Coexistence of foam cells and hypocholesterolemia in mice lacking the ABC transporters A1 and G1

The concept that macrophages can become foam cells as a result of a disturbed balance between the uptake of cholesterol from lipoproteins and cholesterol efflux is generally accepted. ABCA1 and ABCG1 are two cholesterol transporters that may act sequentially to remove cellular cholesterol, but currently their combined role in vivo is unknown. We report here that targeted disruption of both ABCA1 and ABCG1 in mice, despite severe plasma hypocholesterolemia, leads to massive lipid accumulation and foam cell formation of tissue macrophages. A complete ablation of cellular cholesterol efflux in vitro is observed, whereas in vivo macrophage-specific reverse cholesterol transport to the feces is markedly decreased. Despite the massive foam cell formation of tissue macrophages, no lipid accumulation was observed in the vascular wall, even in mice of 1 year old, indicating that the double knockout mice, possibly because of their hypocholesterolemia, lack the trigger to attract macrophages to the vessel wall. In conclusion, even under hypocholesterolemic conditions macrophages can be converted into foam cells, and ABCA1 and ABCG1 play an essential role in the prevention of foam cell formation.     

Drowning

Recent epidemiologic data have shown that the burden of drowning is much greater than expected. Prevention and timely rescue are the most effective means of reducing the number of persons at risk. Early bystander cardiopulmonary resuscitation is the most important factor for survival after submersion. Cerebral damage is a serious threat when the hypoxic period is too long. In most situations, low body temperature is an indication of the severity of the drowning incident. Sometimes hypothermia that occurs during the submersion period can be brain protective. There is also new evidence to support the strategy of inducing mild hypothermia for a period of 12 to 24 hours in comatose drowning victims. In immersed patients, hypothermia should be treated. The most appropriate technique will depend on the available means in the hospital and the condition of the patient. Treatment of pulmonary complications depends on the lung injury that occurred during aspiration and the bacteria involved in aspiration. Understanding the pathophysiology of drowning may help us to understand lung injuries and ischemic brain injuries.     

Assessing measurement invariance in the EORTC QLQ-C30

Purpose

We aimed to investigate measurement invariance (MI) in the European Organisation for research and treatment of cancer quality of life questionnaire core 30 (EORTC QLQ-C30) in a heterogeneous sample of patients with cancer.

Methods

Data from 12 studies within the PROFILES registry were used for secondary analyses (n?=?7007). We tested MI by successive restrictions on thresholds, loadings, and intercepts across subgroups based on primary cancer sites, age, sex, time since diagnosis, and life stage, using multigroup confirmatory factor analysis (MGCFA) for ordered categorical measures. We also evaluated the impact of potentially miss-specified parameter equality across groups on latent factor means by releasing threshold and loading equality constraints for each item at a time.

Results

Results showed that the highest level of MI (invariance of thresholds, loadings, and intercepts) was found across groups based on time since diagnosis and life stage and to a lesser extent across groups based on sex, age, and primary tumor site. On item level, however, changes in the item’s associated factor means were relatively small and in most cases canceled each other out to some extent.

Conclusions

Given only a few instances of non-invariance in our study, there is reason to be confident that valid conclusions can be drawn from between-group comparisons of QLQ-C30 latent means as operationalized in our study. Nonetheless, further research into MI between other subgroups for the QLQ-C30 (i.e., treatment effects and ethnicity) is warranted. We stress the importance of including MI evaluations in the development and validation of measurement instruments.

     

Expression and stability of two isoforms of ABCG1 in human vascular cells

ObjectiveTo evaluate the expression of two ABCG1 isoforms that differ in the presence or absence of a 12 amino acid (AA) peptide between the ABC cassette and the transmembrane region, termed ABCG1(+12) and ABCG1(?12), respectively, in human vascular cells and tissues.Methods and resultsmRNA for both isoforms was expressed in human macrophages, vascular endothelial and smooth muscle cells as well as whole human spleen, lung, liver and brain tissue. However, ABCG1(+12) was not expressed in mouse tissues. 2D gel electrophoresis of ABCG1 protein indicated that both protein isoforms were expressed in human macrophages. Furthermore the half-lives of the two ABCG1 protein isoforms, stably expressed in CHOK1 cells, measured under basal conditions were different, suggesting the presence of a degradation or stabilising signal in or near the 12AA region of ABCG1(+12).ConclusionABCG1(+12) is an isoform of ABCG1 exclusively expressed in human cells at the RNA and protein level. As ABCG1(+12) is not expressed in mice, although mouse models are widely used to elucidate the function of ABCG1, further investigations into the importance of this human ABCG1 isoform are warranted.     

Ranked motives of long-term care providing family caregivers

Family caregivers provide long-term care to their chronically ill loved ones and as a consequence they experience physical, relational and financial problems. This study investigates how long-term family caregivers rank 12 motives for caregiving. Motives are derived from the views of four philosophical anthropologists and are related to self-reported stress and joy and to several different background characteristics of respondents. Motives that focus on feelings concerning the relationship between caregiver and care recipient are more popular as a first choice than motives stemming from feelings of obligation or a general feeling of happiness and are also more popular than more self-directed motives. An analysis of full ranking data shows that two groups can be distinguished, one group of family caregivers with mixed motives and one group of family caregivers with motives that focus on reciprocal mutually equal relationships. The latter are mainly women taking care for a partner or a child, the former report high levels of stress. Implications for intervention programmes and health policy are being discussed.     

Effect of increasing doses of intracaudate haloperidol upon motor expressions that require an intact substantia nigra pars reticulata and/or superior colliculus in cats

In the present study it was investigated whether intracaudate (CN) injections of increasing doses of haloperidol progressively affect movements that require the integrity of the substantia nigra pars reticulata (SNR) and/or the deeper layers of the superior colliculus (dl-SC) in cats. Therefore, cats were trained to walk from one side of a narrow bar to the other side both under full light and under stroboscopic illumination (2 flashes/s). Previously it has been shown that this set-up is useful for assessing changes in the execution of dl-SC and SNR-related non-externally guided targeting movements. Moreover, cats were trained to step out of a startbox on a rotating cylinder which, according to previous studies, also implies the execution of a dl-SC- and SNR-related non-externally guided targeting movement. CN application of 25 micrograms/5 microliters haloperidol, but not CN injection of 12.5 micrograms/5 microliters haloperidol or apomorphine (0.6 micrograms/5 microliters), reduced the occurrence of these dl-SC- and SNR-related targeting movements. Dl-SC injection of picrotoxin (100 ng/0.5 microliter) did not restore the haloperidol (25 micrograms/5 microliter) induced decrement in the occurrence of these targeting movements. In addition, CN application of 25 micrograms/5 microliter haloperidol, but not 12.5 micrograms/5 microliter haloperidol, reduced the feline ability to execute SNR-specific limb movements while crossing a revolving cylinder. The present results show that only a severe but not a moderate inhibition of dopamine receptors within the CN affects motor expressions characteristic of the SNR and/or dl-SC.     

Minimally-invasive parathyroidectomy: a good operative procedure for primary hyperparathyroidism even without the use of intraoperative parathyroid-hormone assessment or a gamma probe

OBJECTIVE: To evaluate the results of minimally-invasive parathyroidectomy without the use of intraoperative parathyroid-hormone assessment or a gamma probe. DESIGN: Retrospective. METHODS: In 2 community hospitals in the Netherlands, 49 patients with primary hyperparathyroidism in whom preoperative investigations had shown a solitary adenoma underwent minimally-invasive surgery by the lateral neck approach. In total 9 men and 40 women with an average age of 58 years (limits: 25-84) underwent this procedure. More extensive preoperative investigations were carried out at the Mesos Medisch Centrum (n = 29) including neck CT in 76% of patients as well as ultrasonography, and scintigraphy. At the Diakonessenhuis (n = 20) scintigraphy was the preferred method of adenoma localisation. Intraoperative parathyroidhormone assessment and a gamma probe were not used in the operative procedure. At the Diakonessenhuis intraoperative frozen-section investigations were done. RESULTS: In 44 of the 49 patients (90%) minimally-invasive parathyroidectomy resulted in normocalcaemia. In the remaining 5 patients a second procedure was necessary--a conventional neck exploration and also resulted in normocalcaemia. In 2 of these patients the adenomas had been missed during first procedure by the surgeon, while in 3 other patients preoperative examinations were falsely positive in the sense that the adenoma proved to be present but in an area other than that indicated by preoperative imaging. Permanent recurrent laryngeal-nerve paralysis complicated the postoperative course in 2 patients. The success rate of the minimally-invasive operation was the same for both groups. CONCLUSION: Without the use of intraoperative parathyroid-hormone assessment or a gamma probe minimally-invasive parathyroidectomy was successful in 90% of patients.