CFTR 5T variant has a low penetrance in females that is partially attributable to its haplotype.

PURPOSE: The study's purpose was to understand the molecular basis for different clinical phenotypes of the 5T variant, a tract of 5 thymidines in intron 8 of the cystic fibrosis transmembrane conductance regulator (CFTR) gene, which disrupts processing of CFTR mRNA and reduces synthesis from the corresponding CFTR alleles. METHOD: We analyzed the polymorphic TG dinucleotide repeat adjacent to the 5T variant in intron 8 and the codon 470 in exon 10. Patients selected for this study were positive for both the 5T variant and the major cystic fibrosis mutation, Delta F508. Almost all Delta F508 mutation alleles occur in a 10TG-9T-470M haplotype. Therefore, it is possible to determine the haplotype of the 5T variant in trans. RESULTS: Of the 74 samples analyzed, 41 (55%) were 11TG-5T-470M, 31 (42%) were 12TG-5T-470V, and 2 (3%) were 13TG-5T-470M. Of the 49 cases for which we had clinical information, 17.6% of females (6/34) and 66.7% of males (10/15) showed symptoms resembling atypical cystic fibrosis. The haplotype with the highest penetrance in females (42% or 5/12) and more than 80% (5/6) in males is 12TG-5T-470V. We also evaluated 12 males affected with congenital bilateral absence of vas deferens and positive for the 5T variant; 10 of 12 had the 12TG-5T-470V haplotype. CONCLUSION: Overall, the 5T variant has a milder clinical consequence than previously estimated in females. The clinical presentations of the 5T variant are associated with the 5T-12TG-470M haplotype.     

Nucleated erythrocytes in maternal blood: quantity and quality of fetal cells in enriched populations

The discovery of nucleated erythrocytes in maternal circulationprovides a potential source for non-invasive prenatal diagnosis.We have evaluated the use of a three-stage procedure to determinethe number of cells that are of fetal rather than maternal origin.First, monoclonal antibodies specific for CD45 and CD14 wereused in conjunction with a magnetic (MACS) column to depleteunwanted leukocytes from maternal blood. This was followed bya positive MACS enrichment for nucleated erythrocytes, usingan anti-CD71 (transferrin receptor) monoclonal antibody. Todiscriminate between fetal nucleated erythrocytes and thoseof maternal origin, enriched fractions were simultaneously stainedwith an anti-fetal haemoglobin (HbF) antibody and hybridizedwith probes specific for X and Y chromosomes. Samples were thensubjected to blind analysis along with negative control samplesfrom non-pregnant volunteers. Using this dual analysis, we wereable to determine that less than one nucleated erythrocyte perml of maternal blood was of fetal origin. Small numbers of thesefetal cells were found in 87.5% of pregnancies, ranging from6 to 35 weeks gestational age. Comparison of HbF and X/Y probedata also suggests that the fetal cells are less suitable forfluorescence in-situ hybridization (FISH) analysis than similarpreparations from other sources. cell separation methods/fluorescence in-situ hybridization/hereditary diseases/polymerase chain reaction/pregnancy     

Cardiac and respiratory patterns in normal infants and victims of the sudden infant death syndrome

Victims of the sudden infant death syndrome (SIDS) have higher overall heart rates prior to death than do control infants (1). The objective of this study was to partition these heart rate differences by state and to identify any state-dependent differences in heart rate variability and respiratory rate and variability. Twenty-two recordings of electrocardiogram (ECG) and respiration from 16 infants who subsequently died of SIDS were compared with 66 recordings of age-matched control infants. Median cardiac and respiratory rate and variability were computed for each sleep state in each recording, and one-way analysis of variance tests were performed for each variable for infants less than 1 month and for infants greater than 1 month of age. Heart rate was higher in SIDS victims less than 1 month of age than in age-matched controls during all sleep-waking states. SIDS victims greater than 1 month showed higher heart rates during rapid eye movement sleep only. Heart rate variability was also diminished during waking in victims less than 1 month, but much of this difference could be attributed to increased heart rate. These results suggest that, as a group, SIDS victims differ physiologically from control infants and that these differences may be especially prominent during particular sleep-waking states.     

The possible role of protein degradation in altered membrane structure and function

Possible changes in membrane lipid assemetry may result in altered function with aging. Membrane proteolysis is an additional factor which must be considered, both with respect to modulation of membrane function and also as a methodological problem in analyses of membrane dynamics.     

Kv1 channels selectively prevent dendritic hyperexcitability in rat Purkinje cells

Purkinje cells, the sole output of the cerebellar cortex, encode the timing signals required for motor coordination in their firing rate and activity pattern. Dendrites of Purkinje cells express a high density of P/Q-type voltage-gated calcium channels and fire dendritic calcium spikes. Here we show that dendritic subthreshold Kv1.2 subunit-containing Kv1 potassium channels prevent generation of random spontaneous calcium spikes. With Kv1 channels blocked, dendritic calcium spikes drive bursts of somatic sodium spikes and prevent the cell from faithfully encoding motor timing signals. The selective dendritic function of Kv1 channels in Purkinje cells allows them to effectively suppress dendritic hyperexcitability without hindering the generation of somatic action potentials. Further, we show that Kv1 channels also contribute to dendritic integration of parallel fibre synaptic input. Kv1 channels are often targeted to soma and axon and the data presented support a major dendritic function for these channels.     

Anatomy of the hyoid apparatus in odontoceli (toothed whales): Specializations of their skeleton and musculature compared with those of terrestrial mammals

Background: The hyoid apparatus of odontocetes (toothed whales) serves as a major attachment point for many of the muscles and ligaments subserving breathing, swallowing, and sound production. Methods: This study examines the hyoid apparatus in 48 specimens of ten odontocete genera (Phocoena, Lagenorhynchus, Stenella, Delphinus, Tursiops, Grampus, Globicephala, Mesoplodon, Physeter, and Kogia) collected post mortem from beach strandings. Results: The odontocete hyoid apparatus, as that of their closest terrestrial relatives, the artiodactyls, is divisible into a basal portion (bashyal, paired thyrohyals) and a suspensory portion (paired ceratohyals, epihyals, stylohyals, and tympanohyals) connecting the basal portion to the skull base. Unlike other terrestrial mammals, the basal portion lies inferior to the laryngeal aditus, is flattened dorso-ventrally, and is relatively large, thus providing a broad surface area for muscle attachments. The suspensory elements are not as flattened and are joined by synovial joints (except for epihyal-stylohyal fusion). Muscular specializations include enlargement of those which retract the hyoid apparatus (e.g., sternohyoid) or control the tongue (e.g., styloglossus, hyoglossus). These muscles may be particularly important in a specialized prey capture behavior called suction feeding. In addition, the hyoid apparatus has a tilted placement, which allows asymmetrical enlargement of the piriform sinuses. Asymmetry is also seen in the muscular attachment between the larynx and the hyoid apparatus. The most pronounced differences from the basic pattern are observed in two families: Physeteridae and Ziphiidae. Conclusions: The derived position and shape of the odontocete hyoid apparatus may have evolved to subserve several specialized upper respiratory/digestive tract functions, such as simultaneous feeding (suction and swallowing) and sound production. © 1994 Wiley-Liss, Inc.     

Exploring online identity construction for the caregivers of adults living with dementia and the value of interactions with health and social care professionals

Becoming an informal caregiver for an adult living with dementia has been shown to have a significant impact upon the conception of identity. This study aimed to identify how identity is constructed online amongst caregivers of individuals living with dementia and how healthcare interactions can influence identity development through the analysis of online web blogs. Sixteen online blogs (172 entries) were selected through purposive and snowball sampling, and discourse analysis was used to analyse online identity construction for informal caregivers of adults living with dementia. Six areas of online identity construction were identified: changing family role; powerful expert social campaigner; being an advocate; guardian of their relative's selfhood; sustaining creative and spiritual individuality and wider community member in online and real life. Further to this, the importance of health and social care service interactions in the development of caregiver identity revealed that professionals must ensure person-centred service contacts for caregivers. This is a challenging task in the pandemic climate where interactions between health and social care professionals and caregivers are limited due to isolation measures. It is evident that the blog format can provide a forum through which the identity of the caregiver of an adult living with dementia can evolve. The six areas of identity construction reveal the multifaceted nature of identity for the caregiver and the value of belonging to an online community both in relation to identity construction and support. This finding is especially applicable in the current pandemic when accessing a face-to-face community is challenging for caregivers who may be shielding or living in isolation. The findings of this research can aid health and social care professionals in understanding the development of caregiver identity and in providing appropriate support during service interactions, on accessing virtual and face to face community support.     

Acculturation,Discrimination and 24-h Activity in Asian American Immigrant Women

Asian American immigrant (AAI) women may have suboptimal 24-h activity patterns due to traditional gender role and caregiving responsibilities. However, little is known about their objectively-measured activity. We measured AAI women’s 24-h activity patterns using accelerometry and examined cultural correlates of time in sedentary behavior (SB), light intensity physical activity (LIPA), moderate-to-vigorous physical activity (MVPA) and sleep. Seventy-five AAI women completed surveys on acculturation (years of U.S. residency and English proficiency), discrimination, and sleep quality, and 7 days of wrist- and hip-accelerometer monitoring. Linear regression was conducted controlling for age, BMI, and education. We also compared activity patterns across Asian subgroups (East, Southeast, South Asians). On average, AAI women had 33 min of MVPA, 6.1 h of LIPA, 10 h of SB, and 5.3 h of sleep per day. South Asian women had the longest SB and the shortest sleep and MVPA hours. English proficiency was negatively related to MVPA (p?=?0.03) and LIPA (p?<?0.01). Years of U.S. residency was positively related to SB (p?=?0.07). Discrimination was related to shorter (p?=?0.03) and poorer quality sleep (p?=?0.06). Culturally-tailored programs targeting SB and sleep and integrating coping strategies against discrimination could help optimize AAI women’s 24-h activity patterns.