Per- and Polyfluoroalkyl Substances and Bone Mineral Density in Mid-childhood

Background: • Identifying factors that impair bone accrual during childhood is a critical step toward osteoporosis prevention. • One potential risk factor not well characterized in childhood is the role of chemicals in the environment. • Perfluoroalkyl substances (PFASs) are synthetic additives used to make clothing, furniture, and cookware stain repellant and are detectable in almost all US adults. • PFASs act as PPAR-γ agonists,2 androgen receptor antagonists, and directly intercalate into bone, raising the possibility that they may lead to low bone accrual. • While two population-based studies in adults have shown associations between PFASs and low areal bone mineral density (aBMD),5,6 the extent to which PFASs may affect aBMD in children is unknown

Actin and myosin contribute to mammalian mitochondrial DNA maintenance.

Mitochondrial DNA maintenance and segregation are dependent on the actin cytoskeleton in budding yeast. We found two cytoskeletal proteins among six proteins tightly associated with rat liver mitochondrial DNA: non-muscle myosin heavy chain IIA and β-actin. In human cells, transient gene silencing of MYH9 (encoding non-muscle myosin heavy chain IIA), or the closely related MYH10 gene (encoding non-muscle myosin heavy chain IIB), altered the topology and increased the copy number of mitochondrial DNA; and the latter effect was enhanced when both genes were targeted simultaneously. In contrast, genetic ablation of non-muscle myosin IIB was associated with a 60% decrease in mitochondrial DNA copy number in mouse embryonic fibroblasts, compared to control cells. Gene silencing of β-actin also affected mitochondrial DNA copy number and organization. Protease-protection experiments and iodixanol gradient analysis suggest some β-actin and non-muscle myosin heavy chain IIA reside within human mitochondria and confirm that they are associated with mitochondrial DNA. Collectively, these results strongly implicate the actomyosin cytoskeleton in mammalian mitochondrial DNA maintenance.Medical Research Council; the European Union; the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development and National Heart; Lung and Blood Institute; National Institutes of Health and grants [CMRPG360491-2, 380651, NSC 97-2321-B-182A-002-MY2] from the Chang Gung Memorial Hospital, Lin-Kou, Taiwan (to C.C.M.). Funding for open access charge: Medical Research Council

A randomised non-inferiority controlled trial of a single versus a four intradermal sterile water injection technique for relief of continuous lower back pain during labour

Background: Almost one third of women suffer continuous lower back pain during labour. Evidence from three systematic reviews demonstrates that sterile water injections (SWI) provide statistically and clinically significant pain relief in women experiencing continuous lower back pain during labour. The most effective technique to administer SWI is yet to be determined. Therefore, the aim of this study is to determine if the single injection SWI technique is no less effective than the routinely used four injection SWI method in reducing continuous lower back pain during labour.Methods/design: The trial protocol was developed in consultation with an interdisciplinary team of clinical researchers. We aim to recruit 319 women presenting at term, seeking analgesia for continuous severe lower back pain during labour. Participants will be recruited from two major maternity hospitals in Australia. Randomised participants are allocated to receive a four or single intradermal needle SWI technique. The primary outcome is the change in self-reported pain measured by visual analogue scale at baseline and thirty minutes post intervention. Secondary outcomes include VAS change scores at 10, 60, 90 and 120 min, analgesia use, mode of birth and maternal satisfaction.Statistical analysis: Sample size was calculated to achieve 90% power at an alpha of 0.025 to detect a non-inferiority margin of ≤ 1 cm on the VAS, using a one-sided, two-sample t-test. Baseline demographic and clinical characteristics will be analysed for comparability between groups. Differences in primary (VAS pain score) and secondary outcomes between groups will be analysed by intention to treat and per protocol analysis using Student's t-test and ANOVA.Conclusion: This study will determine if a single intradermal SWI technique is no less effective than the routinely used four injection technique for lower back pain during labour. The findings will allow midwives to offer women requesting SWI during labour an evidence-based alternative technique more easily administered by staff and accepted by labouring women. Trial Registration: ACTRN12609000964213

Severe male infertility after failed ICSI treatment-a phenomenological study of men's experiences

<p>Abstract</p> <p>Background</p> <p>Male-factor infertility underlies approximately 30% of infertility in couples seeking treatment; of which 10% is due to azoospermia. The development of assisted reproductive technology (ART), enabling the use of epididymal or testicular sperm for fertilization of the partner's oocytes, has made biological fatherhood possible for men with obstructive azoospermia. There is limited knowledge of men's experience of their own infertility. The aim of this study was to describe men's experiences of obstructive azoospermia infertility.</p> <p>Methods</p> <p>Eight men with obstructive azoospermia, who had terminated Swedish public health system ART treatment two years previously without subsequent childbirth, were interviewed using a descriptive phenomenological method.</p> <p>Results</p> <p>The essence of the phenomenon is expressed with a metaphor: climbing a mountain step by step with the aim of reaching the top, i.e. having a child and thus a family with a child. Four constituents are included (1) inadequacy followed by a feeling of redress (2) marginalisation, (3) chivalry (4) extension of life and starting a family as driving forces.</p> <p>Conclusions</p> <p>Knowledge of men's experiences of their own infertility is important as a supporting measure to increase the quality of care of infertile couples. By adopting this facet of gender perspective in fertility treatment guidelines, care can hopefully be optimized.</p

Expression of Linear and Novel Circular Forms of an INK4/ARF-Associated Non-Coding RNA Correlates with Atherosclerosis Risk

Human genome-wide association studies have linked single nucleotide polymorphisms (SNPs) on chromosome 9p21.3 near the INK4/ARF (CDKN2a/b) locus with susceptibility to atherosclerotic vascular disease (ASVD). Although this locus encodes three well-characterized tumor suppressors, p16INK4a, p15INK4b, and ARF, the SNPs most strongly associated with ASVD are ∼120 kb from the nearest coding gene within a long non-coding RNA (ncRNA) known as ANRIL (CDKN2BAS). While individuals homozygous for the atherosclerotic risk allele show decreased expression of ANRIL and the coding INK4/ARF transcripts, the mechanism by which such distant genetic variants influence INK4/ARF expression is unknown. Here, using rapid amplification of cDNA ends (RACE) and analysis of next-generation RNA sequencing datasets, we determined the structure and abundance of multiple ANRIL species. Each of these species was present at very low copy numbers in primary and cultured cells; however, only the expression of ANRIL isoforms containing exons proximal to the INK4/ARF locus correlated with the ASVD risk alleles. Surprisingly, RACE also identified transcripts containing non-colinear ANRIL exonic sequences, whose expression also correlated with genotype and INK4/ARF expression. These non-polyadenylated RNAs resisted RNAse R digestion and could be PCR amplified using outward-facing primers, suggesting they represent circular RNA structures that could arise from by-products of mRNA splicing. Next-generation DNA sequencing and splice prediction algorithms identified polymorphisms within the ASVD risk interval that may regulate ANRIL splicing and circular ANRIL (cANRIL) production. These results identify novel circular RNA products emanating from the ANRIL locus and suggest causal variants at 9p21.3 regulate INK4/ARF expression and ASVD risk by modulating ANRIL expression and/or structure

A novel protocol to assess the impact of prescription stimulants on blood pressure in adults using ambulatory blood pressure monitoring

Prescription stimulants are an important cause of secondary hypertension and their use is increasing in adult patients who are also at risk for essential hypertension. Although stimulants increase blood pressure, a systematic approach for assessing their impact in individual patients is lacking. We developed a protocol using ambulatory blood pressure monitoring for up to 36 h to compare blood pressure over two sequential days. Average blood pressure on the first day (without stimulant medication) was compared to average blood pressure on the second day (after re‐starting stimulant medication). We describe the outcomes of this protocol for a case series of eleven adults. Patients demonstrated one of three outcomes: normal blood pressure on both days, hypertension on both days, or hypertension only on the day patients received their stimulant medications. This novel protocol provides valuable information on the blood pressure effects of stimulant medications and allows clinicians to make personalized decisions regarding treatment

Development of a marine icing monitoring system

A Marine Icing Monitoring System (MIMS) has been developed and deployed on a Marine Atlantic ferry and two offshore supply vessels. The MIMS is a visual based technology for monitoring marine icing accumulation on offshore rigs and vessels where icing poses operational and safety hazards. The system consists of a CPU connected to two high-resolution digital cameras that are positioned to view expansive areas, or smaller areas depending on requirements, where icing could occur when environmental conditions are within certain parameters. The system is stand-alone, requiring no maintenance and needing only a standard 110 VAC power source. All components of the system are weatherproofed so that installation can be anywhere on the deck or superstructure of a facility. The computer controls each camera so that pictures are taken at regular intervals (every 12 minutes) and stored on the computer\u2019s large-capacity hard drive. Data are retrieved from the hard drive at the end of the icing season each year. The system has a satellite phone so that it can be checked and controlled from IOT. Thumbnail images can be quickly downloaded to monitor current conditions at the site, and the cameras can be controlled to zoom in or out. Visual data from the system\u2019s deployments are presented along with some discussion of image analysis strategies, including real-time assessment of icing accumulation. Past and on-going development hurdles are also discussed.Peer reviewed: NoNRC publication: Ye

Pharmacist‐led rapid medication titration for hypertension management by telehealth: A quality improvement initiative

Abstract Hypertension guidelines recommend team‐based care for the treatment of high blood pressure (BP). Clinical pharmacists can help patients get to goal BP with rapid medication titration in conjunction with telehealth visits. We conducted a pharmacist‐led home BP monitoring pilot program from June 2020 to September 2021. Forty‐two patients with a SBP ≥140 despite using ≤2 antihypertensive medications were referred for pharmacist telehealth with expedited medication titration to achieve a BP goal <130/80. The mean enrollment SBP/DBP was 155.2 (SD, 15.8)/89.7 (SD, 11.5) mm Hg, and the mean completion SBP/DBP was 132.1 (SD, 10.9)/77.6 (SD, 10). The number of hypertension medications prescribed increased from 1.3 to 1.6 with no instances of falls or hypotension. At completion, 31% of patients had an automated office blood pressure (AOBP) with SBP <130 mm Hg and DBP <80 mm Hg. A pharmacist‐led, home BP monitoring telehealth pilot program helped patients safely achieve BP goals