The frequency of interleukin-1ß-producing monocytes is significantly associated with varicella-zoster responses of nursing home residents.

Previous studies have demonstrated that the status of the T cell compartment and inflammation-related factors are associated with the immunogenicity of the varicella-zoster virus (VZV) vaccine in older adults; however, little is known about the roles of other immune cell subsets known to influence the generation and maintenance of immunological memory. Responses to a live-attenuated VZV vaccine were studied in relation to peripheral blood mononuclear cell (PBMC) composition and function in a sample of 30 nursing home residents (aged 80-99 years). Interferon-gamma enzyme-linked immunospot (ELISPOT) was used to measure VZV responses at baseline and 6 weeks following vaccination, and associations were sought with the frequencies of monocytes and T, B and natural killer (NK) cells and the production and secretion of cytokines following their ex-vivo stimulation with different agents. While only the frequency of interleukin (IL)-6+ CD14+ monocytes was inversely associated with post-vaccination VZV response, amounts of IL-1ß, IL-10, IL-17A and tumour necrosis factor (TNF) secreted by PBMCs and the frequency of IL-1ß+ CD14+ monocytes was positively correlated with pre-vaccination VZV response. Furthermore, both bivariate correlation and causal mediation analyses supported the notion that IL-1ß+ CD14+ monocytes were significant mediators of the associations between IL-1ß and TNF secretion by PBMCs and pre-vaccination VZV responses. Our findings implicate a strong cytokine response mediated by inflammatory IL-1ß+ monocytes in coordinating responses of long-lived VZV-reactive memory T cells, but with an opposing effect of IL-6+ CD14+ monocytes. Whether monocyte status promotes or inhibits the induction and/or maintenance of these memory T cells later in life has yet to be determined.

Experience beyond the learning curve of transanal total mesorectal excision (taTME) and its effect on the incidence of anastomotic leak.

BACKGROUND: The most important advancement in the surgical management of rectal cancer has been the introduction of total mesorectal excision (TME). Technical limitations to approaching mid and distal lesions remain. The recently described transanal TME makes it possible to minimize some of the difficulties by improving access. Anastomotic leak is a persistent concern after colorectal surgery no matter what technique is used. The objective of this study was to explore the impact of experience on the incidence of anastomotic leak after transanal TME. Secondary endpoints were local recurrence and margin status. METHODS: A retrospective cohort study was conducted over a period of 3 years at a tertiary care center in Northern Ontario with high volume of rectal cancer patients. The initial 100 consecutive patients with rectal neoplasia who had transanal TME surgery were included. All cases were performed by a single team. The main outcome assessed was the incidence of anastomotic leak beyond a pre-determined learning curve, as previously established in the literature. For statistical analysis, associations between patient characteristics and outcomes were estimated using ordinary least squares and logistic regression. RESULTS: Six cases of anastomotic leak occurred over the course of the study, the last of which occurred in the 37th patient. Relative to a baseline anastomotic leak rate of 7.8%, cumulative sum (CUSUM) analysis indicated that a 50% improvement in risk occurred at trial 50 of 85 patients that had an anastomosis performed. Two patients developed local recurrence during the study period. No correlation between learning curve and oncologic outcomes was identified. CONCLUSIONS: Proficiency is likely to have a positive effect on the 30-day occurrence of anastomotic leak. Larger studies are required to explore the impact of experience on local recurrence.

Modifiable factors related to life-space mobility in community-dwelling older adults: results from the Canadian Longitudinal Study on Aging.

BACKGROUND: The most common methods for measuring mobility in older adulthood include performance-based tests, such as the Timed-Up-and-Go and gait speed. While these measures have strong predictive validity for adverse outcomes, they are limited to assessing what older adults do in standardized settings, rather than what they do in their daily life. Life-space mobility, which is the ability to move within environments that expand from one's home to the greater community, has been proposed as a more comprehensive measure of mobility. The aim of this study was to determine the association between modifiable factors and life-space mobility in older adults enrolled in the Canadian Longitudinal Study on Aging (CLSA). METHODS: Life-space mobility was measured using the Life Space Index (LSI). Explanatory factors included physical, psychosocial and cognitive determinants, as well as pain, fatigue, driving status, nutrition, body mass index, smoking status, and vision. To estimate the association between the LSI and explanatory variables, univariate and multivariable ordinary least squares regression analyses were performed. RESULTS: All adults 65 years and older (n = 12,646) were included in the analysis. Fifty percent were women and the mean age was 73.0 (SD5.7). The mean LSI score was 80.5, indicating that, on average, the sample was able to move outside of their neighborhood independently. All explanatory variables were significantly associated with the LSI except for balance and memory. The top 3 variables that explained the most variation in the LSI were driving, social support and walking speed. CONCLUSION: To our knowledge, this was the first study to examine the association between life-space mobility and a comprehensive set of modifiable factors that were selected based on a theoretical framework and existing research evidence. This study had two important messages. First, driving, social support and walking speed emerged as the most significant correlates of life-space mobility in older adults. Second, life-space mobility is multifactorial and interventions that are pragmatic in their design and testing are needed that consider the complexity involved. A multi-disciplinary approach to examining life-space mobility in older adults is needed to optimize opportunities for healthy aging and develop strategies that support mobility in older adulthood.

Proceedings of the Canadian Frailty Network Workshop: Identifying Biomarkers of Frailty to Support Frailty Risk Assessment, Diagnosis and Prognosis. Toronto, January 15, 2018.

The Canadian Frailty Network (CFN), a pan-Canadian not-for-profit organization funded by the Government of Canada through the Networks of Centres of Excellence Program, is dedicated to improving the care of older Canadians living with frailty. The CFN has partnered with the Canadian Longitudinal Study on Aging (CLSA) to measure potential frailty biomarkers in biological samples (whole blood, plasma, urine) collected in over 30,000 CLSA participants. CFN hosted a workshop in Toronto on January 15 2018, bringing together experts in the field of biomarkers, aging and frailty. The overall objectives of the workshop were to start building a consensus on potential frailty biomarker domains and identify specific frailty biomarkers to be measured in the CLSA biological samples. The workshop was structured with presentations in the morning to frame the discussions for the afternoon session, which was organized as a free-flowing discussion to benefit from the expertise of the participants. Participants and speakers were from Canada, Italy, Spain, United Kingdom and the United States. Herein we provide pertinent background information, a summary of all the presentations with key figures and tables, and the distillation of the discussions. In addition, moving forward, the principles CFN will use to approach frailty biomarker research and development are outlined. Findings from the workshop are helping CFN and CLSA plan and conduct the analysis of biomarkers in the CLSA samples and which will inform a follow-up data access competition.

Association of TLR4 polymorphisms with Mycobacterium avium subspecies paratuberculosis infection status in Canadian Holsteins.

Mycobacterium avium ssp. paratuberculosis (MAP) causes chronic enteritis in cattle that results in substantial financial losses to the cattle industry worldwide. Given that susceptibility to MAP infection is determined in part by genetics, marker-assisted selection may help in the breeding of animals that are more resistant to MAP infection. The toll-like receptor 4 gene (TLR4) was selected as a potential candidate gene because of its role in innate immunity and its involvement in MAP recognition and infection. The objective of this study, therefore, was to identify associations between TLR4 polymorphisms and susceptibility to MAP infection in Canadian Holstein cows. Two biologically relevant SNPs, including c.-226G>C in the 5'-untranslated region and the non-synonymous SNP c.2021C>T in the potential TIR domain, were selected for an association analysis with MAP infection status in 409 Canadian Holsteins. The haplotype C-T from these combined SNPs yielded significant association with susceptibility to MAP infection, supporting the involvement of TLR4 in susceptibility to MAP infection.

Bovine CLEC7A genetic variants and their association with seropositivity in Johne's disease ELISA.

Mycobacterium avium ssp. paratuberculosis (MAP) infection in cattle causes significant economic losses to the dairy and beef industries resulting from reduced productivity, premature culling and mortality. Bovine Dectin-1, an important pattern recognition molecule that is able to generate a proinflammatory response by acting alongside Toll like receptor (TLR) signaling, is known to co-operate with TLR2 to specifically activate a macrophage proinflammatory response against mycobacterial infections. Therefore, the goal of this study was to identify single nucleotide polymorphisms (SNPs) in the gene encoding bovine Dectin-1 (CLEC7A) and to assess their association with susceptibility to MAP infection in dairy cattle. Blood and milk samples, collected from commercial dairy operations, were tested for MAP infection using blood and milk ELISAs and a resource population consisting of 197 infected and 242 healthy cattle was constructed. Pooled DNA was used for sequencing and eight single nucleotide polymorphisms (SNPs) were identified. Identified SNPs were genotyped on the resource population using the iPLEX MassARRAY system and statistical analysis was performed using logistic regression fitting the additive and dominance effects of each SNP in the model. Out of a total of eight identified SNPs, five were successfully genotyped, and three out of these five SNPs were found to be in complete linkage. Statistical analysis revealed a strong association between a non-synonymous SNP c.589A>G (p=0.008), and MAP infection status of the resource population inferred by seropositivity in MAP antibody specific ELISAs. This SNP c.589A>G was located in the geneic region that encodes the carbohydrate recognition domain of bovine Dectin-1. Therefore, further investigation of its functional relevance is warranted.

Bovine PGLYRP1 polymorphisms and their association with resistance to Mycobacterium avium ssp. paratuberculosis.

Mycobacterium avium ssp. paratuberculosis (MAP) causes a chronic, granulomatous inflammatory condition of the intestines in ruminants and wild-type species. It causes significant economic losses to the dairy and beef industries owing to reduced productivity, premature culling and mortality. Bovine peptidoglycan recognition protein 1 is an important pattern recognition molecule that is capable of directly killing microorganisms. The goal of this study was to identify single nucleotide polymorphisms (SNPs) in the gene encoding bovine peptidoglycan recognition protein 1 and to assess their association with susceptibility to MAP infection in dairy cattle. Blood and milk samples were collected from Holsteins in Southwestern and Eastern Ontario and tested for MAP infection using blood and milk ELISAs. A resource population consisting of 197 infected (S/P > 0.25) and 242 healthy (S/P < 0.10) cattle was constructed. Sequencing of pooled DNA was used to identify three SNPs (c.102G>C, c.480G>A and c.625C>A) that were genotyped in the resource population. Statistical analysis was performed using a logistic regression model fitting the additive and dominance effects of each SNP in the model. SNP c.480G>A (P = 0.054) was found to be associated with susceptibility to MAP infection. Cows with a copy of the major allele 'G' at this locus had an odds ratio of 1.51 (95% CI: 0.99-2.31) for being infected with MAP.

Single nucleotide polymorphisms alter the promoter activity of bovine MIF.

Macrophage migration inhibitory factor (MIF) is a unique pro-inflammatory cytokine whose chief functions include modulating TLR4 expression, and suppressing the anti-inflammatory effects of glucocorticoids. Not surprisingly, MIF is involved in a number of inflammatory diseases and single nucleotide polymorphisms (SNPs) have been implicated in modulating disease severity. The objective of the present study was to determine if SNPs in 5' region of bovine MIF affects its promoter activity. Three SNPs were identified, -1078A>G, -395A>G, and -400G>C, all of which fall within predicted transcription factor binding regions. Reporter gene assays indicate that the identified SNPs have a significant effect of modulating MIF promoter activity. Finally, gene association analysis suggests a significant relationship of -395A>G with the susceptibility to Mycobacterium avium ssp. paratuberculosis infection, the causative agent of Johne's disease. Given the relationships revealed in the current study, it is clear that the role of MIF in bovine diseases such as Johne's disease merits further investigation.

[Cyclic episodes of confusion and movement disorders: consider hyopglycemia and insulinoma]. / Cyclische episoden van verwardheid en bewegingsstoornissen: denk aan hypoglykemieën en insulinoom.

Insulinomas are rare neuroendocrine tumours of the pancreas which present with neuroglycopenic and autonomic symptoms induced by hypoglycemic periods. The onset is insidious. Because of atypical symptoms like temporary movement disorders and behavioural disturbances the diagnosis is often made at a late stage. We describe two patients with cyclic behavioural and movement disorders caused by already present but not recognised insulinomas. The treatment options are discussed, in which the most common surgical therapy is not always a first choice in elderly patients with comorbidity. With drug therapy patients can be free of symptoms for a longer period without any significant complications.

[Patients at the memory clinic with choreatic movements]. / Chorea bij patiënten op de geheugenpolikliniek.

In this case-report we present two patients who were referred to the memory clinic. In both cases there is doubt about the earlier diagnosis. During the physical examination choreatic movements were observed. After repeating diagnostic tests, both patients were diagnosed with Huntington's disease. The dementia with this disease is often preceded by psychiatric symptoms, which makes it quite difficult to diagnose, especially in an early stage of the disease. That is why it is essential that, in case of even the slightest doubt or confronted with new insights, geriatricians should see patients again in the memory clinic and repeat nosologic diagnosis.

Identification of single nucleotide polymorphisms in the bovine interleukin-12 and interleukin-23 receptor genes and their associations with health and production traits in Holstein cows.

Interleukin-12 (IL-12) and interleukin-23 (IL-23) are proinflammatory cytokines produced by macrophages and dendritic cells in response to infection with intracellular pathogens. The IL-12 receptor (IL-12R) is a heterodimer composed of 2 subunits, ß1 and ß2. The IL-23 receptor (IL-23R) is a heterodimer composed of the IL-12Rß1 subunit and a unique IL-23R subunit. Given the importance of IL-12 and IL-23 for modulating inflammation and the host immune response, the IL-12 and IL-23 receptor genes may be suitable candidate genes for studying disease resistance in dairy cattle. We hypothesize that single nucleotide polymorphisms (SNP) exist within these genes and that they contribute to variation in health and production traits in dairy cattle. To investigate this, a selective DNA pool was constructed using bull semen based on the estimated breeding values for somatic cell score (SCS), an indicator trait used to achieve genetic improvement for resistance to mastitis. Gene segments were amplified from this pool by PCR and the amplicons were sequenced to reveal SNP. A total of 10 SNP, including 2 in IL-12Rß1, 5 in IL-12Rß2, and 3 in IL-23R were identified. The SNP (n=5) were found in the 5' untranslated region (UTR) putative promoter regions of the genes, and SNP IL-23R c.1714A>C was a nonsynonymous SNP. Canadian Holstein bulls (n=492) were genotyped using Sequenom MassARRAY (Sequenom Inc., San Diego, CA). No association was found with SCS based on bull deregressed estimated breeding values for SCS; however, associations of SNP in the IL-12Rß2 gene (c.-511A>G, c.87A>G, c.2957A>C) were found with milk and protein yield. Further investigation will be required to elucidate the biological and practical relevance of these SNP.

Producción de un tejido óseo para injerto procesado, esterilizado por radiación / Production of bone tissue for processed bone graft, sterilized by radiation

Los aloinjertos óseos en Cirugía Traumatológica y Ortopédica son cada vez más empleados en procedimientos que logran mejorar la calidad de vida de los pacientes. El Banco de Huesos del Hospital Alemán, habilitado por el I.N.C.U.C.A.I desde octubre de 2003, sigue normas de trabajo y calidad, nacionales e internacionales. Enel presente análisis se describe la forma de proceder en nuestro Banco para la localización del potencial donante, su selección, la procuración de una determinada pieza (cabeza femoral), el procesamiento de la misma, los controles anatomopatológicos, microbiológicos y el método de esterilización y almacenamiento

Producción de un tejido óseo para injerto procesado, esterilizado por radiación / Production of bone tissue for processed bone graft, sterilized by radiation

Los aloinjertos óseos en Cirugía Traumatológica y Ortopédica son cada vez más empleados en procedimientos que logran mejorar la calidad de vida de los pacientes. El Banco de Huesos del Hospital Alemán, habilitado por el I.N.C.U.C.A.I desde octubre de 2003, sigue normas de trabajo y calidad, nacionales e internacionales. Enel presente análisis se describe la forma de proceder en nuestro Banco para la localización del potencial donante, su selección, la procuración de una determinada pieza (cabeza femoral), el procesamiento de la misma, los controles anatomopatológicos, microbiológicos y el método de esterilización y almacenamiento

Facial identity and facial emotions: speed, accuracy, and processing strategies in children and adults.

As yet, nearly all studies in face and facial affect recognition typically provide only data on the accuracy of processing, invariably also in the absence of reference data on abstract information processing. In this study, accuracy and speed of abstract visuo-spatial processing, face recognition, and facial emotion recognition were investigated in normal school children (7-10 years) and adults (25+/-4 years). In the age range of 7-10 years, accuracy of facial processing hardly increased, while speed did substantially increase with age. Adults, however, were substantially more accurate and faster than children. Differences between facial and abstract information processing were related to type of processing strategy, that is, configural or holistic processing versus featural or piecemeal processing. Improvement in task performance with age is discussed in terms of an enhanced efficiency of the configural organization of facial knowledge (facial information processing tasks), together with a further increase in processing capacity (all tasks). The differential developmental course of speed and accuracy levels indicates that speed is a more sensitive measure when children get older. Moreover, it also suggests that speed of performance, in addition to accuracy, might be successfully used in the assessment of clinical deficits, as has recently been demonstrated in children with autistic disorders of social contact.

Development of ideomotor praxis representation.

To create a short screening instrument to investigate the development of ideomotor praxis representation (IPR), 357 normally developing children between the ages of 2 1/2 and 9 1/2 years were investigated. The IPR screening consisted of six mimed actions which had to be performed on verbal request. The greatest change in the representational style is the transition from performing the action using the body as the object to performing with an imaginary object (i.e. symbolic representation). This transition suggests a development from a concrete and egocentric level of performance to an abstract and allocentric level. Before the age of 6 years differences are evident between self-directed and externally directed gestures. The level of symbolic representation has to be dissociated from the degree of motor precision, which shows hardly any improvement after 6 years of age. With the proposed model one may interpret the level of IPR in clinical practice. IPR screening is clinically relevant from the age of 4 1/2 years onwards.

Risk of left ventricular dysfunction in patients with probable Alzheimer's disease with APOE*4 allele.

OBJECTIVE: To examine the association between the APOE genotype and cardiovascular disease in Alzheimer's disease (AD) patients. DESIGN: Case register study of 100 consecutive referrals to a Memory Clinic where type of dementia and cardiovascular comorbidity were diagnosed and APOE genotype was determined. SETTING: The Memory Clinic, University Hospital Rotterdam Dijkzigt. PARTICIPANTS: One hundred Memory Clinic patients, 59 to 91 years of age, who attended the Memory Clinic in the period between January 1994 and March 1996. MEASUREMENTS: Relative risk of cardiovascular morbidity in probable AD, based on clinical and ECG findings. RESULTS: The diagnosis of probable AD was more frequent in APOE*4 allele-carrying AD patients. When comparing homozygotes for APOE*4 with homozygotes for APOE*3, a nine-fold increase in prevalence of cardiac ischemia on ECG was found in the former. When grouping parameters of left ventricular dysfunction, the prevalence was 7.2 (95% confidence interval 1.2-42.6) times greater in probable Alzheimer patients with APOE4/4. CONCLUSIONS: In patients with probable AD, APOE*4 is associated with cardiac disease indicative of left ventricular dysfunction.

Abnormal amino acid metabolism in patients with early stage Alzheimer dementia.

Plasma levels of several amino acids were studied in 14 patients with early stage probable Alzheimer's disease (AD) and 17 age-matched controls. In the AD patients a possible relationship between amino acid levels and behavioural symptomatology was also investigated. We found significantly reduced levels of tryptophan and methionine in plasma samples from the AD patients compared to the control subjects. Moreover, plasma tyrosine/large neutral amino acids (LNAA) ratio and the ratio of plasma taurine and the product of the plasma levels of methionine and serine (TSM-ratio) were significantly increased in the AD patients in comparison with the controls. However, no difference was found in plasma tryptophan/LNAA ratio and in homocysteine levels between both groups. Concerning the behavioural symptomatology no significant correlation was found between the Reisberg Behave AD scale and plasma amino acid levels or ratios. The reported findings suggest that abnormal amino acid metabolism is present in the early stages of AD. We hypothesize that this abnormality could play a role in the pathogenesis of behavioural changes occurring in later stages of AD.

Attention deficits in children with low performance IQ: arguments for right hemisphere dysfunction.

The attentional component of cognitive functioning in children might be viewed from several interrelated angles that nearly all point to right hemisphere (RH) neural circuits, subserving nonverbal attention. Neuropsychological aspects indicative of RH brain dysfunction are one aspect, studied here. Among children with learning disabilities (LD) we distinguish between LD with emphasis on nonverbal cognitive deficits and LD with verbal dysfunction. We approached this dichotomy by studying the extremes of these two LD categories (89 ss) with respect to attention deficit disorder with (ADHD) or without hyperactivity (ADD). We examined 44 children with at least average verbal IQ (VIQ > or = 95) and lower performance IQ (PIQ at least 25 points lower than VIQ), i.e. the nonverbal group, and 45 children with at least average performance IQ (PIQ > or = 95) and lower verbal IQ (VIQ at least 25 points lower than PIQ). The percentage of AD(H)D among the nonverbal LD group was more than twice as high as among the verbal LD group. Although a convincing right hemisphere (RH) syndrome could not be shown on a neurological basis in most subjects of the non-verbal LD group, a large body of evidence points on the one hand to RH dysfunction associated with nonverbal LD and on the other hand to an association between RH dysfunction and ADD. However, on clinical grounds, discussed here, we consider ADD and low visuospatial cognition, being the most important component of low PIQ, as dissociated functions, largely subserved by the RH.

Relation of early neuromotor and cranial signs with neuropsychological outcome at 4 years.

The persistence and predictive value at 3-5 years of age of three signs detected within the first 18 months of life were investigated: phasic stretch reflex in one or both gastrocnemius muscles, imbalance in passive axial tone with an excess of dorsal extension, and a ridge on the squamous sutures. Phasic stretch reflex and at least one of the other signs were found in 14 children during repeated assessments within the first 18 months. The progress of these children was compared with that of 14 matched controls who had repeatedly normal neurological assessments during the first 18 months in the same clinic in Paris. At the age 3-5 years all the children were then assessed blindly by the second author from a pediatric neurological viewpoint and by two psychologists and two psychomotor therapists as well. The parents of the affected children reported significantly more problems in motor/praxis skills, language development and attention. Abnormal neurological signs were also significantly more frequent than in the controls. Suboptimal cognition did not reach significance. The neurological inclusion criteria were still present at 3-5 years old in 86% (vs. respectively 100% and 93% during the first 18 months of life) of this small group of children, while the cranial suture sign was still present in only 28% (vs. 64%). Findings of these three signs during the first 18 months of life may help in predicting long-term neurobehavioral or long-term neuropsychological problems.

Sacroileitis bacteriana. Hallazgos clínicos y evolutivos en 9 casos / [Bacterial sacroileitis. Clinical findinds and clinical course in 9 cases]

Since septic sacroileitis is one of the less frequent localizations among joint infections, we decided to review 9 cases in a retrospective study of 5 females and 4 males, aged between 22 and 60 years old. None had a clinically predisposing condition. The initiating factor was gynecologic-obstetric in 4 women, the irruption of the skin barrier in 3 cases and finally in one case the infection reached the joint through the psoas muscle. Fever and lumbar pain were present in all cases and allowed diagnostic orientation. Radiologic and centellographic alterations were useful for clinical confirmation. An articular biopsypunction was performed in 4 cases, while in the other 5 cases the clinical and radiologic features and the bacteriologic positivity in the blood cultures were enough criteria for diagnosis. The bacteriologic findings were Staphylococcus aureus (4 cases), Streptococcus group A beta hemolítico (1 case), Staphylococcus coagulase negative (1 case), Streptococcus agalactiae (1 case), Proteus mirabilis (2 cases). Eight out of 9 patients were treated with a B-lactamic and aminoglycoside association. One patient received her treatment per os, with quinolones. Six patients recovered, 2 died and one needed to be sent to another hospital.