AMP-activated protein kinase activation suppresses leptin expression independently of adipogenesis in primary murine adipocytes.

Adipogenesis, defined as the development of mature adipocytes from stem cell precursors, is vital for the expansion, turnover and health of adipose tissue. Loss of adipogenic potential in adipose stem cells, or impairment of adipogenesis is now recognised as an underlying cause of adipose tissue dysfunction and is associated with metabolic disease. In this study, we sought to determine the role of AMP-activated protein kinase (AMPK), an evolutionarily conserved master regulator of energy homeostasis, in adipogenesis. Primary murine adipose-derived stem cells were treated with a small molecule AMPK activator (BI-9774) during key phases of adipogenesis, to determine the effect of AMPK activation on adipocyte commitment, maturation and function. To determine the contribution of the repression of lipogenesis by AMPK in these processes, we compared the effect of pharmacological inhibition of acetyl-CoA carboxylase (ACC). We show that AMPK activation inhibits adipogenesis in a time- and concentration-dependent manner. Transient AMPK activation during adipogenic commitment leads to a significant, ACC-independent, repression of adipogenic transcription factor expression. Furthermore, we identify a striking, previously unexplored inhibition of leptin gene expression in response to both short-term and chronic AMPK activation irrespective of adipogenesis. These findings reveal that in addition to its effect on adipogenesis, AMPK activation switches off leptin gene expression in primary mouse adipocytes independently of adipogenesis. Our results identify leptin expression as a novel target of AMPK through mechanisms yet to be identified.

Novel variant Hendra virus genotype 2 infection in a horse in the greater Newcastle region, New South Wales, Australia.

In October 2021, the first contemporary detection of Hendra virus genotype 2 (HeV-g2) was made by veterinary priority disease investigation in a horse near Newcastle, New South Wales, Australia, as part of routine veterinary priority disease surveillance. This discovery followed an update of Hendra virus diagnostic assays following retrospective identification of this variant from 2015 via sentinel emerging infectious disease research, enabling timely detection of this case. The sole infected horse was euthanized in moribund condition. As the southernmost recognised HeV spill-over detection to date, it extends the southern limit of known cases by approximately 95 km. The event occurred near a large urban centre, characterised by equine populations of diverse type, husbandry, and purpose, with low HeV vaccination rates. Urgent multi-agency outbreak response involved risk assessment and monitoring of 11 exposed people and biosecurity management of at-risk animals. No human or additional animal cases were recognised. This One Health investigation highlights need for research on risk perception and strategic engagement to support owners confronted with the death of companion animals and potential human exposure to a high consequence virus. The location and timing of this spill-over event diverging from that established for prototype HeV (HeV-g1), highlight benefit in proactive One Health surveillance and research activities that improve understanding of dynamic transmission and spill-over risks of both HeV genotypic lineages and related but divergent emerging pathogens.

Impact of radiopacified bone cement on radiotherapy dose calculation.

BACKGROUND AND PURPOSE: Radiopacifiers are introduced to bone cements to provide the appearance of bone in kilovoltage (kV) radiographic images. For higher energy megavoltage (MV) radiotherapy treatment beams, however, these radiopacifiers do not cause a bone-like perturbation of dose. This study therefore aimed to determine the impact of the barium-contrasted plastic-based cement materials on radiotherapy dose calculations. MATERIALS AND METHODS: The radiological properties of a physical sample of bone cement were characterised by computed tomography (CT) imaging and transmission measurements. Monte Carlo simulations of percentage depth-dose profiles were performed to determine the possible dose error for MV treatment beams. Dose differences were then investigated for clinical volumetric modulated radiotherapy treatment plans, with and without density overrides applied. RESULTS: Differences of up to 7% were observed at the downstream interface of a 0.6 cm thick bone cement layer, compared to bone. Differences in planning target volume dose-volume metrics varied between -0.5% and 2.0%. CONCLUSION: Before planning radiotherapy treatments for patients who have undergone cranioplasty, every effort should be made to identify whether a radiopacified bone cement has been implanted. Density overrides should be applied to minimise dose calculation errors, whenever bone cement is used.

'Solemnis(ing) beginnings': theories of same-sex marriage in the USA and South Africa.

This paper explores arguments for and against same-sex marriage as 'movement advocacy' in the USA as a backdrop to the proposition that, despite the influence of US discourses on South African debates about same-sex marriage, US discussions are less important to understanding South African responses than controversies about marriage itself in the country. The paper works in two sections. First it sketches legal and critical tensions within the USA around the implications of same-sex marriage activism, drawing on work from Franke, Brandzel, Grossman, Puar and others. Second, it notes arguments on queer homonationalisms, made most forcefully by Puar, concerning the effects and interests of 'exporting' US legal ideals to countries elsewhere, especially poorer countries. It then moves to offer suggestions for ways of nuancing this argument through stronger critical attention to context concerning radically shifting notions of marriage within those countries themselves, using South Africa as a case study. This section draws on recent work by Judge, van Zyl, Scott, Mkhize and Adebayo and Nyameza, among others.

A longitudinal study of speech timing in young children later found to have reading disability.

PURPOSE: This study examined the development of timing characteristics in early spontaneous speech of children who were later identified as having reading disability (RD). METHOD: Child-adult play sessions were recorded longitudinally at 2 and 3 years of age in 27 children, most of whom were at high familial risk for RD. For each speaking turn, the number of syllables was determined and an acoustic analysis measured the time allocated to articulation, pausing before speaking, and pausing during speaking. RESULTS: In grade school, a reading battery identified 9 children with RD and 18 children without RD (9 at high risk, 9 at low risk). Early speaking rate was significantly slower in the group with RD, with significantly different patterns of pausing compared with children without RD. Group differences became more distinct by age 3, as longer speaking turns were attempted. CONCLUSIONS: The results are discussed in terms of speech and language formulation. Phonetic plans may be shorter and/or less specified in children with RD, surfacing as slow, short speaking turns with increased pausing relative to articulation. This explanation is consistent with several accounts of RD and provides a perspective on how speech and language deficits may manifest during spontaneous verbal interactions between young children and adults.

Reduced speaking rate as an early predictor of reading disability.

PURPOSE: This study evaluated whether developmental reading disability could be predicted in children at the age of 30 months, according to 3 measures of speech production: speaking rate, articulation rate, and the proportion of speaking time allocated to pausing. METHOD: Speech samples of 18 children at high risk and 10 children at low risk for reading disability were recorded at 30 months of age. High risk was determined by history of reading disability in at least 1 of the child's parents. In grade school, a reading evaluation identified 9 children within the high-risk group as having reading disability and 9 children as not having reading disability. The 10 children at low risk for reading disability tested negative for reading disability. RESULTS: Children with reading disability showed a significantly slower speaking rate than children at high risk without reading disability. Children with reading disability allocated significantly more time to pausing, as compared with the other groups. Articulation rate did not differ significantly across groups. CONCLUSIONS: Speaking rate and the proportion of pausing time to speaking time may provide an early indication of reading outcome in children at high risk for reading disability.

Diagnostic value of written referral and/or images for skin lesions.

We examined whether it is possible for a dermatologist to diagnose benign and malignant skin lesions by telemedicine, given a comprehensive history and/or clinical images. A medical student recorded a standardized history and description of 109 skin lesions and took digital photographs of the presenting lesion(s) immediately prior to a normal outpatient dermatology consultation. About 52 dermatologists were invited to participate in online diagnosis. In all, 38 took part and they were provided with the text and/or the image(s) online on a secure Website. When the images and text were provided, 53% of teledermatology diagnoses were the same as the face-to-face diagnosis. When images alone were provided, 57% of diagnoses were the same. When text alone was provided, 41% of diagnoses were the same. The relatively low diagnostic concordance may have been due to the inexperience of many teledermatologists and poor quality image display systems. The teledermatologists were less confident in their diagnoses than face-to-face specialists, especially in the absence of images. The teledermatology management plan was more likely to include biopsy, excision or review than was the case at the face-to-face consultation. Teledermatology may result in an increase in follow-up appointments and surgical procedures.