Nephrin is specifically located at the slit diaphragm of glomerular podocytes

We describe here the size and location of nephrin, the first protein to be identified at the glomerular podocyte slit diaphragm. In Western blots, nephrin antibodies generated against the two terminal extracellular Ig domains of recombinant human nephrin recognized a 180-kDa protein in lysates of human glomeruli and a 150-kDa protein in transfected COS-7 cell lysates. In immunofluorescence, antibodies to this transmembrane protein revealed reactivity in the glomerular basement membrane region, whereas the podocyte cell bodies remained negative. In immunogold-stained thin sections, nephrin label was found at the slit between podocyte foot processes. The congenital nephrotic syndrome of the Finnish type (NPHS1), a disease in which the nephrin gene is mutated, is characterized by massive proteinuria already in utero and lack of slit diaphragm and foot processes. These features, together with the now demonstrated localization of nephrin to the slit diaphragm area, suggests an essential role for this protein in the normal glomerular filtration barrier. A zipper-like model for nephrin assembly in the slit diaphragm is discussed, based on the present and previous data.     

High expression of nitric oxide synthases is a favorable prognostic sign in non-small cell lung carcinoma

Immunohistochemical expression of neuronal (n), endothelial (e), and inducible (i) NOS and their association with the type, grade, apoptotic index, proliferation of tumors and the survival of patients were investigated in 89 biopsies of non-small cell lung carcinoma (NSCLC). In tumor cells, expression of iNOS was detected in 35/89 (40%) cases, while 79/89 (89%) and 72/89 (81%) cases showed weak to intense positivity for eNOS and nNOS, respectively. Strong eNOS staining was seen significantly more often in adenocarcinomas than in squamous cells carcinomas (p=0.016), and iNOS immunoreactivity was seen more often in grade I-II tumors than in grade III tumors (p=0.024). There was no significant difference between the low and high apoptotic indexes or between the low and high proliferation rates of tumors in any instance of NOS staining. The patients with tumors showing high nNOS expression tended to have better survival than the others (p=0.06, log-rank; p=0.04, Bresow; p=0.048, Tarone-Ware). Similarly, the patients with tumors showing high expression of iNOS, eNOS and nNOS, as determined by a combined sum index, had a better survival than those with a low sum index for these enzymes (p<0.05). The results show intense expression of eNOS and nNOS, and moderate expression of iNOS in tumor cells of non-small cell carcinoma. Intense NOSs expression seems to be a favorable prognostic sign in non-small cell lung carcinoma.     

BRCA1 and BRCA2 mutation analysis in breast-ovarian cancer families from northeastern Poland

Sixty high-risk breast and/or ovarian cancer families from North-Eastern Poland were screened for germline mutations in BRCA1 (MIM# 113705) and BRCA2 (MIM# 600185), using a combination of protein truncation test, denaturing high-performance liquid chromatography and direct sequencing. Sixteen (27%) of the families were found to carry nine different BRCA mutations, including 14 families with BRCA1 mutation and two families with BRCA2 mutation. The results suggest the presence of two strong BRCA1 founder mutations in the Polish population - 5382insC (6 families) and 300T>G (Cys61Gly; 3 families). The remaining seven mutations were found in single families and included three previously reported BRCA1 mutations (185delAG, 2682C>T [Gln855Ter] and 3819del5), a novel BRCA1 mutation (IVS14+1G>A), as well as two BRCA2 mutations (4088delA and 7985G>A [Trp2586Ter]) not previously observed in Polish families. We confirm the strong influence of two Central-Eastern European BRCA1 founder mutations in familial breast and/or ovarian cancer in Poland. We also conclude that the Polish population has a more dispersed BRCA mutation spectrum than had been earlier thought. This warrants further careful BRCA mutation screening in order to optimise genetic counselling and disease prevention in affected families.     

Decline in suicidal ideation among patients with MDD is preceded by decline in depression and hopelessness

BACKGROUND: Suicidal ideation is likely to represent a phase preceding suicidal acts among most suicidal patients with major depressive disorder (MDD). Factors predicting reversal of the suicidal process are unknown. Our aim was to test the hypothesis that a decline in suicidal ideation is preceded by a decline in hopelessness among patients with MDD. METHOD: Of the 269 Vantaa Depression Study patients with DSM-IV MDD, 103 patients scored > or = 6 points at baseline on the Scale for Suicidal Ideation (SSI). Seventy of these patients were followed-up weekly either until they scored zero points on the SSI, or up to 26 weeks. RESULTS: The median duration for a decline of suicidal ideation to zero was 2.2 months after baseline. The level of baseline suicidal ideation, depressive symptoms, and the presence of any personality disorder predicted duration of suicidal ideation. A decline in both depression (BDI) and hopelessness (HS) independently predicted a decline in suicidal ideation. LIMITATIONS: Due to study design, we do not know if suicidal ideation relapsed after the first time the patient reached zero score in the SSI. CONCLUSIONS: Among patients with major depressive disorder having suicidal ideation, the decline in suicidal ideation is independently predicted by preceding declines in the levels of both depressive symptoms as well as hopelessness. The findings are consistent with possible causal roles of declines in depression and hopelessness in reversing the suicidal process.     

A randomised controlled multicentre trial of women’s and men’s satisfaction with two models of antenatal education

Objective

to study women’s and men’s satisfaction with two models of antenatal education: natural childbirth preparation with psychoprophylaxis, and standard antenatal education including preparation for childbirth and parenthood but no psychoprophylaxis.

Design

randomised controlled multicentre trial.

Setting

15 antenatal clinics in Sweden between January 2006 and May 2007.

Participants

1087 nulliparous women and 1064 of their partners.

Interventions

both models had four two-hour sessions during pregnancy and one session post partum. The natural model was manual-based and focused on childbirth preparation, including psychoprophylaxis. In the standard care model, the group leader was free to choose her teaching approach, with an equal amount of time allocated to preparation for childbirth and for parenthood.

Measures

women’s and men’s evaluation of antenatal education at three months post partum. The proportion of women and men in each model that expressed satisfaction with the education were compared using χ² test.

Findings

more women and men in the natural groups were satisfied with the education compared with the standard care groups: women 76% versus 68% (p=0.03) and men 73% versus 65% (p=0.03). The figures were similar for satisfaction with the childbirth preparation component: 78% and 62% in women (p<0.001), and 79% and 67% in men (p<0.001) in the natural and standard care groups, respectively. Fewer participants were satisfied with the parenthood preparation component, but the proportions were higher in the standard care groups: women 37% versus 32% (p<0.001) and men 23% versus 20% (p<0.001).

Conclusion and implications for practice

a structured manual-based model of antenatal education which focuses on childbirth preparation with psychoprophylaxis may better meet expectant parents’ expectations than standard antenatal education in Sweden.     

Experiences of physical and sexual abuse and their implications for current health

OBJECTIVE: To estimate the prevalence of a history of physical and sexual abuse in adulthood among gynecological patients and the association with general and reproductive health. METHODS: A cross-sectional questionnaire study on abusive experiences of gynecologic outpatients in a tertiary hospital. The total sample size was 691. RESULTS: Of all women, 42.4% had experienced moderate or severe physical or sexual abuse as an adult. One hundred forty-seven (21.6%) women reported physical abuse, 84 (12.3%) sexual abuse, and 58 (8.5%) both. The abused and nonabused women did not differ in mean age, education, or parity. Sexually abused women and those who were both sexually and physically abused reported poor general health significantly more often (P=.005 and P=.001, respectively) than the nonabused. They also rated their sex life as significantly worse than the nonabused women (P=.002 and P=.012, respectively). Over half of abused women had experienced common physical complaints during the previous 12 months compared with one third of the nonabused (P<.001). Two thirds of both the abused and the nonabused women preferred that their gynecologist not ask directly about abuse. CONCLUSION: Abusive experiences were common in gynecologic outpatients. Women with abusive experiences had ill health and poor sexual life more often than the controls. In contrast to the results of previous studies, most of the women did not want to be asked about abuse by their gynecologist.     

Serum markers of macrophage activation in pre-eclampsia: no predictive value of soluble CD163 and neopterin

BACKGROUND: Alternatively activated macrophages expressing the CD163 and CD206 surface receptors are the dominant immune-cell type found in the placenta. The placental number and distribution of macrophages is altered in pre-eclampsia, and the generalised inflammatory reaction associated with pre-eclampsia might lead to shedding of soluble CD163 into the circulation. METHODS: Serum samples from 18 women with pre-eclampsia and 90 normal pregnancies were obtained from a longitudinal study of 955 pregnant women at Randers County Hospital, Denmark. sCD163 and Neopterin were measured by ELISA on samples collected in weeks 18, 28, 32, and 38 of pregnancy. RESULTS: sCD163 levels in pregnancy (2-3 mg/l) were similar to previously measured levels in non-pregnant women, and did not increase from week 18 to 38. There was a tendency towards higher sCD163 in week 38 in pre-eclamptic women compared to healthy women. Neopterin increased throughout pregnancy in both healthy (from median 5.4 to 6.7 nmol/l, p<0.0001) and pre-eclamptic women (from 5.0 to 8.0 nmol/l, p<0.0001), but there were no differences between groups at any time-point. sCD163 correlated to neopterin in both the control (r=0.25, p<0.0001) and in the pre-eclampsia group (r=0.32, p=0.011). C-reactive protein was higher in pre-eclampsia than in healthy pregnancies by week 38 (159 versus 91 nmol/l, p=0.0189). CONCLUSIONS: The macrophage serum-markers sCD163 and neopterin are not pre-symptomatic nor prognostic markers for pre-eclampsia.     

Comparison of self-reported emotional and behavioural problems in adolescents from Greece and Finland

AIM: To compare self-reported emotional and behavioural problems among Greek and Finnish adolescents. METHODS: Youth Self-Report scores were analysed for 3373 Greek adolescents aged 18 years and 7039 Finnish adolescents aged 15-16 years from the general population in both countries. The impact of country, gender, place of residence, socioeconomic status (SES) and family stability on the scores was evaluated. RESULTS: Only country and gender yielded small to medium effect on the scores. Greek boys scored significantly higher than Finns on 10 of the 11 YSR syndromes, particularly on the anxious/depressed scale. Greek girls scored significantly lower than Finnish girls on the somatic complaints and delinquent behaviour scales. In general, girls scored higher than boys on both internalising and externalising problems. The gender by country interaction revealed that Finnish girls reported more externalising problems. CONCLUSION: The main differences marked in this comparison were the higher level of anxiety and depression in Greeks than Finns and the higher level of externalising problems in Finnish girls than boys. Cultural standards could play an important role in explaining these differences. Overall, it seems that only a small number of differences exist between a northern and southern European region.     

Gender differences in age and BMI distributions in partial upper airway obstruction during sleep

The obstructive sleep apnea-hypopnea syndrome occurs more frequently and with higher apnea-hypopnea indices in men than in women. To investigate the gender differences we extended our respiratory analyses during sleep to cover not only periodic obstruction (apnea and hypopnea) but also nonperiodic partial upper airway obstruction during sleep and their associations with increasing age or body mass index (BMI). The clinical sleep recordings with the static-charge-sensitive bed (SCSB) and oximeter were reviewed in 233 age and BMI-matched men-women pairs. Periodic obstruction increased with increasing BMI only in men. Nonperiodic partial obstruction increased with moderate to morbid obesity in women and men after the age of 65 years. Our findings suggest that while partial upper airway obstruction increases with increasing age and BMI in both genders, men have a gender specific BMI dependent predisposition for periodic obstruction (obstructive sleep apnea). The apnea-hypopnea index is likely to underestimate the impact of sleep-disordered breathing, particularly in elderly patients.