Smoking cessation in pregnant women using financial incentives: a feasibility study.

BACKGROUND: The high prevalence of smoking pregnant women in Dutch areas with lower socioeconomic status and the consecutively harmful exposure to tobacco to both mother and child, depicted a high need for a novel intervention. According to other studies, the utilisation of financial incentives appeared to be a promising method for smoking cessation in pregnant women. Therefore, the aim of this study was to investigate the feasibility of implementing contingent financial incentives as smoking cessation support for pregnant women in the Netherlands. METHODS: Feasibility study consisting of four developmental phases: (1) acceptability of Dutch population regarding financial-incentive-intervention by conducting an online questionnaire, (2) composing a pilot study utilising the financial-incentive-intervention in clinical practice, (3) execution of the composed pilot study and (4) evaluation of the executed pilot study utilising a mixed-methods approach. A financial-incentive-intervention, given in a contingent financial scheme (during five consequential appointments, respectively €25/€50/€100/€150/€250), if smoking abstinence was proven by the amount of cotinine in the urine of the pregnant women measured utilising a urine dipstick test. The public acceptability for the financial-incentive-intervention was assessed using 5-Likert scales. The number of pregnant women able to abstain from smoking during the pilot study and utilising the financial-incentive-intervention in clinical practice were used to assess the prosperity and practicality of the pilot study respectively. The pilot study was evaluated using a mixed-methods approach. RESULTS: In total, 55.1% of the Dutch population sample (n = 328) found a financial incentive inappropriate for smoking cessation in pregnant women, while the healthcare professionals and pilot study participants thought the financial-incentive-intervention to be a helpful approach. Eleven vouchers were given during the pilot study, and one woman completed all test points and tested negative for cotinine at the end of the pilot study. CONCLUSION: Although the financial-incentive-intervention appeared to be a promising approach for smoking cessation in pregnant women, the acceptability of the Dutch population and the number of pregnant women able to abstain smoking during this pilot study was low. Despite the limited study population, this study proved the concept of this financial-incentive-intervention to be feasible for implementation in the Netherlands. TRIAL REGISTRATION: Not applicable since this is a feasibility study prior to a trial.

Women who smoke during pregnancy are more likely to be referred to an obstetrician during pregnancy and birth: results from a cohort study.

BACKGROUND: Women who smoke during pregnancy make less use of prenatal care; the relation of smoking behavior with the use of other forms of maternal healthcare is unknown. The objective of this study is to investigate the association between women's smoking behavior and their use of healthcare during pregnancy, birth and six weeks postpartum. METHODS: We analyzed data from the Dutch Midwifery Case Registration System (VeCaS), period 2012-2019. We included women with a known smoking status, singleton pregnancies, and who had their first appointment before 24 weeks of gestation with the primary care midwife. We compared three groups: non-smokers, early stoppers (stopped smoking in the first trimester), and late- or non-stoppers (stopped smoking after the first trimester or continued smoking). Descriptive statistics were used to report maternal healthcare utilization (during pregnancy, birth and six weeks postpartum), statistical differences between the groups were calculated with Kruskal-Wallis tests. Multivariable logistic regression was conducted to assess the association between smoking behavior and referrals to primary, secondary or tertiary care. RESULTS: We included 41 088 pregnant women. The groups differed significantly on maternal healthcare utilization. The late- or non-stoppers initiated prenatal care later and had less face-to-face consultations with primary care midwives during pregnancy. Compared to the non-smokers, the early- and late- or non-stoppers were statistically signficiantly more likely to be referred to the obstetrician during pregnancy and birth. Postpartum, the early- and late- or non-stoppers were statistically signficantly less likely to be referred to the obstetrician compared to the non-smokers. CONCLUSIONS: Although the early- and late- or non-stoppers initiated prenatal care later than the non-smokers, they did receive adequate prenatal care (according to the recommendations). The results suggest that not smoking during pregnancy may decrease the likelihood of referral to secondary or tertiary care. The large population of smokers being referred during pregnancy underlines the important role of the collaboration between healthcare professionals in primary and secondary or tertiary care. They need to be more aware of the importance of smoking as a medical and as a non-medical risk factor.

Assessing Dutch women's experiences of labour and birth: adaptations and psychometric evaluations of the measures Mothers on Autonomy in Decision Making Scale, Mothers on Respect Index, and Childbirth Experience Questionnaire 2.0.

BACKGROUND: The Mothers Autonomy in Decision Making Scale (MADM) assesses women's autonomy and role in decision making. The Mothers on Respect Index (MORi) asseses women's experiences of respect when interacting with their healthcare providers. The Childbirth Experience Questionnaire 2.0 assesses the overall experience of childbirth (CEQ2.0). There are no validated Dutch measures of the quality of women's experiences in the intrapartum period. Therefore, the aim of this study was to evaluate the psychometric properties of these measures in their Dutch translations. METHODS: The available Dutch versions of the MADM and MORi were adapted to assess experiences in the intrapartum period. The CEQ2.0 was translated by using forward-backward procedures. The three measures were included in an online survey including items on individual characteristics (i.e. maternal, birth, birth interventions). Reliability was assessed by calculating Cronbach's alphas. Mann-Whitney, Kruskal Wallis or Student T-tests were applied where appropriate, to assess discrimination between women who differed on individual characteristics (known group validity). We hypothesized that women who experienced pregnancy complications and birth interventions would have statistically lower scores on the MADM, MORi and CEQ2.0, compared with women who had healthy pregnancies and physiological births. Convergent validity was assessed using Spearman Rank correlations between the MADM, MORi and/or CEQ2.0. We hypothesized moderate to strong correlations between these measures. Women's uptake of and feedback on the measures were tracked to assess acceptability and clarity. RESULTS: In total 621 women were included in the cross sectional study. The calculated Cronbach's alphas for the MADM, MORi and CEQ, were ≥ 0.77. Knowngroup validity was confirmed through significant differences on all relevant individual characteristics, except for vaginal laceration repair. Spearman Rank correlations ranged from 0.46-0.80. In total 98% of the included women out of the eligible population completed the MADM and MORi for each healthcare professional they encountered during childbirth. The proportions of MADM and MORi-items which were difficult to complete ranged from 0.0-10.8%, 0.6-2.7%, respectively. CONCLUSIONS: The results of our study showed that the Dutch version of the MADM, MORi and CEQ2.0 in Dutch are valid instruments that can be used to assess women's experiences in the intrapartum period.

[General health, healthcare costs and dental care use of elderly with differing oral status]. / Algemene gezondheid, zorgkosten en tandartsbezoek van ouderen met verschillende orale status.

Cross-sectional studies have shown that elderly with a natural dentition or implant-retained overdenture have better general health outcomes than elderly with conventional dentures. It is not known whether these findings would be confirmed in longitudinal studies of such groups of elderly. Therefore, in this study a large group of elderly (aged 75 and over) with a natural dentition (n = 143,199), an implant-retained overdenture (n = 6,503) or conventional denture (n=18,420) were followed over a period of 8 years. Elderly with conventional dentures had chronic conditions more often, used more medication and had higher healthcare costs. Remarkably, the general health outcomes of elderly with an implant-retained overdenture declined over the period of 8 years. At the time the implant-retained overdenture was placed, their general health profile seemed comparable to that of elderly with a natural dentition, but as time progressed it declined to the level of elderly with conventional dentures.

Health and quality of life differ between community living older people with and without remaining teeth who recently received formal home care: a cross sectional study.

OBJECTIVE: To assess oral health, health, and quality of life (QoL) of care-dependent community-living older people with and without remaining teeth who recently received formal home care. MATERIALS AND METHODS: For this cross-sectional observational study, community-living older people (≥ 65 years), who recently (< 6 months) received formal home care, were interviewed with validated questionnaires and underwent an oral examination. Oral health, general health, medicines usage, frailty (Groningen Frailty Indicator), cognition (Minimal Mental State Examination), QoL (RAND 36), and oral health-related QoL (Oral Health Impact Profile-14) were assessed. RESULTS: One hundred three out of 275 consecutive eligible older people (median age 79 [IQR (Inter Quartile Range) 72-85 years] participated in the study. Thirty-nine patients had remaining teeth and 64 were edentulous. Compared with edentulous older people, older people with remaining teeth scored significantly better on frailty, QoL, physical functioning, and general health. No significant differences were seen in cognition. Dental and periodontal problems were seen in more than half of the patients with remaining teeth. Two third of the edentulous patients did not visit their dentist regularly or at all. CONCLUSIONS: Care-dependent home-dwelling older people with remaining teeth generally were less frail, scored better on physical functioning and general health and had better QoL than edentulous older people. Dental and periodontal problems were seen in approximately 50% of the elderly. CLINICAL RELEVANCE: Notwithstanding their common dental problems, frailty, health, and QoL are better in home-dwelling older people with remaining teeth. To maintain this status, we advise not only dentists, but also health care workers and governments, to encourage people to maintain good oral health.

Elderly with remaining teeth report less frailty and better quality of life than edentulous elderly: a cross-sectional study.

OBJECTIVE: To assess oral status and self-reported oral health in community-living elderly and to determine differences between relevant subgroups of oral status (remaining teeth, edentulous, implant-retained overdentures) and case complexity (robust, frail, complex care needs). SUBJECTS AND METHODS: In this cross-sectional descriptive study, 1325 Dutch community-living elderly (≥75 years of age) were asked to complete validated questionnaires on frailty, activities of daily living (ADL), complexity of care needs, and QoL. Data on oral status, self-reported oral health, dental care, general health, and medication use were assessed. Differences between relevant subgroups were determined. RESULTS: Data of 1026 (77%) elderly (median 80 years, IQR 77-84) were analyzed: 39% had remaining teeth, 51% were edentulous, and 10% had implant-supported overdentures. Elderly with complex care needs (n = 225, 22%) and frail elderly (n = 217, 21%) were more often edentulous and reported more oral problems than robust elderly (n = 584, 57%). Elderly persons with remaining teeth were less frail, had better QoL and ADL, and used fewer medicines than edentulous elderly. Elderly with implant-supported overdentures performed better on frailty and QoL than edentulous elderly with conventional dentures. CONCLUSION: Community-living elderly commonly suffer from oral health problems, in particular elderly with complex care needs. QoL, ADL, and general health are higher among community-living elderly with remaining teeth and implant-supported overdentures than in edentulous elderly.

Deletion of small ankyrin 1 (sAnk1) isoforms results in structural and functional alterations in aging skeletal muscle fibers.

Muscle-specific ankyrins 1 (sAnk1) are a group of small ankyrin 1 isoforms, of which sAnk1.5 is the most abundant. sAnk1 are localized in the sarcoplasmic reticulum (SR) membrane from where they interact with obscurin, a myofibrillar protein. This interaction appears to contribute to stabilize the SR close to the myofibrils. Here we report the structural and functional characterization of skeletal muscles from sAnk1 knockout mice (KO). Deletion of sAnk1 did not change the expression and localization of SR proteins in 4- to 6-mo-old sAnk1 KO mice. Structurally, the main modification observed in skeletal muscles of adult sAnk1 KO mice (4-6 mo of age) was the reduction of SR volume at the sarcomere A band level. With increasing age (at 12-15 mo of age) extensor digitorum longus (EDL) skeletal muscles of sAnk1 KO mice develop prematurely large tubular aggregates, whereas diaphragm undergoes significant structural damage. Parallel functional studies revealed specific changes in the contractile performance of muscles from sAnk1 KO mice and a reduced exercise tolerance in an endurance test on treadmill compared with control mice. Moreover, reduced Qγ charge and L-type Ca(2+) current, which are indexes of affected excitation-contraction coupling, were observed in diaphragm fibers from 12- to 15-mo-old mice, but not in other skeletal muscles from sAnk1 KO mice. Altogether, these findings show that the ablation of sAnk1, by altering the organization of the SR, renders skeletal muscles susceptible to undergo structural and functional alterations more evident with age, and point to an important contribution of sAnk1 to the maintenance of the longitudinal SR architecture.

[Peri-implant health in people aged 75 and over with an implant-retained overdenture in the mandibula]. / Peri-implantaire gezondheid bij 75-plussers met een overkappingsprothese op implantaten in de onderkaak.

The number of elderly patients with an implant-retained overdenture in the mandibula is increasing. There is, however, insufficient information on how these elderly people are functioning with their overdenture and on their peri--implant health. Therefore, a study was carried out among a group of people aged 75 and over who had been provided with an implant-retained overdenture in a general dental office, measuring their ability to manage independently, their general health and peri-implant health. The study revealed a high degree of ability to manage independently, despite the health problems affecting many over 75. The patients rated their prosthetic overdentures with an average grade of 8.9 ± 1.1. Plaque around the implant (73%) and bleeding on probing (68%) were frequently seen. However, progressive peri-implant bone loss was seldom seen. No relationship was evident between plaque-scores and the ability to manage independently. Except for oral hygiene instruction and/or professional cleaning of peri-implants, no serious interventions were necessary. It was concluded that this group of elderly people, provided with an implant-retained mandibular overdenture, are functioning well. Plaque around the implant and bleeding on probing are often present but progressive peri-implant bone loss is rare.

[Oral health in care-dependent elderly: an inventory in a nursing home in the north of the Netherlands]. / Mondgezondheid van kwetsbare ouderen: een inventarisatie in een verpleeghuis in Noord-Nederland.

When people grow old and dependent on care, it usually becomes increasingly difficult to maintain oral health. The aim of this study was to assess what changes have taken place during the last ten years in oral health and the need for dental care among patients who were admitted to a nursing home between 2002 and 2012. Results revealed that the number of patients with remaining teeth increased significantly, from 7.9% to 28.7%, and that the number of patients with implants increased from 0.0% to 3.2%. More than 80% of the patients had moderate to poor oral health upon arrival. Moreover, almost half of the patients were revealed to be non-cooperative for evaluation and/or treatment, especially those who had remaining teeth. The expectation is that as a result of the increasing number of care-dependent elderly with remaining teeth in combination with poor oral health, the demand for dental care for care-dependent elderly in nursing homes will increase harply in the coming years.

The murine pallid mutation is a platelet storage pool disease associated with the protein 4.2 (pallidin) gene.

Pallid is one of 12 independent murine mutations with a prolonged bleeding time that are models for human platelet storage pool deficiencies in which several intracellular organelles are abnormal. We have mapped the murine gene for protein 4.2 (Epb4.2) to chromosome 2 where it co-localizes with pallid. Southern blot analyses suggest that pallid is a mutation in the Epb4.2 gene. Northern blot analyses demonstrate a smaller than normal Epb4.2 transcript in affected pallid tissues, such as kidney and skin. This is the first gene defect to be associated with a platelet storage pool deficiency, and may allow the identification of a novel structure or biological pathway that influences granulogenesis.

The needs of women and their partners regarding professional smoking cessation support during pregnancy: A qualitative study.

BACKGROUND: Despite the health risks of smoking, some women continue during pregnancy. Professional smoking cessation support has shown to be effective in increasing the proportion of pregnant women who quit smoking. However, few women actually make use of professional support. AIM: To investigate the needs of women and their partners for professional smoking cessation support during pregnancy. METHODS: Semi-structured interviews were held with pregnant women and women who recently gave birth who smoked or quit smoking during pregnancy, and their partners, living in the north of the Netherlands. Recruitment was done via Facebook, LinkedIn, food banks, baby stores and healthcare professionals. The interviews were recorded, transcribed and thematically analysed. RESULTS: 28 interviews were conducted, 23 with pregnant women and women who recently gave birth, and five with partners of the women. The following themes were identified: 1) understanding women's needs, 2) responsibility without criticism, and 3) women and their social network. These themes reflect that women need support from an involved and understanding healthcare professional, who holds women responsible for smoking cessation but refrains from criticism. Women also prefer involvement of their social network in the professional support. CONCLUSION: For tailored support, the Dutch guideline for professional smoking cessation support may need some adaptations. The adaptations and recommendations, e.g. to involve women and their partners in the development of guidelines, might also be valuable for other countries. Women prefer healthcare professionals to address smoking cessation in a neutral way and to respect their autonomy in the decision to stop smoking.

Measuring respect and autonomy in Dutch maternity care: Applicability of two measures.

PROBLEM: In the Netherlands there are no valid measurement tools available to measure respectful maternity care and women's autonomy. BACKGROUND: Respectful maternity care including women's autonomy during childbirth are key components of high quality care. AIM: This study aims to evaluate the applicability of the Canadian measures; the Mothers Autonomy in Decision Making (MADM) scale and the Mothers on Respect index (MORi) measures among pregnant women in the Netherlands. METHODS: We translated the measures MORi and MADM according to the WHO guidelines, adapted them to the Dutch health care system, evaluated their psychometric properties, and pilot tested before administration through an online cross-sectional survey. We assessed feasibility by calculating descriptive statistics on scores, and reliability by calculating Cronbach's alpha. The construct validity was measured by hypotheses on differences between subgroups based on maternal characteristics, pregnancy characteristics and healthcare provision. FINDINGS: Of 557 women included in the study, 83% experienced high respect and 62% experienced high autonomy. Both the MORi and MADM showed feasibility, internal consistency, and with respect to construct validity, both measures discriminated between type of care provision. Compared to women with pregnancy complications, those with a healthy pregnancy reported statistically higher MORi-scores. No differences were observed on MADM-scores. DISCUSSION: Both instruments can be used as quality of care measures aiming to improve care and thus experiences of women. CONCLUSION: The results of this study support the feasibility, reliability, and to a certain extent known group validity of the Dutch MORi and MADM measures in pregnant women.

Isoforms of ankyrin-3 that lack the NH2-terminal repeats associate with mouse macrophage lysosomes.

We have recently cloned and characterized ankyrin-3 (also called ankyrin(G)), a new ankyrin that is widely distributed, especially in epithelial tissues, muscle, and neuronal axons (Peters, L.L., K.M. John, F.M. Lu, E.M. Eicher, A. Higgins, M. Yialamas, L.C. Turtzo, A.J. Otsuka, and S.E. Lux. 1995. J. Cell Biol. 130: 313-330). Here we show that in mouse macrophages, ankyrin-3 is expressed exclusively as two small isoforms (120 and 100 kD) that lack the NH2-terminal repeats. Sequence analysis of isolated Ank3 cDNA clones, obtained by reverse transcription and amplification of mouse macrophage RNA (GenBank Nos. U89274 and U89275), reveals spectrin-binding and regulatory domains identical to those in kidney ankyrin-3 (GenBank No. L40631) preceded by a 29-amino acid segment of the membrane ("repeat") domain, beginning near the end of the last repeat. Antibodies specific for the regulatory and spectrin-binding domains of ankyrin-3 localize the protein to the surface of intracellular vesicles throughout the macrophage cytoplasm. It is not found on the plasma membrane. Also, epitope-tagged mouse macrophage ankyrin-3, transiently expressed in COS cells, associates with intracellular, not plasma, membranes. In contrast, ankyrin-1 (erythrocyte ankyrin, ankyrin(R)), which is also expressed in mouse macrophages, is located exclusively on the plasma membrane. The ankyrin-3-positive vesicles appear dark on phase-contrast microscopy. Two observations suggest that they are lysosomes. First, they are a late compartment in the endocytic pathway. They are only accessible to a fluorescent endocytic tracer (FITC-dextran) after a 24-h incubation, at which time all of the FITC-dextran-containing vesicles contain ankyrin-3 and vice versa. Second, the ankyrin-3-positive vesicles contain lysosomal-associated membrane glycoprotein (LAMP-1), a recognized lysosomal marker. This is the first evidence for the association of an ankyrin with lysosomes and is an example of two ankyrins present in the same cell that segregate to different locations.

Purkinje cell degeneration associated with erythroid ankyrin deficiency in nb/nb mice.

Mice homozygous for the nb mutation (Chromosome 8) have a severe hemolytic anemia and develop a psychomotor disorder at 6 mo of age. The nb/nb mice are deficient in erythroid ankyrin (Ank-1) but, until the present study, the role of Ank-1 and of Ank-2 (brain ankyrin) in disease genesis was unknown. In normal erythroid tissues, we show that two major transcripts are expressed from Ank-1, and one of these is also present at high levels in the cerebellum. By in situ hybridization and immunocytochemistry, Ank-1 localizes to the cerebellar Purkinje cells and, to a lesser extent, the granule cells. In nb/nb mice, Ank-1 transcripts are markedly reduced in both erythroid and neural tissue, and nb/nb Purkinje cells and granule cells are nearly devoid of Ank-1. The neurological syndrome appears concurrently with a dramatic loss of Purkinje cells. Ank-2 maps to Chromosome 3 and its expression is unaffected by the nb mutation. We conclude that Ank-1 is specifically required for Purkinje cell stability and, in its absence, Purkinje cell loss and neurological symptoms appear.

Ank3 (epithelial ankyrin), a widely distributed new member of the ankyrin gene family and the major ankyrin in kidney, is expressed in alternatively spliced forms, including forms that lack the repeat domain.

We cloned a novel ankyrin, Ank3, from mouse kidney cDNA. The full-length transcript is predicted to encode a 214-kD protein containing an 89 kD, NH2 terminal "repeat" domain; a 65 kD, central "spectrin-binding" domain; and a 56 kD, COOH-terminal "regulatory" domain. The Ank3 gene maps to mouse Chromosome 10, approximately 36 cM from the centromere, a locus distinct from Ank1 and Ank2. Ank3 is the major kidney ankyrin. Multiple transcripts of approximately 7.5, 6.9, 6.3, 5.7, 5.1, and 4.6 kb are highly expressed in kidney where Ank1 and Ank2 mRNAs are barely detectable. The smaller mRNAs (< or = 6.3 kb) lack the entire repeat domain. These transcripts have a unique 5'untranslated region and NH2-terminal sequence and encode a predicted protein of 121 kD. Two small sequences of 21 and 18 amino acids are alternatively spliced at the junction of the repeat and spectrin-binding domains in the larger (> or = 6.9 kb) RNAs. Alternative splicing of a 588 bp sequence (corresponding to a 21.5-kD acidic amino acid sequence) within the regulatory domain also occurs. Ank3 is much more widely expressed than previously described ankyrins. By Northern hybridization or immunocytochemistry, it is present in most epithelial cells, in neuronal axons, in muscle cells, and in megakaryocytes/platelets, macrophages, and the interstitial cells of Leydig (testis). On immunoblots, an antibody raised to a unique regions of the regulatory domain detects multiple Ank3 isoforms in the kidney (215, 200, 170, 120, 105 kD) and in other tissues. The 215/200 kD and 120/105-kD kidney proteins are close to the sizes predicted for the 7.5/6.9- and 6.3/5.7-kb RNAs (with/without the 588-bp acidic insert). Interestingly, it appears that Ank3 exhibits a polarized distribution only in tissues that express the approximately 7.0-kb isoforms, the only isoforms in the kidney that contain the repeat domain. In tissues where smaller transcripts (< or = 6.3 kb) are expressed. Ank3 is diffusely distributed in some or all cells and may be associated with cytoplasmic structures. We conclude that Ank3 is a broadly distributed epithelial ankyrin and is the major ankyrin in the kidney and other tissues, where it plays an important role in the polarized distribution of many integral membrane proteins.

The posterior pituitary: regulation of anterior pituitary prolactin secretion.

Removal of the posterior pituitary from anesthetized male rats results in a prompt and significant increase in circulating prolactin that is reversed by the injection of dopamine. Posterior pituitary extracts, which contain high concentrations of endogenous dopamine, inhibit prolactin secretion from isolated anterior pituitary cells. This inhibition is prevented by incubation of the cells with the dopamine receptor antagonist (+)-butaclamol. The data show that posterior pituitary dopamine reaches the anterior pituitary via the short hypophysial portal vessels and participates in the regulation of prolactin secretion.

Mild spherocytosis and altered red cell ion transport in protein 4. 2-null mice.

Protein 4.2 is a major component of the red blood cell (RBC) membrane skeleton. We used targeted mutagenesis in embryonic stem (ES) cells to elucidate protein 4.2 functions in vivo. Protein 4. 2-null (4.2(-/-)) mice have mild hereditary spherocytosis (HS). Scanning electron microscopy and ektacytometry confirm loss of membrane surface in 4.2(-/-) RBCs. The membrane skeleton architecture is intact, and the spectrin and ankyrin content of 4. 2(-/-) RBCs are normal. Band 3 and band 3-mediated anion transport are decreased. Protein 4.2(-/-) RBCs show altered cation content (increased K+/decreased Na+)resulting in dehydration. The passive Na+ permeability and the activities of the Na-K-2Cl and K-Cl cotransporters, the Na/H exchanger, and the Gardos channel in 4. 2(-/-) RBCs are significantly increased. Protein 4.2(-/-) RBCs demonstrate an abnormal regulation of cation transport by cell volume. Cell shrinkage induces a greater activation of Na/H exchange and Na-K-2Cl cotransport in 4.2(-/-) RBCs compared with controls. The increased passive Na+ permeability of 4.2(-/-) RBCs is also dependent on cell shrinkage. We conclude that protein 4.2 is important in the maintenance of normal surface area in RBCs and for normal RBC cation transport.

Protein 4.1R-deficient mice are viable but have erythroid membrane skeleton abnormalities.

A diverse family of protein 4.1R isoforms is encoded by a complex gene on human chromosome 1. Although the prototypical 80-kDa 4.1R in mature erythrocytes is a key component of the erythroid membrane skeleton that regulates erythrocyte morphology and mechanical stability, little is known about 4.1R function in nucleated cells. Using gene knockout technology, we have generated mice with complete deficiency of all 4.1R protein isoforms. These 4.1R-null mice were viable, with moderate hemolytic anemia but no gross abnormalities. Erythrocytes from these mice exhibited abnormal morphology, lowered membrane stability, and reduced expression of other skeletal proteins including spectrin and ankyrin, suggesting that loss of 4. 1R compromises membrane skeleton assembly in erythroid progenitors. Platelet morphology and function were essentially normal, indicating that 4.1R deficiency may have less impact on other hematopoietic lineages. Nonerythroid 4.1R expression patterns, viewed using histochemical staining for lacZ reporter activity incorporated into the targeted gene, revealed focal expression in specific neurons in the brain and in select cells of other major organs, challenging the view that 4.1R expression is widespread among nonerythroid cells. The 4.1R knockout mice represent a valuable animal model for exploring 4.1R function in nonerythroid cells and for determining pathophysiological sequelae to 4.1R deficiency.

cDNA sequence and chromosomal localization of mouse Dlgh3 gene adjacent to the BRCA1 tumor suppressor locus.

Membrane associated guanylate kinase homologues (MAGUKs) function in tumor suppression and receptor clustering pathways presumably by modulating signaling events at the interface of the membrane cytoskeleton. The p55 subclass of MAGUKs includes two novel cDNAs that were originally identified by virtue of their genomic location to human chromosome 17q12-21 where the BRCA1 tumor suppressor gene has been mapped. The predicted primary structure of the human MPP3 contains a single copy of the PDZ domain, an SH3 motif, and a carboxy-terminal guanylate kinase-like domain. Here we report the full-length coding cDNA sequence of the mouse homologue of MPP3. The translated amino acid sequence of murine Dlgh3 contains 568 amino acids that show 87% sequence identity with the human MPP3 protein. Northern blot analysis shows abundant expression of a approximately 3.0 kb transcript of Dlgh3 in mouse brain and skeletal muscle, and a relatively less abundant approximately 5.0 kb transcript in skeletal muscle, testis, kidney, and lung. Using an interspecific backcross panel, the Dlgh3 gene was mapped to a segment of mouse chromosome 11 that is conserved with human chromosome 17q12-21. The close proximity of murine Dlgh3 gene to the BRCA1 locus and the high conservation of the primary structure of human and murine proteins provide a framework for testing the role of Dlgh3 in cell proliferation pathways using the mouse as a model system.

Construct validity of the Groningen Frailty Indicator established in a large sample of home-dwelling elderly persons: Evidence of stability across age and gender.

BACKGROUND: The primary objective of the present study was to evaluate the validity of the Groningen Frailty Indicator (GFI) in a sample of Dutch elderly persons participating in LifeLines, a large population-based cohort study. Additional aims were to assess differences between frail and non-frail elderly and examine which individual characteristics were associated with frailty. METHODS: By December 2012, 5712 elderly persons were enrolled in LifeLines and complied with the inclusion criteria of the present study. Mann-Whitney U or Kruskal-Wallis tests were used to assess the variability of GFI-scores among elderly subgroups that differed in demographic characteristics, morbidity, obesity, and healthcare utilization. Within subgroups Kruskal-Wallis tests were also used to examine differences in GFI-scores across age groups. Multivariate logistic regression analyses were performed to assess associations between individual characteristics and frailty. RESULTS: The GFI discriminated between subgroups: statistically significantly higher GFI-median scores (interquartile range) were found in e.g. males (1 [0-2]), the oldest old (2 [1-3]), in elderly who were single (1 [0-2]), with lower socio economic status (1 [0-3]), with increasing co-morbidity (2 [1-3]), who were obese (2 [1-3]), and used more healthcare (2 [1-4]). Overall age had an independent and statistically significant association with GFI scores. Compared with the non-frail, frail elderly persons experienced statistically significantly more chronic stress and more social/psychological related problems. In the multivariate logistic regression model, psychological morbidity had the strongest association with frailty. CONCLUSION: The present study supports the construct validity of the GFI and provides an insight in the characteristics of (non)frail community-dwelling elderly persons participating in LifeLines.