Frequent hospital presenters' use of health information during COVID-19: results of a cross-sectional survey.

BACKGROUND: High-frequency hospital users often present with chronic and complex health conditions and are at increased risk of serious morbidity and mortality if they contract COVID-19. Understanding where high-frequency hospital users are sourcing their information, whether they understand what they find, and how they apply the information to prevent the spread of COVID-19 is essential for health authorities to be able to target communication approaches. METHODS: Cross-sectional survey of 200 frequent hospital users (115 with limited English proficiency) informed by the WHO's "Rapid, simple, flexible behavioral insights on COVID-19". Outcome measures were source of, and trust in information, and knowledge of symptoms, preventive strategies, restrictions, and identification of misinformation. RESULTS: The most frequently cited source of information was television (n = 144, 72%) followed by the internet (n = 84, 42%). One in four television users sought their information from overseas news outlets from their country of origin, while for those using the internet, 56% relied on Facebook and other forms of social media including YouTube and WeChat. Overall, 41.2% of those surveyed had inadequate knowledge about symptoms, 35.8% had inadequate knowledge about preventative strategies, 30.2% had inadequate knowledge about government-imposed restrictions, and 69% believed in misinformation. Half of the respondents (50%) trusted all information, and only one in five (20%) were uncertain or untrusting. English-speaking participants were almost three times more likely to have adequate knowledge about symptoms (OR 2.69, 95%CI 1.47;4.91) and imposed restrictions (OR 2.10 95%CI 1.06; 4.19), and 11 times more likely to recognize misinformation (OR 11.52 95%CI 5.39; 24.60) than those with limited English. CONCLUSION: Within this population of high-frequency hospital users with complex and chronic conditions, many were sourcing their information from less trustworthy or locally relevant sources, including social media and overseas news outlets. Despite this, at least half were trusting all the information that they found. Speaking a language other than English was a much greater risk factor for having inadequate knowledge about COVID-19 and believing in misinformation. Health authorities must look for methods to engage diverse communities, and tailor health messaging and education in order to reduce disparities in health outcomes.

Proximal humerus fractures in adolescents: Experience from East of Scotland.

BACKGROUND: The management of proximal humerus fractures (PHF) in adolescent has not been agreed upon. We aim to investigate the outcomes of PHF managed conservatively in adolescents. METHODS: All shoulder radiographs performed in patients aged from 10 to 18 years and from 2008 to 2015 were reviewed. The radiological parameters, including anatomical side, Neer and Horwitz displacement grade, angulation and any residual deformities were recorded. Mail questionnaires based on the modified 15-Upper Extremities Functional Index (15-UEFI), with a maximum of 59 points, were sent out. The return of the completed anonymized questionnaire was considered as implied consent. RESULTS: 118 patients with a median age of 12 at the time of fracture were identified. The majority of the fractures were Neer and Horwitz grade I displacement and 3 children had Neer and Horwitz grade III and IV displacement. The median angulation was 25°. The median follow-up length was 26 days. 55 patients had residual angulation and 25 patients had worsened angulation. No non-union was identified. No patients underwent subsequent corrective surgeries. 35 patients responded to the questionnaire. The median 15-UEFI was 59 points. None of the patients have contacted the research or clinical team regarding any concerns. CONCLUSION: The vast majority of non-displaced and minimally displaced PHF in adolescent were managed conservatively in our unit. The functional outcomes for this cohort remain excellent even for those with residual deformities in the follow-up radiographs. Further large prospective multicenter studies on adolescent cohort with significantly displaced PHF are warranted.

Design, structure-activity relationship study and biological evaluation of the thieno[3,2-c]isoquinoline scaffold as a potential anti-cancer agent.

Several derivatives of a series that share a thienoisoquinoline scaffold have demonstrated potent activity against cancer cell lines A549, HeLa, HCT-116, and MDA-MB-231 in the submicromolar concentration range. Structure-activity relationship (SAR) studies on a range of derivatives aided in identifying key pharmacophores in the lead compound. A series of compounds have been identified as the most promising with submicromolar IC50 values against a lung cancer cell line (A549). Microscopy studies of cancer cells treated with the lead compound revealed that it causes mitotic arrest and disrupts microtubules. Further evaluation via an in vitro microtubule polymerization assay and competition studies indicate that the lead compound binds to tubulin via the colchicine site.

A Comprehensive Approach to the Management of Benign and Malignant Ampullary Lesions: Management in Hereditary and Sporadic Settings.

PURPOSE OF REVIEW: The purpose of this review was to examine the historical roots of endoscopic management of ampullary lesions and explore emerging data on improved techniques, technologies, and outcomes. Of specific interest was answering whether there exists a reasonable body of data to support one resection technique or strategy above others. RECENT FINDINGS: Review of recent literature suggests the continued use of endoscopic ampullectomy is a safe and effective means of curative treatment of ampullary adenomas. Complications are relatively infrequent and complete endoscopic resection is possible in a majority of cases, with proper patient and lesion selection. Greater than 2 decades of experience with endoscopic ampullectomy have shown this to be a viable, well-tolerated, and highly effective means of treating ampullary adenomas. While few concrete guidelines exist to advise endoscopists on the ideal technique for resection, experience, patient selection, and prior planning can greatly influence the technical and clinical success of endoscopic ampullectomy.

Capitated Telehealth Coaching Hospital Readmission Service in Australia: Pragmatic Controlled Evaluation.

BACKGROUND: MonashWatch is a telehealth public hospital outreach pilot service as a component of the Government of Victoria's statewide redesign initiative called HealthLinks: Chronic Care. Rather than only paying for hospitalizations, projected funding is released earlier to hospitals to allow them to reduce hospitalization costs. MonashWatch introduced a web-based app, Patient Journey Record System, to assess the risk of the journeys of a cohort of patients identified as frequent admitters. Telecare guides call patients using the Patient Journey Record System to flag potential deterioration. Health coaches (nursing and allied health staff) triage risk and adapt care for individuals. OBJECTIVE: The aim was a pragmatic controlled evaluation of the impact of MonashWatch on the primary outcome of bed days for acute nonsurgical admissions in the intention-to-treat group versus the usual care group. The secondary outcome was hospital admission rates. The net promoter score was used to gauge satisfaction. METHODS: Patients were recruited into an intention-to-treat group, which included active telehealth and declined/lost/died groups, versus a systematically sampled (4:1) usual care group. A rolling sample of 250-300 active telehealth patients was maintained from December 23, 2016 to June 23, 2019. The outcome-mean bed days in intervention versus control-was adjusted using analysis of covariance for age, gender, admission type, and effective days active in MonashWatch. Time-series analysis tested for trends in change patterns. RESULTS: MonashWatch recruited 1373 suitable patients who were allocated into the groups: usual care (n=293) and intention-to-treat (n=1080; active telehealth: 471/1080, 43.6%; declined: 485, 44.9%; lost to follow-up: 178 /1080, 10.7%; died: 8/1080, 0.7%). Admission frequency of intention-to-treat compared to that of the usual care group did not significantly improve (P=.05), with a small number of very frequent admitters in the intention-to-treat group. Age, MonashWatch effective days active, and treatment group independently predicted bed days. The analysis of covariance demonstrated a reduction in bed days of 1.14 (P<.001) in the intention-to-treat group compared with that in the usual care group, with 1236 bed days estimated savings. Both groups demonstrated regression-to-the-mean. The downward trend in improved bed days was significantly greater (P<.001) in the intention-to-treat group (Sen slope -406) than in the usual care group (Sen slope -104). The net promoter score was 95% in the active telehealth group compared with typical hospital scores of 77%. CONCLUSIONS: Clinically and statistically meaningful reductions in acute hospital bed days in the intention-to-treat group when compared to that of the usual care group were demonstrated (P<.001), although admission frequency was unchanged with more short stay admissions in the intention-to-treat group. Nonrandomized control selection was a limitation. Nonetheless, MonashWatch was successful in the context of the HealthLinks: Chronic Care capitation initiative and is expanding.

The MAZ transcription factor is a downstream target of the oncoprotein Cyr61/CCN1 and promotes pancreatic cancer cell invasion via CRAF-ERK signaling.

Myc-associated zinc-finger protein (MAZ) is a transcription factor with dual roles in transcription initiation and termination. Deregulation of MAZ expression is associated with the progression of pancreatic ductal adenocarcinoma (PDAC). However, the mechanism of action of MAZ in PDAC progression is largely unknown. Here, we present evidence that MAZ mRNA expression and protein levels are increased in human PDAC cell lines, tissue samples, a subcutaneous tumor xenograft in a nude mouse model, and spontaneous cancer in the genetically engineered PDAC mouse model. We also found that MAZ is predominantly expressed in pancreatic cancer stem cells. Functional analysis indicated that MAZ depletion in PDAC cells inhibits invasive phenotypes such as the epithelial-to-mesenchymal transition, migration, invasion, and the sphere-forming ability of PDAC cells. Mechanistically, we detected no direct effects of MAZ on the expression of K-Ras mutants, but MAZ increased the activity of CRAF-ERK signaling, a downstream signaling target of K-Ras. The MAZ-induced activation of CRAF-ERK signaling was mediated via p21-activated protein kinase (PAK) and protein kinase B (AKT/PKB) signaling cascades and promoted PDAC cell invasiveness. Moreover, we found that the matricellular oncoprotein cysteine-rich angiogenic inducer 61 (Cyr61/CCN1) regulates MAZ expression via Notch-1-sonic hedgehog signaling in PDAC cells. We propose that Cyr61/CCN1-induced expression of MAZ promotes invasive phenotypes of PDAC cells not through direct K-Ras activation but instead through the activation of CRAF-ERK signaling. Collectively, these results highlight key molecular players in PDAC invasiveness and may help inform therapeutic strategies to improve clinical management and outcomes of PDAC.

Expert Elicitation for Estimation of the Proportion Foodborne for Selected Microbial Pathogens in New Zealand.

Objectives: To estimate the proportions of human cases of nine specific microbial diseases in New Zealand that were due to transmission by food and the proportion of the foodborne burden that was due to transmission by some specific foods. Materials and Methods: Subjective probability distributions were elicited from 10 food safety experts using a modified Delphi approach. In addition to uniform weighting of experts' opinions, two techniques were used to measure individual's expertise; self-assessment and performance-based weighting using Cooke's classical method. Aggregate estimates were derived by simulation. Results: Food was estimated to be the primary route of transmission for infections due to Campylobacter spp., Listeria monocytogenes, nontyphoid Salmonella spp., Vibrio parahaemolyticus, and Yersinia enterocolitica. Uncertainties were lowest for organisms where the self-assessed expertise level was highest. Conclusions: Foodborne proportion estimates were more "polarized" than for a similar elicitation in 2005. That is, where food was the primary transmission route the estimated proportion on account of food was higher (62.1-90.6% in the current study for self-assessed expertise weighted estimates, compared to 56.2-89.2% in 2005); where food was not the primary transmission route the estimated proportion because of food was lower (27.6-34.0% in the current study compared to 31.5-39.5% in 2005). These estimates represent an essential resource for determining the burden of foodborne disease in New Zealand.

What is the impact of systems of care for heart failure on patients diagnosed with heart failure: a systematic review.

BACKGROUND: Hospital admissions for heart failure are predicted to rise substantially over the next decade placing increasing pressure on the health care system. There is an urgent need to redesign systems of care for heart failure to improve evidence-based practice and create seamless transitions through the continuum of care. The aim of the review was to examine systems of care for heart failure that reduce hospital readmissions and/or mortality. METHOD: Electronic databases searched were: Ovid MEDLINE, EMBASE, CINAHL, grey literature, reviewed bibliographies and Cochrane Central Register of Controlled Trials for randomised controlled trials, non-randomised trials and cohort studies from 1st January 2008 to 4th August 2015. Inclusion criteria for studies were: English language, randomised controlled trials, non-randomised trials and cohort studies of systems of care for patients diagnosed with heart failure and aimed at reducing hospital readmissions and/or mortality. Three reviewer authors independently assessed articles for eligibility based on title and abstract and then full-text. Quality of evidence was assessed using Newcastle-Ottawa Scale for non-randomised trials and GRADE rating tool for randomised controlled trials. RESULTS: We included 29 articles reporting on systems of care in the workforce, primary care, in-hospital, transitional care, outpatients and telemonitoring. Several studies found that access to a specialist heart failure team/service reduced hospital readmissions and mortality. In primary care, a collaborative model of care where the primary physician shared the care with a cardiologist, improved patient outcomes compared to a primary physician only. During hospitalisation, quality improvement programs improved the quality of inpatient care resulting in reduced hospital readmissions and mortality. In the transitional care phase, heart failure programs, nurse-led clinics, and early outpatient follow-up reduced hospital readmissions. There was a lack of evidence as to the efficacy of telemonitoring with many studies finding conflicting evidence. CONCLUSION: Redesigning systems of care aimed at improving the translation of evidence into clinical practice and transitional care can potentially improve patient outcomes in a cohort of patients known for high readmission rates and mortality.

A double blind randomized placebo control crossover trial on the effect of dietary nitrate supplementation on exercise tolerance in stable moderate chronic obstructive pulmonary disease.

BACKGROUND: Dietary nitrate supplementation has been shown to decrease the oxygen cost of exercise and prolong exercise tolerance, as measured by sub-maximal exercise endurance distance and time at 85% V̇O2max, in both elite athletes and normal healthy subjects. Patients with chronic obstructive pulmonary disease (COPD) have reduced quality of life and ability to perform activities of daily living attributable to diminished exercise tolerance, and dietary nitrate may be able to ameliorate this. METHODS: We performed a double-blind, computer-randomized placebo control crossover trial at a tertiary Australian hospital to investigate whether dietary nitrate supplementation as beetroot juice (BR) would augment submaximal exercise endurance in individuals with spirometrically confirmed stable moderate COPD. Volunteers underwent an incremental shuttle walk test to determine V̇O2max followed by a test dose of BR to establish safety in the study population. Participants performed an endurance shuttle walk test (ESWT) at 85% V̇O2max after randomization to either a 3 day wash-in of BR (4.8 mmol twice a day) or placebo (nitrate deplete BR), with a final dose on the morning of testing. They then crossed over after 4 day washout. Repeated measures two sided paired t-tests were employed. RESULTS: 35 participants were recruited with 19 completing the trial. In the initial safety phase, we measured systolic blood pressure over four hours post first dose of BR, and found a mean 10 mmHg decrement maximal at 1 hour. One individual developed symptomatic postural hypotension and was excluded. The primary outcomes of ESWT distance and time to fatigue improved by 11% and 6% respectively; however these differences did not achieve statistical significance (p = 0.494 and 0.693 respectively). CONCLUSIONS: Our study does not support a role for routine dietary nitrate supplementation for enhancement of exercise endurance in COPD. TRIAL REGISTRATION: Australia and New Zealand Clinical Trial Register: ACTRN12611001088932.

How Critical is Patient Positioning in Radiographic Assessment of the Hip in Cerebral Palsy When Measuring Migration Percentage?

BACKGROUND: Migration percentage (MP) is an accepted method of assessing lateral displacement of the femoral head in children with cerebral palsy (CP). Difficulty in positioning of patients for pelvic radiography remains a concern for the reliability of the MP. METHODS: This 2-part quantitative study examined 100 anteroposterior pelvic radiographs for children with CP. Fifty were from a region that had a positioning protocol for hip surveillance of children with CP and 50 images were from a region without. Images were assessed for acceptability of position in relation to hip abduction/adduction and/or pelvic rotation.Ten images deemed Acceptable or Borderline from the region with no protocol were then randomly selected. MP was measured on 2 separate occasions by 5 children's orthopaedic surgeons and statistically analyzed for intrarater and interrater reliability. RESULTS: There was no statistically significant difference in the acceptability of images between the 2 regions with 60% to 66% of the images meeting the criteria outright. When allowances were made for slight variation of abduction/adduction within 5 degrees, 74% to 80% of the images were acceptable.Reliability was variable with limits of agreement between 4.96% and 15.15%. Observers more familiar with the software measuring package had higher reliability within and between occasions. Variability within and between observers decreased as MP increased. CONCLUSIONS: Poor positioning did not appear to be the main reason for the variation in reliability of MP. Repeat measurements were reliable although standardized technique, training, and familiarity with software measuring programmes did influence outcomes.

Geographic divergence of bovine and human Shiga toxin­producing Escherichia coli O157:H7 genotypes, New Zealand.

Shiga toxin-producing Escherichia coli (STEC)O157:H7 is a zoonotic pathogen of public health concern worldwide. To compare the local and large-scale geographic distributions of genotypes of STEC O157:H7 isolates obtained from various bovine and human sources during 2008­2011, we used pulsed-field gel electrophoresis and Shiga toxin­encoding bacteriophage insertion (SBI) typing. Using multivariate methods, we compared isolates from the North and South Islands of New Zealand with isolates from Australia and the United States. The STEC O157:H7 population structure differed substantially between the 2 islands and showed evidence of finer scale spatial structuring, which is consistent with highly localized transmission rather than disseminated foodborne outbreaks. The distribution of SBI types differed markedly among isolates from New Zealand, Australia, and the United States. Our findings also provide evidence for the historic introduction into New Zealand of a subset of globally circulating STEC O157:H7 strains that have continued to evolve and be transmitted locally between cattle and humans.

Who performs neonatal hip assessment: is there a cause for concern?

OBJECTIVE: The UK falls behind other European countries in the early detection of developmental dysplasia of the hip (DDH) and screening strategies differ for early detection. Clinical detection of DDH is challenging and recognised to be dependent on examiner experience. No studies exist assessing the number of personnel currently involved in such assessments.Our objective was to review the current screening procedure by studying a cohort of newborn babies in one teaching hospital and assess the number of health professionals involved in neonatal hip assessment and the number of examinations undertaken during one period by each individual. METHODS: This was a retrospective observational study assessing all babies born consecutively over a 14-week period in 2020. Record of each initial baby check was obtained from BadgerNet. Follow-up data on ultrasound or orthopaedic outpatient referrals were obtained from clinical records. RESULTS: 1037 babies were examined by 65 individual examiners representing 9 different healthcare professional groups. The range of examinations conducted per examiner was 1-97 with a median of 5.5 examinations per person. 49% of individuals examined 5 or less babies across the 14 weeks, with 18% only performing 1 examination. Of the six babies (0.48%) treated for DDH, one was picked up on neonatal assessment. CONCLUSION: In a system where so many examiners are involved in neonatal hip assessment, the experience is limited for most examiners. Currently high rates of late presentation of DDH are observed locally, which are in accordance with published national experience. The potential association merits further investigation.

A prospective case-control and molecular epidemiological study of human cases of Shiga toxin-producing Escherichia coli in New Zealand.

BACKGROUND: Shiga toxin-producing Escherichia coli (STEC) O157:H7 and related non-O157 STEC strains are enteric pathogens of public health concern worldwide, causing life-threatening diseases. Cattle are considered the principal hosts and have been shown to be a source of infection for both foodborne and environmental outbreaks in humans. The aims of this study were to investigate risk factors associated with sporadic STEC infections in humans in New Zealand and to provide epidemiological information about the source and exposure pathways. METHODS: During a national prospective case-control study from July 2011 to July 2012, any confirmed case of STEC infection notified to regional public health units, together with a random selection of controls intended to be representative of the national demography, were interviewed for risk factor evaluation. Isolates from each case were genotyped using pulsed-field gel electrophoresis (PFGE) and Shiga toxin-encoding bacteriophage insertion (SBI) typing. RESULTS: Questionnaire data from 113 eligible cases and 506 controls were analysed using multivariate logistic regression. Statistically significant animal and environmental risk factors for human STEC infections were identified, notably 'Cattle livestock present in meshblock' (the smallest geographical unit) (odds ratio 1.89, 95% CI 1.04-3.42), 'Contact with animal manure' (OR 2.09, 95% CI 1.12-3.90), and 'Contact with recreational waters' (OR 2.95, 95% CI 1.30-6.70). No food-associated risk factors were identified as sources of STEC infection. E. coli O157:H7 caused 100/113 (88.5%) of clinical STEC infections in this study, and 97/100 isolates were available for molecular analysis. PFGE profiles of isolates revealed three distinctive clusters of genotypes, and these were strongly correlated with SBI type. The variable 'Island of residence' (North or South Island of New Zealand) was significantly associated with PFGE genotype (p = 0.012). CONCLUSIONS: Our findings implicate environmental and animal contact, but not food, as significant exposure pathways for sporadic STEC infections in humans in New Zealand. Risk factors associated with beef and dairy cattle suggest that ruminants are the most important sources of STEC infection. Notably, outbreaks of STEC infections are rare in New Zealand and this further suggests that food is not a significant exposure pathway.

An outbreak of Salmonella Typhimurium phage type 42 associated with the consumption of raw flour.

A cluster of salmonellosis cases caused by Salmonella Typhimurium phage type 42 (STM42) emerged in New Zealand in October 2008. STM42 isolates from a wheat-based poultry feed raw material (broll; i.e., product containing wheat flour and particles of grain) had been identified in the 2 months prior to this cluster. Initial investigations indicated that eating uncooked baking mixture was associated with illness. A case-control study was conducted to test the hypothesis that there was an association between STM42 cases and consumption of raw flour or other baking ingredients. Salmonella isolates from human and non-human sources were compared using pulsed-field gel electrophoresis (PFGE) and multiple-locus variable number tandem repeat analysis (MLVA). Environmental investigations included testing flour and other baking ingredients from case homes, unopened bags of flour purchased from retail stores, and inspection of an implicated flour mill. A case-control study of 39 cases and 66 controls found cases had 4.5 times the odds of consuming uncooked baking mixture as controls (95% confidence interval [CI] 1.6-12.5, p-value 0.001). Examination of individual baking ingredients found that, after adjusting for eggs, flour had an odds ratio (OR) of 5.7 (95% CI 1.1-29.1, p-value 0.035). After adjusting for flour, eggs had an OR of 0.8 (95% CI 0.2-3.4, p-value 0.762). PFGE patterns were identical for all STM42 isolates tested; however, MLVA distinguished isolates that were epidemiologically linked to the cluster. STM42 was recovered from flour taken from four cases' homes, two unopened packs purchased from retail stores and packs from three batches of retrieved (recalled) product. This outbreak was associated with the consumption of uncooked baking mixture containing flour contaminated with STM42. The implicated flour mill initiated a voluntary withdrawal from sale of all batches of flour thought to be contaminated. Media releases informed the public about implicated flour brands and the risks of consuming uncooked baking mixture.

An Organocatalytic Oxy-Cope/Michael Cascade Reaction.

Ethyl diazepane carboxylate catalyzes the oxy-Cope rearrangement of 4-hydroxy- and 4-alkoxy-1,5-hexadiene-2-carboxaldehydes via iminium ion activation. The resulting intermediate undergoes an intramolecular Michael reaction to furnish cyclopentane-containing products. The reaction proceeds with a range of substrates, including both cyclic and acyclic substrates, and tolerates substitution on the vinyl substituent. Substrates fused on a cycloalkane framework undergo net ring expansion/cyclopentannulation with a high degree of stereocontrol via chairlike transition states. The reaction extends iminium organocatalysis to the oxy-Cope rearrangement, embedded within a complexity-generating cascade transformation.

A decade's experience of managing suspected pancreatic adenocarcinoma at a tertiary cancer center.

Background: We present our experience and established management strategy for endoscopic ultrasonography-guided fine-needle aspiration (EUS-FNA) in diagnosing suspected pancreatic neoplasms at a tertiary referral cancer hospital. Method: Relevant data were extracted from our database for patients who underwent EUS-FNA for suspected pancreatic neoplasms at our institution between 2007 and 2016. Results: Among the 309 patients, the median age was 67 years and 56% were men. The most common presenting symptoms were abdominal pain (37%) and jaundice (29%). Concordance between radiographic diagnosis and final pathology was 89%. The mean lesion size was 34.9 mm on computed tomography and 31.5 mm on EUS. There were 197 patients (64%) with localized disease, of whom 115 (58%) had resectable lesions, 61 (31%) had borderline resectable, and 21 (11%) had unresectable lesions (mean CA 19-9 levels 1705 U/mL, 2490 U/mL, and 479 U/mL, respectively). A median of 3 FNA passes were performed to establish a pathologic diagnosis. Two patients (1%) had postprocedural adverse events. Median overall survival was 47 months in those who underwent surgery after EUS and 12 months in those who did not (P<0.001). Conclusions: A multidisciplinary approach is employed for management of suspected pancreatic neoplasm at our tertiary cancer center. A combination of cross-sectional imaging and EUS-FNA serves as a highly effective duo in establishing a tissue diagnosis and staging with a low adverse event rate. Counterintuitively, CA 19-9 is not necessarily higher with resectable lesions than with unresectable lesions, indicating the limitation of CA 19-9 as a pancreatic tumor marker.

Cysteine-rich 61-connective tissue growth factor-nephroblastoma-overexpressed 5 (CCN5)/Wnt-1-induced signaling protein-2 (WISP-2) regulates microRNA-10b via hypoxia-inducible factor-1α-TWIST signaling networks in human breast cancer cells.

MicroRNAs (miRNAs) are naturally occurring single-stranded RNA molecules that post-transcriptionally regulate the expression of target mRNA transcripts. Many of these target mRNA transcripts are involved in regulating processes commonly altered during tumorigenesis and metastatic growth. These include cell proliferation, differentiation, apoptosis, migration, and invasion. Among the several miRNAs, miRNA-10b (miR-10b) expression is increased in metastatic breast cancer cells and positively regulates cell migration and invasion through the suppression of the homeobox D10 (HOXD10) tumor suppressor signaling pathway. In breast metastatic cells, miR-10b expression is enhanced by a transcription factor TWIST1. We find that miR-10b expression in breast cancer cells can be suppressed by CCN5, and this CCN5 effect is mediated through the inhibition of TWIST1 expression. Moreover, CCN5-induced inhibition of TWIST1 expression is mediated through the translational inhibition/modification of hypoxia-inducible factor-1α via impeding JNK signaling pathway. Collectively, these studies suggest a novel regulatory pathway exists through which CCN5 exerts its anti-invasive function. On the basis of these findings, it is plausible that reactivation of CCN5 in miR-10b-positive invasive/metastatic breast cancers alone or in combination with current therapeutic regimens could provide a unique, alternative strategy to existing breast cancer therapy.

No evidence for thick deposits of ice at the lunar south pole.

Shackleton crater at the Moon's south pole has been suggested as a possible site of concentrated deposits of water ice, on the basis of modelling of bi-static radar polarization properties and interpretations of earlier Earth-based radar images. This suggestion, and parallel assumptions about other topographic cold traps, is a significant element in planning for future lunar landings. Hydrogen enhancements have been identified in the polar regions, but these data do not identify the host species or its local distribution. The earlier Earth-based radar data lack the resolution and coverage for detailed studies of the relationship between radar scattering properties, cold traps in permanently shadowed areas, and local terrain features such as the walls and ejecta of small craters. Here we present new 20-m resolution, 13-cm-wavelength radar images that show no evidence for concentrated deposits of water ice in Shackleton crater or elsewhere at the south pole. The polarization properties normally associated with reflections from icy surfaces in the Solar System were found at all the observed latitudes and are strongly correlated with the rock-strewn walls and ejecta of young craters, including the inner wall of Shackleton. There is no correlation between the polarization properties and the degree of solar illumination. If the hydrogen enhancement observed by the Lunar Prospector orbiter indicates the presence of water ice, then our data are consistent with the ice being present only as disseminated grains in the lunar regolith.