Using the Actor-Partner Interdependence Model to explore the psychological impact of COVID-19 on anxiety in dyads of patients with cancer and caregivers.

BACKGROUND: Delineating the compound psychological effect of the pandemic on cancer care, and the interdependency across cancer patient-caregiver dyads have yet to be explored. This study examines the levels of psychological impact of COVID-19 on patient-caregiver dyads anxiety, and the interdependent associations between their COVID-19 and cancer concerns, and risk perceptions. METHOD: There were 352 patients and caregivers (patient-caregiver dyads, N = 176) included in this study (43.2% spousal dyads). Generalized Anxiety Disorder-7 and questionnaires regarding risk perception, perceived confidence in healthcare system, COVID-19, and cancer-related concerns were administered. Actor-Partner Interdependence Model (APIM) analyses were used to determine the interdependent effects. Indirect effects were tested using mediation pathway analyses. RESULTS: Patients reported significantly higher levels of risk perceptions and anxiety than their caregivers (p < 0.01). Anxiety rates (GAD-7 ≥ 10) were also significantly higher (26.7% vs 18.2%, p < 0.01). Dyads' anxiety, "general COVID-19 concerns," "cancer-related concerns," and risk perceptions were correlated (ps < 0.01). APIM showed only actor effects of general COVID-19 concerns, cancer-related COVID-19 concerns, and risk perceptions on anxiety (ßs = 0.19-0.53, ps < 0.01). No partner effects were observed. Similar results were found in the composite APIM. Indirect effects of the patient/caregiver's variables on their partner's anxiety were observed in the mediation analyses. CONCLUSION: Concerns about COVID-19 and cancer care could be indirectly associated in patient-caregiver dyads and need to be proactively addressed. As pandemic evolves into endemicity, engagement with patients and caregivers should strive to be sensitive to their differential needs and messages should be tailored to the informational needs of each.

Stability of Pattern Formation in Systems with Dynamic Source Regions.

We explain the principles of gene expression pattern stabilization in systems of interacting, diffusible morphogens, with dynamically established source regions. Using a reaction-diffusion model with a step-function production term, we identify the phase transition between low-precision indeterminate patterning and the phase in which a traveling, well-defined contact zone between two domains is formed. Our model analytically explains single- and two-gene domain dynamics and provides pattern stability conditions for all possible two-gene regulatory network motifs.

Update on the Recommendations on Breast Cancer Screening by the Cancer Expert Working Group on Cancer Prevention and Screening.

Breast cancer (BC) is the most common cancer among women in Hong Kong. The Food and Health Bureau commissioned The University of Hong Kong (HKU) to conduct the Hong Kong Breast Cancer Study (HKBCS) with the aim of identifying relevant risk factors for BC in Hong Kong and developing a locally validated BC risk assessment tool for Hong Kong Chinese women. After consideration of the most recent international and local scientific evidence including findings of the HKBCS, the Cancer Expert Working Group on Cancer Prevention and Screening (CEWG) has reviewed and updated its BC screening recommendations. Existing recommendations were preserved for women at high risk and slightly changed for women at moderate risk. The following major updates have been made concerning recommendations for other women in the general population: Women aged 44 to 69 with certain combinations of personalised risk factors (including presence of history of BC among first-degree relative, a prior diagnosis of benign breast disease, nulliparity and late age of first live birth, early age of menarche, high body mass index and physical inactivity) putting them at increased risk of BC are recommended to consider mammography screening every 2 years. They should discuss with their doctors on the potential benefits and harms before undergoing mammography screening. A risk assessment tool for local women (eg, one developed by HKU) is recommended to be used for estimating the risk of developing BC with regard to the personalised risk factors described above.

Thoracic kyphosis assessment in postmenopausal women: an examination of the Flexicurve method in comparison to radiological methods.

The Flexicurve ruler is an alternative method to radiographs for measuring thoracic kyphosis (curvature), but it is not certain that it is comparable. This study shows that Flexicurve can estimate radiographic vertebral centroid angles with less error than Cobb angles but that its accuracy would be inadequate for most clinical purposes. INTRODUCTION: The Flexicurve ruler provides a non-radiological method of measuring thoracic kyphosis (TK) that has moderately strong correlations with the gold-standard radiographic Cobb angle method, while consistently underestimating the TK angle. Cobb angles can include measurement errors that may contribute to poor agreement, particularly in older populations. The vertebral centroid angle could be a better radiographic reference method for the validation of Flexicurve. Using two separate radiographic measurements of TK, we examined the validity of Flexicurve. We aimed to ascertain the level of agreement between measures and to empirically explore reasons for between-method differences. METHODS: TK angles determined using Flexicurve and radiographic Cobb and vertebral centroid methods were compared using data from 117 healthy postmenopausal women (mean (SD) age 61.4 (7.0) years). Bland and Altman plots were used to assess differences between methods. Age, bone mineral density and body mass index were examined as characteristics that might explain any differences. RESULTS: Flexicurve angles were scaled prior to analysis. There was no statistically significant difference between angles produced by Flexicurve and vertebral centroid methods (MD - 2.16°, 95%CI - 4.35° to 0.03°) although differences increased proportionally with TK angles. Flexicurve angles were significantly smaller than radiographic Cobb angles and depending on the scaling method used, systematic error ranged between - 2.48° and - 5.19°. Age accounts for some of the differences observed (R2 < 0.08, p < 0.005). CONCLUSIONS: TK measured using the Flexicurve shows better agreement with the radiographic vertebral centroid method, but inaccuracy of the Flexicurve increases with increasing angle of kyphosis.

Teleological explanation and positive emotion serially mediate the effect of religion on well-being.

OBJECTIVE: Previous research has demonstrated a robust relationship between religion and well-being, and it has been proposed that positive emotions are important mediators of this effect. Yet the mechanism via which religion promotes positive emotions has not been widely studied. We sought to examine whether teleological explanations of daily events and resulting positive emotions serially mediated the effects of religion on well-being. METHOD: These hypotheses were tested over three studies involving full-time and part-time university students in Singapore. In Study 1, participants completed measures of religiousness and well-being, and explained and described three recent personally significant events and their resulting emotions. Studies 2 and 3 adopted an ecological momentary assessment approach to measure teleological explanations, resulting emotions, and well-being in almost real time. RESULTS: In Study 1, teleological explanations and positive emotions serially mediated the effects of religiousness on well-being. In Study 2, momentary teleological explanations of daily events mediated the positive relationship between religiousness and momentary positive emotions. In Study 3, serial mediation of the relationship between religiousness and momentary well-being by momentary teleological explanations and positive emotions was observed. CONCLUSIONS: These results provide evidence of the importance of teleological explanations of daily events in religious enhancement of well-being.

Biosynthesis of 1α-hydroxycorticosterone in the winter skate Leucoraja ocellata: evidence to suggest a novel steroidogenic route.

The present study explores the ability of intracellular bacteria within the renal-inter-renal tissue of the winter skate Leucoraja ocellata to metabolize steroids and contribute to the synthesis of the novel elasmobranch corticosteroid, 1α-hydroxycorticosterone (1α-OH-B). Despite the rarity of C1 hydroxylation noted in the original identification of 1α-OH-B, literature provides evidence for steroid C1 hydroxylation by micro-organisms. Eight ureolytic bacterial isolates were identified in the renal-inter-renal tissue of L. ocellata, the latter being the site of 1α-OH-B synthesis. From incubations of bacterial isolates with known amounts of potential 1α-OH-B precursors, one isolate UM008 of the genus Rhodococcus was seen to metabolize corticosteroids and produce novel products via HPLC analysis. Cations Zn2+ and Fe3+ altered metabolism of certain steroid precursors, suggesting inhibition of Rhodococcus steroid catabolism. Genome sequencing of UM008 identified strong sequence and structural homology to that of Rhodococcus erythropolis PR4. A complete enzymatic pathway for steroid-ring oxidation as documented within other Actinobacteria was identified within the UM008 genome. This study highlights the potential role of Rhodococcus bacteria in steroid metabolism and proposes a novel alternative pathway for 1α-OH-B synthesis, suggesting a unique form of mutualism between intracellular bacteria and their elasmobranch host.

HBx mutants differentially affect the activation of hypoxia-inducible factor-1α in hepatocellular carcinoma.

BACKGROUND: Mutations in HBx gene are frequently found in HBV-associated hepatocellular carcinoma (HCC). Activation of hypoxia-inducible factor-1α (HIF-1α) contributes to HCC development and progression. Wild-type HBx has been demonstrated to activate HIF-1α, but the effect of HBx mutations on HIF-1α has not been elucidated. METHODS: HBx mutations were identified by gene sequencing in 101 HCC tissues. Representative HBx mutants were cloned and transfected into HCC cells. Expression and activation of HIF-1α were analysed by western blot and luciferase assays, respectively. The relationship between HBx mutants and HIF-1α expression in HCC tissues was also evaluated. RESULTS: The dual mutations K130M/V131I enhanced the functionality of HBx as they upregulated the expression and transcriptional activity of HIF-1α. The C-terminal truncations and deletion mutations, however, weakened the ability of HBx to upregulate HIF-1α. Meanwhile, the C-terminus was further found to be essential for the stability and transactivation of HBx. In the HCC tissues, there was a positive association between the HBx mutants and HIF-1α expression. CONCLUSION: Different mutations of HBx exert differentiated effects on the functionality of HIF-1α, however, the overall activity of HBx mutants appears to increase the expression and transcriptional activity of HIF-1α.

A low-power, high-speed, 9-channel germanium-silicon electro-absorption modulator array integrated with digital CMOS driver and wavelength multiplexer.

We demonstrate the first germanium-silicon C-band electro-absorption based waveguide modulator array and echelle-grating-based silicon wavelength multiplexer integrated with a digital CMOS driver circuit. A 9-channel, 10Gbps SiGe electro-absorption wavelength-multiplexed modulator array consumed a power of 5.8mW per channel while being modulated at 10.25Gbps by 40nm CMOS drivers delivering peak-to-peak voltage swings of 2V, achieving a modulation energy-efficiency of ~570fJ/bit including drivers. Performance up to 25Gbps on a single-channel SiGe modulator and CMOS driver is also reported.

Serum tumour necrosis factor-alpha is associated with poor health-related quality of life and depressive symptoms in patients with systemic lupus erythematosus.

OBJECTIVES: While patients with systemic lupus erythematosus (SLE) have poorer health-related quality of life (HRQoL) and are more depressed than healthy people, the impact of proinflammatory cytokines, particularly tumour necrosis factor-alpha (TNFα), on these unfavourable psychosocial parameters is unclear. We aim to explore potential relationships between lupus-related proinflammatory cytokines, HRQoL and depressive symptoms in patients with SLE. METHODS: Patients with SLE and age-matched healthy subjects were assessed for HRQoL and depressive and anxiety symptoms by the Short Form Health Survey-36 (SF-36) and Hospital Anxiety and Depression Scale (HADS) respectively. Using multiplex immunoassay, a panel of serum proinflammatory cytokines including TNFα, interleukin (IL)-1ß, IL-6, IL-17, IL-23 and IL-33 were determined and compared between both groups. Independent associations between SF-36, serum proinflammatory cytokine levels and HADS scores were studied by regression models. RESULTS: In total, 54 patients and 54 healthy controls were studied. Lupus patients had significantly poorer HRQoL (p < 0.001) and were significantly more depressed (p = 0.006) and anxious (p = 0.022) than their healthy counterparts. Amongst the proinflammatory cytokines studied, serum TNFα was significantly higher in lupus patients (p < 0.001). After multivariate adjustment, higher serum TNFα (ß = -0.224, p = 0.047) remained significantly associated with lower SF-36, along with smoking (ß = -0.253, p = 0.014) and more severe depressive symptoms (ß = -0.433, p = 0.002). In healthy subjects, serum TNFα was associated with depressive symptoms but not with SF-36. CONCLUSIONS: Higher serum TNFα level is independently associated with poorer HRQoL and more severe depressive symptoms in SLE patients. These associations suggest a potential impact of inflammatory response on depressive symptoms and the quality of life in patients with SLE.

Systematic review evaluating cardiovascular events of the 5-alpha reductase inhibitor - Dutasteride.

WHAT IS KNOWN AND OBJECTIVES: A recently published large, long-term randomized controlled trial (RCT) brought into question the safety of dutasteride after a significantly increased risk of 'cardiac failure' was noted in the dutasteride arm of the trial compared with placebo. Our objective was to perform a meta-analysis to assess the risk of cardiovascular adverse events with the use of dutasteride for the prevention or treatment of prostatic disease. METHODS: We searched MEDLINE and EMBASE, unpublished articles identified through FDA/EMEA websites, study registers of pharmaceutical companies and reference lists of articles. Parallel-group, randomized controlled trials where men received dutasteride for the prevention of prostate cancer or treatment of prostatic hyperplasia against any comparator intervention were included. Heart failure was the primary outcome of interest but we also looked at myocardial infarction and stroke. Fixed-effect meta-analysis of pooled relative risk (RR) ratios of adverse effect outcomes was conducted. RESULTS AND DISCUSSION: In all, 12 RCTs were included in the meta-analysis after detailed screening of 564 citations. The total number of participants was 18,802, and study duration ranged from 6 to 208 weeks. Only two trials provided details on adequate allocation concealment, whereas all the trials stated they were double blind in nature. Dutasteride was not associated with a statistically significant increased risk of heart failure (RR 1·05; 95% confidence interval [CI], 0·71-1·57, I(2) = 20%), myocardial infarction (RR 1·00; 95% CI 0·77-1·30, I(2) = 0%) and stroke (RR, 1·20; 95% CI 0·88-1·64, I(2) = 0%) as compared to controls. WHAT IS NEW AND CONCLUSION: We did not find consistent evidence of a significant association between dutasteride therapy and the risk of cardiovascular adverse events.

Viewing and engaging in an art therapy exhibit by people living with mental illness: implications for empathy and social change.

OBJECTIVE: To determine how healthcare professionals, family members and community members responded to an art exhibit created by people living with mental illness. STUDY DESIGN: Phenomenological study with qualitative analysis. METHODS: Forty-six participants with various relationships with people living with mental illness attended an art therapy exhibit and art making workshop. Surveys, response art, reflective writing and discussion groups were used in this qualitative research study. RESULTS: Responses were categorized into four cluster themes: empathic, self-oriented, other-oriented and world-oriented. CONCLUSIONS: Each response category has strengths and weaknesses, indicating implications for increasing awareness and understanding of the artists and mental illness. They also inform educational interventions that can be utilized when using art exhibits for the purpose of confronting bias and stigma towards people living with mental illness.

Lumbar spine bone mineral density predicts endothelial reactivity in patients with systemic lupus erythematosus.

OBJECTIVES: To explore whether endothelial function is related to bone mineral density (BMD) in patients with systemic lupus erythematosus (SLE). METHODS: Consecutive adult SLE patients and age-, sex-, BMI- and smoking-status-matched healthy controls were studied. Subjects with hypertension, hyperlipidemia, diabetes mellitus, renal impairment, dysthyroidism, history of or treatment for cardiovascular and cerebrovascular disorders, antiphospholipid syndrome, positive antiphospholipid antibodies or bone loss were excluded. Endothelial function was assessed by measuring flow-mediated dilatation (FMD) at the brachial artery and carotid intima-media thickness (IMT) by ultrasound. Lumbar and hip BMD were measured by dual-energy x-ray absorptiometry. Fasting blood samples were assayed for atherogenic index and high sensitivity C-reactive protein (hsCRP). Regression models were constructed to study the relationship between FMD and BMD. RESULTS: One hundred and ten subjects (55 SLE and 55 matched healthy controls) were studied. While there were no differences between SLE patients and controls in menopausal status, blood pressure, atherogenic index, carotid IMT and BMD, SLE patients had significantly poorer FMD even after adjustment for age, gender, smoking and baseline brachial artery diameter. Also, SLE patients with lumbar osteopenia had significantly lower FMD than those with normal BMD. Multivariate regression revealed that lower FMD was associated with lower lumbar BMD and higher serum hsCRP in SLE patients, but these relationships were absent amongst healthy controls. CONCLUSIONS: Lumbar vertebral BMD predicted endothelial reactivity in SLE patients without clinically-overt bone loss and atherosclerosis. Thus, early atherosclerotic disease should be considered in lupus patients especially if vertebral bone loss is evident.

Changes in breast cancer patients after psychosocial intervention as indicated in drawings.

OBJECTIVE: The present study attempts to understand the experience of breast cancer patients who had participated in an Eastern-based body-mind-spirit (BMS) psychosocial intervention program by observing changes in the images made by the patients. METHODS: Pre- and post-intervention drawings on the theme of 'my cancer' were collected from 67 primary breast cancer patients. Two creative art therapists compared the drawings according to the structural and formal art elements (body), the symbols used (mind), and the emotions and feelings presented in the drawings (spirit). Numbers of pre- and post-intervention drawings, showing the presence of each element in these three dimensions, were also counted and compared. RESULTS: There were several changes noted between pre- and post-intervention drawings. The use of color, space, and multiplicity increased from 12 to 17%. Images of breasts decreased from 13 to 0%. Representations of cancer decreased from 15 to 7%. There was a slight increase in symbolic representations of natural, landscapes, and social support in post-drawings (3-6%). The portrayal of negative emotions was greatly reduced from 52 to 3%, while positive emotions increased from 28 to 93% in post-drawings. CONCLUSIONS: The comparison of pre- and post-intervention drawings revealed changes in subject matter and accompanying emotions. Overall, there was a trend in changes toward a more peaceful and hopeful attitude. Through the use of realistic and symbolic images, participants depicted a range of emotions. Limitations and recommendations for using art-making, as an assessment tool and intervention, are addressed.

Extracolonic findings on CT colonography increases yield of colorectal cancer screening.

OBJECTIVE: The purpose of this study is to evaluate the impact of extracolonic findings when screening is undertaken by CT colonography (CTC). MATERIALS AND METHODS: We performed a retrospective cohort study of patients completing a screening CTC from August 2003 to June 2006 at Walter Reed Army Medical Center. Extracolonic findings were categorized using a CTC reporting and data system that classifies findings as highly significant, likely significant, and insignificant. All final diagnoses, surgeries, malignancies, and costs of diagnostic radiology procedures were calculated for each category. RESULTS: Of 2,277 patients (mean +/- SD age, 59 +/- 11 years; 60% white; 56% male) undergoing CTC, extracolonic findings were identified in 1,037 (46%) patients, with 787 (34.5%) insignificant and 240 (11.0%) significant findings. Evaluation of significant findings generated 280 radiology procedures and 19 surgeries over a mean follow-up time of 19 +/- 10 months. The total cost of the radiology studies was $113,179; the studies added approximately $50 extra per patient. Seven high-risk lesions were identified (six extracolonic malignancies and one large aortic aneurysm) in patients with significant findings. CTC also identified six intracolonic malignancies and three adenomas with high-grade dysplasia. When considering extracolonic findings, CTC increased the odds of identifying high-risk lesions by 78% (nine intracolonic lesions vs 16 intracolonic plus extracolonic lesions; p = 0.0156). Of the 16 intracolonic and extracolonic high-risk lesions, 11 (69%) underwent curative resection, and 5 of 11 (44.4%) were extracolonic. CONCLUSION: CTC increased the odds of identifying high-risk lesions by 78%. CTC should be considered as an alternative to optical colonoscopy for colorectal cancer screening or as a onetime procedure to identify significant treatable intracolonic and extracolonic lesions.

Low-level laser therapy for carpal tunnel syndrome: systematic review and network meta-analysis.

BACKGROUND: Splinting is recommended by various organisations as a non-surgical first-line treatment for carpal tunnel syndrome (CTS), despite the limited evidence supporting its effectiveness. Previous studies on the effectiveness of low-level laser therapy (LLLT) have reported mixed results, and this systematic review aimed to resolve this controversy. OBJECTIVE: To perform a network meta-analysis (NMA) for evaluating the effectiveness of LLLT compared with other conservative treatments for CTS. METHODS: Eighteen electronic databases were searched for potential randomised controlled trials (RCTs). RCTs evaluating LLLT or other non-surgical treatments as an add-on to splinting were included. Included RCTs measured at least one of the following three outcomes with validated instruments: pain, symptom severity and functional status. RESULTS: Six RCTs (418 patients) were included. NMA suggested that LLLT plus splinting has the highest probability (75%) of pain reduction, compared with sham laser plus splinting (61%), ultrasound plus splinting (57%) and splinting alone (8%). However, while LLLT plus splinting is significantly more effective than sham laser plus splinting for pain reduction, the magnitude is not clinically significant (Visual Analogue Scale mean difference -0.53cm, 95% confidence interval -1.01 to -0.05cm; P=0.03, I2=25%). The effect of LLLT plus splinting on symptom severity and functional status was not superior to splinting alone. CONCLUSION: The use of LLLT in addition to splinting for the management of CTS is not recommended, as LLLT offers limited additional benefits over splining alone in terms of pain reduction, reduction of symptom severity or improved functional status. PROSPERO for systematic reviews and meta-analyses registration number CRD42017082650.

iPSC modeling of young-onset Parkinson's disease reveals a molecular signature of disease and novel therapeutic candidates.

Young-onset Parkinson's disease (YOPD), defined by onset at <50 years, accounts for approximately 10% of all Parkinson's disease cases and, while some cases are associated with known genetic mutations, most are not. Here induced pluripotent stem cells were generated from control individuals and from patients with YOPD with no known mutations. Following differentiation into cultures containing dopamine neurons, induced pluripotent stem cells from patients with YOPD showed increased accumulation of soluble α-synuclein protein and phosphorylated protein kinase Cα, as well as reduced abundance of lysosomal membrane proteins such as LAMP1. Testing activators of lysosomal function showed that specific phorbol esters, such as PEP005, reduced α-synuclein and phosphorylated protein kinase Cα levels while increasing LAMP1 abundance. Interestingly, the reduction in α-synuclein occurred through proteasomal degradation. PEP005 delivery to mouse striatum also decreased α-synuclein production in vivo. Induced pluripotent stem cell-derived dopaminergic cultures reveal a signature in patients with YOPD who have no known Parkinson's disease-related mutations, suggesting that there might be other genetic contributions to this disorder. This signature was normalized by specific phorbol esters, making them promising therapeutic candidates.

Diminished mitochondrial DNA integrity and repair capacity in OA chondrocytes.

OBJECTIVES: Osteoarthritis (OA) is characterized by the failure of chondrocytes to respond to injury and perform the cartilage remodeling process. Human articular chondrocytes actively produce reactive oxygen and nitrogen species (ROS and RNS) capable of causing cellular dysfunction and death. A growing body of evidence indicates that mitochondrial dysfunction and mitochondrial DNA (mtDNA) damage play a causal role in disorders linked to excessive generation of oxygen free radicals. The aim of this study was to determine whether mtDNA damage was present in OA chondrocytes, and whether mtDNA repair capacity is compromised in OA chondrocytes following oxidative stress, leading to chondrocyte death. METHODS: Human articular cartilage was isolated from knee joints of cadavers available through the Anatomical Gifts Program at the University of South Alabama (normal donors) or OA patients undergoing total knee replacement surgeries (OA patients). Total DNA was isolated from either chondrocytes released following collagenase digestion, or from first passage chondrocytes grown in culture and exposed to ROS or RNS. mtDNA integrity and repair capacity were analyzed by quantitative Southern blot analysis, using a mtDNA-specific radioactive probe. Cell viability was determined by the trypan blue exclusion method. RESULTS: mtDNA damage was found in chondrocytes from OA patients compared to normal donors. It was accompanied with reduced mtDNA repair capacity, cell viability, and increased apoptosis in OA chondrocytes following exposure to ROS and RNS. CONCLUSIONS: These results indicate that mtDNA damage and poor mtDNA repair capacity for removing damage caused by oxidative stress may contribute to the pathogenesis of OA.

Atherogenic serum lipid profile is an independent predictor for gouty flares in patients with gouty arthropathy.

OBJECTIVE: Atherogenic serum lipid profile possesses pro-inflammatory properties and is associated with more active RA. While prevalent in patients with gout, whether atherogenic lipid profile is associated with gouty flares is unknown. This study aims to investigate whether atherogenic serum lipid predicts gouty flares in patients with gout. METHODS: Adult patients (age > or =21 yrs) who suffered from gout were prospectively followed between September 2006 and November 2007 and their demographic, clinical and laboratory data were collected. Episodes of gouty flares over this observation period were recorded and factors predictive of gouty flares were studied by regression models. RESULTS: Of the 100 patients, 80 were men, 65 were ethnic Chinese, 31 were Malay and the rest were Indian and Caucasian. The mean age and duration of gout (+/-S.D.) were 61.9 +/- 14.0 and 6.6 +/- 7.8 yrs, respectively. The mean serum uric acid and creatinine levels were 537.6 +/- 142.8 and 173.6 +/- 119.9 micromol/l, respectively. In univariate analysis, longer duration of gout, higher adjusted mean serum creatinine, lower adjusted mean fasting serum, total cholesterol and high-density lipoprotein cholesterol (HDL-C) levels were associated with gouty flares. After adjustment for potential confounders in multivariate regression models, longer duration of gout and lower adjusted mean fasting serum HDL-C level remained independently predictive of gouty flares. CONCLUSIONS: Low serum high-density lipoprotein cholesterol level was an independent predictor for gouty flares. Whether optimizing serum HDL-C level can benefit patients with gout in terms of reducing gouty flares needs to be addressed by controlled trials.

Commitment of cell fate in the early zebrafish embryo.

When do single cells in the early zebrafish embryo become irreversibly committed to a specific fate? Work with lineage tracing and fate mapping has shown that the marginal cells of the blastoderm give rise to hypoblast-derived fates (mesoderm and endoderm). However, experiments described here show that these marginal blastoderm cells remain pluripotent and uncommitted throughout the late blastula and early gastrula stages. Embryonic cells become committed to a hypoblast-derived fate at mid-gastrulation. Time-lapse photographic analysis reveals that committed cells, when transplanted heterotopically and heterochronically, can migrate along atypical pathways to reposition themselves within a more correct environment.