No detectable indirect effects of late-onset Cytomegalovirus disease after valganciclovir (VGC) prophylaxis in kidney transplant recipients

Background: Cytomegalovirus (CMV) disease remains an important cause of morbidity after kidney transplantation and has been associated with acute rejection, graft loss and other indirect effects. A 3-month course of VGC prophylaxis reduces the incidence of CMV disease. However, little is known about the indirect effects of lateonset CMV disease after VGC prophylaxis. Objective: To evaluate the impact and indirect consequences of late-onset CMV disease after VGC prophylaxis in kidney transplant recipients. Methods: Retrospective analysis of 61 consecutive adult kidney transplant recipient with positive CMV serology (donor or recipient) who received VGC prophylaxis for 3 months and completed a follow-up of at least 2 years post-transplantation. Patients who developed CMV disease within 1 year after transplantation were compared to CMV disease-free patients for renal function (plasma creatinine values) at 1, 6, 12 and 24 months and for the incidence of graft loss, acute rejection, diabetes, cancer and opportunistic infections. Results: 8/61 (13%) patients developed CMV disease at a median of 131 days after transplantation (range: 98-220). The CMV incidence in D+/R- high risk patients was 6/18 (33%), while it was 2/43 (5%) in intermediate-risk patients (p < 0.01). All 8 patients were treated by oral valganciclovir (median 39 days; range: 19-119) with a complete resolution of CMV disease. As shown in the figure, there was no difference in creatinine values between the two groups at any time during follow-up. There was no graft loss, and the incidence of acute rejection, cancer and opportunistic infections did not differ between the two groups. The incidence of post-transplant diabetes was higher (38% vs 15%) in patients with CMV disease, but this difference was not significant (p = 0.4). Conclusions: An incidence of 13% of late-onset CMV disease was observed despite 3 months VGC prophylaxis. However, no indirect consequences were found. Moreover, therapy of CMV disease by oral VGC was effective and safe. Larger trials are needed to study whether late-onset CMV disease is associated with indirect consequences, as described with early-onset CMV.

Phenotypic and molecular characterization of the onset of neuropathy in rodent models of diabetes mellitus

Abstract : The principal focus of this work was to study the molecular changes leading to the development of diabetic peripheral neuropathy (DPN). DPN is the most common complication associated with both type I and II diabetes mellitus (DM). This pathology is the leading cause of non-traumatic amputations. Even though the pathological and morphological changes underlying DPN are relatively well described, the implicated molecular mechanisms remain poorly understood. The following two approaches were developed to study the development of DPN in a rodent model of DM type I. As a first approach, we studied the implication of lipid metabolism in DPN phenotype, concentrating on Sterol Response Element Binding Protein (SREBP)-lc which is the key regulator of storage lipid metabolism. We showed that SREBP-1c was expressed in peripheral nerves and that its expression profile followed the expression of genes involved in storage lipid metabolism. In addition, the expression of SREBP-1c in the endoneurium of peripheral nerves was dependant upon nutritional status and this expression was also perturbed in type I diabetes. In line with this, we showed that insulin elevated the expression of SREBP-1c in primary cultured Schwann cells by activating the SREBP-1c promoter. Taken together, these findings reveal that SREBP-1c expression in Schwann cells responds to metabolic stimuli including insulin and that this response is affected in type I diabetes mellitus. This suggests that disturbed SREBP-1c regulated lipid metabolism may contribute to the pathophysiology of DPN. As a second approach, we performed a comprehensive analysis of the molecular changes associated with DPN in the Akital~1~+ mouse which is a model of spontaneous early-onset type I diabetes mellitus. This mouse expresses a mutated non-functional isoform of insulin, leading to hypoinsulinemia and hyperglycaemia. To determine the onset of DPN, weight, blood glucose and motor nerve conduction velocity (MNCV) were measured in Akital+/+ mice during the first three months of life. A decrease in MNCV was evident akeady one week after the onset of hyperglycemia. To explore the molecular changes associated with the development of DPN in these mice, we performed gene expression profiling using sciatic nerve endoneurium and dorsal root ganglia (DRG) isolated from early diabetic male Akita+/+ mice and sex-matched littermate controls. No major transcriptional changes were detected either in the DRG or in the sciatic nerve endoneurium. This experiment indicates that the phenotypic changes observed during the development of DPN are not correlated with major transcriptional alterations, but mainly with alterations at the protein level. Résumé Lors ce travail, nous nous sommes intéressés aux changements moléculaires aboutissant aux neuropathies périphériques dues au diabète (NPD). Les NPD sont la complication la plus commune du diabète de type I et de type II. Cette pathologie est une cause majeure d'amputations. Même si les changements pathologiques et morphologiques associés aux NPD sont relativement bien décrits, les mécanismes moléculaires provoquant cette pathologie sont mal connus. Deux approches ont principalement été utilisées pour étudier le développement des NPD dans des modèles murins du diabète de type I. Nous avons d'abord étudié l'impact du métabolisme des lipides sur le développement des NPD en nous concentrant sur Sterol Response Element Binding Protein (SREBP)-1 c qui est un régulateur clé des lipides de stockage. Nous avons montré que SREBP-1 c est exprimé dans les nerfs périphériques et que son profil d'expression suit celui de gènes impliqués dans le métabolisme des lipides de stockage. De plus, l'expression de SREBP-1c dans l'endoneurium des nerfs périphériques est dépendante du statut nutritionnel et est dérégulée lors de diabète de type I. Nous avons également pu montrer que l'insuline augmente l'expression de SREBP-1c dans des cultures primaires de cellules de Schwann en activant le promoteur de SREBP-1c. Ses résultats démontrent que l'expression de SREBP-1c dans les cellules de Schwann est contrôlée par des stimuli métaboliques comme l'insuline et que cette réponse est affectée dans le cas d'un diabète de type I. Ces données suggèrent que la dérégulation de l'expression de SREBP-1c lors du diabète pourrait affecter le métabolisme des lipides et ainsi contribuer à la pathophysiologie des NPD. Comme seconde approche, nous avons réalisé une analyse globale des changements moléculaires associés au développement des NPD chez les souris Akita+/+, un modèle de diabète de type I. Cette souris exprime une forme mutée et non fonctionnelle de l'insuline provoquant une hypoinsulinémie et une hyperglycémie. Afin de déterminer le début du développement de la NPD, le poids, le niveau de glucose sanguin et la vitesse de conduction nerveuse (VCN) ont été mesurés durant les 3 premiers mois de vie. Une diminution de la VCN a été détectée une semaine seulement après le développement de l'hyperglycémie. Pour explorer les changements moléculaires associés avec le développement des NPD, nous avons réalisé un profil d'expression de l'endoneurium du nerf sciatique et des ganglions spinaux isolés à partir de souris Akital+/+ et de souris contrôles Akita+/+. Aucune altération transcriptionnelle majeure n'a été détectée dans nos échantillons. Cette expérience suggère que les changements phénotypiques observés durant le développement des NPD ne sont pas corrélés avec des changements importants au niveau transcriptionnel, mais plutôt avec des altérations au niveau protéique. Résumé : Lors ce travail, nous nous sommes intéressés aux changements moléculaires aboutissant aux neuropathies périphériques dues au diabète (NPD). Les NPD sont la complication la plus commune du diabète de type I et de type II. Cette pathologie est une cause majeure d'amputations. Même si les changements pathologiques et morphologiques associés aux NPD sont relativement bien décrits, les mécanismes moléculaires provoquant cette pathologie sont mal connus. Deux approches ont principalement été utilisées pour étudier le développement des NPD dans des modèles murins du diabète de type I. Nous avons d'abord étudié l'impact du métabolisme des lipides sur le développement des NPD en nous concentrant sur Sterol Response Element Binding Protein (SREBP)-1c qui est un régulateur clé des lipides de stockage. Nous avons montré que SREBP-1 c est exprimé dans les nerfs périphériques et que son profil d'expression suit celui de gènes impliqués dans le métabolisme des lipides de stockage. De plus, l'expression de SREBP-1c dans l'endoneurium des nerfs périphériques est dépendante du statut nutritionnel et est dérégulée lors de diabète de type I. Nous avons également pu montrer que l'insuline augmente l'expression de SREBP-1c dans des cultures primaires de cellules de Schwann en activant le promoteur de SREBP-1c. Ses résultats démontrent que l'expression de SREBP-1c dans les cellules de Schwann est contrôlée par des stimuli métaboliques comme l'insuline et que cette réponse est affectée dans le cas d'un diabète de type I. Ces données suggèrent que la dérégulation de l'expression de SREBP-1c lors du diabète pourrait affecter le métabolisme des lipides et ainsi contribuer à la pathophysiologie des NPD. Comme seconde approche, nous avons réalisé une analyse globale des changements moléculaires associés au développement des NPD chez les souris Akita~~Z~+, un modèle de diabète de type I. Cette souris exprime une forme mutée et non fonctionnelle de l'insuline provoquant une hypoinsulinémie et une hyperglycémie. Afin de déterminer le début du développement de la NPD, le poids, le niveau de glucose sanguin et la vitesse de conduction nerveuse (VCN) ont été mesurés durant les 3 premiers mois de vie. Une diminution de la VCN a été détectée une semaine seulement après le développement de l'hyperglycémie. Pour explorer les changements moléculaires associés avec le développement des NPD, nous avons réalisé un profil d'expression de l'endoneurium du nerf sciatique et des ganglions spinaux isolés à partir de souris Akital+/+ et de souris contrôles Akita+/+. Aucune altération transcriptionnelle majeure n'a été détectée dans nos échantillons. Cette expérience suggère que les changements phénotypiques observés durant le développement des NPD ne sont pas corrélés avec des changements importants au niveau transcriptionnel, mais plutôt avec des altérations au niveau protéique.

Dissecting the genetic heterogeneity of depression through age at onset.

Genome-wide studies in major depression have identified few replicated associations, potentially due to heterogeneity within the disorder. Several studies have suggested that age at onset (AAO) can distinguish sub-types of depression with specific heritable components. This paper investigates the role of AAO in the genetic susceptibility for depression using genome-wide association data on 2,746 cases and 1,594 screened controls from the RADIANT studies, with replication performed in 1,471 cases and 1,403 controls from two Munich studies. Three methods were used to analyze AAO: First a time-to-event analysis with controls censored, secondly comparing controls to case-subsets defined using AAO cut-offs, and lastly analyzing AAO as a quantitative trait. In the time-to-event analysis three SNPs reached suggestive significance (P < 5E-06), overlapping with the original case-control analysis of this study. In a case-control analysis using AAO thresholds, SNPs in 10 genomic regions showed suggestive association though again none reached genome-wide significance. Lastly, case-only analysis of AAO as a quantitative trait resulted in 5 SNPs reaching suggestive significance. Sex specific analysis was performed as a secondary analysis, yielding one SNP reaching genome-wide significance in early-onset males. No SNPs achieved significance in the replication study after correction for multiple testing. Analysis of AAO as a quantitative trait did suggest that, across all SNPs, common genetic variants explained a large proportion of the variance (51%, P = 0.04). This study provides the first focussed analysis of the genetic contribution to AAO in depression, and establishes a statistical framework that can be applied to a quantitative trait underlying any disorder. © 2012 Wiley Periodicals, Inc.

Étude pangénomique de la variabilité dans le nombre de copies liée à l’hypertension artérielle et ses anomalies métaboliques associées

L’hypertension artérielle essentielle (HTA) est une pathologie complexe, multifactorielle et à forte composante génétique. L’impact de la variabilité dans le nombre de copies sur l’HTA est encore peu connu. Nous envisagions que des variants dans le nombre de copies (CNVs) communs pourraient augmenter ou diminuer le risque pour l’HTA. Nous avons exploré cette hypothèse en réalisant des associations pangénomiques de CNVs avec l’HTA et avec l’HTA et le diabète de type 2 (DT2), chez 21 familles du Saguenay-Lac-St-Jean (SLSJ) caractérisées par un développement précoce de l’HTA et de la dyslipidémie. Pour la réplication, nous disposions, d’une part, de 3349 sujets diabétiques de la cohorte ADVANCE sélectionnés pour des complications vasculaires. D’autre part, de 187 sujets de la cohorte Tchèque Post-MONICA (CTPM), choisis selon la présence/absence d’albuminurie et/ou de syndrome métabolique. Finalement, 134 sujets de la cohorte CARTaGENE ont été analysés pour la validation fonctionnelle. Nous avons détecté deux nouveaux loci, régions de CNVs (CNVRs) à effets quantitatifs sur 17q21.31, associés à l’hypertension et au DT2 chez les sujets SLSJ et associés à l’hypertension chez les diabétiques ADVANCE. Un modèle statistique incluant les deux variants a permis de souligner le rôle essentiel du locus CNVR1 sur l’insulino-résistance, la précocité et la durée du diabète, ainsi que sur le risque cardiovasculaire. CNVR1 régule l’expression du pseudogène LOC644172 dont le dosage est associé à la prévalence de l’HTA, du DT2 et plus particulièrement au risque cardiovasculaire et à l’âge vasculaire (P<2×10-16). Nos résultats suggèrent que les porteurs de la duplication au locus CNVR1 développent précocement une anomalie de la fonction bêta pancréatique et de l’insulino-résistance, dues à un dosage élevé de LOC644172 qui perturberait, en retour, la régulation du gène paralogue fonctionnel, MAPK8IP1. Nous avons également avons identifié six CNVRs hautement hérités et associés à l'HTA chez les sujets SLSJ. Le score des effets combinés de ces CNVRs est apparu positivement et étroitement relié à la prévalence de l’HTA (P=2×10-10) et à l’âge de diagnostic de l’HTA. Dans la population SLSJ, le score des effets combinés présente une statistique C, pour l’HTA, de 0.71 et apparaît aussi performant que le score de risque Framingham pour la prédiction de l’HTA chez les moins de 25 ans. Un seul nouveau locus de CNVR sur 19q13.12, où la délétion est associée à un risque pour l’HTA, a été confirmé chez les Caucasiens CTPM. Ce CNVR englobe le gène FFAR3. Chez la souris, il a été démontré que l’action hypotensive du propionate est en partie médiée par Ffar3, à travers une interférence entre la flore intestinale et les systèmes cardiovasculaire et rénal. Les CNVRs identifiées dans cette étude, affectent des gènes ou sont localisées dans des QTLs reliés majoritairement aux réponses inflammatoires et immunitaires, au système rénal ainsi qu’aux lésions/réparations rénales ou à la spéciation. Cette étude suggère que l’étiologie de l’HTA ou de l’HTA associée au DT2 est affectée par des effets additifs ou interactifs de CNVRs.

Obsessive-compulsive disorder: Influence of age at onset on comorbidity patterns

Purpose. - This study investigates the influence of age at onset of OCS on psychiatric comorbidities, and tries to establish a cut-off point for age at onset. Methods. - Three hundred and thirty OCD patients were consecutively recruited and interviewed using the following structured interviews: Yale-Brown Obsessive Compulsive Scale; Yale Global Tic Severity Scale and the Structured Clinical Interview for DSM-IV. Data were analyzed with regression and cluster analysis. Results. - Lower age at onset was associated with a higher probability of having comorbidity with tic, anxiety, somatoform, eating and impulse-control disorders. Longer illness duration was associated with lower chance of having tics. Female gender was associated with anxiety, eating and impulse-control disorders. Tic disorders were associated with anxiety disorders and attention-deficit/hyperactivity disorder. No cutoff age at onset was found to clearly divide the sample in homogeneous subgroups. However, cluster analyses revealed that differences started to emerge at the age of 10 and were more pronounced at the age of 17, suggesting that these were the best cut-off points on this sample. Conclusions. - Age at onset is associated with specific comorbidity patterns in OCD patients. More prominent differences are obtained when analyzing age at onset as an absolute value. (C) 2008 Elsevier Masson SAS. All rights reserved.

Obsessive-compulsive disorder: Influence of age at onset on comorbidity patterns

Purpose: This study investigates the influence of age at onset of OCS on psychiatric comorbidities, and tries to establish a cut-off point for age at onset. Methods: Three hundred and thirty OCD patients were consecutively recruited and interviewed using the following structured interviews: Yale-Brown Obsessive Compulsive Scale; Yale Global Tic Severity Scale and the Structured Clinical Interview for DSM-IV. Data were analyzed with regression and cluster analysis. Results: Lower age at onset was associated with a higher probability of having comorbidity with tic, anxiety, somatoform, eating and impulse-control disorders. Longer illness duration was associated with lower chance of having tics. Female gender was associated with anxiety, eating and impulse-control disorders. Tic disorders were associated with anxiety disorders and attention-deficit/hyperactivity disorder. No cut-off age at onset was found to clearly divide the sample in homogeneous subgroups. However, cluster analyses revealed that differences started to emerge at the age of 10 and were more pronounced at the age of 17, suggesting that these were the best cut-off points on this sample. Conclusions: Age at onset is associated with specific comorbidity patterns in OCD patients. More prominent differences are obtained when analyzing age at onset as an absolute value. © 2008 Elsevier Masson SAS. All rights reserved.

Late-onset obsessive-compulsive disorder: Risk factors and correlates

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Cone contrast influence on components of the pattern onset/offset VECP

Transient visual evoked cortical potentials (VECP) were recorded from the scalp of healthy normal trichromats (n = 12). VECPs were elicited by onset/offset presentation of patterned stimuli of two kinds: isochromatic luminance-modulated, and equiluminant red-green modulated, sine wave gratings. The amplitude and latency of the major onset components of the onset/offset VECP were measured and plotted as a function of the logarithm of pooled cone contrast. The early onset components, achromatic C1 and chromatic N1, increase linearly with log contrast, but N1 has a higher contrast gain than C1. The late onset components, achromatic C2 and chromatic N2, have similar contrast gain, and similar response as a function of contrast level: both increase in the low-to-medium range of contrasts and saturate at high contrast levels. In the range of pooled cone contrast tested, C1 and N1 show similar latencies, whilst C2 shows shorter latencies than N2. We suggest that C1 and N1 are generated by the same visual mechanism with high red-green contrast gain and low luminance contrast gain, whilst C2 and N2 are generated by different visual mechanisms.

Mitochondrial tRNA(Leu(UUR)) mutation m.3302A > G presenting as childhood-onset severe myopathy: threshold determination through segregation study

Mitochondrial tRNA(Leu(UUR)) mutation m.3302A > G is associated with respiratory chain complex I deficiency and has been described as a rare cause of mostly adult-onset slowly progressive myopathy. Five families with 11 patients have been described so far; 5 of them died young due to cardiorespiratory failure. Here, we report on a segregation study in a family with an index patient who already presented at the age of 18 months with proximal muscular hypotonia, abnormal fatigability, and lactic acidosis. This early-onset myopathy was rapidly progressive. At 8 years, the patient is wheel-chair bound, requires nocturnal assisted ventilation, and suffers from recurrent respiratory infections. Severe complex I deficiency and nearly homoplasmy for m.3302A > G were found in muscle. We collected blood, hair, buccal swabs and muscle biopsies from asymptomatic adults in this pedigree and determined heteroplasmy levels in these tissues as well as OXPHOS activities in muscle. All participating asymptomatic adults had normal OXPHOS activities. In contrast to earlier reports, we found surprisingly little variation of heteroplasmy levels in different tissues of the same individual. Up to 45% mutation load in muscle and up to 38% mutation load in other tissues were found in non-affected adults. The phenotypic spectrum of tRNA(Leu(UUR)) m.3302A > G mutation seems to be wider than previously described. A threshold of more than 45% heteroplasmy in muscle seems to be necessary to alter complex I activity leading to clinical manifestation. The presented data may be helpful for prognostic considerations and counseling in affected families.

Early- and delayed antipsychotic response and prediction of outcome in 528 severely impaired patients with schizophrenia treated with amisulpride

'Early-onset' studies have shown that symptomatic response often occurs early and that early symptomatic response is predictive for later outcome. Limiting factors of these studies include the restriction on symptomatic outcome, the inclusion of mostly moderately ill patients, and the use of various antipsychotics.

The Application of Comorbidity Indices to Predict Early Postoperative Outcomes After Laparoscopic Roux-en-Y Gastric Bypass: A Nationwide Comparative Analysis of Over 70,000 Cases

BACKGROUND: Patients undergoing laparoscopic Roux-en-Y gastric bypass (LRYGB) often have substantial comorbidities, which must be taken into account to appropriately assess expected postoperative outcomes. The Charlson/Deyo and Elixhauser indices are widely used comorbidity measures, both of which also have revised algorithms based on enhanced ICD-9-CM coding. It is currently unclear which of the existing comorbidity measures best predicts early postoperative outcomes following LRYGB. METHODS: Using the Nationwide Inpatient Sample, patients 18 years or older undergoing LRYGB for obesity between 2001 and 2008 were identified. Comorbidities were assessed according to the original and enhanced Charlson/Deyo and Elixhauser indices. Using multivariate logistic regression, the following early postoperative outcomes were assessed: overall postoperative complications, length of hospital stay, and conversion to open surgery. Model performance for the four comorbidity indices was assessed and compared using C-statistics and the Akaike's information criterion (AIC). RESULTS: A total of 70,287 patients were included. Mean age was 43.1 years (SD, 10.8), 81.6 % were female and 60.3 % were White. Both the original and enhanced Elixhauser indices modestly outperformed the Charlson/Deyo in predicting the surgical outcomes. All four models had similar C-statistics, but the original Elixhauser index was associated with the smallest AIC for all of the surgical outcomes. CONCLUSIONS: The original Elixhauser index is the best predictor of early postoperative outcomes in our cohort of patients undergoing LRYGB. However, differences between the Charlson/Deyo and Elixhauser indices are modest, and each of these indices provides clinically relevant insight for predicting early postoperative outcomes in this high-risk patient population.

The maturity-onset diabetes of the young (MODY1) transcription factor HNF4α regulates expression of genes required for glucose transport and metabolism

Hepatocyte nuclear factor 4α (HNF4α) plays a critical role in regulating the expression of many genes essential for normal functioning of liver, gut, kidney, and pancreatic islets. A nonsense mutation (Q268X) in exon 7 of the HNF4α gene is responsible for an autosomal dominant, early-onset form of non-insulin-dependent diabetes mellitus (maturity-onset diabetes of the young; gene named MODY1). Although this mutation is predicted to delete 187 C-terminal amino acids of the HNF4α protein the molecular mechanism by which it causes diabetes is unknown. To address this, we first studied the functional properties of the MODY1 mutant protein. We show that it has lost its transcriptional transactivation activity, fails to dimerize and bind DNA, implying that the MODY1 phenotype is because of a loss of HNF4α function. The effect of loss of function on HNF4α target gene expression was investigated further in embryonic stem cells, which are amenable to genetic manipulation and can be induced to form visceral endoderm. Because the visceral endoderm shares many properties with the liver and pancreatic β-cells, including expression of genes for glucose transport and metabolism, it offers an ideal system to investigate HNF4-dependent gene regulation in glucose homeostasis. By exploiting this system we have identified several genes encoding components of the glucose-dependent insulin secretion pathway whose expression is dependent upon HNF4α. These include glucose transporter 2, and the glycolytic enzymes aldolase B and glyceraldehyde-3-phosphate dehydrogenase, and liver pyruvate kinase. In addition we have found that expression of the fatty acid binding proteins and cellular retinol binding protein also are down-regulated in the absence of HNF4α. These data provide direct evidence that HNF4α is critical for regulating glucose transport and glycolysis and in doing so is crucial for maintaining glucose homeostasis.

Computational Tracking of Mental Health in Youth: Latin American Contributions to a Low-Cost and Effective Solution for Early Psychiatric Diagnosis

The early onset of mental disorders can lead to serious cognitive damage, and timely interventions are needed in order to prevent them. In patients of low socioeconomic status, as is common in Latin America, it can be hard to identify children at risk. Here, we briefly introduce the problem by reviewing the scarce epidemiological data from Latin America regarding the onset of mental disorders, and discussing the difficulties associated with early diagnosis. Then we present computational psychiatry, a new field to which we and other Latin American researchers have contributed methods particularly relevant for the quantitative investigation of psychopathologies manifested during childhood. We focus on new technologies that help to identify mental disease and provide prodromal evaluation, so as to promote early differential diagnosis and intervention. To conclude, we discuss the application of these methods to clinical and educational practice. A comprehensive and quantitative characterization of verbal behavior in children, from hospitals and laboratories to homes and schools, may lead to more effective pedagogical and medical intervention

Widespread exploitation of the honeybee by early Neolithic farmers

The pressures on honeybee (Apis mellifera) populations, resulting from threats by modern pesticides, parasites, predators and diseases, have raised awareness of the economic importance and critical role this insect plays in agricultural societies across the globe. However, the association of humans with A. mellifera predates post-industrial-revolution agriculture, as evidenced by the widespread presence of ancient Egyptian bee iconography dating to the Old Kingdom (approximately 2400 bc)1. There are also indications of Stone Age people harvesting bee products; for example, honey hunting is interpreted from rock art2 in a prehistoric Holocene context and a beeswax find in a pre-agriculturalist site3. However, when and where the regular association of A. mellifera with agriculturalists emerged is unknown4. One of the major products of A. mellifera is beeswax, which is composed of a complex suite of lipids including n-alkanes, n-alkanoic acids and fatty acyl wax esters. The composition is highly constant as it is determined genetically through the insect’s biochemistry. Thus, the chemical ‘fingerprint’ of beeswax provides a reliable basis for detecting this commodity in organic residues preserved at archaeological sites, which we now use to trace the exploitation by humans of A. mellifera temporally and spatially. Here we present secure identifications of beeswax in lipid residues preserved in pottery vessels of Neolithic Old World farmers. The geographical range of bee product exploitation is traced in Neolithic Europe, the Near East and North Africa, providing the palaeoecological range of honeybees during prehistory. Temporally, we demonstrate that bee products were exploited continuously, and probably extensively in some regions, at least from the seventh millennium cal bc, likely fulfilling a variety of technological and cultural functions. The close association of A. mellifera with Neolithic farming communities dates to the early onset of agriculture and may provide evidence for the beginnings of a domestication process.

La concentración de calcio iónico se asocia a la presencia de fibrilación auricular post operatoria en pacientes llevados a revascularización miocardica

Objetivo. Determinar en un grupo de pacientes llevados a revascularización miocárdica si existió asociación entre la presencia de niveles de calcio iónico inferiores a 1,1 en las 24 horas del post operatorio y la ocurrencia de fibrilación auricular post operatoria. Metodología. Estudio observacional, analítico de casos y controles, en donde de manera consecutiva se incluyeron 110 sujetos (57 en el grupo de casos con presencia de fibrilación auricular post operatoria y 54 en el grupo de controles sin evidencia de fibrilación auricular) estos sujetos fueron llevados a revascularización miocárdica en la Fundación Cardioinfantil en los años 2010 a 2015. Resultados. Hubo 13 casos de fibrilación auricular post operatoria en pacientes con niveles de calcio iónico inferiores a 1,1 mmol/l en las primeras 24 horas del post operatorio OR: 0,5, IC (0,2-1,2) p: 0,1. Sin determinarse asociación por limitaciones del estudio, sin embargo un 29% de los pacientes con fibrilación auricular tuvieron niveles de calcio inferiores a 1,1 mmol/l en las primeras 24 horas del post operatorio, este valor aumenta a 31% cuando se analizan por separado los valores de calcio obtenidos a las 12 horas. Conclusiones. Aunque no se logró determinar asociación entre la fibrilación auricular post operatoria y las concentraciones de calcio iónico, de manera exploratoria se pudo establecer que un 29% de los pacientes con fibrilación auricular tuvieron concentraciones de calcio iónico inferiores a 1,1 mmol/l, este valor aumenta a 31% cuando se analizan los niveles de calcio iónico por separado.