Distinct roles of CSF family cytokines in macrophage infiltration and activation in glioma progression and injury response

Gliomas attract brain‐resident (microglia) and peripheral macrophages and reprogram these cells into immunosuppressive, pro‐invasive cells. M‐CSF (macrophage colony‐stimulating factor, encoded by the CSF1 gene) has been implicated in the control of recruitment and polarization of macrophages in several cancers. We found that murine GL261 glioma cells overexpress GM‐CSF (granulocyte–macrophage colony‐stimulating factor encoded by the CSF2 gene) but not M‐CSF when compared to normal astrocytes. Knockdown of GM‐CSF in GL261 glioma cells strongly reduced microglia‐dependent invasion in organotypical brain slices and growth of intracranial gliomas and extended animal survival. The number of infiltrating microglia/macrophages (Iba1⁺ cells) and intratumoural angiogenesis were reduced in murine gliomas depleted of GM‐CSF. M1/M2 gene profiling in sorted microglia/macrophages suggests impairment of their pro‐invasive activation in GM‐CSF‐depleted gliomas. Deficiency of M‐CSF (op/op mice) did not affect glioma growth in vivo and the accumulation of Iba1⁺ cells, but impaired accumulation of Iba1⁺ cells in response to demyelination. These results suggest that distinct cytokines of the CSF family contribute to macrophage infiltration of tumours and in response to injury. The expression of CSF2 (but not CSF1) was highly up‐regulated in glioblastoma patients and we found an inverse correlation between CSF2 expression and patient survival. Therefore we propose that GM‐CSF triggers and drives the alternative activation of tumour‐infiltrating microglia/macrophages in which these cells support tumour growth and angiogenesis and shape the immune microenvironment of gliomas. Copyright © 2013 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

Menarcheal age and socio-economic factors in Poland

Background:?Menarcheal age is the most important measure of sexual maturation in girls and a sensitive indicator of environmental conditions during childhood.

Objective:?The study analysed the association between age at menarche and socio-economic characteristics (urbanization, population size, education of parents and number of children in the family).

Subjects and methods:?Questionnaire data were collected from 3271 female schoolchildren born between 1981 and 1984, living in three provinces of southern Poland. Menarcheal age was estimated by the recall method and based on the date of menarche given by the study participants. ANCOVA and multiple regression analyses were applied to test statistical significance of differences between groups.

Results:?Girls from families with high socio-economic status experience menarche at an earlier age than girls from families with lower socio-economic status. However, depending on the geographical region and the population size, other factors influence menarcheal age. In the Krakow province, factors that significantly differentiate age at menarche are urbanization, father's education and number of children in the family; in the Opole province, these factors include urbanization and number of children in the family, while in the Nowy Sacz province, number of children in the family is significant.

Conclusions:?Socio-economic differences are greater in a large urban city (Krakow), and affect variation in age at menarche. However, within smaller populations (Opole, Nowy Sacz) living in towns and villages, the difference in age at menarche is less visible. In addition, variation between areas reveals a lower age at menarche in urban as compared with non-urban areas.

Résumé. Arrière plan: L’âge aux premières règles est une mesure importante de la maturation sexuelle des filles ainsi qu’un indicateur sensible des conditions du milieu au cours de l’enfance.

Objectif: Cette étude analyse l’association entre âge aux premières règles et facteurs socio-économiques (urbanisation, taille de la population, éducation parentale et nombre d’enfants dans la famille).

Sujets et méthodes: Des données par questionnaire ont été rassemblées sur 3271 écoliers habitant dans trois provinces du sud de la Pologne, nés entre 1981 et 1984. L’âge aux premières règles a été estimé par la méthode de mémorisation. Des analyses de régression multiple et de covariance (ANCOVA) ont été effectuées afin d’évaluer la signification statistique des différences entre groupes.

Résultats: Les filles de familles à statut socio-économique élevé sont plus précoces que celles de statut socio-économique défavorable, mais suivant la région et la dimension de la population, d’autres facteurs influencent l’âge aux premières règles. Dans la province de Cracovie, l’urbanisation, l’éducation du père et le nombre d’enfants dans la famille jouent un rôle significatif. Dans la province d’Opole, ce sont l’urbanisation, l’éducation du père et le nombre d’enfants dans la famille qui interviennent, alors que dans la province de Nowi Sacz, est significatif le nombre d’enfants dans la famille.

Conclusions: Les différences socio-économiques sont plus significatives dans une grande ville (Cracovie), alors que dans les ensembles populationnels plus restreints (Opole, Nowy Sacz), elles sont de moindre importance. Par ailleurs, la variation entre régions révèle un âge aux premières règles plus précoce chez les filles urbaines que chez les rurales.

Zusammenfassung. Hintergrund: Das Menarchealter ist das wichtigste Maß für die sexuelle Reife bei Mädchen und ein empfindlicher Indikator für Umweltbedingungen während der Kindheit.

Ziel: Die Studie analysierte die Beziehung zwischen Menarchealter und sozio-ökonomischen Kennzeichen (Urbanisation, Populationsgröße, Schulbildung der Eltern und Anzahl der Kinder pro Familie).

Probanden und Methoden: Mittels Fragebögen wurden Daten von 3271 Schülerinnen, geboren zwischen 1981 und 1984, aus drei Provinzen Südpolens erhoben. Das Menarchealter wurde retrospektiv erfragt und basiert auf Angaben zur Menarche von den Studienteilnehmerinnen. Es wurden ANCOVA und multiple Regressionsanalysen verwendet, um Unterschiede zwischen den Gruppen auf statistische Signifikanz zu testen.

Ergebnisse: Mädchen aus Familien der oberen sozio-ökonomischen Schicht menstruieren früher als Mädchen aus Familien niederer sozio-ökonomischer Schichten. Je nach geographischer Region und Populationsgröße gibt es jedoch noch weitere Faktoren, die das Menarchealter beeinflussten. Faktoren, die in der Provinz Krakau signifikanten Einfluss auf das Menarchealter zeigen, sind Urbanisationsgrad, Schulbildung des Vaters und Anzahl der Kinder in der Familie; in der Provinz Oppeln beinhalten diese Faktoren den Urbanisationsgrad und die Anzahl der Kinder in der Familie, während in der Provinz Novy Sacz nur die Anzahl der Kinder in der Familie Signifikanzniveau erreichen.

Zusammenfassung: Sozio-ökonomische Unterschiede sind in einer Großstadt (Krakau) größer und nehmen Einfluss auf die Variation des Menarchealters. In den weniger umfangreichen Populationen (Oppeln, Novy Sacz) aus kleineren Städten und Dörfern ist dagegen der Unterschied im Menarchealter weniger offensichtlich. Darüber hinaus zeigt die Variation zwischen Regionen, dass das Menarchealter in städtischen Gegenden niedriger ist als in ländlichen.

Resumen. Antecedentes: La edad de menarquia es la medida más importante de la maduración sexual en chicas y un sensible indicador de las condiciones ambientales durante la infancia.

Objetivo: El estudio analizó la asociación entre la edad de menarquia y características socioeconómicas (urbanización, tamaño poblacional, educación de los padres y número de hijos en la familia).

Sujetos y métodos: Los datos del cuestionario se recogieron en 3271 niñas escolares nacidas entre 1981 y 1984, que residían en tres provincias del sur de Polonia. La edad de menarquia se estimó por el método retrospectivo y se basó en la fecha de menarquia proporcionada por las participantes en el estudio. Se aplicaron los análisis ANCOVA y de regresión múltiple para comprobar la significación estadística de las diferencias entre grupos.

Resultados: Las chicas de familias con un nivel socioeconómico elevado experimentan la menarquia a una edad más temprana que las de familias con un nivel socioeconómico bajo. Sin embargo, dependiendo de la región geográfica y del tamaño poblacional, existen otros factores que influyen sobre la edad de menarquia. En la provincia de Cracovia, los factores que producen diferencias significativas en la edad de menarquia son la urbanización, la educación del padre y el número de hijos en la familia; en la provincia de Opole, estos factores incluyen la urbanización y el número de hijos de la familia, mientras que en la provincia de Nowy Sacz, es significativo el número de hijos por familia.

Conclusiones: Las diferencias socioeconómicas son mayores en una gran urbe (Cracovia) y afectan a la variación en la edad de menarquia. Sin embargo, dentro de poblaciones más pequeñas (Opole, Nowy Sacz), viviendo en pueblos y aldeas, la diferencia en la edad de menarquia es menos evidente. Además, la variación entre áreas revela una menor edad de menarquia en el medio urbano comparado con las áreas no urbanas.     

Is there a relation between vitamin D,interleukin-17, and bone mineral density in patients with inflammatory bowel disease?

IntroductionIn inflammatory bowel diseases (IBD), osteopenia and osteoporosis constitute a significant medical problem. Cytokines, especially IL-17, play an important role in the pathogenesis of IBD and osteoporosis. Vitamin D is a regulator of bone metabolism, and helps maintain immune system homeostasis.Material and methodsThe research sample consisted of 208 persons: 83 patients (age 35 ±11.99 years) with Crohn’s disease (CD); 86 patients (age 39.58 ±14.74 years) with ulcerative colitis (UC); and 39 persons (age 30.74 ±8.63 years) in the control group (CG). Clinical data on bone mineral density of the lumbar spine (L2-L4), bone mineral density of the femoral neck (FN), and body mass index (BMI) were collected. 25OHD and IL-17 serum concentrations were also measured.ResultsBody mass index (kg/m²) results: in CD, 21.51 ±3.68; in UC, 23.31 ±4.38; and in CG, 24.57 ±3.45 (p < 0.01). Densitometry results for L2–L4 T-score SD: in CD –0.83 ±1.45; in UC –0.47 ±1.15; in CG 0.09 ±0.70. Densitometry results for FN T-score SD: in CD –0.62 ±1.26; in UC –0.29±1.17; in CG 0.41 ±1.03 25OHD (ng/ml) serum concentrations: in CD, 21.33±12.50; in UC, 22.04±9.56; in CG, 21.56±9.11 (ns). IL-17 (pg/ml) serum concentrations: in CD, 8.55±10.99; in UC, 11.67±12.97; in CG, 5.16±9.11 (ns).ConclusionsInflammatory bowel diseases patients and persons from the CG did not differ in vitamin D or IL-17 levels. Patients with a mild course of the disease had a higher vitamin D concentration and bone mineral density. In UC, higher vitamin D concentrations were associated with lower IL-17 concentrations. The IBD patients with a severe course of the disease had a lower body mass than those in the CG and the patients with a mild course of the disease.     

Differences between older and younger adults with Borderline Personality Disorder on clinical presentation and impairment

Background

Borderline Personality Disorder (BPD) is well-known to be a clinically severe and impairing diagnosis. Research shows that BPD symptoms decrease in severity over time. However, a subset of patients with BPD continue to meet criteria for the disorder in older adulthood. Little is known about this subset. Perception of BPD as a young-person's diagnosis could lead to under recognition in older patients. As such, the objective of the present report is to provide the first direct comparison between older and younger adults with BPD on demographics, clinical presentation, and functional impairment.

Method

Over 3000 psychiatric outpatients were evaluated with semi-structured diagnostic interviews. Forty-six older adults (age 45–68) and 97 younger adults (age 18–25) met criteria for BPD.

Results

Both groups reported high levels of functional impairment and Axis I comorbidity. Older adults were more likely to endorse chronic emptiness, and less likely to endorse impulsivity, self-harm, and affective instability. Older adults also reported fewer substance use disorders, more lifetime hospitalizations and higher social impairment.

Conclusion

Older adults with BPD had a significantly different clinical presentation from younger adults with BPD, including differences in likelihood of endorsing specific BPD criteria, social impairment, and comorbid substance use. It is important to assess less prototypic features of BPD to avoid overlooking borderline personality features in this population.     

The influence of vascular risk factors on the survival rate of patients with dementia with Lewy bodies and Alzheimer disease

Background and purposeThe aim of this study was to determine whether dementia with Lewy bodies (DLB) progresses more rapidly than Alzheimer disease (AD) and to compare survival after dementia onset and mortality in both dementia groups.Material and methodsA medical records analysis of AD (n = 183) and DLB (n = 51) patients was performed to determine age at onset of symptoms, the date of first presentation to the psychiatric services, dementia severity at diagnosis (MMSE score), and mean disease duration before diagnosis. Categorical data regarding vascular risk factors were collected. Projected decline rate (MMSE/year), survival rate after the diagnosis of dementia, mean survival time after diagnosis and mortality rate were calculated and compared between DLB and AD groups.ResultsThe comparison of clinical and demographic parameters revealed no significant differences between groups, apart from a more pronounced decline rate in the DLB group. Diabetes, and to a lesser extent hypertension, influenced survival in AD, but not in DLB subjects. Overall, however, the difference in mortality rates and survival time between DLB and AD subjects cannot be attributed to the presence of any vascular risk factor analysed. DLB, independently of the presence of vascular risk factors, seems to be a more aggressive disorder than AD, when mortality and survival time are taken into account.ConclusionsMore rapid progression of cognitive decline and shorter duration of dementia were found in DLB in this naturalistic study. The findings may have important implications for the management and treatment of DLB and should be confirmed in prospective studies.     

Sustained unemployment in psychiatric outpatients with bipolar disorder: frequency and association with demographic variables and comorbid disorders

Zimmerman M, Galione JN, Chelminski I, Young D, Dalrymple K, Ruggero CJ. Sustained unemployment in psychiatric outpatients with bipolar disorder: frequency and association with demographic variables and comorbid disorders.
Bipolar Disord 2010: 12: 720–726. © 2010 The Authors.
Journal compilation © 2010 John Wiley & Sons A/S. Objectives: The negative impact of bipolar disorder on occupational functioning is well established. However, few studies have examined the persistence of unemployment, and no studies have examined the association between diagnostic comorbidity and sustained unemployment. In the present report from the Rhode Island Methods to Improve Diagnostic Assessment and Services (MIDAS) project, we described the amount of time unemployed in the five years before the evaluation in a large cohort of outpatients diagnosed with bipolar disorder, and determined the demographic and clinical correlates of sustained unemployment. Methods: A total of 206 patients diagnosed with DSM‐IV bipolar I or bipolar II disorder were interviewed with semi‐structured interviews assessing comorbid Axis I and Axis II disorders, demographic and clinical variables. The interview included an assessment of the amount of time missed from work due to psychiatric reasons during the past five years. Persistent unemployment was defined as missing up to two years or more from work. Results: Less than 20% of the patients reported not missing any time from work due to psychiatric reasons, and more than one‐third missed up to two years or more from work. Prolonged unemployment was associated with increased rates of current panic disorder and a lifetime history of alcohol abuse or dependence. Patients with prolonged unemployment were older and experienced more episodes of depression. Conclusions: Most patients presenting for the treatment of bipolar disorder have missed some time from work due to psychiatric reasons, and the persistence of employment problems is considerable. Comorbid psychiatric disorders are a potentially treatable risk factor for sustained unemployment. It is therefore of public health significance to determine if current treatments are effective in bipolar disorder patients with current panic disorder, and if not, to attempt to develop treatments that are effective.     

Evidence for a relatively high proportion of DM2 mutations in a large group of Polish patients

Introduction

Myotonic dystrophies (DMs) type 1 (DM1) and type 2 (DM2) are autosomal dominant, multisystem disorders, considered the most common dystrophies in adults. DM1 and DM2 are caused by dynamic mutations in the DMPK and CNBP genes, respectively.

Microbiological effects in patients with leg ulcers and diabetic foot treated with Lucilia sericata larvae

Lucilia sericata bottle fly worms can be used to heal infected, chronic, or necrotic wounds, including those associated with ulceration and diabetic foot. The study aimed to evaluate changes in the microflora in patients treated with L sericata larvae due to leg ulcers and diabetic foot. One hundred twenty-nine patients diagnosed with lower limb ulceration and diabetic foot were enrolled in the study, of which 80 of them met the eligibility criteria for maggot debridement therapy (MDT). On the contrary, 49 unqualified patients were offered ozone therapy (22 with leg ulcers; 27 with diabetic foot). In each of these patients, a microbiological swab was performed before and after the start of therapy. The group of 80 patients was further divided into four equal groups in terms of the treated area (lower leg vs foot) and the number of larvae/cm² (5 vs 10). Twenty-three particular species of bacteria in the infected wound were studied microbiologically in terms of presence/absence within the wound environment before and after treatment of patients with diabetic foot and lower limb ulceration. It was noted that there was a more intensive bacterial accumulation in the feet of patients compared to legs; furthermore, this applies to almost all analysed species. Diabetes status is also a clinical factor that generates a lower chance of bacterial appearance in the wound environment. Densification of MDT larvae per wound area unit also reduced the chance of the presence of Corynebacterium species, Enterobacteriaceae, Pseudomonas aeruginosa, Staphylococcus aureus MSSA, and Streptococcus coagulase negativa; however, it increased the likelihood of occurrence for Proteus mirabilis and the Proteus species. A microbiological analysis in this non-reference study shows the efficacy of larval therapy for leg and foot ulcers. Rearrangement of the microflora within the wound has been reported as a result of the therapy.