CFAP45, a heterotaxy and congenital heart disease gene, affects cilia stability.

Congenital heart disease (CHD) is the most common and lethal birth defect, affecting 1.3 million individuals worldwide. During early embryogenesis, errors in Left-Right (LR) patterning called Heterotaxy (Htx) can lead to severe CHD. Many of the genetic underpinnings of Htx/CHD remain unknown. In analyzing a family with Htx/CHD using whole-exome sequencing, we identified a homozygous recessive missense mutation in CFAP45 in two affected siblings. CFAP45 belongs to the coiled-coil domain-containing protein family, and its role in development is emerging. When we depleted Cfap45 in frog embryos, we detected abnormalities in cardiac looping and global markers of LR patterning, recapitulating the patient's heterotaxy phenotype. In vertebrates, laterality is broken at the Left-Right Organizer (LRO) by motile monocilia that generate leftward fluid flow. When we analyzed the LRO in embryos depleted of Cfap45, we discovered "bulges" within the cilia of these monociliated cells. In addition, epidermal multiciliated cells lost cilia with Cfap45 depletion. Via live confocal imaging, we found that Cfap45 localizes in a punctate but static position within the ciliary axoneme, and depletion leads to loss of cilia stability and eventual detachment from the cell's apical surface. This work demonstrates that in Xenopus, Cfap45 is required to sustain cilia stability in multiciliated and monociliated cells, providing a plausible mechanism for its role in heterotaxy and congenital heart disease.

Decreasing sound and vibration during ground transport of infants with very low birth weight.

OBJECTIVE: To measure the effectiveness of modifications to reduce sound and vibration during interhospital ground transport of a simulated infant with very low birth weight (VLBW) and a gestational age of 30 weeks, a period of high susceptibility to germinal matrix and intraventricular hemorrhage. STUDY DESIGN: Researchers measured vibration and sound levels during infant transport, and compared levels after modifications to the transport incubator mattresses, addition of vibration isolators under incubator wheels, addition of mass to the incubator mattress and addition of incubator acoustic cover. RESULT: Modifications did not decrease sound levels inside the transport incubator during transport. The combination of a gel mattress over an air chambered mattress was effective in decreasing vibration levels for the 1368 g simulated infant. CONCLUSION: Transport mattress effectiveness in decreasing vibration is influenced by infant weight. Modifications that decrease vibration for infants weighing 2000 g are not effective for infants with VLBW. Sound levels are not affected by incubator covers, suggesting that sound is transmitted into the incubator as a low-frequency vibration through the incubator's contact with the ambulance. Medical transportation can apply industrial methods of vibration and sound control to protect infants with VLBW from excessive physical strain of transport during vulnerable periods of development.

Family ecology of young children with cerebral palsy.

BACKGROUND: Family ecology in early childhood may influence children's activity and participation in daily life. The aim of this study was to describe family functioning, family expectations of their children, family support to their children, and supports for families of young children with cerebral palsy (CP) based on children's gross motor function level. METHODS: Participants were 398 children with CP (mean age = 44.9 months) and their parents residing in the USA and Canada. Parents completed four measures of family ecology, the Family Environment Scale (FES), Family Expectations of Child (FEC), Family Support to Child (FSC) and Family Support Scale (FSS). RESULTS: The median scores on the FES indicated average to high family functioning and the median score on the FSS indicated that families had helpful family supports. On average, parents reported high expectations of their children on the FEC and strong support to their children on the FSC. On the FES, higher levels of achievement orientation were reported by parents of children in Gross Motor Function Classification System (GMFCS) level II than parents of children in level I, and higher levels of control were reported by parents of children in level I than parents of children in level IV. On the FEC, parents of children with limited gross motor function (level V) reported lower expectations than parents of children at all other levels. CONCLUSIONS: Family ecology, including family strengths, expectations, interests, supports and resources, should be discussed when providing interventions and supports for young children with CP and their families.

Screening tools to identify hospitalised elderly patients at risk of functional decline: a systematic review.

BACKGROUND: The elderly patient admitted to the emergency department (ED) of an acute care hospital is at risk of declining functionally, both during the stay at the hospital as an inpatient and postdischarge. Accurate and early identification of this population may lead to improved outcomes through targeted early interventions. OBJECTIVES: To identify, critically appraise and characterise available screening tools to screen for elderly patients at risk of functional decline presenting to the ED of acute care hospitals. SELECTION CRITERIA: Screening tools administered in the ED to identify elderly patients at risk of functional decline during hospital stay and/or postdischarge. All primary quantitative and qualitative study types were included. Population included age > 65 years presenting to the ED of an acute care hospital. RESULTS: Six studies reporting on five screening tools were identified. Two instruments reported acceptable discriminative ability; however, one of these has not been prospectively validated. No studies that validated any of the instruments in a setting other than the development setting were identified. A single study reported good test-retest reliability data for one instrument, the Identification of Seniors at Risk. CONCLUSION: This review was unable to identify a 'gold standard' tool to screen for risk of functional decline for the elderly patient admitted to the ED. Further research should be carried out to determine adjunctive processes to increase the accuracy of the identification of elderly patients at risk of functional decline. Further research should also be carried out to determine the appropriateness, or generalisability of these tools in different healthcare settings.

First-trimester diagnosis of placenta previa percreta by magnetic resonance imaging.

Placenta previa percreta with bladder involvement is a rare but devastating complication of pregnancy. Antepartum diagnosis of this serious condition allows the obstetrician to alter his or her management of abdominal delivery and minimize the magnitude of bleeding. We report a case in which magnetic resonance imaging was able to detect placenta percreta in the first trimester. If further research demonstrates usefulness of this diagnostic modality, magnetic resonance imaging may prove to be useful in caring for patients with this condition.

Predictors of cerebral infarction following transient ischemic attack.

Transient ischemic attack (TIA) is a warning sign for impending cerebral infarction, mainly within several months following the attack. To determine if any clinical characteristics could prognosticate cerebral infarction following a TIA, we studied and followed 68 consecutive patients who presented with a TIA. We determined the vascular risk factors, frequency, duration, vascular territory involved, and presumed etiology of the attacks. Diagnostic tests and treatment were individualized. Follow-up ranged from 1 day to 36 months (mean, 19 months). Four patients died from non-neurologic causes without having had a stroke. Cerebral infarction occurred in five patients (7%), 6 hours, 1 day, 10 days, 5 months, and 14 months after the presenting TIA. Two clinical characteristics were associated with a significantly increased risk of cerebral infarction: diabetes mellitus (p < 0.001) and history of multiple TIAs > 1/month at the time of presentation (p = 0.005). Patients presenting with a recent TIA and these risk factors may benefit from more aggressive treatment.

Antibacterial halogenoacetyl derivatives of amino acids and simple peptides.

The vital role of D-alanine and L-lysine in the peptidoglycan crosslinking process in the bacterial cell wall prompted preparation of various small peptides incorporating these amino acids. N-Iodoacetyl or -bromoacetyl derivatives of the peptides were then prepared in the hope that they would serve as active-site-directed irreversible inhibitors of cell wall transpeptidases. Certain of the halogenoacetyl dipeptide esters, but not the corresponding free acids, showed slight antistaphylococcal activity. Subsequent structural variation showed that inclusion of C-alanine or L-lysine was not necessary, since antibacterial activity was at least as good when the dipeptide unite was replaced by glycylglycine or by an omega-aminoalkanoic acid. It was concluded that the observed antibacterial activity was probably not due to specific inhibition of a cell wall transpeptidase.

Vitamin K and oxidative phosphorylation.

1. Oxidative phosphorylation was studied in a cell-free preparation of Mycobacterium phlei and in rat-liver mitochondria. Phosphorylation was destroyed in both systems by long-wave ultraviolet radiation and restored by the addition of small amounts of [2-Me-(14)C,(3)H]phylloquinone. When the radioactive quinones were recovered from the phosphorylating system and chromatographed with carrier phylloquinone and menaquinone-4 in adsorption and partition systems, only the phylloquinone band was labelled, and its isotopic ratio was identical with that of the original [2-Me-(14)C,(3)H]phylloquinone. This result does not support the contention that the role of vitamin K in oxidative phosphorylation involves a cyclic mechanism with intermediate formation of a quinone methide. 2. When the [2-Me-(14)C,(3)H]phylloquinone was given intravenously to rats and radioactive phylloquinone isolated from their liver mitochondria and microsomes 20hr. later, its isotopic ratio was unchanged. There was thus no evidence for quinone methide formation in vivo. No measurable conversion of phylloquinone into menaquinone-4 was observed. 3. When [(14)C]menadione was given intraperitoneally to rats whose alimentary tract had been treated with neomycin, conversion into menaquinone-4 was found in the liver mitochondria and microsomes, but there was also some indication that there had been synthesis of phylloquinone.