Prevalence and Correlates of Caregiver Anxiety in Family Caregivers of Patients With Advanced Cancer: a Cross-Sectional Study in a Palliative Care Unit in Hong Kong.

OBJECTIVES: To assess the prevalence of caregiver anxiety and to identify correlates of caregiver anxiety in family caregivers of patients with advanced cancer in a palliative care unit in Hong Kong. METHODS: Family caregivers of patients admitted to the palliative care ward for the first time between July 2019 and September 2019 were screened for recruitment. Caregiver demographics (age, sex, marital status, occupation, education level, housing condition, relationship with the patient, known diagnosis of anxiety or depression, and Charlson comorbidity index) were collected, as were caregiver understanding of patient's diagnosis and prognosis, perceived patient's distress, frequency of witnessing confusion or delirium of patients in past month, perceived adequacy of psychological support (other than general social support), and perceived anxiety towards patient's approaching death. Caregiver anxiety was assessed using the 7-item Generalised Anxiety Disorder scale (GAD-7). Caregiver depression status was assessed using the 9-item Patient Health Questionnaire (PHQ-9). Caregiver psychological well-being was assessed using the 11-item Psychological Well-being Scale for Family Caregivers (PWS-C). Caregiver overall burden was assessed using the Chinese version of the 13-item Modified Caregiver Strain Index (C-M-CSI). RESULTS: 70 caregivers (of 66 patients) were included, with a response rate of 98.6%. 16 (22.9%) caregivers had moderate to severe anxiety (GAD-7 score of ≥10). The GAD-7 score was higher in female caregivers than in male caregivers (mean rank: 39.26 vs 27.83, p = 0.026). 26 (37.1%) caregivers had depression (PHQ-9 score of ≥7). The GAD-7 score of caregivers was associated with the PHQ-9 score (rs = 0.834, p < 0.01), the four subscales of PWS-C: social support (rs = -0.308, p = 0.01), life meaning (rs = -3.30, p < 0.01), emotional distress (rs = 0.615, p < 0.01), and caregiver inadequacy (rs = 0.41, p < 0.01), and the C-M-CSI score for caregiver overall burden (rs = 0.332, p < 0.01). In multiple linear regression, predictors for GAD-7 score were the PHQ-9 score, caregiver's feeling of anxiety towards patient's approaching death, and caregiver sex. CONCLUSIONS: 22.9% of family caregivers of patients with advanced cancer have moderate to severe anxiety. Anxiety of caregivers was associated with depression, caregiver's feeling of anxiety towards patient's approaching death, psychological support, and life meaning. All these are potentially amendable by interventions. A structured screening of anxiety in family caregivers of patients with advanced cancer should be considered as routine practice.

The effect of pH on the interaction of substrates and effector to yeast and rabbit muscle pyruvate kinase.

The interaction of fructose 1,6-bisphosphate, phosphoenolpyruvate and ADP with pyruvate kinase (ATP: pyruvate 2-O-phosphotransferase, EC 2.7.1.40) from yeast and rabbit muscle has been studied as a function of pH utilizing the quenching of protein fluorescence at 330 nm by these ligands. Both the muscle and the yeast pyruvate kinase interact with either ADP or phosphoenolpyruvate with similar affinity, indicating that the substrate-binding sites for these two isozymes are similar. The major difference between the yeast and muscle isozymes is their affinity with fructose 1,6-bisphosphate. Fructose 1,6-bisphosphate interacts with the yeast isozyme in orders of magnitude more strongly than with the muscle isozyme. Moreover, the affinity of fructose 1,6-bisphosphate to the yeast isozyme is strongly pH-dependent, while the interaction of fructose 1,6-bisphosphate with the muscle isozyme is independent of pH. The data indicate that yeast pyruvate kinase undergoes a conformational change as the pH is increased from 6.0 to 8.5.

Interventions to reduce high-volume portable headsets: "turn down the sound"!

Two studies examined effects of interventions to reduce noise levels from portable stereo headphones. Study 1 examined the effectiveness of warning signs posted in and nearby public elevators with 567 passengers possessing a portable headphone (total N = 7,811). During a 9-day baseline, the mean percentage of headphones played at an observer-audible level was 85%. During a subsequent 6-day warning sign phase, the mean percentage of audible headphones declined to 59%, which increased to a mean of 76% during a second baseline phase (5 days). Study 2 assessed the impact of a student confederate who lowered his or her observer-audible headphone volume at the polite request of a second student confederate. Of the 4,069 elevator passengers, 433 possessed a portable headset. The mean percentage of observer-audible headphones during a 4-day baseline was 85%. Subsequently, a 5-day modeling intervention reduced audible volumes to a mean of 46%. During a second baseline phase of 4 days, the mean level was 77%, and during reintroduction of the modeling phase (9 days) the mean level was 42%. The modeling intervention was significantly more effective with women (53% compliance) than men (29% compliance).

Does gestational diabetes mellitus affect respiratory outcome in late-preterm infants?

BACKGROUND: Both gestational diabetes mellitus (GDM) and late-preterm delivery at 34-36 weeks' gestation are independently associated with neonatal respiratory complications, but it is unknown whether their combination increases further its risk. We therefore appraised the independent effect of GDM on the respiratory outcome of late-preterm infants. METHODS: In a retrospective cohort study, respiratory outcome of 911 infants delivered at 34-36 weeks' gestation between 1 January 2009 and 30 August 2012 from mothers with GDM (study group, n=130) was compared with infants delivered at the same gestation by mothers without GDM (control group, n=781). RESULTS: The study group had significantly higher incidence of transient tachypnoea of newborn (TTN, p=0.02) and air leak (p=0.012), and required more respiratory support, including oxygen, continuous positive airway pressure (CPAP), mechanical ventilation and neonatal intensive care, with a longer length of hospital stay, but not duration on respiratory support. On logistic regression analysis, GDM is an independent risk factor for TTN (aOR=1.5, 95% C.I.1.0-2.4), CPAP (aOR=2.37, 95% C.I. 1.05-4.89), mechanical ventilation (aOR=4.02 95% C.I. 1.57-10.32) and neonatal intensive care (aOR 1.83, 95% C.I. 1.05-3.87). CONCLUSIONS: Our results demonstrated an independent effect of GDM on the risk of severe respiratory complications in late-preterm infants. Additional close monitoring and timely intervention are necessary in the management of these infants.

Regulation of extracellular matrix RNA levels in cultured smooth muscle cells. Relationship to cellular quiescence.

We have examined how the alpha 2(I), alpha 1(III), alpha 1(IV), and alpha 2(V) collagen genes as well as the thrombospondin and fibronectin genes are regulated by conditions that modulate the proliferation of smooth muscle cells in vitro. We find that smooth muscle cells (SMC) arrested by low serum containing media continue to express similar or slightly lower levels of mRNA for all the genes studied except type III collagen which exhibited a 5-fold increase. By contrast, when SMC are density-arrested, a coordinate increase in mRNA levels for all the extracellular matrix genes studied is observed. The increases range from approximately 1.5-fold for fibronectin to 5-fold for type III collagen. The mRNA levels for beta-tubulin and vimentin, however, are decreased in these density-arrested cells. Interestingly, the time course of increase for type IV collagen and fibronectin can be distinguished from the other extracellular matrix genes and best correlates with an increase in cell-cell contact. The increase in steady-state RNA levels for alpha 1(IV) collagen is not shared by fibroblasts similarly treated and may provide a useful marker for SMC in culture. Heparin, a potent inhibitor of SMC growth, increased the level of type III collagen mRNA about 2.5-fold and also increased the level of alpha 2(V) collagen and fibronectin. Transforming growth factor-beta is found to be a cell density-dependent modulator of SMC growth. Surprisingly, transforming growth factor-beta had little effect on most of the extracellular matrix genes studied. However, transforming growth factor-beta treatment of SMC increased thrombospondin mRNA levels about 4-fold, whereas type IV collagen mRNA exhibited a 2-fold increase. We conclude that type III collagen mRNA levels are positively and tightly coupled to SMC quiescence. The effect of cellular quiescence on other extracellular matrix mRNAs is complex but, in general, positive. This is particularly evident in SMC arrested by high cell density.

Self-concept among hearing Chinese children of deaf parents.

This paper discusses a study of Chinese children in Hong Kong that compared the self-concepts of hearing children of deaf parents with the self-concepts of hearing children of hearing parents. The study was based on the responses to a questionnaire given to 42 deaf couples and their 70 hearing children, and 41 hearing couples and their 82 hearing children. It found no differences in the self-concepts of hearing children of deaf parents and hearing children of hearing parents. However, it did find that deaf parents had lower self-concepts than hearing parents.

Increased ferritin gene expression is both promoted by cAMP and a marker of growth arrest in rabbit vascular smooth muscle cells.

To facilitate an understanding of the molecular events associated with vascular smooth muscle cells (SMC) growth arrest and differentiation, we have isolated a number of cDNAs encoding mRNAs that are more abundantly expressed in high density growth-arrested SMC. From 40,000 recombinant plaques, we identified 6 cDNA clones which encoded genes more highly expressed in density-arrested SMC. DNA sequence analysis of a cDNA clone which hybridized to a 5.5-kilobase mRNA revealed a 96% sequence homology to the carboxyl-terminal propeptide region of the human alpha 2(I) collagen gene. Sequence analysis of 3 other cDNA clones which all recognized a 1-kilobase mRNA, indicated that they encode the ferritin H-chain subunit gene. The large increase in ferritin H-chain mRNA expression was both growth arrest and high density-dependent, but did not appear to be cell-cell contact-dependent. The increase in H-chain was partially accounted for by an increase in the transcription of this gene, but a post-transcriptional mechanism likely accounts for the majority of the observed difference in mRNA level. A greater than 3-fold higher expression of ferritin H-chain mRNA was also observed in BC3H1s (a nonfusing myogenic cell line) during the process of differentiation, but no elevation in ferritin H-chain mRNA was associated with density-dependent growth arrest in fibroblasts. Hemin (an intracellular iron donor) induced an elevation in ferritin H-chain mRNA expression in both preconfluent and post-confluent SMC, but was unable to elevate the preconfluent mRNA level to an untreated postconfluent level. In addition, deferoxamine (an intracellular iron chelator) was unable to reduce the ferritin mRNA level in postconfluent SMC. These results suggest that high density growth arrest-mediated elevation in ferritin H-chain occurs by a mechanism distinct from that induced by an increase in intracellular iron. cAMP was also a powerful modulator of the expression of ferritin H-chain gene since cells treated with forskolin or dibutyryl cAMP had a 5-7-fold higher level of ferritin H-chain mRNA. We propose that the increase in the ferritin H-chain mRNA level in postconfluent SMC may occur through a cAMP-dependent pathway and may be associated with an enhanced differentiated phenotype.

A novel human suspension culture packaging cell line for production of high-titre retroviral vectors.

Retroviruses are currently the most widely used vectors in clinical trials for gene therapy. These vectors are, however, limited by low titres partly due to the restrictive nature of monolayer cell culture. We have developed a stable suspension producer cell line derived from human lymphoblastoid cells (WIL-2) by electroporating these cells with the necessary trans components required for production of defective retrovirus particles which encode a nuclear localising beta-galactosidase gene. We show that this anchorage-independent cell line generates viruses at a titre of 7 x 10(5) iu/ml on NIH3T3 indicator cells which remains constant after at least 2 months in culture. The producer cells can be cultured at a density of 6 x 10(6) cells/ml with consistent virus titre production. WIL-2 can also be grown as single cells by rotation culture while maintaining virus production. By treating the cells with the transcriptional activator sodium butyrate titres above 1 x 10(6) i.u./ml are achieved. Concentrating viral supernatants by ultrafiltration can further increase virus titre to 5 x 10(8) i.u./ml. Even at these high titres no replication-competent virus was detected. Virus titre fell only slightly when cells were placed in serum-free media before harvest. The generation of this novel cell line provides proof-of-principle that large-scale production of retroviral vectors in serum-free growth conditions can be safely generated for use in gene therapy.

Collagen-fibronectin interactions in normal and Rous sarcoma virus-transformed avian tendon cells: possible mechanisms for increased extracellular matrix turnover after transformation.

Using gelatin, casein, and fibronectin as substrates and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), we have identified protein-degrading enzymes in both normal and Rous sarcoma virus-transformed primary avian tendon cells. Although there are some consistent differences in the profile of the gelatinolytic activities (mainly metalloproteinases) between normal and transformed cells, the amounts of fibronectin-degrading activities seem to be comparable. In vitro studies reported here demonstrate that the degradation of fibronectin is partially and specifically inhibited by gelatin and collagen. We therefore propose that the abundant collagen present in normal tendon cells protects fibronectin against degradation. Conversely, in transformed cells, where collagen levels are drastically reduced, fibronectin may be more accessible to degradation. Thus differences in the steady-state levels of fibronectin on normal and transformed cells may be, at least in part, a consequence of changes in collagen levels.