living, consulting the emergency department for minor trauma. Functional status, fear of falling, and grip strength measurements were collected. Functional decline was measured at 3 and 6 months. STATISTICS: Two groups were compared : one with functional decline, the other without. A ROC curve explored the predictive power of grip strength and initial fear of falling on the occurrence of functional decline. RESULTS: Participants were 74.7 years old, 52 % men. Initial peak grip strengths were identical (p superior to 0.05). Grip strength and fear of falling were not predictive of functional decline (p = 0.55 and p = 0.53). However, fear of falling was associated with functional decline (OR: 1.141 95 % CI [1.032-1.261]; p = 0.009). CONCLUSION: In the autonomous elder with minor trauma in the emergency department, grip strength is not associated with subsequent functional decline. But fear of falling is associated with decline at 6 months.

Objectif : Déterminer si la force de préhension et la peur de tomber sont associées au déclin fonctionnel à 3 ou 6 mois d'un traumatisme mineur évalué aux urgences. Méthode : Étude prospective de cohorte multicentrique des patients de 65 ans et plus, autonomes pour les activités de la vie quotidienne, consultant aux urgences pour traumatismes mineurs. Le statut fonctionnel, la peur de tomber, et la mesure de la force de préhension ont été recueillis. Le déclin fonctionnel a été mesuré à 3 et 6 mois. Statistiques : Deux groupes sont comparés : un avec déclin fonctionnel, l'autre sans. Une courbe ROC a exploré la puissance prédictive de la force de préhension et de la peur de tomber initiale sur l'apparition du déclin fonctionnel. Résultats : Les participants avaient 74 ± 7 ans, 52 % d'hommes. Les forces de préhension maximales initiales étaient identiques (p sup�rieur a 0,05). La force de préhension et la peur de tomber ne sont pas prédictives du déclin fonctionnel (p = 0,55 et p = 0,53). Cependant, la peur de tomber est associée au déclin fonctionnel (OR: 1,141 IC95 % [1,032-1,261]; p = 0,009). Conclusion : Chez l'aîné autonome avec un traumatisme mineur aux urgences, la force de préhension n'est pas associée au déclin fonctionnel ultérieur. Mais la peur de tomber est associée à un déclin à 6 mois.

Screen of whole blood responses to flagellin identifies TLR5 variation associated with outcome in melioidosis.

Melioidosis is a severe infection caused by the flagellated bacterium Burkholderia pseudomallei. The nonsense polymorphism TLR51174C>T is associated with improved outcome in Thais with melioidosis. We hypothesized that other TLR5 variants may modulate the host response and determine outcome in melioidosis. We genotyped 12 TLR5 variants selected de novo from the HapMap database and examined the association of each with cytokines induced by flagellin stimulation of whole blood from healthy Thai subjects. We found a blunted cytokine response for three related markers that were in linkage disequilibrium (LD) with a non-synonymous variant, TLR51846T>C. Carriers of TLR51846T>C had broadly impaired cytokine responses induced by flagellin. TLR51846T>C was associated with protection against death in melioidosis patients (odds ratio: 0.62, 95% confidence interval: 0.42-0.93, P=0.021). We observed no impairment in TLR51846C-dependent nuclear factor κB activation, however, suggesting an alternative mechanism for the effect. We found that TLR51846T>C was in strong LD with TLR51174C>T. Many of the blunted cytokine responses observed and the association of TLR51846T>C with survival in melioidosis patients may be attributable to TLR51174C>T, but we could not exclude an independent effect of TLR51846T>C. These data identify novel associations for TLR51846T>C, enhance our understanding of TLR5 genetic architecture in Thais and highlight the role of TLR5 in melioidosis.

Advanced practice physiotherapy care in emergency departments for patients with musculoskeletal disorders: a pragmatic cluster randomized controlled trial and cost analysis.

BACKGROUND: Advanced practice physiotherapy (APP) models of care where physiotherapists are primary contact emergency department (ED) providers are promising models of care to improve access, alleviate physicians' burden, and offer efficient centered patient care for patients with minor musculoskeletal disorders (MSKD). OBJECTIVES: To compare the effectiveness of an advanced practice physiotherapist (APPT)-led model of care with usual ED physician care for persons presenting with a minor MSKD, in terms of patient-related outcomes, health care resources utilization, and health care costs. METHODS: This trial is a multicenter stepped-wedge cluster randomized controlled trial (RCT) with a cost analysis. Six Canadian EDs (clusters) will be randomized to a treatment sequence where patients will either be managed by an ED APPT or receive usual ED physician care. Seven hundred forty-four adults with a minor MSKD will be recruited. The main outcome measure will be the Brief Pain Inventory Questionnaire. Secondary measures will include validated self-reported disability questionnaires, the EQ-5D-5L, and other health care utilization outcomes such as prescription of imaging tests and medication. Adverse events and re-visits to the ED for the same complaint will also be monitored. Health care costs will be measured from the perspective of the public health care system using time-driven activity-based costing. Outcomes will be collected at inclusion, at ED discharge, and at 4, 12, and 26 weeks following the initial ED visit. Per-protocol and intention-to-treat analyses will be performed using linear mixed models with a random effect for cluster and fixed effect for time. DISCUSSION: MSKD have a significant impact on health care systems. By providing innovative efficient pathways to access care, APP models of care could help relieve pressure in EDs while providing efficient care for adults with MSKD. TRIAL REGISTRATION: ClinicalTrials.gov NCT05545917 . Registered on September 19, 2022.

High-'n'-dry? A comparison of cannabis and alcohol use in drivers presenting to hospital after a vehicular collision.

DESIGN: This was a prospective observational study. BACKGROUND AND AIMS: The characteristics of cannabis-involved motor vehicle collisions are poorly understood. This study of injured drivers identifies demographic and collision characteristics associated with high tetrahydrocannabinol (THC) concentrations. SETTING: The study was conducted in 15 Canadian trauma centres between January 2018 and December 2021. CASES: The cases (n = 6956) comprised injured drivers who required blood testing as part of routine trauma care. MEASUREMENTS: We quantified whole blood THC and blood alcohol concentration (BAC) and recorded driver sex, age and postal code, time of crash, crash type and injury severity. We defined three driver groups: high THC (THC ≥ 5 ng/ml and BAC = 0), high alcohol (BAC ≥ 0.08% and THC = 0) and THC/BAC-negative (THC = 0 = BAC). We used logistic regression techniques to identify factors associated with group membership. FINDINGS: Most injured drivers (70.2%) were THC/BAC-negative; 1274 (18.3%) had THC > 0, including 186 (2.7%) in the high THC group; 1161 (16.7%) had BAC > 0, including 606 (8.7%) in the high BAC group. Males and drivers aged less than 45 years had higher adjusted odds of being in the high THC group (versus the THC/BAC-negative group). Importantly, 4.6% of drivers aged less than 19 years had THC ≥ 5 ng/ml, and drivers aged less than 19 years had higher unadjusted odds of being in the high THC group than drivers aged 45-54 years. Males, drivers aged 19-44 years, rural drivers, seriously injured drivers and drivers injured in single-vehicle, night-time or weekend collisions had higher adjusted odds ratios (aORs) for being in the high alcohol group (versus THC/BAC-negative). Drivers aged less than 35 or more than 65 years and drivers involved in multi-vehicle, daytime or weekday collisions had higher adjusted odds for being in the high THC group (versus the high BAC group). CONCLUSIONS: In Canada, risk factors for cannabis-related motor vehicle collisions appear to differ from those for alcohol-related motor vehicle collisions. The collision factors associated with alcohol (single-vehicle, night-time, weekend, rural, serious injury) are not associated with cannabis-related collisions. Demographic factors (young drivers, male drivers) are associated with both alcohol and cannabis-related collisions, but are more strongly associated with cannabis-related collisions.

Toll-like receptor 4 region genetic variants are associated with susceptibility to melioidosis.

Melioidosis is a tropical infection caused by the Gram-negative soil saprophyte Burkholderia pseudomallei. Despite broad exposure of northeastern Thais, disease develops in only a small proportion of individuals. Although diabetes is a risk factor, the mechanisms of host susceptibility to melioidosis are still poorly understood. We postulated that Toll-like receptors (TLRs) regulate host susceptibility to disease, and that genetic variation in TLRs is associated with melioidosis. We analyzed the frequency of eight previously described TLR pathway polymorphisms in 490 cases compared with 950 non-hospitalized controls or 458 hospitalized controls. Based on these results, we then analyzed the frequency of additional TLR4 or TLR6-1-10 region polymorphisms in cases and controls. We found that the TLR4(1196C>T) variant was associated with protection from melioidosis when compared with non-hospitalized controls. The TLR1(742A>G) and TLR1(-7202A>G) variants were associated with melioidosis when compared with hospitalized controls. In further analyses, we found that two additional TLR4 region polymorphisms were associated with disease. In diabetics, three other TLR6-1-10 region polymorphisms were associated with disease when compared with hospitalized controls. We conclude that TLR genetic variants may modulate host susceptibility to melioidosis. Confirmation of these findings and further investigation of the mechanisms are required.

Reduction of age-associated pathology in old mice by overexpression of catalase in mitochondria.

We describe the effects of mitochondrially targeted catalase (MCAT) expression on end-of-life pathology in mice using detailed semiquantitative histopathological evaluation. We previously reported that the median and maximum life spans of MCAT mice were extended relative to those of wild-type littermates. We now report that MCAT expression is associated with reduced malignant nonhematopoietic tumor burden, reduced cardiac lesions, and a trend toward reduced systemic inflammation, with no effect on hematopoietic neoplasia or glomerulonephropathy. Combined disease burden and comorbidity are also reduced, and MCAT expression is not associated with any detrimental clinical effects. The results suggest that oxidative damage is involved in aging of C57BL/6J mice via modulation of a subset of age-associated lesions. Antioxidant interventions targeting mitochondria may therefore be a viable strategy for prevention or postponement of some age-associated diseases. The variability of the MCAT effect across tissues, however, illustrates the importance of developing semiquantitative histopathology for assessment of comorbidity in life-span studies.

Feasibility, Acceptability and Effects of a Home-Based Exercise Program Using a Gerontechnology on Physical Capacities after a Minor Injury in Community-Living Older Adults: A Pilot Study.

CONTEXT: Several studies have demonstrated that physical activity can help limit decline in functional capacities of older adults. Nevertheless, many adults aged 65 and over are inactive. OBJECTIVE: To explore the feasibility, the acceptability and the effects of a home-based exercise program (HEP) using a motion capture gerontechnology in independent community-living older adults at risk of function decline. DESIGN: Interventionnal clinical trial. PARTICIPANTS: Sixteen previously independent individuals aged 65 and older recruited at the Emergency Department after being treated for a minor injury and discharged home were assigned to a home-based exercise program group (HEP=8) or to a control group (CONTR=8). Twelve participants completed the study, 6 in each group Setting: Canadian Community-dwelling in Montreal area. INTERVENTION: The HEP group engaged in a twelve-week physical activity intervention using a gerontechnology while the CONTR group continued with discharge plan from ED. MEASUREMENTS: Participants were evaluated for functional status using validated questionnaires and objective physical measures at baseline, three and six months later. Feasibility and acceptability of the HEP was assessed using data reports from the gerontechnology and from self-reported assessments. RESULTS: There was no differences between groups at baseline except for the fallrelated self-efficacy: HEP=8.33/28±1.51 vs CONTR=7/28±0 p=0.022. The HEP was found to be feasible and acceptable (adherence rate at 86% and average quality of movements at 87.5%). Significant improvement in walking speed on 4m was observed three months after baseline for HEP vs CONTR group (+0.25 vs +0.05 m/sec, p=0.025). Effects remained at follow-up. Only CONTR group resulted in a significant increase in SF-36 global score. CONCLUSION: This twelve-week HEP intervention using the Jintronix® gerontechnology is feasible, acceptable and safe for community-living older adults who sustained a minor injury. This intervention could increase walking speed, the most important predictor of adverse events in the elderly population, and that the improvement could be maintained over time.

TLR4 genetic variation is associated with inflammatory responses in Gram-positive sepsis.

OBJECTIVES: To identify important pathogen recognition receptor (PRR) pathways regulating innate immune responses and outcome in Staphylococcus aureus sepsis. METHODS: We analysed whether candidate PRR pathway genetic variants were associated with killed S. aureus-induced cytokine responses ex vivo and performed follow-up in vitro studies. We tested the association of our top-ranked variant with cytokine responses and clinical outcomes in a prospective multicentre cohort of patients with staphylococcal sepsis. RESULTS: An intronic TLR4 polymorphism and expression quantitative trait locus, rs1927907, was highly associated with cytokine release induced by stimulation of blood from healthy Thai subjects with S. aureus ex vivo. S. aureus did not induce TLR4-dependent NF-κB activation in transfected HEK293 cells. In monocytes, tumor necrosis factor (TNF)-α release induced by S. aureus was not blunted by a TLR4/MD-2 neutralizing antibody, but in a monocyte cell line, TNF-α was reduced by knockdown of TLR4. In Thai patients with staphylococcal sepsis, rs1927907 was associated with higher interleukin (IL)-6 and IL-8 levels as well as with respiratory failure. S. aureus-induced responses in blood were most highly correlated with responses to Gram-negative stimulants whole blood. CONCLUSIONS: A genetic variant in TLR4 is associated with cytokine responses to S. aureus ex vivo and plasma cytokine levels and respiratory failure in staphylococcal sepsis. While S. aureus does not express lipopolysaccharide or activate TLR4 directly, the innate immune response to S. aureus does appear to be modulated by TLR4 and shares significant commonality with that induced by Gram-negative pathogens and lipopolysaccharide.

Comparing the retinal structures and functions in two species of gulls (Larus delawarensis and Larus modestus) with significant nocturnal behaviours.

Ring-billed gulls (Larus delawarensis) and gray gulls (Larus modestus) are two species active both by day and night. We have investigated the retinal adaptations that allow the diurnal and nocturnal behaviours of these two species. Electroretinograms and histological analyses show that both species have a duplex retina in which cones outnumber rods, but the number of rods appears sufficient to provide vision at night. Their retinas respond over the same scotopic dynamic range of 3.4logcdm(-2), which encompasses all of the light levels occurring at night in their photic environment. The amplitudes of the scotopic saturated a- and b-wave responses as well as the photopic saturated b-wave response and the photopic sensitivity parameter S are however higher in ring-billed gulls than in gray gulls. Moreover, the process of dark adaptation is about 30min faster in gray gulls than in ring-billed gulls. Our results suggest that both species have acquired in the course of their evolution functional adaptations that can be related to their specific photic environment.

p16INK4a promoter is hypermethylated at a high frequency in esophageal adenocarcinomas.

Loss of heterozygosity (LOH) of 9p21, which contains the p16INK4a tumor suppressor gene locus, is one of the most frequent genetic abnormalities in human neoplasia, including esophageal adenocarcinomas. Only a minority of Barrett's adenocarcinomas with 9p21 LOH have a somatic mutation in the remaining p16 allele, and none have been found to have homozygous deletions. To determine whether p16 promoter hypermethylation may be an alternative mechanism for p16 inactivation in esophageal adenocarcinomas, we examined the methylation status of the p16 promoter in flow-sorted aneuploid cell populations from 21 patients with premalignant Barrett's epithelium or esophageal adenocarcinoma. Using bisulfite modification, primer-extension preamplification, and methylation-specific PCR, we demonstrate that the methylation assay can be performed on 2 ng of DNA (approximately 275 cells). Eight of 21 patients (38%) had p16 promoter hypermethylation and 9p21 LOH, including 3 patients who had only premalignant Barrett's epithelium. Our data suggest that promoter hypermethylation with LOH is a common mechanism for inactivation of p16 in the pathogenesis of esophageal adenocarcinomas.

Genetic instability and hematologic disease risk in Werner syndrome patients and heterozygotes.

Werner syndrome (WRN) is an uncommon autosomal recessive disease in which progeroid features are associated with genetic instability and an elevated risk of neoplasia. We have used the glycophorin A (GPA) somatic cell mutation assay to analyze genetic instability in vivo in WRN patients and heterozygotes. GPA variant frequencies were determined for 11 WRN patients and for 10 heterozygous family members who collectively carry 10 different WRN mutations. Genetic instability as measured by GPA O/N allele loss variant frequency was significantly increased, and this increase was strongly age-dependent in WRN patients. GPA O/N allele loss variants were also significantly elevated in heterozygous family members, thus providing the first evidence for in vivo genetic instability in heterozygous carriers in an autosomal recessive genetic instability syndrome. Our results and comparable data on other human genetic instability syndromes allow an estimate of the level of genetic instability that increases the risk of human bone marrow dysfunction or neoplasia.

Pancolonic chromosomal instability precedes dysplasia and cancer in ulcerative colitis.

Patients with long-standing ulcerative colitis (UC) are at increased risk for colon cancer. These cancers are thought to arise from preexisting dysplasia in a field of abnormal cells that often exhibits aneuploidy and p53 abnormalities. Using dual color fluorescence in situ hybridization with centromere probes and locus-specific arm probes for chromosomes 8, 11, 17, and 18, we demonstrate that chromosomal instability (CIN) is present throughout the colon of UC patients with high-grade dysplasia or cancer. In rectal biopsies that were negative for dysplasia, abnormalities in chromosomal arms, especially losses, were most common, whereas centromere gains were most common in dysplasia and cancer. The frequency and type of abnormalities varied between the chromosomes examined; chromosome 8 was the least affected, and 17p loss was found to be an early and frequent event. Chromosomal arm instability showed 100% sensitivity and specificity for distinguishing control biopsies from histologically negative rectal biopsies from these UC patients, raising the possibility that a screen for CIN might detect the subset of UC patients who are at greatest risk for development of dysplasia and cancer. These results suggest that dysplasia and cancer in UC arise from a process of CIN that affects the entire colon; this may provide the mutator phenotype that predisposes to loss of tumor suppressor genes and evolution of cancer.

Determination of the frequency of loss of heterozygosity in esophageal adenocarcinoma by cell sorting, whole genome amplification and microsatellite polymorphisms.

It is well established that the progression to human cancer is characterized by the evolution of clones of cells with accumulated genetic abnormalities. However, technical difficulties limit the ability to study this process in some premalignant and malignant conditions. For example, the progression to esophageal adenocarcinoma in the premalignant condition Barrett's esophagus is characterized by the evolution of genetic and cell cycle abnormalities, but it has been difficult to characterize this process completely because of the small size of biopsies and the relative abundance of genetically normal stromal cells in some esophageal adenocarcinomas and premalignant mucosa. We have combined flow cytometric cell sorting to obtain purified populations of neoplastic cells with whole genome amplification and analysis of microsatellite polymorphisms to determine the frequency of allelic loss on every nonacrocentric autosomal arm in 20 esophageal adenocarcinomas and two high-grade dysplasias. DNA samples of purified flow-sorted aneuploid and corresponding normal tissue were amplified with a degenerate 15mer primer. Aliquots of these reactions were then screened with forty-three highly polymorphic simple sequence repeat markers in PCR-based assays. Allelic losses were observed at polymorphic loci in 38 of the 40 chromosome arms that were analysed and the median fractional allelic loss (FAL) observed in the samples was 0.28. The background allelic loss frequency was estimated at 0.23 with the highest rates of loss observed at 17p (100%), 5q (80%), 9p (64%), 13q (43%), 18q (43%) and 1p (41%). These data represent the first comprehensive allelotype of esophageal adenocarcinoma and show the feasibility of multiloci analyses with small highly purified human biopsy material.

Allelic loss of 9p21 and mutation of the CDKN2/p16 gene develop as early lesions during neoplastic progression in Barrett's esophagus.

High frequency allelic loss of chromosome 9p21 has been reported in a number of human cancers, including those of the esophagus. The CDKN2 gene on chromosome 9p21 that encodes the p16 inhibitor of cyclinD/Cdk4 complexes is a target of allelic loss and inactivation in a variety of human cancers and cell lines. However, the roles of 9p21 allelic losses and CDKN2 mutations in human neoplastic progression in vivo remain controversial. We determined the prevalence of allelic loss at 9p21 and mutations in CDKN2 in esophageal adenocarcinomas and investigated the order in which they occurred relative to the development of aneuploidy and cancer during neoplastic progression. Aneuploid cell populations from 32 patients with Barrett's esophagus who had premalignant epithelium, cancer, or both, were purified by DNA content flow cytometric cell sorting and evaluated by polymerase chain reaction. Twenty-four of 32 informative patients (75%) had allelic loss at 9p21 in aneuploid cell populations. Premalignant epithelium was available for seven of the patients who had 9p21 allelic losses in cancer; allelic loss of 9p21 was detected before cancer in all seven (100%). Allelic loss of 9p21 preceded the development of aneuploidy in 13 of 15 patients (87%) who had aneuploid cell populations detected in premalignant epithelium, and the two events were detected simultaneously in the remaining two patients. Five of 22 aneuploid populations (23%) with 9p21 loss had somatic mutations in the remaining CDKN2 allele. The same mutations and 9p21 allelic losses were also found in the corresponding diploid cells from premalignant epithelium in all three cases that were evaluable. However, there was no evidence for mutation or homozygous deletion of p16 in the other 17 patients with 9p21 allelic loss. Our results indicate that 9p21 allelic losses and CDKN2 mutations develop as early lesions in diploid cells before aneuploidy and cancer during neoplastic progression in Barrett's esophagus.

I-PpoI and I-CreI homing site sequence degeneracy determined by random mutagenesis and sequential in vitro enrichment.

Plasmid libraries containing partially randomized cleavage sites for the eukaryotic homing endonucleases I-PpoI and I-CreI were constructed, and sites that could be cleaved by I-PpoI or I-CreI were selectively recovered by successive cycles of cleavage and gel separation followed by religation and growth in Escherichia coli. Twenty-one different I-PpoI-sensitive homing sites, including the native homing site, were isolated. These sites were identical at four nucleotide positions within the 15 bp homing site, had a restricted pattern of base substitutions at the remaining 11 positions and displayed a preference for purines flanking the top strand of the homing site sequence. Twenty-one different I-CreI-sensitive homing sites, including the native site, were isolated. Ten nucleotide positions were identical in homing site variants that were I-CreI-sensitive and required the addition of SDS for efficient cleavage product release. Four of these ten positions were identical in homing sites that did not require SDS for product release. There was a preference for pyrimidines flanking the top strand of the homing site sequence. Three of the 24 I-CreI homing site nucleotide positions apparently lacked informational content, i. e. were permissive of cleavage when occupied by any nucleotide. These results suggest that I-PpoI and I-CreI make a large number of DNA-protein contacts across their homing site sequences, and that different subsets of these contacts may be sufficient to maintain a high degree of sequence-specific homing site recognition and cleavage. The sequential enrichment protocol we used should be useful for defining the sequence degeneracy and informational content of other homing endonuclease target sites.

Zebrafish calsyntenins mediate homophilic adhesion through their amino-terminal cadherin repeats.

The calsyntenins are atypical members of the cadherin superfamily that have been implicated in learning in Caenorhabditis elegans and memory formation in humans. As members of the cadherin superfamily, they could mediate cell-cell adhesion, although their adhesive properties have not been investigated. As an initial step in characterizing the calsyntenins, we have cloned clstn1, clstn2 and clstn3 from the zebrafish and determined their expression in the developing zebrafish nervous system. The three genes each have broad, yet distinct, expression patterns in the zebrafish brain. Each of the ectodomains mediates homophilic interactions through two, amino-terminal cadherin repeats. In bead sorting assays, the calsyntenin ectodomains do not exhibit homophilic preferences. These data support the idea that calsyntenins could either act as adhesion molecules or as diffusible, homophilic or heterophilic ligands in the vertebrate nervous system.

Renal disease in hepatitis C-positive liver transplant recipients.

Glomerular abnormalities are frequent in patients undergoing liver transplantation; however, renal dysfunction following transplantation is mainly attributed to cyclosporine toxicity. Membranoproliferative glomerulonephritis (MPGN) is seen in patients infected with hepatitis C virus (HCV), the virus responsible for 30% of the end-stage liver disease leading to liver transplantation. To determine the incidence of renal abnormalities in liver transplant recipients and the association with HCV, we undertook a longitudinal study in HCV-positive (n=91) and HCV-negative (n=106) liver transplant recipients. Mean creatinine clearance before transplantation was 94 ml/min/1.73 m2 in HCV+ patients and 88 ml/min/1.73 m2 in HCV- patients. By 3 months after transplantation, the mean creatinine clearance decreased by approximately one third in both groups. A greater proportion of HCV+ patients excreted >2 g protein/day after transplantation (P=0.05) and had renal biopsies showing MPGN than did HCV- recipients (4/10 HCV+ patients vs. 0/7 HCV- patients; P=0.1). In the HCV+ group, proteinuria was not associated with recurrent HCV hepatitis, DQ matching, posttransplant diabetes, or hypertension. Treatment of HCV-related MPGN with interferon-alpha2b appeared to stabilize proteinuria and renal function but did not reverse renal dysfunction nor cause liver allograft rejection. After transplantation, HCV+ patients had similar renal function over 3 years after transplantation, compared with HCV- patients, but they had an increased risk of proteinuria and occurrence of MPGN that was only partially responsive to interferon.

Chromosomal changes in a dedifferentiated chondrosarcoma: a case report and review of the literature.

The chromosome abnormalities observed in a dedifferentiated chondrosarcoma are reported. A new molecular cytogenetic technique, spectral karyotyping, was used to identify and confirm structural rearrangements in this case. A review of the literature revealed that nine cases have been reported, in eight of which a complete description of the cytogenetic abnormalities was described. Structural aberrations were most frequently reported in chromosomes 1 and 9, and chromosomes 7 and 19 were most frequently observed to be involved in numerical aberrations (trisomy and tetrasomy). In chondrosarcomas, structural aberrations in chromosomes 1 and 9 and trisomy or tetrasomy of chromosome 7 are among the more frequently observed aberrations.

Fos-like immunoreactivity in vagal and hypoglossal nuclei in different feeding states: a quantitative study.

This study characterized the distribution of Fos-like immunoreactivity (FLI) in three hindbrain nuclei: dorsal motor nucleus of the vagus (DMN), nucleus of the solitary tract (NST) and hypoglossal nucleus (HG) in response to eating or activation of specific components of feeding behavior. The degree of FLI was quantified by automated image analysis software that provided an efficient and sensitive method for counting the number of cells labelled with Fos antibody. Ingestion, and anticipation, of a meal both increased FLI in the DMN and HG, but not in the NST. Sham feeding 1 M sucrose was a more potent stimulus for FLI activation in DMN and NST than combined oral plus gastric/postingestive stimulation provided by real feeding the same food. The results indicate that the physiological stimulus of eating is sufficient to elicit FLI in the hindbrain and that specific components of the feeding act, especially oral stimulation provided by sham feeding, can activate FLI. The results suggest further that, under specific experimental conditions, gastric and/or postgastric stimulation may decrease FLI in the NST and DMN.