Communication patterns in families affected by parental cancer from the healthy parents' perspective-process evaluation of the complex intervention Family-SCOUT.

PURPOSE: Within families affected by parental cancer, open communication impacts the well-being of parents and their children; however, limited research exists on communication patterns in these families. This sub-study addresses this through the Family-SCOUT study, a multicenter, prospective, interventional, and non-randomized investigation with intervention (IG) and control group (CG). The purpose of this sub-study was to identify and compare the differences in communication patterns between the IG and CG as part of the process evaluation. The research question was addressed in both groups: What communication patterns do healthy parents perceive within their families? METHODS: Using a qualitative approach, the study involved interviewing healthy parents as surrogates for their families. The interviews were audio-recorded, transcribed, and coded using a template analysis. The resulting data were analyzed at the group level. RESULTS: Twenty-three interviews were conducted in the IG and 27 interviews in the CG. The analysis of themes centered on communication patterns as seen in the family structure. Both groups exhibited instances of open communication about fears and wishes as well as the use of child-friendly language when discussing cancer. Notable differences were observed: challenges in open communication with children were sorely reported in CG interviews, and "the illness is discussed when necessary" was sorely described in IG interviews. CONCLUSION: This study underscores the need to address and encourage open communication within families with parental cancer.

Effectiveness of a comprehensive support program for families with parental cancer (Family-SCOUT): results of a multicenter non-randomized controlled trial.

BACKGROUND: Cancer patients with minor children but also their families suffer from significant psychological distress and comorbidity. Protective factors predicting successful coping are well known. Corresponding systematic interventions are rare and limited by access barriers. We developed a comprehensive family-centered intervention for cancer patients with at least one dependent minor. PATIENTS AND METHODS: Family-SCOUT represents a multicentric, prospective, interventional, and controlled study for families with parental cancer and their minor children. In the intervention group (IG), all family members were addressed using a care and case management approach for nine months. Families in the control group (CG) received standard of care. Participating parents were asked to complete the Hospital-Anxiety-Depression-Scale (HADS) questionnaire at enrolment (T0) and after 9 months (T2). The primary outcome was a clinically relevant reduction of distress in at least one parent per family, measured as minimal important difference (MID) of ≥1.6 in the HADS total score. The percentage of families achieving MID is compared between the IG and CG by exact Fisher's test, followed by multivariate confounder analyses. RESULTS: T0-questionnaire of at least one parent was available for 424 of 472 participating families, T2-questionnaire after 9 months was available for 331 families (IG n = 175, CG n = 156). At baseline, both parents showed high levels of distress (HADS total: sick parents IG: 18.7 ± 8.1; CG: 16.0 ± 7.2; healthy partners: IG: 19.1 ± 7.9; CG: 15.2 ± 7.7). The intervention was associated with a significant reduction in parental distress in the IG (MID 70.4% in at least one parent) compared with the CG (MID 55.8%; P = 0.008). Adjustment for group differences from specific confounders retained significance (P = 0.047). Bias from other confounders cannot be excluded. CONCLUSIONS: Parental cancer leads to a high psychosocial burden in affected families. Significant distress reduction can be achieved through an optimized and structured care approach directed at the family level such as family-SCOUT.

Cell lineage in molluscan development.

Cell lineage specification in molluscs is brought about by two mechanism: the segregation of morphogenetic plasms and inductive cell interactions. The evidence for the existence of morphogenetic plasms is largely circumstantial, but in one species, Bithynia, such a plasm has been identified in the polar lobe that forms at first cleavage. Inductive cell interactions are thought to be a prerequisite for the development of a large number of tissues and organs. The most extensively studied example is the specification of the mesodermal stem cell in Lymnaea and Patella, which occurs between 5th and 6th cleavage through an interaction between one macromere and a large number of micromeres. Both segregation and induction are tuned to the animal-vegetal polarity of the egg, at least during early development. This polarity probably arises during oogenesis and is manifest in regional differentiations of the surface architecture of the egg, in the distribution of inner membrane particles in the plasma membrane, in membrane fluidity characteristics, in ionic conductance properties of the plasma membrane, etc. All these phenomena have in common that they represent properties of the egg surface, suggesting that the polarity of the egg is somehow imprinted into the plasma membrane and the cortex of the egg during oogenesis.

Effect of vitamin A deficiency on the activity of macrophages in Newcastle disease virus-infected chickens.

The effect of vitamin A deficiency on the activity of peritoneal macrophages (PM) was investigated in noninfected and Newcastle disease virus (NDV)-infected chickens. Day-old chickens with limited vitamin A reserves were fed diets containing either marginal (120 retinol equivalents (RE)/kg) or adequate (1200 RE/kg) levels of vitamin A. At 4 weeks of age, half of the chickens in each group were infected with the La Sota strain of NDV and PM were isolated 11 or 12 days later. These were used for counting the uptake of fluorescein isothiocyanate-labeled yeast cells as an indicator of phagocytic activity and for measuring the reduction of nitroblue tetrazolium (NBT), which provides an estimate of oxygen-dependent killing of microorganisms. Vitamin A deficiency impaired NBT reduction and, to a lesser extent, phagocytosis in both infected and noninfected chickens. NDV infection increased phagocytosis and NBT reduction in normal and, to a lesser extent, in vitamin A-deficient chickens.

Relationship between intra-uterine bacterial contamination, endotoxin levels and the development of endometritis in postpartum cows with dystocia or retained placenta.

A study was conducted to investigate the relationship between intra-uterine bacterial contamination, endotoxin levels and the development of endometritis in cows that experienced a dystocia or retained their placenta. Fifteen healthy cows, 31 cows with retained placenta (RP) and 13 cows that had dystocia were clinically examined 1 or 2 days after parturition when a uterine swab for bacteriological examination was taken. In addition, plasma and uterine lochia samples were collected to determine lipopolysaccharide (LPS) and the plasma IgG anti-LPS concentrations. Subsequently, 15 RP and 6 dystocia cows were initially left untreated and another uterine swab was collected at 2 and 4 wk postpartum. Immediately after calving, RP cows had significantly higher LPS levels in uterine lochia (average of 2.24 x 10(4) Endotoxin Units (EU)/mL) as compared to dystocia and healthy postpartum cows (average of 0.10 and 0.26 EU/mL, respectively). However, plasma LPS levels were below the detection limit (<0.036 EU/mL platelet-rich plasma) in all groups of cows. IgG anti-LPS levels in plasma were not significantly different between the 3 groups immediately postpartum (average of 26, 16 and 44 Median Units (MU)/mL) for healthy, dystocia and RP cows, respectively), but they were significantly lower when compared to plasma IgG anti-LPS levels of healthy cows at more than 2 months postpartum (mean 83 MU/mL). High LPS levels in lochia at 1 or 2 days postpartum were significantly related to abnormal cervical discharge, the presence of Escherichia coli, black pigmented gram-negative anaerobes and Clostridium spp. shortly after calving, and Arcanobacterium pyogenes and gram-negative anaerobes in the uterus at 14 days postpartum. These results suggest that the presence of E. coli and LPS (endotoxins) in lochia early postpartum favor the development of uterine infections by A. pyogenes and gram-negative anaerobes later postpartum. LPS were not observed in plasma, suggesting that either they are not absorbed into the blood, or they are efficiently detoxified by IgG anti-LPS or other detoxification mechanisms.

Loss of function of the ALS protein SigR1 leads to ER pathology associated with defective autophagy and lipid raft disturbances.

Intracellular accumulations of altered, misfolded proteins in neuronal and other cells are pathological hallmarks shared by many neurodegenerative diseases including amyotrophic lateral sclerosis (ALS). Mutations in several genes give rise to familial forms of ALS. Mutations in Sigma receptor 1 have been found to cause a juvenile form of ALS and frontotemporal lobar degeneration (FTLD). We recently described altered localization, abnormal modification and loss of function of SigR1 in sporadic ALS. In order to further elucidate the molecular mechanisms underlying SigR1-mediated alterations in sporadic and familial ALS, we extended our previous studies using neuronal SigR1 knockdown cell lines. We found that loss of SigR1 leads to abnormal ER morphology, mitochondrial abnormalities and impaired autophagic degradation. Consistent with these results, we found that endosomal trafficking of EGFR is impaired upon SigR1 knockdown. Furthermore, in SigR1-deficient cells the transport of vesicular stomatitis virus glycoprotein is inhibited, leading to the accumulation of this cargo protein in the Golgi apparatus. Moreover, depletion of SigR1 destabilized lipid rafts and associated calcium mobilization, confirming the crucial role of SigR1 in lipid raft and intracellular calcium homeostasis. Taken together, our results support the notion that loss of SigR1 function contributes to ALS pathology by causing abnormal ER morphology, lipid raft destabilization and defective endolysosomal pathways.

Local surface modulation correlated with ooplasmic segregation in eggs ofSabellaria alveolata (annelida, polychaeta).

In the eggs ofSabellaria alveolata specific morphogenetic determinants are segregated into the vegetal part of the egg which is constricted off to form a polar lobe during the first cleavages. Segregation is supposed to take place during meiosis. In this paper we describe the appearance of a patch of small blebs at the vegetal pole of the eggs after both the first and the second meiotic division and after the first cleavage, as assessed by scanning electron microscopy. We investigated the possible functional relationship between the segregation process and the modulation of the surface architecture at the vegetal pole by treating the eggs with cytochalasin B during meiosis. As a result, both the appearance of the blebs and the development of lobe-dependent structures in the larva are suppressed. From this result it is argued that cortical processes at the vegetal pole are likely to be involved in the segregation of morphogenetic determinants.

The ultrastructure of the polar lobe of Crepidula fornicata (Gastropoda, Prosobranchia).

Some novel structural features of the polar lobe of the egg of Crepidula are described. The significance of two kinds of aggregate is discussed in relation to the morphogenetic factors present in polar lobes generally. Surface configurations of the polar lobe are also described.

Ionic Currents in Lymnaea stagnalis Eggs During Maturation Divisions and First Mitotic Cell Cycle.

The eggs of the mollusc Lymnaea stagnalis generate weak extracellular ionic currents, which have been mapped from oviposition through first cleavage. Throughout this period the current is inward in the animal hemisphere, with highest density at the animal pole, and outward in the vegetal hemisphere, with highest density at the vegetal pole. Peak current densities are measured at the time of first and second polar body formation. During anaphase and telophase of the first mitotic cell cycle, the outward current at the vegetal pole reaches its minimum density and its direction is reversed in most eggs, whereas the inward current at the animal pole gradually increases. This coincides with the segregation of the so-called animal pole plasm to the animal pole (Raven, 1970). The organic calcium channel blockers diltiazem and D600 cause abnormal maturation division(s) and/or first cleavage. At the same time they reduce and eventually abolish the associated ionic currents. These results suggest the existence of a cell-cycle correlated, calcium-dependent component of ionic currents in Lymnaea eggs.

Cell lineage-specific inhibition of cytokinesis by concanavalin A in a molluscan embryo (Nassarius reticulatus, Gastropoda).

The effects of the lectin concanavalin A (Con A) on cleavage were studied in early embryos of the gastropodNassarius reticulatus. Progression of the first cleavage furrow is inhibited by incubating eggs before the first cleavage with 0.3-20 µg/ml Con A. Treatment with 1.0-20 µg/ml Con A during first cleavage causes regression of the cleavage furrow. Treatment with low concentrations (0.3-1.0 µg/ml) during the same period does not affect first cleavage. However, when further development of such eggs is followed, one finds that second cleavage is inhibited typically in only one of the two blastomeres of the 2-cell stage, i.e. the CD-blastomere. As a result, a 3-cell embryo is formed. At third cleavage of such embryos, the CD-blastomere forms either one double-sized micromere (1cd-micromere) or two normal-sized micromeres (1c and 1d) simultaneously. Sometimes micromere formation in the CD-blastomere is inhibited. Con A binding does not affect karyokinesis, nor does it affect the division asynchronies typical for normal development. On the basis of these and other results it is argued that binding of Con A to sites located at the vegetal pole of the egg is responsible for the cell lineage-specific inhibition of cleavage by Con A. This effect is most probably mediated by changes in the organization of the egg cortex.

Polar effects of concanavalin A on the cortical cytoskeleton of a molluscan egg (Nassarius reticulatus, Gastropoda).

The organization of the surface of fertilizedNassarius reticulatus eggs was probed by investigating the effects of treatment with concanavalin A (Con A). This lectin causes abnormal polar lobe formation as well as inhibition of cleavage. At low concentrations of Con A (0.3-1.0 µg/ml) the polar lobe constriction becomes considerably elongated, whereas at higher concentrations (2.5-50 µ/ml) the position of the constriction undergoes an extreme shift towards the animal pole. In the latter case, the surface of the animal part of the egg forms large protrusions and folds. Con A also causes resorption of microvilli and disappearance of the extracellular layer covering these villi; this process starts at the vegetal pole and propagates towards the animal pole. These changes in surface architecture are associated with profound changes in the organization of filamentous (F-) actin as assessed by confocal laser scanning microscopy of NBD-phallacidin-labelled eggs. Divalent succinyl-Con A has the same effects on polar lobe formation and surface architecture as tetravalent Con A, but only at very high concentrations (100-200 µg/ml), indicating that Con A exerts its effects by cross-linkage of its binding sites. Experiments with cytoskeleton inhibitors (cytochalasin D, colchicine, and nocodazole) reveal that in Con A-treated eggs - as in untreated eggs - microfilaments, but not microtubules, are involved in the formation of the polar lobe constriction. The calcium ion channel blocker D600 affects neither normal nor Con A-induced abnormal polar lobe formation, which suggests that influx of external calcium is not required. In contrast, treatment with TMB-8, an antagonist of internal calcium release, prevents the formation of a polar lobe in both normal and Con A-treated eggs. Finally, eggs from which the polar lobe has been removed prior to Con A treatment show none of the effects described, whereas isolated polar lobes react similarly to intact eggs. These results suggest that binding of Con A to sites present at the vegetal pole of the egg is responsible for the observed effects of the lectin.

Manipulation of cytokinesis affects polar ionic current around the egg of Lymnaea stagnalis.

The fertilized egg of the mollusc Lymnaea stagnalis generates a polarized current pattern as measured with the vibrating probe. Here we investigated the basis of these polar ionic currents. Ionic currents were measured around eggs during the second meiotic division after interference with cytokinesis. Cytokinesis was either displaced by centrifugation or inhibited with cytochalasin or nocodazole. Furthermore, ectopic constrictions were induced with lectin treatment. It appeared that the inward current of the animal pole can be displaced by centrifugation and remains associated with the position of the meiotic apparatus. The influence of the meiotic apparatus on the polar current pattern seems to be directly related to membrane constrictions rather than to karyokinesis. This was demonstrated by a change in current density after induction of an ectopic constriction at the vegetal pole and by the abolishment of currents after cytochalasin treatment. Since the location of the outward current was not sensitive to centrifugation, it may be concluded that the vegetal outward current depends upon properties of the vegetal cortex. On the basis of these results, we conclude that the Lymnaea egg generates two types of ionic currents during the second meiotic division. The first is an inward current activated at the site of membrane constrictions. The second is an outward current associated with the vegetal cortex.

Localization of morphogenetic determinants in a special cytoplasm present in the polar lobe ofBithynia tentaculata (Gastropoda).

In the first polar lobe ofBithynia eggs a special plasm, the vegetal body, is present. It consists of a cupshaped aggregate of small vesicles. Centrifugation of eggs prior to first cleavage may result in displacement of the vegetal body. In about 50% of thecentriguged eggs the vegetal body is found outside the polar lobe, in one of the blastomeres. Removal of the polar lobe from non-centrifuged eggs always leads to severe defects in development. When the lobe is removed from centrifuged eggs, however, about 50% of the eggs develop into normal embryos. It is concluded that the presence of the vegetal body in a blastomere suffices to ensure normal development and, hence, that the polar lobe-specific morphogenetic determinants are contained within the vegetal body.

Localization of biotransformational enzymes along the crypt-villus axis of the rat intestine. Evaluation of two cell isolation procedures.

Rat intestinal epithelial cells were isolated by EDTA-chelation, combined with gentle shaking (modified Weiser procedure) or with strong longitudinal vibration (Harrison/Webster procedure). Both methods yield large numbers of viable cells and are relatively easy to use. Electronmicroscopical and biochemical data indicate that cell fractions from different levels of the villous region can be obtained only by the modified Weiser procedure. When strong mechanical forces are involved (Harrison-Webster procedure) the villus epithelium is released according to an all-or-nothing process. The biotransformational capacity of cell fractions, obtained from different levels of the villi by the modified Weiser procedure, was investigated. It was shown that the rate of metabolism of 7-ethoxycoumarin and 1-naphthol was substantially higher in lower villous cells than in cells isolated from the upper villous region. O-Deethylation of 7-ethoxycoumarin decreases from 145 +/- 13 pmole/min mg cell protein (72 +/- 4% conjugated) in lower villous cells to 62 +/- 12 pmole/min mg cell protein (37 +/- 6% conjugated) in tip cells. Glucuronidation of 1-naphthol decreased from 495 +/- 23 pmole/min mg cell protein (lower villous cells) to 137 +/- 13 pmole/min mg cell protein (tip cells).