Circulating microRNAs as Specific Biomarkers for Breast Cancer Detection

Background: We previously showed microRNAs (miRNAs) in plasma are potential biomarkers for colorectal cancer detection. Here, we aimed to develop specific blood-based miRNA assay for breast cancer detection. Methodology/Principal Findings: TaqMan-based miRNA profiling was performed in tumor, adjacent non-tumor, corresponding plasma from breast cancer patients, and plasma from matched healthy controls. All putative markers identified were verified in a training set of breast cancer patients. Selected markers were validated in a case-control cohort of 170 breast cancer patients, 100 controls, and 95 other types of cancers and then blindly validated in an independent set of 70 breast cancer patients and 50 healthy controls. Profiling results showed 8 miRNAs were concordantly up-regulated and 1 miRNA was concordantly down-regulated in both plasma and tumor tissue of breast cancer patients. Of the 8 up-regulated miRNAs, only 3 were significantly elevated (p<0.0001) before surgery and reduced after surgery in the training set. Results from the validation cohort showed that a combination of miR-145 and miR-451 was the best biomarker (p<0.0001) in discriminating breast cancer from healthy controls and all other types of cancers. In the blind validation, these plasma markers yielded Receiver Operating Characteristic (ROC) curve area of 0.931. The positive predictive value was 88% and the negative predictive value was 92%. Altered levels of these miRNAs in plasma have been detected not only in advanced stages but also early stages of tumors. The positive predictive value for ductal carcinoma in situ (DCIS) cases was 96%. Conclusions: These results suggested that these circulating miRNAs could be a potential specific biomarker for breast cancer screening. © 2013 Ng et al.published_or_final_versio

Prevalence and factors associated with anxiety during the COVID-19 pandemic among Malaysians: a cross-sectional study

The COVID-19 pandemic is a significant public health threat with wide-reaching psychological implications. The drastic changes in lifestyle due to the implementation of the movement control order (MCO) were associated with adverse effects on mental health. This study aimed to examine the prevalence of anxiety among Malaysians during the COVID-19 pandemic and its associated factors. The following questionnaires were self-administered online through google form which included: (i) Generalised Anxiety Disorder-7; (ii) Short Boredom Proneness Scale; (iii) Short Scale for Measuring Loneliness in Large Surveys; and (iv) The World Health Organisation (WHO) well-being index. Higher scores denoted higher levels of anxiety, boredom, loneliness, and well-being. Out of the 543 participants, more than half (55.2%) reported mild (25.6%), moderate (13.8%) to severe (19.8%) anxiety. Multiple logistic regression showed higher odds of moderate to severe anxiety were reported among those divorced/separated/widowed (aOR 6.778, 95% CI [1.200, 38.296]), adults aged 25 to 34 years (aOR 2.038, 95% CI [1.049, 3.958]), 35 to 44 years (aOR 2.279, 95% CI [1.064, 4.882]), and with higher boredom levels (aOR 1.063, 95% CI [1.035, 1.092]). One in five Malaysians surveyed experienced severe anxiety. Adults within the working age range (between 25 and 44 years old) were at higher odds of having anxiety. Boredom increased the odds of anxiety compared to loneliness, well-being and coping. Thus, addressing the risk factors through public health messages is deemed important

The MothersBabies Study, an Australian Prospective Cohort Study Analyzing the Microbiome in the Preconception and Perinatal Period to Determine Risk of Adverse Pregnancy, Postpartum, and Child-Related Health Outcomes: Study Protocol

The microbiome has emerged as a key determinant of human health and reproduction, with recent evidence suggesting a dysbiotic microbiome is implicated in adverse perinatal health outcomes. The existing research has been limited by the sample collection and timing, cohort design, sample design, and lack of data on the preconception microbiome. This prospective, longitudinal cohort study will recruit 2000 Australian women, in order to fully explore the role of the microbiome in the development of adverse perinatal outcomes. Participants are enrolled for a maximum of 7 years, from 1 year preconception, through to 5 years postpartum. Assessment occurs every three months until pregnancy occurs, then during Trimester 1 (5 + 0–12 + 6 weeks gestation), Trimester 2 (20 + 0–24 + 6 weeks gestation), Trimester 3 (32 + 0–36 + 6 weeks gestation), and postpartum at 1 week, 2 months, 6 months, and then annually from 1 to 5 years. At each assessment, maternal participants self-collect oral, skin, vaginal, urine, and stool samples. Oral, skin, urine, and stool samples will be collected from children. Blood samples will be obtained from maternal participants who can access a study collection center. The measurements taken will include anthropometric, blood pressure, heart rate, and serum hormonal and metabolic parameters. Validated self-report questionnaires will be administered to assess diet, physical activity, mental health, and child developmental milestones. Medications, medical, surgical, obstetric history, the impact of COVID-19, living environments, and pregnancy and child health outcomes will be recorded. Multiomic bioinformatic and statistical analyses will assess the association between participants who developed high-risk and low-risk pregnancies, adverse postnatal conditions, and/or childhood disease, and their microbiome for the different sample types

The Use of a Compression Device as an Alternative to Hand-Sewn and Stapled Colorectal Anastomoses: Is Three a Crowd?

BackgroundThe NiTi CAR™ 27 is a newer device that uses compression to create an anastomosis. An analysis of this device in the creation of colorectal anastomoses in humans has yet to be reported in the USA.MethodsA non-randomized, prospective pilot study of the NiTi CAR™ 27 device in patients undergoing a left-sided colectomy between March 2008 and August 2009 was performed.ResultsTwenty-three patients (9 men and 14 women) underwent a left-sided colectomy and compression anastomosis with the CAR™ 27 device. Minor morbidities, 3 of 23 (13%) patients, included one small postoperative abscess requiring antibiotics alone and two postoperative anastomotic strictures requiring balloon dilation. Major morbidities, 1 of 23 (4%) patients, included a partial anastomotic dehiscence/leak requiring surgical dismantling of the anastomosis and diversion.ConclusionThe CAR™ 27 device shows promise as a safe and effective alternative for the creation of colorectal anastomoses. However, studies in a larger patient population are warranted to demonstrate equivalence of this device

Comparison of Mortality Outcomes in Acute Myocardial Infarction Patients With or Without Standard Modifiable Cardiovascular Risk Factors

Background: Acute myocardial infarction (AMI) cases have decreased in part due to the advent of targeted therapies for standard modifiable cardiovascular disease risk factors (SMuRF). Recent studies have reported that ST-elevation myocardial infarction (STEMI) patients without SMuRF (termed "SMuRF-less") may be increasing in prevalence and have worse outcomes than "SMuRF-positive" patients. As these studies have been limited to STEMI and comprised mainly Caucasian cohorts, we investigated the changes in the prevalence and mortality of both SMuRF-less STEMI and non-STEMI (NSTEMI) patients in a multiethnic Asian population. Methods: We evaluated 23,922 STEMI and 62,631 NSTEMI patients from a national multiethnic registry. Short-term cardiovascular and all-cause mortalities in SMuRF-less patients were compared to SMuRF-positive patients. Results: The proportions of SMuRF-less STEMI but not of NSTEMI have increased over the years. In hospitals, all-cause and cardiovascular mortality and 1-year cardiovascular mortality were significantly higher in SMuRF-less STEMI after adjustment for age, creatinine, and hemoglobin. However, this difference did not remain after adjusting for anterior infarction, cardiopulmonary resuscitation (CPR), and Killip class. There were no differences in mortality in SMuRF-less NSTEMI. In contrast to Chinese and Malay patients, SMuRF-less patients of South Asian descent had a two-fold higher risk of in-hospital all-cause mortality even after adjusting for features of increased disease severity. Conclusion: SMuRF-less patients had an increased risk of mortality with STEMI, suggesting that there may be unidentified nonstandard risk factors predisposing SMuRF-less patients to a worse prognosis. This group of patients may benefit from more intensive secondary prevention strategies to improve clinical outcomes

Satellite Telemetry and Long-Range Bat Movements

Background: Understanding the long-distance movement of bats has direct relevance to studies of population dynamics, ecology, disease emergence, and conservation. Methodology/Principal Findings: We developed and trialed several collar and platform terminal transmitter (PTT) combinations on both free-living and captive fruit bats (Family Pteropodidae: Genus Pteropus). We examined transmitter weight, size, profile and comfort as key determinants of maximized transmitter activity. We then tested the importance of bat-related variables (species size/weight, roosting habitat and behavior) and environmental variables (day-length, rainfall pattern) in determining optimal collar/PTT configuration. We compared battery- and solar-powered PTT performance in various field situations, and found the latter more successful in maintaining voltage on species that roosted higher in the tree canopy, and at lower density, than those that roost more densely and lower in trees. Finally, we trialed transmitter accuracy, and found that actual distance errors and Argos location class error estimates were in broad agreement. Conclusions/Significance: We conclude that no single collar or transmitter design is optimal for all bat species, and that species size/weight, species ecology and study objectives are key design considerations. Our study provides a strategy for collar and platform choice that will be applicable to a larger number of bat species as transmitter size and weight continue to decrease in the future

Analysis of RNA splicing defects in PITX2 mutants supports a gene dosage model of Axenfeld-Rieger syndrome

BACKGROUND: Axenfeld-Rieger syndrome (ARS) is associated with mutations in the PITX2 gene that encodes a homeobox transcription factor. Several intronic PITX2 mutations have been reported in Axenfeld-Rieger patients but their effects on gene expression have not been tested. METHODS: We present two new families with recurrent PITX2 intronic mutations and use PITX2c minigenes and transfected cells to address the hypothesis that intronic mutations effect RNA splicing. Three PITX2 mutations have been analyzed: a G>T mutation within the AG 3' splice site (ss) junction associated with exon 4 (IVS4-1G>T), a G>C mutation at position +5 of the 5' (ss) of exon 4 (IVS4+5G>C), and a previously reported A>G substitution at position -11 of 3'ss of exon 5 (IVS5-11A>G). RESULTS: Mutation IVS4+5G>C showed 71% retention of the intron between exons 4 and 5, and poorly expressed protein. Wild-type protein levels were proportionally expressed from correctly spliced mRNA. The G>T mutation within the exon 4 AG 3'ss junction shifted splicing exclusively to a new AG and resulted in a severely truncated, poorly expressed protein. Finally, the A>G substitution at position -11 of the 3'ss of exon 5 shifted splicing exclusively to a newly created upstream AG and resulted in generation of a protein with a truncated homeodomain. CONCLUSION: This is the first direct evidence to support aberrant RNA splicing as the mechanism underlying the disorder in some patients and suggests that the magnitude of the splicing defect may contribute to the variability of ARS phenotypes, in support of a gene dosage model of Axenfeld-Rieger syndrome