Differential gene expression in classic giant cell tumours of bone: Tenascin C as biological risk factor for local relapses and metastases

Pazzaglia L, Conti A, Chiechi A, Novello C, Magagnoli G, Astolfi A, Pession A, Krenacs T, Alberghini M, Picci P & Benassi M S (2010) Histopathology 57 , 59–72
Differential gene expression in classic giant cell tumours of bone: Tenascin C as biological risk factor for local relapses and metastases Aims: To identify candidate prognostic biological markers useful in selecting high‐risk patients with classic primary giant cell tumours (GCT). GCT specimens with different behaviour associated with an increased risk of local and/or distant relapses were studied. Methods and results: Screening mRNA microarray analysis followed by real‐time polymerase chain reaction and immunohistochemistry on tissue microarray sections was used to validate the prognostic role of differentially expressed genes on a larger series by statistical analysis tests. Global gene expression profiling identified 109 differentially expressed genes according to prognosis. A correlation was found between mRNA levels and clinical outcome identifying Tenascin C (TNC) as the most significant prognostic biological marker. By means of backward Wald logistic regression, TNC overexpression defined an eightfold increased risk for metastasis and fourfold for local recurrence. At the protein level, TNC immunoreactivity resulted in a significant difference in the disease‐free survival probability curves, providing a stratification for GCT patients, useful for predicting relapse. Conclusions: Our study provides important data for the selection of biomarkers with a significant clinical impact and suggests the importance of TNC expression in identifying GCT patients at a higher risk of relapse for closer follow‐up and adjuvant medical therapy.     

El torbellino de la violencia. Relatos biográficos de mujeres que sufren maltrato

ObjectivesTo analyse the experience from the point of view of women who have suffered domestic violence. To identify factors related to continuing or resolving the problem.DesignQualitative interpretative research from a phenomenological perspective.Population sampleWomen, detected in primary care, who have suffered domestic violence and have recognised the problem, and who accepted to participate in this research.Multicentre StudySix health centres in the city of Malaga.Methods and techniquesThe technique used is the biographical narration using individual open interviews between social workers and women. This narration was tape-recorded and verbatim transcribed to written text. Grounded theory. Qualitative analysis was made with ATLAS-TI 5.2.OutcomesA total of 35 narrations were analysed. The abuse situation was described as “whirl-wind” metaphor (blindness-isolation-helplessness-suffering-destiny-dependence-fantasies -about love, protection, happiness, change- and vicious circles). Enduring experience is reported to be related to several factors: inculcated gender values, family-ideal, uncertainty, annulment, personal failure sensation, love, support defects, self-image, children protection, multiple fears and material aspects. They identified two types of “exit”: passive and active with different mechanisms and repercussions. Exit experience is related to: limit situations, children intervention, family ideal attempts, and fear-loss. Leaving is a transitional process or “pathway”. Institutional support is not always guaranteed and emotional support is better evaluated than a legal one.ConclusionsEnduring and coming out are reported as two qualitatively different states, which involve many cultural and personal factors. There is a gap between these two states with a process that varies depending on the involvement of the women in decision-making.     

Multilocus Analyses Reveal Involvement of the ESR1, ESR2, and FSHR Genes in Migraine

Objective.— Female hormone genes have been investigated in migraine in recent years. Research in this field has been controversial, especially in regard to ESR1 gene findings. None of the reports have yet to approach the problem from a multigenic point of view. Methods.— We investigated 5 polymorphisms implicated in female hormone metabolism (FSHR, CYP19A1, ESR1, NRIP1, and ESR2) in a cohort of 730 subjects matched for age and sex. The effect of gene–gene interaction was assessed using the set association approach, and the corresponding haplotypes were studied with PM Plus software. To corroborate initial results, we analyzed the selected markers using a cohort of 134 families in which 168 trios were suitable for transmission‐disequilibrium test (TDT) analysis under the migraine with aura (MA) phenotype. Results.— A total of 356 consecutive migraine patients (198 with MA [76% females] and 158 migraine without aura [MO, 74% females], and 374 matched controls [71% females]) were genotyped. In the 2‐point analyses, the ESR1 and ESR2 polymorphisms showed nominal association under MA/MO phenotype, and this association was higher with the FSHR polymorphism in MA females (P = .004, uncorrected). Using the SUMSTAT program, we observed ESR2‐ESR1‐FSHR significant gene–gene interaction, suggesting association with the MA/MO phenotype (P = .005; P = .003 in females), and with MA alone (P = .021; P = .030 for females). We corroborated that ESR2‐ESR1‐FSHR haplotypes interacted for migraine under a model‐free hypothesis (empirical P = .010 for the whole sample; P = .001 for females), and the association was stronger for the MA phenotype alone (empirical P = 5.0e‐4, under the heterogeneity model; P = .001 for females). These results were corroborated using family‐based association approaches. We observed nominal association for ESR2 and ESR1 (P = .031 and .034, respectively) in the TDT study, and significant association for ESR1 using family‐based association test statistics. Haplotype‐TDT analyses showed further significant gene–gene interaction for ESR1‐ESR2 (global P = .009), ESR2‐FSHR (global P = .011), and nominally significant interaction for ESR2‐ESR1‐FSHR genes (global P = .037). Conclusion.— We found significant association of female hormone metabolism polymorphisms under the perspective of multigene approach.     

History of violence and subjective health of mother and child

Objective: To study the self-reported prevalence of experienced violence among a cohort of women about two years after giving birth, their health during pregnancy, pregnancy outcomes and their experience of their child’s health.

Setting and subjects: In 2011, a total of 657 women participated in phase III of the Childbirth and Health Cohort Study in Icelandic Primary Health Care, 18 to 24 months after delivery. The women had previously participated in phase I around pregnancy week 16 and phase II 5–6 months after delivery. Data were collected by postal questionnaires.

Main outcome measures: Women’s reported history of experienced violence, sociodemographic and obstetric background, self-perceived health, the use of medications and their child’s perceived health.

Results: In phase III, 16% of women reported experiencing violence. These women felt less support from their current partner (p?p?p?p?p?p?=?0.008).

Conclusions: Our study confirms that a history of violence is common among women. A history of violence is associated with various maternal health problems during and after pregnancy, a higher rate of caesarean sections and maternal reports of health problems in their child 18–24 months after birth.

• KEY POINTS

• Violence is a major concern worldwide. Understanding the impact of violence on human health and developing effective preventive measures are important elements of any public health agenda.

• ??The reported prevalence of experiencing violence was 16% among women attending antenatal care in the primary health care setting in Iceland.

• ??Women with a history of violence reported worse health in general during pregnancy and delivered more often by caesarean section, compared to women with no such history.

• ??Mothers with a history of violence also evaluated the general health of their child as worse than women with no such history.

• ??The findings of this study support the importance of recognizing and addressing experienced violence among women in primary care.

     

Retrospective survey on falls among hospitalized patients

Patients' falls are a frequent event, especially for hospitalised patients, with a substantial impact on their health and healthcare costs. In the Careggi Hospital (Florence) the reports of patients' falls were analysed to provide real-life based information on the problem and to explore the possibility of preventive planning. During the year 2000, 359 patients (0.44% of all admitted patients) suffered an event of fall. Medical wards and wards with stroke patients show the higher incidence of falls (0.71% and 0.66% of all admitted patients respectively). The larger majority of patients who fall (68.2%) were over 65 years and almost half (46.7%) of the falls occurred during the night shift. Up to 79% of patients reported some consequences but only 3.6% of them reported major consequences requiring a prognosis > 10 days. The preventive strategies adopted are described.     

Pathway of free fatty acid oxidation in human subjects. Implications for tracer studies.

To determine the pathway of plasma FFA oxidation and the site(s) of label fixation observed during infusion of FFA tracers, [1-13C]palmitate and [1-14C]acetate were infused intravenously for 3 h in five volunteers. Breath 13CO2 enrichment and 14CO2 specific activity were followed for 6 h to determine the labeled CO2 decay rates. Acetate enters directly into the TCA cycle; hence, if palmitate transits a large lipid pool before oxidation, 13CO2 enrichment (from palmitate) should decay slower than 14CO2 specific activity (from acetate). Breath 13CO2 enrichment and 14CO2 specific activity decayed at a similar rate after stopping the tracer infusions (half-lives of 13CO2 and 14CO2 decay: mean [+/- SE] 106.6 +/- 8.9 min, and 96.9 +/- 6.0 min, respectively, P = NS), which suggests that palmitate enters the TCA cycle directly and that label fixation occurs after citrate synthesis. Significant label fixation was shown in plasma glutamate/glutamine and lactate/pyruvate during infusion of either [1,2-13C]acetate or [U-13C]palmitate, suggesting that TCA cycle exchange reactions are at least partly responsible for label fixation. This was consistent with our finding that the half-lives of 13CO2 enrichment and 14CO2 specific activity decreased significantly during exercise to 14.4 +/- 3 min and 16.8 +/- 1 min, respectively, since exercise significantly increases the rate of the TCA cycle in relation to that of the TCA cycle exchange reactions. We conclude that plasma FFA entering cells destined to be oxidized are directly oxidized and that tracer estimates of plasma FFA oxidation will underestimate the true value unless account is taken of the extent of label fixation.     

Maternal hepatitis B virus or hepatitis C virus carrier status as an independent risk factor for adverse perinatal outcome

Objective: To examine the impact of maternal hepatitis B virus (HBV) or hepatitis C virus (HCV) carrier status on pregnancy outcomes. Methods: A population‐based study was performed by comparing all pregnancies of HBsAg and/or anti‐HCV seropositive women who delivered during the years 1988–2007 with all other pregnant women who delivered in the same period. Multivariable logistic regression models were constructed to control for confounders. Results: Seven hundred and forty‐nine hepatitis seropositive pregnant women were identified out of 186 619 deliveries (0.4%). Maternal characteristics, as well as perinatal outcomes, were comparable between the HBV and HCV carriers. HBV/HCV carriers had higher rates of preterm deliveries (<37 weeks gestation; 11.5 vs. 7.9%, P<0.001), premature rupture of membranes (8.9 vs. 6.9%, P=0.026), placental abruption (1.5 vs. 0.7%, P=0.018), labour induction (33.9 vs. 28.1%, P<0.001) and Caesarean deliveries (19.0 vs. 13.2%, P<0.001). Higher rates of perinatal mortality (2.3 vs. 1.3%, P=0.016), congenital malformations (7.2 vs. 5.1%, P=0.01) and low birth weight (<2500 kg; 10.4 vs. 7.8%, P=0.009) were noted in newborns of hepatitis carriers compared with the control group. Controlling for possible confounders such as maternal age and parity by using multivariable analyses, the significant association between HBV or HCV carrier status and perinatal mortality, congenital malformations and low birth weight remained significant. Conclusions: Maternal HBV or HCV carrier status is an independent risk factor for adverse perinatal outcome and careful surveillance is warranted.